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Articles 1 - 30 of 152
Full-Text Articles in Medicine and Health Sciences
Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) Infection By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh
Auctus: The Journal of Undergraduate Research and Creative Scholarship
Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing …
Relative Efficacy Of Resource Constrained Forward And Backward Contact Tracing In An Open Population, Nicholas Roberts
Relative Efficacy Of Resource Constrained Forward And Backward Contact Tracing In An Open Population, Nicholas Roberts
Biology and Medicine Through Mathematics Conference
No abstract provided.
Exploring The Dynamics Of Bacterial Populations In The Gut Microbiota, Shaikh Obaidullah
Exploring The Dynamics Of Bacterial Populations In The Gut Microbiota, Shaikh Obaidullah
Biology and Medicine Through Mathematics Conference
No abstract provided.
Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit
Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit
VCU's Medical Journal Club: The Work of Future Health Professionals
In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.
A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose
VCU's Medical Journal Club: The Work of Future Health Professionals
Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.
Dermatologic Manifestations Of Rheumatic Disease: Cutaneous Manifestations Of Vasculitides, Julianna S. Kang, Julia Nunley, Tiffany Ho, Mavra Masood, Fnu Nutan, Beth Rubinstein
Dermatologic Manifestations Of Rheumatic Disease: Cutaneous Manifestations Of Vasculitides, Julianna S. Kang, Julia Nunley, Tiffany Ho, Mavra Masood, Fnu Nutan, Beth Rubinstein
Open and Affordable Course Content at VCU
Cutaneous Manifestations of Vasculitides is a Powerpoint based learning module that begins with the definition of terms and findings often found in vasculitis, followed by a review of several systemic vasculitides, highlighting how characteristic cutaneous lesions may be predictive of the vessel of involvement as well as the associated histologic changes. Moreover, significant clinical and laboratory findings utilized to make the correct diagnosis will be emphasized. This module is not meant to be an exhaustive review of vasculitis, but to serve as an introduction to understanding disease processes and how systemic vasculitis and skin findings interrelate.
It is part of …
Dermatologic Manifestations Of Rheumatic Disease: Malignant Cutaneous Tumors, Divya Shan, Julianna S. Kang, Allison Cinats, Julia R. Nunley, Beth Rubinstein
Dermatologic Manifestations Of Rheumatic Disease: Malignant Cutaneous Tumors, Divya Shan, Julianna S. Kang, Allison Cinats, Julia R. Nunley, Beth Rubinstein
Open and Affordable Course Content at VCU
Malignant Cutaneous Tumors is a Powerpoint-based learning module that focuses on skin cancers. It begins with the definition of terms and findings, followed by a review of several clinical cases. The goal of the module is to provide the students with the ability to differentiate the most common types of skin cancer and precancerous lesions and gain an awareness of cutaneous lymphomas. This module will include images and clinical findings from diverse skin tones to prepare students to identify cutaneous findings in a heterogeneous patient population. This module is not a comprehensive review of skin cancers but an introduction to …
Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky
Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky
Theses and Dissertations
Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …
Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh
Undergraduate Research Posters
Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …
Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens
Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens
Undergraduate Research Posters
About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes.
To addressing this gap, our laboratory utilized …
The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman
The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman
Undergraduate Research Posters
This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …
Evaluation Of Spliceai For Improved Genetic Variant Classification In Inherited Ophthalmic Disease Genes, Melissa Reeves
Evaluation Of Spliceai For Improved Genetic Variant Classification In Inherited Ophthalmic Disease Genes, Melissa Reeves
Theses and Dissertations
ABSTRACT
EVALUATION OF SPLICEAI FOR IMPROVED GENETIC VARIANT CLASSIFICATION IN INHERITED OPHTHALMIC DISEASE GENES
By Melissa Jean Reeves, Ph.D.
A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.
Virginia Commonwealth University, 2023
Major Director: Melissa Jamerson, PhD, MLS(ASCP)
Associate Professor, Department of Medical Laboratory Sciences
Inherited ophthalmic diseases impact individuals around the globe. Inherited retinal diseases (IRDs) are the leading cause of blindness in individuals aged 15 to 45. The personal, social, and economic impact of vision loss is profound. Due to individual differences, symptoms can be variable, and …
Multi-Strain Epidemic Model With Infected Vaccinated And Re-Infected Recovered Population: Application To Covid-19 Pandemic, Olusegun Michael Otunuga
Multi-Strain Epidemic Model With Infected Vaccinated And Re-Infected Recovered Population: Application To Covid-19 Pandemic, Olusegun Michael Otunuga
Biology and Medicine Through Mathematics Conference
No abstract provided.
A Within-Host Modeling Framework For Sars-Cov-2 Infection To Support Vaccine Strategies, Morgan Rose, Rachel Jennings, Jeffry Schroeter
A Within-Host Modeling Framework For Sars-Cov-2 Infection To Support Vaccine Strategies, Morgan Rose, Rachel Jennings, Jeffry Schroeter
Biology and Medicine Through Mathematics Conference
No abstract provided.
