Digital Commons Network^™

Differential Patterns Of Gut And Oral Microbiomes In Hispanic Individuals With Cognitive Impairment, Yannick N. Wadop, Erin L. Vasquez, Julia J. Mathews, Jazmyn A. S. Muhammad, Rosa P. Mavarez, Claudia Satizabal, Mitzi M. Gonzales, Jeremy A. Tanner, Gladys E. Maestre, Bernard Fongang

School of Medicine Publications

Alterations in both oral and gut microbiomes have been associated with Alzheimer's disease and related dementia (ADRD). While extensive research has focused on the role of gut dysbiosis in ADRD, the contribution of the oral microbiome remains relatively understudied. This study aims to evaluate distinct patterns and potential synergistic effects of oral and gut microbiomes in a cohort of predominantly Hispanic individuals with cognitive impairment (CI) and without cognitive impairment (NC). We conducted 16S rRNA gene sequencing on stool and saliva samples from 32 participants (17 CI, 15 NC; 62.5% female, mean age = 70.4 ± 6.2 years) recruited in …

Evaluation Of Anti-Bacterial Efficacy Of Ginger, Resin Gum, And Nigella Sativa Irrigants Against Enterococcus Faecalis: An In Vitro Study, Iman El Ghazzawy, Leen Imad Hasbini, Reem Chamseddine, Wael Betbout, Roula Abiad

International Arab Journal of Dentistry

Objectives: To evaluate the antibacterial efficacy of Ginger, Resin Gum, and Nigella Sativa, against Enterococcus Faecalis.

Methods: Thirty-eight extracted single-rooted premolars were inoculated with E.faecalis, except the negative control, and incubated for 4 weeks. After instrumentation samples were divided into 4 groups (n=7) according to final irrigation: NaOCl+EDTA (Group A), Nigella sativa (B), Resin Gum (C), Ginger (D), plus 2 control groups (n=5): Saline (E), and Saline without bacterial inoculation (F). Cultures were collected at baseline and after irrigation.

Results: One-way ANOVA showed that in groups A-D a statistically significant reduction of bacterial load was observed at …

Molecular Determinants Of Neoadjuvant Chemotherapy Resistance In Breast Cancer: An Analysis Of Gene Expression And Tumor Microenvironment, Hedda Michelle Guevara-Nieto, Carlos A. Orozco-Castaño, Rafael Parra-Medina, Jenny Nathaly Poveda-Garavito, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba Lucia Combita

School of Graduate Studies Faculty Publications

Neoadjuvant chemotherapy (NAC) is a critical component of breast cancer treatment, but the molecular mechanisms underlying resistance remain poorly understood. This study aimed to identify transcriptomic changes associated with NAC resistance across four breast cancer subtypes: Luminal A, Luminal B/HER2-positive, Luminal B/HER2-negative, and Triple-Negative Breast Cancer (TNBC). RNA-seq analysis was performed on paired pre- and post-NAC breast cancer samples from 32 nonresponders. Differentially expressed genes (DEGs) were identified, and functional enrichment analyses were conducted. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Tumor microenvironment (TME) infiltration was estimated using deconvolution algorithms. The results revealed distinct gene expression profiles …

Hesperidin Efficacy Of Epidural Fibrosis In A Post Laminectomy Rat Model: An Experimental Study, Emrah Keski̇n, Mehmet Seli̇m Gel

Turkish Journal of Medical Sciences

Background/aim: Epidural fibrosis (EF) plays a significant role in the development of failed back surgery syndrome (FBSS). This study evaluates the antifibrotic effect of hesperidin, a citrus-derived bioflavonoid, within a rat laminectomy model.

Materials and methods: Thirty-two female Wistar albino rats were randomized into four groups (n = 8 each). Group 1 received laminectomy alone (control); Group 2 received a gelatin sponge; Groups 3 and 4 intraperitoneally received 50 mg/kg and 100 mg/kg of hesperidin, respectively, for 7 days post-laminectomy. After 6 weeks, epidural tissues were assessed histopathologically, and hydroxyproline levels were measured.

