Medicine and Health Sciences Commons^™

Fair Header Reference Genome: A Trustworthy Standard, Adam Wright, Mark D Wilkinson, Christopher Mungall, Scott Cain, Stephen Richards, Paul Sternberg, Ellen Provin, Jonathan L Jacobs, Scott Geib, Daniela Raciti, Karen Yook, Lincoln Stein, David C Molik

Faculty, Staff and Students Publications

The lack of interoperable data standards among reference genome data-sharing platforms inhibits cross-platform analysis while increasing the risk of data provenance loss. Here, we describe the FAIR bioHeaders Reference genome (FHR), a metadata standard guided by the principles of Findability, Accessibility, Interoperability and Reuse (FAIR) in addition to the principles of Transparency, Responsibility, User focus, Sustainability and Technology. The objective of FHR is to provide an extensive set of data serialisation methods and minimum data field requirements while still maintaining extensibility, flexibility and expressivity in an increasingly decentralised genomic data ecosystem. The effort needed to implement FHR is low; FHR's …

Effectiveness Of The Minder Mobile Mental Health And Substance Use Intervention For University Students: Randomized Controlled Trial, Melissa Vereschagin, Angel Y Wang, Chris G Richardson, Hui Xie, Richard J Munthali, Kristen L Hudec, Calista Leung, Katharine D Wojcik, Lonna Munro, Priyanka Halli, Ronald C Kessler, Daniel V Vigo

Faculty, Staff and Students Publications

Background: University attendance represents a transition period for students that often coincides with the emergence of mental health and substance use challenges. Digital interventions have been identified as a promising means of supporting students due to their scalability, adaptability, and acceptability. Minder is a mental health and substance use mobile app that was codeveloped with university students.

Objective: This study aims to examine the effectiveness of the Minder mobile app in improving mental health and substance use outcomes in a general population of university students.

Methods: A 2-arm, parallel-assignment, single-blinded, 30-day randomized controlled trial was used to evaluate Minder using …

Affinity-Tagged Smad1 And Smad5 Mouse Lines Reveal Transcriptional Reprogramming Mechanisms During Early Pregnancy, Zian Liao, Suni Tang, Kaori Nozawa, Keisuke Shimada, Masahito Ikawa, Diana Monsivais, Martin Matzuk

Faculty, Staff and Students Publications

Endometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci (Smad1^HA/HA and Smad5^PA/PA). By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated …

Sex-Based Differences In Melanoma Survival Improvement From 2004 To 2018, Vikram R Shaw, Angela Hudock, Baoyi Zhang, Christopher Amos, Chao Cheng

Faculty, Staff and Students Publications

Simple Summary

Melanoma is the deadliest form of skin cancer and its incidence and mortality may vary by demographic factors, such as sex, age, race, and socioeconomic status. Few studies, however, have characterized disparities in survival improvement across these demographic groups in melanoma. In the present study, the authors highlight disparities in melanoma survival improvement, both in diagnosed melanoma and carcinoma in situ. While melanoma survival has improved overall, some patient subgroups have experienced a lower improvement in survival from 2004 to 2018.

Abstract

Background: Melanoma is the deadliest form of skin cancer and its incidence and mortality vary by …

The Effects Of Genetic And Modifiable Risk Factors On Brain Regions Vulnerable To Ageing And Disease, Jordi Manuello, Joosung Min, Paul Mccarthy, Fidel Alfaro-Almagro, Soojin Lee, Stephen Smith, Lloyd T. Elliott, Anderson M. Winkler, Gwenaëlle Douaud

School of Medicine Publications

We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal …

Study Protocol: Identifying Transcriptional Regulatory Alterations Of Chronic Effects Of Blast And Disturbed Sleep In United States Veterans, Molly J. Sullan, Kelly A. Stearns-Yoder, Zhaoyu Wang, Andrew J. Hoisington, Adam D. Brenoweth, Walter Carr, Yongchao Ge, Hanga Galfalvy, Fatemah Haghighi, Lisa A. Brenner

Faculty Publications

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of …

Translational Impact Of Ubtf In Developing New Therapeutic Strategy For Pancreatic Cancer Treatment, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Muhammad Bangash, Genaro Antonio Ramirez-Correa, Dae Joon Kim, Subhash Chauhan, Bilal Hafeez

Research Symposium

Pancreatic cancer (PanCa) is the third leading cause of cancer-related deaths in the United States. It shows only a marginal survival benefits of 6 months with the available therapeutics. Thus, to understand the biology of PanCa and discovery of new molecular targets will help in designing the new therapeutic strategies for the management of advanced PanCa. Aberrant ribosome biogenesis is the hallmark of many cancers and has been associated with poor prognosis. Cancer cells show significantly high demand of protein synthesis and to meet this demand modify ribosomal machinery at genetic and epigenetic level. The UBTF (upstream binding transcription factor, …

