Digital Commons Network^™

Higher Adherence To A Mediterranean Diet Is Associated With Improved Insulin Sensitivity And Selected Markers Of Inflammation In Individuals Who Are Overweight And Obese Without Diabetes, Surbhi Sood, Jack Feehan, Catherine Itsiopoulos, Kirsty Wilson, Magdalena Plebanski, David Scott, James Hébert Scd, Nitin Shivappa Mbbs, Mph, Ph.D., Aya Mousa, Elena S. George, Barbora De Courten

Faculty Publications

Insulin resistance (IR) and chronic low-grade inflammation are risk factors for chronic diseases including type 2 diabetes (T2D) and cardiovascular disease. This study aimed to investigate two dietary indices: Mediterranean Diet Score (MDS) and Dietary Inflammatory Index (DII®), and their associations with direct measures of glucose metabolism and adiposity, and biochemical measures including lipids, cytokines and adipokines in overweight/obese adults. This cross-sectional study included 65 participants (males = 63%; age 31.3 ± 8.5 years). Dietary intake via 3-day food diaries was used to measure adherence to MDS (0–45 points); higher scores indicating adherence. Energy-adjusted DII (E-DII) scores were calculated with …

Perturbative Theoretical Model Of Electronic Transient Circular Dichroism Spectroscopy Of Molecular Aggregates, Paul C. Arpin, Daniel B. Turner

Materials Science and Engineering Faculty Publications and Presentations

A chiral analog of transient absorption spectroscopy, transient circular dichroism (TCD) spectroscopy is an emerging time-resolved method. Both spectroscopic methods can probe the electronic transitions of a sample, and TCD is additionally sensitive to the dynamic aspects of chirality, such as those induced by molecular excitons. Here, we develop a theoretical description of TCD for electronic multi-level models in which the pump pulse is linearly polarized and probe pulse is alternately left- and right-circularly polarized. We derive effective response functions analogous to those often used to describe other four-wave mixing methods and then simulate and analyze TCD spectra for three …

Structure Of The Pre-Mrna Leakage 39-Kda Protein Reveals A Single Domain Of Integrated Zf-C3hc And Rsm1 Modules, Hideharu Hashimoto, Daniel H. Ramirez, Ophélie Lautier, Natalie Pawlak, Günter Blobel, Benoît Palancade, Erik W. Debler

Department of Biochemistry and Molecular Biology Faculty Papers

In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP …

A Machine Learning Model Of Response To Hypomethylating Agents In Myelodysplastic Syndromes, Nathan Radakovich, David A. Sallman, Rena Buckstein, Andrew Brunner, Amy Dezern, Sudipto Mukerjee, Rami Komrokji, Najla Al-Ali, Jacob Shreve, Yazan Rouphail, Anne Parmentier, Alexandre Mamedov, Mohammed Siddiqui, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal Jha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Aziz Nazha

Department of Medical Oncology Faculty Papers

Hypomethylating agents (HMA) prolong survival and improve cytopenias in individuals with higher-risk myelodysplastic syndrome (MDS). Only 30-40% of patients, however, respond to HMAs, and responses may not occur for more than 6 months after HMA initiation. We developed a model to more rapidly assess HMA response by analyzing early changes in patients’ blood counts. Three institutions’ data were used to develop a model that assessed patients’ response to therapy 90 days after the initiation using serial blood counts. The model was developed with a training cohort of 424 patients from2 institutions and validated on an independent cohort of 90 patients. …

Maternal Prenatal Cortisol Trajectories Predict Accelerated Growth In Infancy, Jennifer Hahn-Holbrook, Elysia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth …

Going Flat: Challenging Gender, Stigma, And Cure Through Lesbian Breast Cancer Experience, Beth Gaines

USF Tampa Graduate Theses and Dissertations

This paper explores the decision-making process of reconstruction surgery among lesbian breast cancer patients to better understand how identity impacts healthcare decisions. Breast cancer patients experience the disease in unique ways due to gender, sexuality, race, and class, impacting their individual decisions regarding treatment plans. Many breast cancer patients face mastectomy surgery as the first plan of treatment after diagnosis. By exploring the impact of gender, sexuality, stigma, and ideas of cure, this research aims to advance research about breast cancer by recognizing why some lesbian breast cancer patients forego reconstruction surgery and instead choose to “go flat.