Results: Group 4 showed significantly lower EF …

Unveiling The Potential Of Marine Peptides In Leukemia: Mechanistic Insights And Future Horizon In Peptide Research, Salman Ahmed, Waqas Alam, Khalaf Alsharif, Michael Aschner, Esra Küpeli̇ Akkol, Mamdouh Allahyani, Hayaa Alhuthali, Luci̇ano Saso, Esra Gi̇zem Türkcanoğlu, Haroon Khan

Turkish Journal of Medical Sciences

Leukemia is a malignant disorder that affects the bone marrow and blood. It is frequently diagnosed in adults, with a higher incidence in males than females. Globally, it ranks as the 15th most widespread cancer and is the 11th leading cause of cancer-related fatalities. The intensity and severity of treatment have increased, leading to a rise in relapse rates, toxicity, and adverse health effects. Therefore, there is a critical need for new treatments. The antileukemic properties of natural compounds have been extensively studied. Aquatic organisms are a rich source of potential medicinal compounds. Anticancer peptides offer an ideal treatment approach …

Probabilistic Data Linkage To Study The Epidemiology Of Unintentional Fatal Drowning In A Large Metropolitan Region, Rohit P Shenoi, Ned Levine, Elizabeth A Camp, Linh Nguyen, Sandra Mckay, Shaila Zaman

Faculty, Staff and Students Publications

Background: It is difficult to study the epidemiology of drowning at the regional level because of multiple data sources, many of which have a high degree of unstandardized and missing data. We aimed to link multiple datasets to identify demographics and geographic locations of unintentional fatal drowning in a metropolitan region and compare linked data with vital statistic data.

Methods: This cross-sectional study included unintentional drowning fatalities among persons of all ages in metropolitan Houston between 2016 and 2022. Probabilistic linking was used to link multiple datasets and geographical mapping to identify drowning locations. The effectiveness of data linkage was …

Optimizing Genetic Ancestry Adjustment In Dna Methylation Studies: A Comparative Analysis Of Approaches, Kira D Höffler, Seyma Katrinli, Matthew W Halvorsen, Anne-Kristin Stavrum, Kevin S O'Connell, Alexey Shadrin, Srdjan Djurovic, Ole A Andreassen, James J Crowley, Jan Haavik, Kristen Hagen, Gerd Kvale, Kerry Ressler, Bjarne Hansen, Jair C Soares, Gabriel R Fries, Alicia K Smith, Stéphanie Le Hellard

Faculty, Staff and Student Publications

Background: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry.

Methods: We developed and adapted the adapted EpiAnceR+ approach, which includes (1) residualizing the CpG data overlapping with common SNPs for control …

A Randomized Controlled Prospective Study Comparing Surgical Outcomes Of Median Umbilical Ligament Lift-Up And Veress Needle Entry Techniques In Gynecologic Laparoscopic Surgery, Gazi̇ Güner, Ayşe Bacaksiz, Can Berk Karabudak, Fi̇gen Efe Çami̇li, Çi̇sem Ertok, Si̇nem Özşahi̇n Kiliç, Zeli̇ha Zeynep Satilmişoğlu, Can Tercan, Nazli Ayli̇n Vural

Turkish Journal of Medical Sciences

Background/aim: Laparoscopic surgery has become the preferred minimally invasive technique for both diagnostic and therapeutic procedures in gynecology. Although it is associated with lower overall complication rates compared to open surgery, most serious complications occur during the initial step of abdominal entry. Therefore, developing faster and safer entry methods is critical to improving surgical outcomes. This study aimed to compare the surgical results of the Median Umbilical Ligament Lift-Up (MULU) technique routinely used in our clinic with the commonly preferred Veress needle (VN) entry technique.