The Fortify Resilience Initiative, Maria Hernandez, Yvette Cantu

Research Symposium

The Fortify Resilience Initiative focuses on building and sustaining a culture of wellbeing for Residents and Fellows (R/Fs) at The University of Texas Rio Grande Valley (UTRGV) School of Medicine’s (SOM) Graduate Medical Education (GME) residency and fellowship programs. In order to address the multitude of threats to physician wellness and to mitigate the silent, but pernicious effects of burnout on these physician learners serving in the RGV, this Initiative from the Office of GME will strengthen existing wellbeing pathways while expanding additional solutions that will work to sustain wellbeing. Utilizing a combination of prevention, promotion, and intervention strategies targeted …

The Carcinogenic Effect Of Heavy Metals And Its Association With Epigenetic Changes In Urothelial Bladder Cancer Patients, Ganesh Kumar Verma, A. Sen, S. Saha, A. Mirza, A. Atif

Research Symposium

Background: According to Global Cancer Observatory (GLOBOCON) 2020, urothelial bladder cancer (UBC) is the 17th most common malignancy in India, and bladder cancer represents a significant health problem due to the potential morbidity and mortality. UBC is commonly associated with industrialized regions and the most accountable risk factors have been tobacco smoke along with occupational chemical exposures including heavy metals. A massive increase in human exposure to heavy metals has been noticed due to industrial activities since last century and an emerging understanding of the carcinogenic effects of certain heavy metals is now being considered as causative agents for UBC. …

Smoking And Drinking Activate Nf-Κb /Il-6 Axis To Promote Inflammation During Cervical Carcinogenesis, Vivek Kumar Kashyap

Research Symposium

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated the molecular mechanisms involved in the interplay of smoking and/or drinking with HPV infectivity and defined a systematic therapeutic approach for their attenuation in cervical cancer.

Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their biophysical, cell migration, and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was …

Primary Care Behavioral Health Partnerships Advancing & Transforming Health Sciences (Pcbh Paths), Mayrin Perez, Maria Hernandez

Research Symposium

Primary Care Behavioral Health Partnerships Advancing & Transforming Health Sciences (PCBH PATHS) is a workforce development pipeline project aimed at permanently augmenting UTRGV’s institutional capacity to address shortage of an Integrated Behavioral Health (IBH) competent workforce locally, regionally and nationally. Our initiative, aligned with UTRGV strategic priorities and key initiatives, will integrate basic(model specific strategy and operational elements), mid-level (role identity and profession specific behavioral competencies specific to each health profession), and advanced (behavioral medicine clinical skills) applications of the evidence based PCBH model of delivery. A PCBH focused delivery system (clinical and educational), in which primary care providers (PCPs) …

P22 Viral Capsid Nanocomposites For Enzyme Prodrug Therapy Of Breast Cancer, Astrid Rebeca Luna Rios

Research Symposium

Background: Current treatment strategies against breast cancer have limitations due to lack in selectivity. Most drugs, such as tamoxifen, require metabolic activation by cytochrome P450 (CYP) enzymes to perform greater anticancer effects. However, the concentration of CYP varies and is low in tumor cells, resulting in side-effects. In enzyme prodrug therapy (EPT), enzymes are targeted to the tumor cells for prodrug transformation, involving the sequential delivery of the enzyme followed by prodrug. However, differences in pharmacokinetics and pharmacodynamics are a major hindrance. Thus, co-delivery of prodrug and enzyme is essential to ensure their favorable interaction at target site.

Results: This …

Novel Nanoformulation Of Sabizabulin (Veru-111) For Pancreatic Cancer Therapy, Vivek Kumar Kashyap

Research Symposium

Background: Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortality in the United States due to very limited therapeutic options. Thus, developing novel therapeutic strategies will help for the management of this disease. We recently identified VERU-111, a novel synthetic molecule which showed potent anti-cancer effect against PanCa via targeting clinically important βIII and βIV tubulin isoforms. In this study, we synthesized and characterized its novel nanoformulation (MNP-VERU) and evaluated its therapeutic effects in vitro and xenograft mouse model.