The Effect Of Prep Uptake And Adherence On The Spread Of Hiv In The Presence Of Casual And Long-Term Partnerships, Sylvia J. Gutowska, Katharine Gurski, Kathleen Hoffman
The Effect Of Prep Uptake And Adherence On The Spread Of Hiv In The Presence Of Casual And Long-Term Partnerships, Sylvia J. Gutowska, Katharine Gurski, Kathleen Hoffman
Biology and Medicine Through Mathematics Conference
No abstract provided.
Dynamics Of The Climax And Attack Communities In Cystic Fibrosis, Peter Uhl
Dynamics Of The Climax And Attack Communities In Cystic Fibrosis, Peter Uhl
Biology and Medicine Through Mathematics Conference
No abstract provided.
Dermatologic Manifestations Of Rheumatic Disease: Cutaneous Manifestations Of Sarcoidosis, Sarah Shapiro, Sindhuja Koppu, Mavra Masood, Beth Rubinstein, Huzaefah Syed
Dermatologic Manifestations Of Rheumatic Disease: Cutaneous Manifestations Of Sarcoidosis, Sarah Shapiro, Sindhuja Koppu, Mavra Masood, Beth Rubinstein, Huzaefah Syed
Open and Affordable Course Content at VCU
Cutaneous Manifestations of Sarcoidosis is a Powerpoint based learning module that depicts fictional patient scenarios detailing sarcoidosis and erythema nodosum. It explores other cutaneous and non-cutaneous manifestations, diagnostic criteria, and medical evaluation of sarcoidosis and the possible etiologies, workup, treatment, and prognosis of erythema nodosum. Health and racial disparities experienced by patients with sarcoidosis are also highlighted and discussed. It takes approximately 25 minutes to complete. This module was created for use in the VCU School of Medicine M1 Movement block, Rheumatology and Dermatology sections.
It is part of the Dermatologic Manifestations of Rheumatic Disease project, which provides overviews of …
Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko
Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko
Theses and Dissertations
Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …
Human Papillomavirus 16 E2 Regulates Host Cell Pathways Important For Cancer Progression And Treatment Sensitivity Which May Contribute To Cancer Outcomes, Christian Fontan
Human Papillomavirus 16 E2 Regulates Host Cell Pathways Important For Cancer Progression And Treatment Sensitivity Which May Contribute To Cancer Outcomes, Christian Fontan
Theses and Dissertations
Human papillomaviruses (HPVs) are causative agents in around 5% of all cancers, including cervical and oropharyngeal. A feature of HPV cancers is their better clinical outcome compared with non-HPV anatomical counterparts. In turn, the presence of E2 predicts a better clinical outcome in HPV-positive cancers; the reason(s) for the better outcome of E2-positive patients is not fully understood.
Previously, we demonstrated that HPV16 E2 regulates host gene transcription that is relevant to the HPV16 lifecycle in N/Tert-1 cells. One of the genes repressed by E2 and the entire HPV16 genome in N/Tert-1 cells is TWIST1. In these studies, we demonstrate …
Changes In Physical Activity And Relationships To Submaximal Exercise Capacity And Cardiac Function During Breast Cancer Therapy, Moriah P. Bellissimo
Changes In Physical Activity And Relationships To Submaximal Exercise Capacity And Cardiac Function During Breast Cancer Therapy, Moriah P. Bellissimo
Theses and Dissertations
Background: Breast cancer (BC) survivors are at high risk for heart failure due to curative cancer therapies. In non-cancer populations, physical activity is a first line treatment for preventing cardiovascular disease. This study examined whether more physical activity was associated with better submaximal exercise capacity and cardiac function during the first three months of cancer therapy.
Methods: Participants included 223 women with stage I-III BC before therapy and after three months of undergoing treatment and 126 controls. Leisure time physical activity was reported using the Godin Sheppard leisure time exercise questionnaire. Cardiac function was assessed by cardiac magnetic resonance, and …
Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay
Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay
Theses and Dissertations
The cell cycle is a highly regulated process that ensures the timely and accurate division of cells. Events of the normal cell cycle fall under two categories - positive and negative regulatory mechanisms. The first category, positive regulatory machinery, includes active protein complexes of cyclins in association with their partnering cyclin-dependent kinases (cyclin/CDK), which mediate series of phosphorylation events that relay a cell cycle progression from one stage to the next. The second category, the negative regulatory mechanisms, include the checkpoint controls consisting of the retinoblastoma (RB) family of proteins, some of which can form a transcriptional repressor complex DREAM. …
Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe
Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe
Pharmacotherapy and Outcomes Science Publications
Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.