Materials and methods: This randomized, controlled, prospective study included 124 patients: 64 underwent abdominal entry …

Clinical Characteristics And Outcomes In Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma: A Retrospective Multicenter Study, Ebru Kiliç Güneş, Hacer Berna Afacan Öztürk, Esra Ki̇ri̇kti̇r, Asena Di̇kyar, Bi̇lge Uğur, Ahmet Kürşad Güneş, Meltem Ayli

Turkish Journal of Medical Sciences

Background/aimEpstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), represents a rare and aggressive subtype of B-cell lymphoma, officially classified as a distinct entity in the revised 4th edition of the World Health Organization (WHO) 2016 classification. This retrospective study aims to evaluate the prevalence, clinical characteristics, histopathological characteristics, and survival results of patients diagnosed with EBV+ DLBCL-NOS.Materials and methodsOur retrospective study included 92 newly diagnosed DLBCL patients treated at two centers between 2016 and 2024. EBV status was determined using in situ hybridization for EBER, with positivity defined as; ≥50% nuclear staining in tumor cells. ResultsAmong 92 …

Baseline Neurofilament Light Chain And Brain-Derived Neurotrophic Factor Levels Predict Development Of Aggressive Multiple Sclerosis, Ruzi̇ye Erol Yildiz, Ece Akbayir, Tuğçe Kizilay, Ayça Si̇may Ersöz, Duygu Özkan Yaşargün, Devran Süer, Vuslat Yilmaz, Erdem Tüzün, Recai̇ Türkoğlu

Turkish Journal of Medical Sciences

Background/aim: Patients with multiple sclerosis (MS) may present with a rapidly disabling clinical course in the first few years of disease. It is imperative to find biomarkers to predict patients with aggressive MS (AMS) and have an opportunity to prevent disability accumulation through appropriate treatment strategies. Our aim was to explore the prognostic value of neurofilament light chain (NFL) and brain-derived neurotrophic factor (BDNF) levels in cerebrospinal fluid (CSF) obtained in the early stages of MS.

Materials and methods: Relapsing-remitting multiple sclerosis (RRMS) patients presenting with first-time attacks were screened, of which 26 fulfilled AMS criteria in the 3-year follow-up …

The Importance Of Galectin-3 In The Diagnosis Of Childhood Acute Appendicitis ​, Onur Yalçin, Aybegüm Kalyoncu Ayçenk, Ali̇ Aygün, Ahmet Burak Günpinar, Mehmet Seyfetti̇n Saribaş, Volkan Altinok, Tevfi̇k Noyan

Turkish Journal of Medical Sciences

Background/aim: Acute appendicitis (AA) is a frequent indication for emergency surgery in children; accurate diagnosis is essential to prevent complications. We examined whether serum Galectin-3 is associated with pediatric AA and quantified its diagnostic performance relative to routine inflammatory markers.

Materials and methods: This prospective, single-center study was conducted in a tertiary emergency department between July 1, 2023, and January 31, 2024. Children younger than 18 years with pathologically confirmed AA were enrolled as cases; age-compatible healthy volunteers served as controls. Venous blood was obtained at presentation before any therapeutic intervention. Galectin-3 concentrations were quantified using a commercial enzyme-linked immunosorbent …

Investigating Patient Non-Attendance To Healthcare Appointments In Türkiye: Data From A State Hospital And An Oral And Dental Health Center, Eyüp Sari, Ali̇ Ni̇yazi̇ Kurtcebe, Ci̇han Döğer, Recep Aydin

Turkish Journal of Medical Sciences

Background/aim: To determine the frequency and reasons for appointment nonattendance in a state hospital and a dental health center in a densely populated district of Türkiye, and to identify related factors to guide preventive measures.

Materials and methods: This retrospective cross-sectional study included patients who scheduled appointments at Ankara Etimesgut State Hospital and Etimesgut Oral and Dental Health Center through the Centralized Patient Appointment System (Merkezi Hekim Randevu Sistemi; MHRS) in February 2024. Nonattendees were contacted in March 2024 to determine reasons for nonattendance.