Not Just A Trick: A Survey Study Exploring How ‘Exposing’ Exhibition Visitors To Science Of Magic Concepts Impacts Their Appreciation Of Magic, Gabriel Medeiros, Mathew Tompkins, Steve Bagienski, Gustav Kuhn

School of Psychology

The recent rise in scientific research on magic raises important issues about the impact that the dissemination of magic knowledge has on people’s appreciation of magic.Deception, secrecy, and mystery are inexorably intertwined with the idea of performance magic. Magicians traditionally do not reveal their secret methods to non-magicians. This study used a survey to assess how people’s appreciation of magic was impacted by a magic exhibition designed to highlight and reveal the psychological mechanisms that underpin magic. Visitors to the exhibition were asked to rate the impact of the exhibition on a range of measures assessing people’s interest and appreciation …

Biological Networks And Complexity In Early-Onset Motor Neuron Diseases, Matthew E. R. Butchbach, Rod C. Scott

Department of Pediatrics Faculty Papers

Motor neuron diseases (MNDs) are neuromuscular disorders where the spinal motor neurons–either the cell bodies themselves or their axons–are the primary cells affected. To date, there are 120 different genes that are lost or mutated in pediatric-onset MNDs. Most of these childhood-onset disorders, aside from spinal muscular atrophy (SMA), lack viable therapeutic options. Previous research on MNDs has focused on understanding the pathobiology of a single, specific gene mutation and targeting therapies to that pathobiology. This reductionist approach has yielded therapeutic options for a specific disorder, in this case SMA. Unfortunately, therapies specific for SMA have not been effective against …

Lacticaseibacillus Casei Strain Shirota Modulates Macrophage-Intestinal Epithelial Cell Co-Culture Barrier Integrity, Bacterial Sensing And Inflammatory Cytokines, Andrew Foey, Neama Habil, Alex Strachan, Jane Beal

School of Biomedical Sciences

Probiotic bacteria modulate macrophage immune inflammatory responses, with functional cytokine responses determined by macrophage subset polarisation, stimulation and probiotic strain. Mucosal macrophages exhibit subset functional heterogeneity but are organised in a 3-dimensional tissue, over-laid by barrier epithelial cells. This study aimed to investigate the effects of the probiotic Lacticaseibacillus casei strain Shirota (LcS) on macrophage-epithelial cell cytokine responses, pattern recognition receptor (PRR) expression and LPS responses and the impacts on barrier integrity. THP-1-derived M1 and M2 subset macrophages were co-cultured in a transwell system with differentiated Caco-2 epithelial cells in the presence or absence of enteropathogenic LPS. Both Caco-2 cells …

Sex Difference Leads To Differential Gene Expression Patterns And Therapeutic Efficacy In Mucopolysaccharidosis Iva Murine Model Receiving Aav8 Gene Therapy, Matthew Matthew Piechnik, Paige C. Amendum, Kazuki Sawamoto, Molly Stapleton, Shaukat Khan, Nidhi Fnu, Victor Álvarez, Angelica Maria Herreño Pachon, Olivier Danos, Joseph T. Bruder, Subha Karumuthil-Melethil, Shunji Tomatsu

Student Papers, Posters & Projects

Adeno-associated virus (AAV) vector-based therapies can effectively correct some disease pathology in murine models with mucopolysaccharidoses. However, immunogenicity can limit therapeutic effect as immune responses target capsid proteins, transduced cells, and gene therapy products, ultimately resulting in loss of enzyme activity. Inherent differences in male versus female immune response can significantly impact AAV gene transfer. We aim to investigate sex differences in the immune response to AAV gene therapies in mice with mucopolysaccharidosis IVA (MPS IVA). MPS IVA mice, treated with different AAV vectors expressing human N-acetylgalactosamine 6-sulfate sulfatase (GALNS), demonstrated a more robust antibody response in female mice resulting …

Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …

Sensitive Image-Based Chromatin Binding Assays Using Inducible Erα To Rapidly Characterize Estrogenic Chemicals And Mixtures, Adam T Szafran, Maureen G Mancini, Fabio Stossi, Michael A Mancini

Faculty, Staff and Students Publications

The United States Environmental Protection Agency (EPA) has been pursuing new high throughput in vitro assays to characterize endocrine disrupting chemicals (EDCs) that interact with estrogen receptor signaling. We characterize two new PRL-HeLa cell models expressing either inducible C-terminal (iGFP-ER) or N-terminal (iER-GFP) tagged estrogen receptor-α (ERα) that allows direct visualization of chromatin binding. These models are an order of magnitude more sensitive, detecting 87 - 93% of very weak estrogens tested compared to only 27% by a previous PRL-HeLa variant and compares favorably to the 73% detected by an EPA-developed computational model using in vitro data. Importantly, the chromatin …

Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

AIMS: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.

METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus …

Evidence For Phylogenetic Signal And Correlated Evolution In Plant-Water Relations Traits, Eleinis Ávila-Lovera, Klaus Winter, Gregory R. Goldsmith

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Evolutionary relationships are likely to play a significant role in shaping plant physiological and structural traits observed in contemporary taxa. We review research on phylogenetic signal and correlated evolution in plant-water relations traits, which play important roles in allowing plants to acquire, use and conserve water. We found more evidence for a phylogenetic signal in structural traits (e.g., stomatal length, stomatal density) than in physiological traits (e.g., stomatal conductance, water potential at turgor loss). Although water potential at turgor loss is the most-studied plant-water relations trait in an evolutionary context, it is the only trait consistently found to not have …

Unraveling The Pathways Involved In Intestinal Repair After Ionizing Radiation Damage, Blaine Pattavina

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Exposure to genotoxic environmental agents has detrimental effects on health span and aging. Macromolecular damage caused by these factors is also known to lead to diseases like cancer. Radiation therapy is the treatment of choice for malignant tumors and several non-malignant diseases. Despite its effectiveness, it often leads to unintended complications. Radio-sensitivity of healthy ‘bystander’ cells is an important factor in mediating these complications, which often result in several long-term and debilitating side effects. This incurs huge costs in patient care to maintain the well-being of survivors. Current efforts to understand the underlying molecular patho-physiology of radiation damage involve the …

The Effect Of Species Diversity And Shade On Milkweed Growth And Cardenolide Concentration, Estrella V. Silva, Rylee Mattson, Katherine Klassen, Laurie Dizney

RURALS: Review of Undergraduate Research in Agricultural and Life Sciences

Monarch butterflies (Danaus plexippus) rely upon milkweed plants for survival, as it is the only plant upon which female monarchs oviposit and it is the sole food supply for monarch larvae. Additionally, cardenolide, a defense toxin within milkweed tissue, is sequestered by monarchs, making them unpalatable to most predators. Eastern and Western monarch populations in the United States are in sharp decline, in part due to the growing scarcity of milkweed, and reestablishing milkweed habitat is crucial to the monarch’s long-term survival. This study aimed to study the effects of plant species diversity and shade on the growth …

Silver Carp Hypopthalmichthys Molitrix Movements In The Lower Tennessee And Lower Cumberland River, Miranda Belanger, Timothy Spier

Student Scholarship & Creative Works

Silver Carp Hypophthalmichthys molitrix are an invasive species making up a large portion of the fish biomass in the lower portions of the Tennessee River and the Cumberland River. This species is expanding its range throughout the upper portions of these rivers, beginning with Kentucky Lake and Lake Barkley. Silver Carp rarely spawn in Kentucky Lake and Lake Barkley, but they can enter these reservoirs through the lock chamber. Thus, the bottleneck created by lock chambers can be used to control expansion of invasive Silver Carp. Although Silver Carp movement patterns have been studied in other portions of the Tennessee …

Medical School Watercooler Newsletter - October 20, 2022, Lindsey Lyle

Watercooler Newsletter

This is the October 20, 2022 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents include:

• What are you thankful for? Send us your stories!
• Donations begin for Operation Christmas Child
• Register Now: Sixth Annual Conference on Ethics and Opioids
• Hospitalist joins internal medicine faculty
• Meet a Med Student: Isabella Dinelli
• Pediatric emergency physician joins USA Health
• Whiddon College of Medicine to host 'Journey to a Ph.D.'