Methods: …
Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock
Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock
Theses and Dissertations
The neuroendocrine hormone prolactin (PRL) and its cognate receptor (PRLr) have been implicated in the pathogenesis of breast cancer. PRL signaling relies on activating kinases such as the tyrosine kinase Jak2 and serine/threonine kinases ERK1/2, NEK3, PI3K, and AKT. In the canonical pathway of PRL signaling, JAK2 phosphorylates the transcription factor STAT5a at tyrosine residue 694 (pY694-STAT5a), preceding STAT5a nuclear translocation and transcriptional activity. However, STAT5a exists with functional duality as a transcription factor, having both pro-differentiative and pro-proliferative target genes. Other STAT family members (STATs 1, 3, and 6) have been shown to have transcriptional activity in the un-tyrosine-phosphorylated …
Evaluating Racial And Ethnic Disparities In Access To Primary Care Among Gay And Bisexual Men In The Us, A Population At High-Risk Of Hiv Infection, Jessica S. Kiernan, April D. Kimmel
Evaluating Racial And Ethnic Disparities In Access To Primary Care Among Gay And Bisexual Men In The Us, A Population At High-Risk Of Hiv Infection, Jessica S. Kiernan, April D. Kimmel
Graduate Research Posters
BACKGROUND: 69% of new HIV diagnoses in the US are among gay and bisexual men, with disparities by race and ethnicity. Primary care providers increasingly provide HIV prevention. Racial and ethnic disparities in primary care access are well-documented, but their persistence among gay and bisexual men is unknown. We examined racial and ethnic disparities in access to primary care among this population.
METHODS: We used nationally representative person-level sociodemographic, health status and utilization data, and data on organizational- and socially determinant barriers to care, from the National Health Interview Survey, 2013-2018. Outcomes were: 1) general physician visit
RESULTS: The sample …
Validity Of The Actigraph Gt9x Accelerometer Step-Count Function In Adults With Heart Failure With Preserved Ejection Fraction, Jonathan D. Kenyon, Hayley Billingsley, Natalie J. Bohmke, Danielle Kirkman, Salvatore Carbone, Youngdeok Kim
Validity Of The Actigraph Gt9x Accelerometer Step-Count Function In Adults With Heart Failure With Preserved Ejection Fraction, Jonathan D. Kenyon, Hayley Billingsley, Natalie J. Bohmke, Danielle Kirkman, Salvatore Carbone, Youngdeok Kim
Graduate Research Posters
Low physical activity is associated with heart failure with preserved ejection fraction (HFpEF). Step-counts, a measure of physical activity, can be measured via accelerometry. To date, few studies have examined validity of accelerometer-derived step-counts in the adults with HFpEF.
PURPOSE To assess criterion validity of the Actigraph GT9X accelerometer step-count function in adults with HFpEF via ankle, waist, and wrist placement, compared with manually counted, directly observed steps.
METHODS Six adults with HFpEF (age: 57.2 ± 9.4 y; African American: 50%; females: 100%) completed a cardiopulmonary exercise test (CPET) on a treadmill while wearing synchronized GT9X accelerometers on the ankle, …
Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence
Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence
Theses and Dissertations
Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …
Molecular Basis Of Cross-Sensitization In Colonic Inflammation-Induced Somatic Hypersensitivity, Parshva K. Mehta
Molecular Basis Of Cross-Sensitization In Colonic Inflammation-Induced Somatic Hypersensitivity, Parshva K. Mehta
Theses and Dissertations
A major portion of pain experienced by patients with an Irritable Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS) can be attributed to visceral hypersensitivity. Visceral stimuli transmitted through primary afferent neurons in the dorsal root ganglia (DRG) induce a nociceptive response. Notably, a subset of patients has also experienced the development of somatic pain, such as leg pain, after diagnosis of a bowel disorder. The aim of this investigation is to ascertain which biochemical mediators are involved in the development of such viscerosomatic cross-sensitization. Initially, the Von Frey Test was used to find behavioral evidence of somatic referred pain; …
Cost-Effectiveness Of Interventions Targeting Hard-To-Reach Populations Living With Hiv In Eastern And Southern Africa, Deo Mujwara
Theses and Dissertations
In Eastern and Southern Africa, hard-to-reach populations (e.g., long distance truck drivers and female sex workers), defined as populations that are difficult to interact or engage with due to their unique behaviors and characteristics, are disproportionately affected by the HIV epidemic and are at high-risk of acquiring and transmitting HIV. Further, these populations have substantially low uptake of HIV testing services, and those that have been diagnosed with HIV and on antiretroviral therapy experience high loss-to-follow-up from treatment programs.
Hard-to-reach populations face unique barriers in accessing and utilizing routine HIV care such as provider stigmatization towards sex workers and highly …
Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer
Theses and Dissertations
Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …
Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia
Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia
Theses and Dissertations
Background: Adverse events and impairments associated with cancer and its treatments causes worse outcomes. Increased incidence of renal diseases among cancer patients is of particular concern. Objective: To determine the risk factors for renal disease in cancer patients and compare healthcare costs, utilization and health-related quality of life (HRQoL) of cancer patients with a renal disease and cancer patients without renal diseases. Methods: Medical Expenditure Panel Survey files from 2009 – 2018 for cancer patients was used for this study. Multiple logistic regression, generalized linear model, Poisson regression and multiple linear regression for analyses after adjusting for demographic, socioeconomic and …