Results: A total of 30,552 appointments were analyzed (1978 dental, 28,574 hospital). The overall nonattendance rate …

Generative Modeling For Interpretable Anomaly Detection In Medical Imaging: Applications In Failure Detection And Data Curation, Mckell E Woodland, Mais Altaie, Caleb S O'Connor, Austin H Castelo, Olubunmi C Lebimoyo, Aashish C Gupta, Joshua P Yung, Paul E Kinahan, Clifton D Fuller, Eugene J Koay, Bruno C Odisio, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

This work aims to leverage generative modeling-based anomaly detection to enhance interpretability in AI failure detection systems and to aid data curation for large repositories. For failure detection interpretability, this retrospective study utilized 3339 CT scans (525 patients), divided patient-wise into training, baseline test, and anomaly (having failure-causing attributes—e.g., needles, ascites) test datasets. For data curation, 112,120 ChestX-ray14 radiographs were used for training and 2036 radiographs from the Medical Imaging and Data Resource Center for testing, categorized as baseline or anomalous based on attribute alignment with ChestX-ray14. StyleGAN2 networks modeled the training distributions. Test images were reconstructed with backpropagation and …

The Clingen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications For Classification Of Variants In Ada, Dclre1c, Il2rg, Il7r, Jak3, Rag1, And Rag2, Vanessa C Jacovas, Michelle Zelnick, Shannon Mcnulty, Justyne E Ross, Namrata Khurana, Xueyang Pan, Alejandro Nieto, Shiloh Martin, Benjamin Mclean, Marwa A Elnagheeb, Morton J Cowan, Jennifer M Puck, Mike S Hershfield, James Verbsky, Jolan Walter, Eric J Allenspach, Alice Y Chan, Nicolai S C Van Oers, Rajarshi Ghosh, Megan Piazza, Bo Yuan, Luigi D Notarangelo, Britt A Johnson, Ivan K Chinn, Severe Combined Immunodeficiency Variant Curation Expert Panel

Faculty, Staff and Students Publications

Purpose: This collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID. The effort focused on the 7 most common SCID-related genes identified by SCID newborn screening in North America: ADA, DCLRE1C, IL2RG, IL7R, JAK3, RAG1, and RAG2.

Methods: The SCID-VCEP conducted a rigorous review of variants that involved database analyses, literature review, and expert feedback to derive gene-specific modifications to the ACMG/AMP guidelines. These …

Efficacy And Safety Of Different Treatment Strategies In Pediatric Fecal Incontinence: A Systematic Review, Seham M. Abd El-Moghny, Wessam A. Al-Kholy, Mohamed I. Elsepaee, Ahmed M. Elgamal, Rabab S. Mohamed

Journal of Medicine in Scientific Research

Background Fecal incontinence (FI) in children is a challenging condition with significant impacts on quality of life (QoL). Multiple therapeutic approaches, including neuromodulation techniques such as sacral nerve stimulation (SNS), biofeedback therapy, botulinum toxin (Botox) injections, and transcutaneous functional electrical stimulation (TFES), have been explored. This systematic review evaluates the efficacy and safety of these interventions in pediatric patients. Methods A thorough investigation was performed in PubMed, Scopus, Web of Science, and the Cochrane Library databases up to February 2025. Studies assessing the effectiveness and safety of SNS, biofeedback, Botox injections, and other interventions in pediatric FI were included. Risk …

Early Outcomes Of Y-Incision Vs. Conventional Techniques For Aortic Root Dilatation, Ahmed Shafeek Ali, Mahmoud Maher Abdou Ibrahim, Haitham Alshahat Ramadan