Vol.50 N.13 October 20th 2022, Voice Media Ventures

Black Voice News

No abstract provided.

Genomics And Transcriptomics To Protect Rice (Oryza Sativa L.) From Abiotic Stressors: -Pathways To Achieving Zero Hunger, Mushtaq Ahmad

Center for Plant Science Innovation: Faculty Publications

More over half of the world’s population depends on rice as a major food crop. Rice (Oryza sativa L.) is vulnerable to abiotic challenges including drought, cold, and salinity since it grown in semi-aquatic, tropical, or subtropical settings. Abiotic stress resistance has bred into rice plants since the earliest rice cultivation techniques. Prior to the discovery of the genome, abiotic stressrelated genes were identified using forward genetic methods, and abiotic stress-tolerant lines have developed using traditional breeding methods. Dynamic transcriptome expression represents the degree of gene expression in a specific cell, tissue, or organ of an individual organism at …

The Immune Signatures Data Resource, A Compendium Of Systems Vaccinology Datasets., Joann Diray-Arce, Helen E R Miller, Evan Henrich, Bram Gerritsen, Matthew P Mulè, Slim Fourati, Jeremy Gygi, Thomas Hagan, Lewis Tomalin, Dmitry Rychkov, Dmitri Kazmin, Daniel G Chawla, Hailong Meng, Patrick Dunn, John Campbell, The Human Immunology Project Consortium (Hipc), Minnie Sarwal, John S Tsang, Ofer Levy, Bali Pulendran, Rafick Sekaly, Aris Floratos, Raphael Gottardo, Steven H Kleinstein, Mayte Suárez-Fariñas

Faculty Research 2022

Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines. However, comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies …

Hyperexcitable And Immature-Like Neuronal Activity In The Auditory Cortex Of Adult Rats Lacking The Language-Linked Cntnap2 Gene., Kaela E Scott, Rajkamalpreet S Mann, Ashley L Schormans, Susanne Schmid, Brian L Allman

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in …

Stinnett Selected For A Prestigious Program By The Society Of Research Administrators International, Staff

Browse All News

No abstract provided.

Understanding The Interconnection Between Public Health And Political Behaviors In A Politically Polarized Context: The Impact Of Race, Political Attitudes, And Policy Factors On The Us Covid-19 Pandemic Response., Florent Nkouaga

Political Science ETDs

This dissertation evaluates the interconnection between health and political behaviors in a polarized context such as the United States. The COVID-19 pandemic unveiled the current political polarization and the structural health disparities among racial communities. Using the system theory delineated by David Easton, this dissertation demonstrates that health attitudes and behaviors in the electorate can influence voting behaviors, as was the case with the 2020 US presidential election. An evaluation of the 2021 African American COVID-19 Vaccine Polls (AACVP), and the 2020 Collaborative Multiracial Postelection Survey (CMPS) demonstrates that factors such as public health compliance, trust in federal health institutions, …

Monodelphis Domestica Induced Pluripotent Stem Cells Reveal Metatherian Pluripotency Architecture, Satish Kumar, Erica De Leon, Jose C. Granados, Deanne J. Whitworth, Jane F. Vandeberg

School of Medicine Publications

Marsupials have been a powerful comparative model to understand mammalian biology. However, because of the unique characteristics of their embryology, marsupial pluripotency architecture remains to be fully understood, and nobody has succeeded in developing embryonic stem cells (ESCs) from any marsupial species. We have developed an integration-free iPSC reprogramming method and established validated iPSCs from two inbred strains of a marsupial, Monodelphis domestica. The monoiPSCs showed a significant (6181 DE-genes) and highly uniform (r2 [95% CI] = 0.973 ± 0.007) resetting of the cellular transcriptome and were similar to eutherian ESCs and iPSCs in their overall transcriptomic profiles. …