Methods: MNPs were prepared by chemical precipitation method and loaded with VERU-111 using diffusion method. This formulation was …

Muc13- A Novel Cancer Biomarker For Early Pancreatic Cancer Diagnosis And Imaging, Sheema Khan, Anupam Dhasmana

Research Symposium

Pancreatic adenocarcinoma (PDAC) has a very poor survival rate due to late diagnosis. Therefore, identification approaches that aid in early diagnosis are highly desirable. MUC13 is a recently identified high molecular weight glycoprotein that is aberrantly expressed in PDAC and allows its progression via alterations of multiple tumor signaling pathways. Overexpression of MUC13 in PDAC cells leads to enhanced tumorigenic and metastatic phenotypes. These characteristics of PDAC cells are mediated by physical interactions between MUC13 and HER2/Neu. This study elucidates significance of MUC13, as a diagnostic and imaging marker of PDAC. Additionally, a collaborative effort has commenced to investigate the …

Interdisciplinary Integrated Primary And Behavioral Healthcare (I2pbh) Initiative, John Ronnau, Deepu George, Maria Hernandez, Salvador Arellano Iii, Myrna Ruiz

Research Symposium

Purpose: The Interdisciplinary Integrated Primary and Behavioral Healthcare (I2PBH) Initiative will train University of Texas Rio Grande Valley (UTRGV) mental health graduates to deliver high quality, evidence-based Integrated Behavioral Health (IBH) services in the Rio Grande Valley (RGV) – a high-need, high-demand, medically underserved Hispanic region along the US-Mexico border. Specifically, the I2PBH initiative will train 24 UTRGV mental health graduates annually to deliver high-quality IBH clinical services through the evidence based Primary Care Behavioral Health (PCBH) model. With a training emphasis on basic/advanced theory and clinical skills in the PCBH model, students will serve as Behavioral Health Consultants (BHC) …

Integrative Transcriptomics Data Analysis Of Trpv1 In Hepatocellular Carcinoma, Vivek Kumar Kashyap, Bhuvnesh Sharma, Himanshu Narayan Singh, Deepak Verma, Deepak Parashar, Murali M. Yallapu, Subhash C. Chauhan

Research Symposium

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective Ca2+ channel protein that is widely expressed and plays a significant role in cancer initiation and progression. However, the biological significance of TRPV1 in HCC has not been systematically and comprehensively investigated. Using deep data mining and transcriptomics analyses, in this study, we described the significance of TRPV1 expression and its association with HCC prognosis.

Methods: TRPV1 mRNA expression in HCC was examined using the Cancer Genome Atlas (TCGA), the Genotype Tissue Expression Atlas (GTEx), the Tumor Immune Estimation …

Icg-Loaded Mesoporous Nanohybrid (Nd-Doped Hydroxyapatite/Fe3o4) For Photonic/Magnetic Hyperthermia And Photodynamic Therapy, Prakhar Sengar, K. Chauhan, A. G. Rodríguez-Hernández, G. A. Hirata

Research Symposium

Background: Multimodality nanoplatforms play a crucial role in advancing medical interventions by integrating multiple functionalities into a single system. However, issues like intricate production processes and biocompatibility persist. Herein, a facile synthesis of a biomaterial-based mesoporous nanocarrier, HAp:Nd+SPIONs@mSiO2, loaded with the near-infrared (NIR) emitting dye indocyanine green (ICG) is reported.

Methods: HAp:Nd nanoparticles were synthesized via combustion methods. Thereafter, commercial SPIONs and HAp:Nd were integrated within a mesoporous silica via a modified Stöber approach. HAp:Nd+SPIONs@mSiO2 nanoplatform was characterized for particle size, porosity, and luminescence using TEM, BET, and luminescence spectroscopy. The synthesized nanoplatform was further loaded with ICG dye and …

Integrated Cancer Research Core (Icrc) At The University Of Texas Rio Grande Valley, Iris Enriquez

Research Symposium

Background: The University of Texas Rio Grande Valley-School of Medicine (UTRGV-SOM) has founded the South Texas Centre of Excellence in Cancer Research to address disproportionate cancer related health issues in the Valley. UTRGV-SOM intends to establish an Integrated Cancer Research Core (ICRC) Facility at the UTRGV campus to provide cutting-edge technologies to support cancer research investigators of the Rio Grande Valley.

Methods: The ICRC will house most recent technologies (Flow Cytometry, Image Stream Flow, Droplet Digital PCR, molecular imaging, microPET/CT imaging, etc) to support flow cytometric analyses in cell suspension and tissues, cell sorting, analysis of tumor immune components, microbiome …

Graphene Nanoparticles For Microrna Delivery, Eswara Naga Hanuma Kumar Ghali

Research Symposium

Background: Graphene (G) has been established as an exciting prospect for a broad range of applications owing to its remarkable properties. As the molecular structure of G itself is achiral thus introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. The recent innovations of G chiral nanosystems have been extended to drug delivery. Herein, we have developed a novel and facile synthesis method for producing chiral G for its application in chirality-dependent microRNA delivery.

Methods: L-graphene and D-graphene were produced in a single step by …

Exploring The Role Of Mucin 13 In Hepatocellular Carcinoma, Shabnam Malik, Mohammed Sikander, Daniel Zubieta

Research Symposium

Background: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of early diagnostic marker. Accumulating studies have shown that elevated expression of mucin 13 as potential oncogene and predictive biomarker for various cancer. However, very little is known about its expression and function for development and progression of HCC.

Objective: To investigate mucin 13 expression in chemically induced hepatocellular carcinoma model.

Methodology: Diethyl nitrosamine (DEN) and 2-Acetylaminofluorene (2-AAF) induced method was employed for the development of hepatocellular carcinoma in Male Wistar rats. Serum and tissues were collected at regular intervals of time and routinely validated …

Evaluating Who, Cci, And Cfs Performance In Predicting Non-Small Cell Lung Cancer Survival In Finland: Insights Beyond Concord-3, Ville Paappanen

Research Symposium

Background: Set against the backdrop of the 2018 CONCORD-3 study, our research focuses on Finland's lung cancer survival rates. Despite similar tax-funded and public healthcare systems, these rates lag behind those of other Nordic countries, prompting an investigation into the underlying causes. This research aims to unravel these disparities, particularly in the context of Finland's success in other cancer domains, contributing to broader efforts to elevate lung cancer outcomes to the level of other Nordic cancer success stories.

Study objective: Our study focuses on evaluating clinical performance classification systems like WHO Score, Charlson Comorbidity Index (CCI), and Clinical Frailty Scale …

Embolic Protection During Radical Nephrectomy With Inferior Vena Cava Thrombectomy Using The Protrieve Sheath, Mia Rose Schmolze

Research Symposium

Renal Cell Carcinoma (RCC) is complicated by inferior vena cava (IVC) involvement in 4-10% of cases with intraoperative tumor embolization associated with 60-75% mortality. Currently, there is no high-level evidence demonstrating which surgical techniques provide optimal outcomes. The Protrieve SheathTM (Inari Medical®) has been used in the vascular setting for complex deep vein thrombosis(DVT) and non-tumor IVC thrombectomy cases. We aim to describe its first use in the setting of RCC with IVC thrombectomy to help prevent intraoperative tumor embolization. The Protrieve SheathTM successfully provided potentially life-saving protection from clot embolization when performing radical nephrectomy with IVC thrombectomy.

Development Of Mirna Therapeutics Targeting Atp Citrate Lyase (Acly) For The Treatment Of Oral Cancer, Uzini Devi Daimary

Research Symposium

Background: The global incidence of oral cancer (OC) has seen a consistent rise, with India accounting for nearly one-third of reported cases. Thus, there is an urgent need to gain a comprehensive understanding of the underlying pathophysiology of OC and develop effective and novel therapeutic interventions for the prevention and treatment of this deadly disease. Lipogenesis, a primary metabolic alteration in cancer cells, is linked to ACLY, a key enzyme in lipid biogenesis making it a promising target for OC treatment. Aberrant expression of ACLY regulates vital signaling pathways in tumorigenesis, indicating its potential as a novel therapeutic strategy against …

Development Of Mirna Mimics Targeting Tumor Necrosis Factor-Α Induced Protein Eight (Tnfaip8/Tipe) In Oral Cancer, Aviral Kumar

Research Symposium

Background: The prevalence of oral cancer worldwide is on the rise, with India accounting for almost a third of all documented cases. Despite significant progress in therapeutic approaches, elevated mortality rates and recurrent disease incidences pose a considerable challenge to India’s emerging healthcare sector. Hence, there is an urgent need to comprehend the underlying pathophysiology of oral cancer and devise innovative and effective therapeutic interventions for both prevention and treatment of this lethal ailment. TNFAIP8 is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of various malignancies. Therefore, targeting TNFAIP8 protein might …

Cucurbitacin B: A Novel Agent For Inducing Tumor-Immune Response., Sahir S. Alvi, Emmanuel Anning, Mudassier Ahmad, Carlos Perez, Mehdi Chaib, Subhash C. Chuahan, Taha Merghoub, Bilal B. Hafeez

Research Symposium

Despite the emergence of immunotherapy as a potential breakthrough in cancer treatment, it showed only a marginal response in pancreatic and liver cancers. Thus, novel strategies are highly desirable to take full advantage of immunotherapy in the treatment of these cancers. One of the critical factors that influence the efficacy of immunotherapy is the increased infiltration of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAM) into tumors that alter the immune landscape and serve as facilitators of tumor proliferation, metastatic growth, and immunotherapy resistance. Thus, we believe that selecting a potent molecule that has the ability to suppress the function …

Assessment Of Cytochrome P450 Isoforms In Colorectal Cancer And Utilization Of Phytochemicals For Their Modulation., Sudha Gahlawat

Research Symposium

Cytochrome P450 (CYPs) belongs to Phase I enzymes and exists in multiple isoforms. CYPs are present in all tissues with the highest concentrations in the liver and small intestine. These are mainly involved in drug detoxification, cellular homeostasis, metabolism of endogenous & exogenous substrates and in the inactivation/ activation of several anticancer drugs. As these CYPs are selectively and differentially expressed in CRC, which could not only provide a mechanism for drug resistance, but also insights into future therapies that may use these enzymes as therapeutic targets. This study is designed to evaluate the differential expression of various CYPs isoforms …

Assessment Of Anti-Cancerous Properties Of Nyctanthes Arbor-Tristis Linn Natural Compounds, Qazi Mohammad Sajid Jamal, Varish Ahmad

Research Symposium

Purpose: Nyctanthes arbor-tristis Linn., the lovely and fragrant flowering tree, sometimes called night-blooming jasmine or parijat, is native to Southeast and South Asia. For ages, this has been utilized in traditional medicine. There are claims that its leaves and blossoms have anti-inflammatory, antimicrobial, and anti-diabetic qualities. Plants contain anti-cancer capabilities; however, this has not yet been investigated. Therefore, we propose to explore mechanistic interaction with different cancer targets and active chemicals of this plant through computational methods, which will be further subjected to in vitro/in vivo experimental validation to show its anti-cancerous potentialities.

Description: Nyctanthes arbor-tristis Linn. plant contains several …

A Translational Approach Towards More Cost-Effective Lung Cancer Treatments, Tuula Klaavuniemi, Subhash C. Chauhan, Ville Paappanen, Artturi Mäkinen, Tuomas Rauramaa, Juha Väyrynen, Arja Jukkola, Hanne Kuitunen, Outi Kuittinen

Research Symposium

Lung cancer, globally the second most common cancer, causes 1.8 million deaths annually with 2 million new cases. It's also one of Finland's deadliest cancers. Chemotherapeutic agents, targeted drugs and radiation therapy have been the mainstay in oncologic treatment for lung cancer patients for decades. Checkpoint inhibitors (e.g. nivolumab, pembrolizumab, atezolizumab) have changed the landscape also in lung cancer. These drugs awake patients own immune system to attack cancer cells. These drugs are widely used in different cancers and they have efficacy also in lung cancer, but only in a minority of patients. Checkpoint inhibitors also induce autoimmune side effects. …

A Novel Exo-Glow Nano-System For Bioimaging, Nycol Cotto, Benilde Adriano, Neeraj Chauhan, Deepak S. Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Milk exosomes are widely used to improve the performance of various small macromolecules, oligonucleotides, and imaging agents for delivery and imaging applications. Indocyanine green (ICG) based Near-Infrared (NIR) fluorescent imaging is an attractive and safer technique used for number of clinical applications. However, ICG tend to have poor photostability, short half-life, non-specific proteins binding, and concentration-dependent aggregation. Therefore, there is an unmet clinical need to develop newer modalities to package and deliver ICG. Bovine milk exosomes are natural, biocompatible, safe, and feasible nanocarriers that facilitate the delivery of micro and macro molecules. Herein, we developed a novel exosomes based …

Near-Neutral Balanced Selection Theory (Nnbst): Implication On The Molecular Evolution Of Sars-Cov-2 And Zika Virus, Nicholas J. Paradis

Graduate Student and Postdoctoral Fellow Symposium

Virus pandemics have significantly impacted human welfare and development. Understanding the true molecular evolution of viruses is critical for preventing future pandemics and developing the next-generation drugs and vaccines. Unfortunately, viruses exhibiting constant genomic substitution rates (GSRs) despite increasing vaccinations and human infections (SARS-CoV-2) and viruses under seemingly extreme conservation (ZIKV) paints a confusing picture of viral evolution, and the main evolutionary theories (Selectionist Theory, Kimura’s Neutral Theory) cannot explain their molecular evolution. Here, we developed a first-principle model, c/u, to characterize reproductive fitness changes in viruses based on variations in the nucleotide/codon mutation rate (c) with respect to the …