Journal of Medicine in Scientific Research

Background The y-incision method for expanding the aortic annulus has proven its effectiveness and safety in the short term. We aim to compare the early results of this method with those of the conventional annular dilatation techniques. Methods From March 2022 to April 2024, Eighty consecutive patients at the National Heart Institute in Cairo, Egypt, received aortic valve replacement (AVR) combined with aortic root dilatation (ARD) Utilizing either conventional annular dilatation techniques (group 1, n=40), including Manouguian [12.5% (10/80)], Nicks [35% (28/80)], and others [2.5% (2/80)], or method of Y-incision (group 2, n=40) [ 50% (40/80)]. Preoperative, intraoperative, and early …

Temperamental Traits For Infants And Toddlers With Rickets, Rabab Salah Eldin Mohamed

Journal of Medicine in Scientific Research

Background Rickets is a deficiency in the mineralization of developing bone. Infant temperament comprises a collection of qualities that define individual behavior. The objective of this work was to determine if there were variations in temperamental qualities between ricketic and normal babies and toddlers, and whether such differences varied by sex. Methods This cross-sectional work had been conducted on 100 children aged from 6 to 24 months both sexes, with rickets (Group 1), and 100 normal sex- and age-matched children as a control group (Group 2). All patients underwent evaluation of temperamental traits. The assessment of psychological aspects for both …

A Recent Insight On Prevalence Of Atopic Diseases In Children With Type 1 Diabetes, Randa Mohamed Darwish, Ayat Ibrahim Ghanem

Journal of Medicine in Scientific Research

Background Type 1 diabetes mellitus (T1DM) and atopic diseases are both prevalent immunemediated conditions in children. Although traditionally viewed as immunologically opposing disorders—T1DM being Th1-mediated and atopy Th2-mediated—recent studies suggest possible overlap in genetic susceptibility and environmental triggers. This study aimed to evaluate the prevalence and association of various atopic conditions in pediatric T1DM patients. Aim of the study To investigate the prevalence of atopic diseases—including atopic dermatitis, allergic rhinitis, allergic conjunctivitis, bronchial asthma, food allergy, and anaphylaxis—among children with T1DM compared to healthy age- and sex-matched controls, and to analyze contributing risk factors. Methods A retrospective cohort study was …

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …

Understanding The Nutrition Ecology And Related Distal And Proximal Research Gaps Impacting School-Aged Children's And Adolescents' Functioning-A Report From The "Biomarkers Of Nutrition For Development: Knowledge Indicating Dietary Sufficiency (Bond-Kids)" Project Working Group 2., Maureen M Black, Meg M Bruening, Amy Carroll-Scott, Jayna M Dave, Kristie L Ebi, Lora L Iannotti, Susan L Johnson, Lorrene D Ritchie, Elizabeth Y Jimenez, Alison L Steiber, Daniel J Raiten

Children’s Nutrition Research Center Staff Publications

Nutrition is critical to the health, development, and well-being of children and adolescents, operating through nutrients and the social and physical influences of dietary behaviors. Child and adolescent growth and development depend on complex biological systems interacting with the nutrition ecology. In this review, we focus on bidirectional interactions with the multilevel nutrition ecology, including distal systems (climate, geopolitical, and food systems) and proximal systems (community food options; health, social, and food services; and school policies and programs), all mediated by the family. Thus, the impact of nutrition on children's and adolescents' functional outcomes is dependent on understanding the multilevel …

Proteomic Characterization Of The Neuronal Bin1 Interactome In Homeostatic And Alzheimer’S Disease Mouse Brains, Joseph Mcmillan

USF Tampa Graduate Theses and Dissertations

The gene BIN1 is the second-largest genetic risk factor for late-onset Alzheimer’s disease (LOAD). It is expressed in neurons and glia in the brain as cell-type specific and ubiquitous isoforms. BIN1 is an adaptor protein that regulates membrane dynamics in many cell types. Previously, we reported that BIN1 predominantly localizes to presynaptic terminals in neurons and regulates presynaptic vesicular release. However, the function of neuronal BIN1 in relation to LOAD is not yet fully understood. A significant gap in the field is the unbiased characterization of neuronal BIN1-interacting proteins and proximal neighbors. To address this gap and help define the …

Inhibition Of Osteosarcoma Lung Metastases By Β-Glucan And Cd40 Agonist Is Mediated By Activation Of Macrophages And Nk Cells, Pradeep Shrestha, Rejeena Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: Osteosarcoma (OS) lung metastases remain a significant therapeutic challenge. Innate immune activation is a promising therapeutic approach. Innate immune agonists can modulate the tumor immune microenvironment and improve therapeutic response.