The Relationship Between Game Art Students’ Achievement And Their Perceived Quality Of Assessment, Nicole R. Lesher

Doctoral Dissertations and Projects

The purpose of this quantitative, non-experimental, predictive correlational study is to analyze the relationship between Game Art students’ perceptions of quality of assessment practices in higher education and their achievement of learning. Assessment in higher education has become increasingly significant due to accreditation and regulatory requirements around accountability of student outcomes. Institutions must commit a high level of resources toward appropriate assessment practices in order to answer tough questions about the value of higher education. This work has been met with adversity by students and educators, often resulting in overextended departments and poor-quality assessment practices. Questions pertaining to the benefits …

Disturbances In North American Boreal Forest And Arctic Tundra: Impacts, Interactions, And Responses, Adrianna C. Foster, Jonathan A. Wang, Gerald V. Frost, Scott J. Davidson, Elizabeth Hoy, Kevin W. Turner, Oliver Sonnentag, Howard Epstein, Logan T. Berner, Amanda H. Armstrong, Mary Kang, Brendan M. Rogers, Elizabeth Campbell, Kimberley R. Miner, Kathleen M. Orndahl, Laura Bourgeau-Chavez, David A. Lutz, Nancy H. F. French, Dong Chen, Jinyang Du, Tatiana A. Shestakova, Jacquelyn K. Shuman, Ken Tape, Anna Maria Virkkala, Christopher Potter, Scott Goetz

Michigan Tech Publications, Part 1

Ecosystems in the North American Arctic-Boreal Zone (ABZ) experience a diverse set of disturbances associated with wildfire, permafrost dynamics, geomorphic processes, insect outbreaks and pathogens, extreme weather events, and human activity. Climate warming in the ABZ is occurring at over twice the rate of the global average, and as a result the extent, frequency, and severity of these disturbances are increasing rapidly. Disturbances in the ABZ span a wide gradient of spatiotemporal scales and have varying impacts on ecosystem properties and function. However, many ABZ disturbances are relatively understudied and have different sensitivities to climate and trajectories of recovery, resulting …

Adaptive Multi-Scale Place Cell Representations And Replay For Spatial Navigation And Learning In Autonomous Robots, Pablo Scleidorovich

USF Tampa Graduate Theses and Dissertations

Place cells are one of the most widely studied neurons thought to play a vital role in spatial cognition. Extensive studies show that their activity in the rodent hippocampus is highly correlated with the animal’s spatial location, forming “place fields” of smaller sizes near the dorsal pole and larger sizes near the ventral pole. Despite advances, it is yet unclear how this multi-scale representation enables navigation in complex environments.

In this dissertation, we analyze the place cell representation from a computational point of view, evaluating how multi-scale place fields impact navigation in large and cluttered environments. The objectives are to …

Proportioning Collection Space And Learning In An Academic Library: Collection Performance Indicators, Christopher Stewart, Louise Lowe

Faculty Scholarship

Assessment on university campuses increasingly emphasizes learning outcomes and student success. Academic librarians need to identify relationships between their collection spaces and the learning activities of the university in order to play a role in the environment of assessment. Measuring the propor- tions of discipline-oriented content of library collections and comparing those proportions to discipline-oriented learning activities produces collection performance indicators. Academic libraries can use collection performance indicators to assess how well their collection spaces correspond to student demand and student success using readily available metrics. Collection performance indicators answers a gap in library literature per- taining to relationships between …

Complete Genome Sequence Of The Uropathogenic Methicillin-Resistant Staphylococcus Aureus Strain Mrsa-1369, Hasan Tükenmez, Taylor M Nye, Mari Bonde, Michael G Caparon, Fredrik Almqvist, Scott J Hultgren, Jörgen Johansson

2020-Current year OA Pubs

MRSA-1369 is a uropathogenic methicillin-resistant Staphylococcus aureus (MRSA) strain. Here, we present the complete genome sequence of MRSA-1369, which consists of one chromosome (2.87 Mb) and two plasmids (16.68 kb and 3.13 kb). This will serve as a reference genome for future Staphylococcus aureus pathogenesis and multiomic studies.