Methods: Using an experimental syngeneic OS lung metastasis BALB/c mouse model with K7M3-luc OS cells, we evaluated the antitumor effects of yeast-derived particulate β-glucan in prevention and therapeutic settings. We then assessed whether the CD40 agonist (CD40a) in combination with β-glucan increased therapeutic response in two different immune-competent mouse models of OS lung tumor burden.

Results: In the pretreatment settings, mice treated with β-glucan prior to OS cell infusion …

Intracranial Neural Biomarkers Of Psychiatric Symptoms And Their Utility For Guiding Neuromodulation Therapy: A Systematic Review, Katherine E Kabotyanski, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

The quest to develop and improve neuromodulatory therapies for treatment-resistant psychiatric disorders has been fueled by the discovery of intracranial neural biomarkers of symptom dimensions. These neural correlates shed light on the underlying neurophysiology of the disorder and may even be useful in guiding therapy delivery. This systematic review summarizes recent efforts in this field relating neural activity to behavior and symptomatology. For years, the majority of these neurobehavioral relationships had been studied in the hospital or clinic environment. Recent technological advances in implanted neuromodulation devices that permit not only stimulation, but also intracranial neural recording have enabled this research …

Functional Roles Of The Complement Immune System In Cardiac Inflammation And Hypertrophy, Kathryn D Hok, Haydn E Rich, Anthony Shadid, Lavanya Gunamalai, Tingting Weng-Mills, Rajarajan A Thandavarayan, Nirmal K Banda, Marie-Francoise Doursout, Marcos I Restrepo, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

Cardiac inflammation and hypertrophy develop as a pathologic response to an array of insults, such as myocardial infarctions, chronic systemic hypertension, and valvular defects. Due to the high prevalence of such conditions, there is an increasing need to prevent and halt cardiac hypertrophy. Because cardiac damage and subsequent remodeling can lead to arrhythmias, heart failure, and even sudden cardiac death, inhibition of cardiac hypertrophy is key to reducing cardiovascular-related mortality. The immune system is the driving force behind inflammatory reactions. All three pathways of complement system activation-classical, lectin, and alternative-are implicated in developing cardiac damage, inflammation, and hypertrophy due to …

Genetic Engineering Of Esophageal Organoids: Crispr-Based Knock-In For Cell Lineage Tracing, Kyung-Pil Ko, Jae-Il Park

Faculty, Staff and Student Publications

Esophageal organoids serve as powerful systems to study epithelial lineage hierarchies and cancer biology. Gene manipulation in these organoids has traditionally involved overexpression or knockout strategies. However, CRISPR-/Cas9-based knock-in (KI) approaches now enable precise cell lineage tracing and live imaging. Here, we describe protocols to generate fluorescent KI organoids from murine esophageal epithelium by tagging Krt13 (BFP) and Sox2 (mNeon). These dual-reporter organoids allow direct monitoring of growth dynamics and differentiation trajectories. We outline CRISPR/Cas9 design, donor construction using homology-independent approaches (CRISPaint), delivery into organoid cells, enrichment and single-clone isolation, and validation by fluorescence. For organoids, homology-directed repair (HDR) can …

Dna Methylation And Machine Learning: Challenges And Perspective Toward Enhanced Clinical Diagnostics, Erfan Aref-Eshghi, Arash B Abadi, Mohammad-Erfan Farhadieh, Amirreza Hooshmand, Fatemeh Ghasemi, Leila Youssefian, Hassan Vahidnezhad, Taylor Martin Kerrins, Xiaonan Zhao, Mahdi Akbarzadeh, Hakon Hakonarson, Amir Hossein Saeidian

Faculty, Staff and Students Publications

DNA methylation is an epigenetic modification that regulates gene expression by adding methyl groups to DNA, affecting cellular function and disease development. Machine learning, a subset of artificial intelligence, analyzes large datasets to identify patterns and make predictions. Over the past two decades, advances in bioinformatics technologies for arrays and sequencing have generated vast amounts of data, leading to the widespread adoption of machine learning methods for analyzing complex biological information for medical problems. This review explores recent advancements in DNA methylation studies that leverage emerging machine learning techniques for more precise, comprehensive, and rapid patient diagnostics based on DNA …

Vaccine And Treatment Evaluation Units: A Historical Perspective, Robert B Belshe, David I Bernstein, Kathryn M Edwards, Sharon E Frey, Wendy A Keitel, Myron M Levine, John J Treanor, Peter F Wright

Faculty, Staff and Students Publications

On 27 February 1962, Surgeon General Luther Terry announced a new vaccine development program within the National Institute of Allergy and Infectious Diseases (NIAID). Initially, the plan had three components: (1) special laboratories and facilities for development of prototype vaccines; (2) pilot lot production facilities and preliminary vaccine trial sites; and (3) larger lot production capacity and expanded human testing. Respiratory viruses were targeted as the top priority for vaccine development. Over 5 decades, this program has evolved and expanded to include multiple academic vaccine evaluation sites within the network, now labeled as the Vaccine and Treatment Evaluation Units (VTEUs). …

Just-In-Time Adaptive Intervention To Improve Hiv Prevention And Substance Use In Youth Experiencing Homelessness (My-Ride): Protocol For A Randomized Controlled Trial, Diane Santa Maria, Nikhil Padhye, Michael Businelle, Natasha Slesnick, Stefani Ricondo, Marguerita Lightfoot

Faculty, Staff and Students Publications

Background: Youth who are experiencing homelessness face a higher risk of HIV infection compared to their housed peers, and suicide and overdose remain the leading causes of death among homeless youth. Just-in-Time Adaptive Interventions (JITAIs) are gaining momentum for HIV prevention and substance use research. Yet, most interventions for homeless youth have not addressed modifiable real-time factors.

Objective: This paper describes the development and implementation of a randomized attention-controlled trial to assess the efficacy of motivating youth to reduce infections, disconnections, and emotional dysregulation (MY-RIDE), a JITAI to improve HIV prevention and substance use in homeless youth.

Methods: This study …

The Effect Of Type 2 Diabetes Genetic Predisposition On Non-Cardiovascular Comorbidities, Ana Luiza Arruda, Ozvan Bocher, Henry J Taylor, Davis Cammann, Satoshi Yoshiji, Xianyong Yin, Chi Zhao, Jingchun Chen, Alexis C Wood, Ken Suzuki, Josep M Mercader, Cassandra N Spracklen, James B Meigs, Marijana Vujkovic, George Davey Smith, Jerome I Rotter, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Students Publications

Type 2 diabetes is associated with a range of non-cardiovascular non-oncologic comorbidities. To move beyond associations and evaluate causal effects between type 2 diabetes genetic predisposition and 21 comorbidities, we apply Mendelian randomization analysis using genome-wide association studies across multiple genetic ancestries. Additionally, leveraging eight mechanistic clusters of type 2 diabetes genetic profiles, each representing distinct biological pathways, we investigate causal links between cluster-stratified type 2 diabetes genetic predisposition and comorbidity risk. We identify causal effects of type 2 diabetes genetic predisposition driven by distinct genetic clusters. For example, the risk-increasing effects of type 2 diabetes genetic predisposition on cataracts …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …