Digital Commons Network^™

The Role Of B Cells In Promoting Lipid Absorption By Promoting Lacteal Development, Kenny Johnson

Theses and Dissertations

The absorption of dietary lipids in the gut is necessary to maintain the metabolic tone of tissues. Inflammation in the gut can cause defects in lipid absorption, which can result in tissue wasting, otherwise known as cachexia. Cachexia is commonly observed in patients with inflammatory bowel disease and cancer patients. The underlying cause of cachexia is unknown, and there are currently no effective therapeutic options available to treat it. Lymphatic drainage in the small intestine (SI) is specialized to promote the transport of dietary lipids into circulation. Lacteals are blunt-ended lymphatic vessels localized to the central axes of villi in …

Host Range And Efficiency Of Plating Determination Of Phages Infecting Caulobacter And Non-Caulobacter Species, Christopher Scott

Senior Theses

Seven bacteriophages were studied to determine their host range among Caulobacter and non-Caulobacter bacteria. Recently, Caulobacter-associated phages have been shown to have broader host ranges than previously believed. Thus, it is crucial to thoroughly verify the range of bacteria strains that these phages can infect. To understand the extent of each phage’s host range, phage lysates were spotted on bacterial lawns to determine whether lysis could occur. Host-range analyses in this project conclude that these Dolichocephalovirinae phages were able to infect multiple genera and species of host bacteria. Plating efficiency experiments were also conducted to compare the phage’s …

Developing And Validating Brain Tumor Organoid Models To Evaluate Novel Therapeutics In Vitro, Dev P. Patel

Senior Theses

Glioblastoma (GBM), a World Health Organization Grade IV brain tumor, remains one of the most aggressive and treatment-resistant malignancies. It is characterized by rapid proliferation, deep infiltration, and a high level of genotypic and phenotypic heterogeneity. Despite advancements in medical technology and neuro-oncology, GBM remains one of the most treatment-resistant cancers with a median survival rate of only nine months post-diagnosis and less than 5% of patients surviving beyond 5 years of diagnosis. The standard treatment constitutes maximum surgical resection followed by chemotherapy and radiation. These therapeutic strategies are blocked by significant challenges like the blood-brain barrier (BBB), and intratumoral …

The Effect Of Grape Seed Extract Against The Formation Of S.Aureus Biofilms In A Clinical Setting, Srestha Samaddar

Senior Theses

The rise of antibiotic-resistant bacterial infections, particularly those caused by Staphylococcus aureus, poses a serious threat to public health and clinical care. A major contributor to the persistence of these infections is the formation of bacterial biofilms, structured communities that protect S. aureus from antibiotics and immune responses, especially on surgical sites and medical devices. As conventional treatments become less effective, interest in alternative, natural antimicrobial agents has increased, due to public dissatisfaction with conventional medicine and a growing trust in complementary and alternative medicine. Grape seed extract (GSE), a polyphenol-rich byproduct of winemaking, has emerged as a promising candidate …

Augmented, Not Replaced: The Impact Of Ai On Equity Research Analysts, Lawrence Carrea

Senior Theses

The adoption of AI tools into professional workflows has the chance to revolutionize major industries such as the financial services industry. Because equity research is a space that is heavily dependent on data aggregation, forecasting, and report generation, there is a threat of AI replacing human analysts in the next five years. The goal of this study is to determine how the adoption of AI tools will affect the equity research career field. To achieve this goal, a mixed-method approach is employed through a quantitative and qualitative survey. Results from the survey indicate that most finance professionals are already using …

Methods Comparison For Collecting Subjective Valence And Arousal Judgements, Esha Gandhi

Senior Theses

Human emotion and affect are critical for regulating behavior, guiding decision-making and facilitating social communications. In everyday language, emotion and affect are interchangeable. However, in psychology, they are conceptualized as two distinct constructs. Emotion refers to discrete, prototypical subjective experiences elicited by specific stimuli. Affect, in contrast, refers to more elementary feelings that can be described along two continuous dimensions: valence (positive-negative) and arousal (low-high). According to the circumplex model (Russell, 1980), emotion can be represented within a two-dimensional core affective space defined by valence and arousal. Although valence and arousal are conceptually interrelated, most studies measure them separately using …

The Impact Of Discretion On Human Service Workers Supporting The Health Of Unaccompanied Minors In Foster Care, Diana M. Clark

Senior Theses

Unaccompanied children (UCs) are a vulnerable population that enters government custody and accesses healthcare via the Office of Refugee Resettlement (ORR)'s system of care. While prior research has focused on generating policy recommendations to improve healthcare services available to UCs both in ORR custody and following release from custody, this thesis will instead expand upon the experiences of staff members working at ORR-contracted agencies. These workers make decisions that have short- and long-term implications on the health and wellbeing of UCs. Drawing from 65 in-depth interviews with human service workers in ORR-contracted voluntary agencies, this thesis uses street-level bureaucracy framework …

Differential Gene Coexpression In 16p11.2 Autism Spectrum Disorder, Joseph Patacsil

Senior Theses

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has been associated with several genetic factors. One of these factors is a mutation of the 16p11.2 region on chromosome 16, in which both deletions and duplications have been strongly associated with ASD. KCTD13 is a gene in the 16p11.2 gene locus that has recently been shown to influence brain development and is also associated with ASD. This study analyzes the differential gene expression and gene pathways of these different phenotypes. KCTD13 deletion had a significant up-regulation effect on genes and shares similar pathways to the 16p11.2 duplication mutation. Mutations in …

Role Of Race And Ethnicity In The Development, Diagnosis, And Treatment Of Gestational Diabetes Mellitus, Gabrielle D. Shupard

Senior Theses

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy, and rates of this disease have been steadily increasing over the past ten years. GDM disproportionately impacts racial and ethnic minorities at higher rates than their Caucasian counterparts. In this study, the PRECEDE model framework was employed during a literature review to gain a greater understanding of the complex risk factors contributing to differences in the development, diagnosis, and treatment of GDM among these population subgroups. The second part of this study concentrated on reviewing the extent to which current literature evaluates the role of race and ethnicity …

Impact Of Msx1 And Irf6 Gene Variants On Orofacial Cleft And Facial Development, Elaine Vanterpool, Lisa Banks

Student Posters

A cleft lip or palate is a congenital anomaly that occurs when a baby's mouth doesn’t form properly during pregnancy. It happens when the tissues that shape the upper lip or roof of the mouth fail to join during development. It is among the most common birth defects associated with genetic conditions or syndromes. Orofacial cleft can be caused by a combination of genes and other factors like the mother's exposure to environmental things, diet, and medications during pregnancy. Examining the genes involved and making connections that provide insight into the improper formations of the maxillary tissues during fetal stages …

Effects Of Cell-Free Supernatants Of Commercial Yogurt Products On Salmonella Survival, Juliet Durant, Akayla King

Student Posters

Salmonellosis remains a global public health challenge and Salmonella enterica serovar Enteritidis and Typhimurium are the primary causes. Salmonella virulence mechanisms involve attachment and invasion of intestinal epithelial cells. Gut microbiota and probiotics that contain Lactobacillus species have been shown to prevent Salmonella infection. Yogurt is a commonly consumed probiotic product containing Lactobacillus species. Yogurts made under laboratory conditions and the cell-free supernatants have been shown to inhibit Salmonella growth. The many commercial yogurt products on the market may vary in antimicrobial components based on production methods. Therefore, the present study aimed to evaluate the survival of 5 log CFU/mL …

Title: An Analysis Of Hmbs Variants Associated With Acute Intermittent Porphyria, Elaine Vanterpool, Jason Kahari

Student Posters

HMBS, also known as hydroxymethylbilane synthase, is a gene that is responsible for providing instructions for making the enzyme named hydroxymethylbilane synthase. This enzyme is involved in the creation of a molecule called heme. Heme plays an important part in all of the body’s vital organs. It is important to all organs however, it is most prevalent in the blood, bone marrow, and liver. Heme is essential in making iron-containing proteins called hemeproteins. To produce heme, an eight-step process must occur that requires 8 different enzymes. “Hydroxymethylbilane synthase is responsible for the third step in this process, which combines four …

The Association Of Abca3 Variants In Hypertension Pathogenesis, Elaine Vanterpool, Jea Joseph

Student Posters

Hypertension affects around 48.1% of people living in the United States. This number of adults with hypertension between the ages of 30-70 has increased from 650 million to 1.28 billion in the last 30 years. Hypertension is characterized as a condition that affects the arteries of the blood. High blood pressure and high cholesterol have a huge correlation to each other. When the body cannot rid cholesterol from the blood stream, it can deposit along artery walls and clog them, making blood flow harder and increases blood pressure. ABCA3 is a member of the ATP binding cassette family of proteins …

An Analysis Of Oas1 Variants Associated In Diabetes Mellitus, Elaine Vanterpool, Ashley Tannis

Student Posters

Type 1 diabetes is caused by a combination of multiple genetic and environmental factors that precipitate autoimmune destruction of the insulin-producing β-cells of the pancreas. Individuals with type 1 diabetes have higher frequencies of OAS1 GG and GA genotypes than nondiabetic's.OAS1, an interferon-induced gene, also known by its official name, 2'-5'-oligoadenylate synthetase 1, encodes proteins that play a crucial role in innate cellular antiviral response which prevents viral replication by activating the adaptive immune system to erase the virus trying to spread. OAS1 is also involved in additional cellular processes such as cell growth and cell death. This gene is …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Klf4 Enhances Transplantation-Induced Hematopoiesis By Inhibiting Tlrs And Noncanonical Nfκb Signaling At A Steady State, Chun Shik Park, Cory S Bridges, Andrew H Lewis, Taylor J Chen, Saptarsi Shai, Wa Du, Monica Puppi, Barry Zorman, Sumazin Pavel, H Daniel Lacorazza

Faculty, Staff and Students Publications

The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the Klf4 gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and …

Clinical Management And Therapeutic Optimization Of Patients With Heart Failure With Reduced Ejection Fraction And Low Blood Pressure. A Clinical Consensus Statement Of The Heart Failure Association (Hfa) Of The Esc, Hadi Skouri, Nicolas Girerd, Luca Monzo, Mark C Petrie, Michael Böhm, Marianna Adamo, Wilfried Mullens, Gianluigi Savarese, Mehmet Birhan Yilmaz, Offer Amir, Antoni Bayes-Genis, Biykem Bozkurt, Javed Butler, Ovidiu Chioncel, Alexandre Mebazaa, Jose L Merino, Brenda Moura, Piotr Ponikowski, Petar Seferovic, Giuseppe M C Rosano, Marco Metra

Faculty, Staff and Students Publications

Despite major advancements in heart failure (HF) management and guideline recommendations over the past two decades, real-world evidence highlights suboptimal implementation of guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Low blood pressure (BP) is common in HFrEF patients and represents a major perceived barrier to implementing life-saving treatments in clinical practice, as physicians are often concerned about symptomatic hypotension and its consequences. Although low BP can be seen in those hospitalized with signs of shock, the most common scenario involves non-severe, asymptomatic hypotension in patients receiving foundational therapy for HFrEF, where premature down-titration or discontinuation of …

International Multispecialty Expert Physician Preoperative Identification Of Extranodal Extension In Patients With Oropharyngeal Cancer Using Computed Tomography: Prospective Blinded Human Inter-Observer Performance Evaluation, Onur Sahin, Serageldin Kamel, Kareem A Wahid, Cem Dede, Nicolette Taku, Renjie He, Mohamed A Naser, Christina S Sharafi, Antti Mäkitie, Benjamin H Kann, Kimmo Kaski, Jaakko Sahlsten, Joel Jaskari, Moran Amit, Gregory M Chronowski, Eduardo M Diaz, Adam S Garden, Ryan P Goepfert, Jeffrey P Guenette, G Brandon Gunn, Jussi Hirvonen, Frank Hoebers, Katherine A Hutcheson, Nandita Guha-Thakurta, Jason Johnson, Diana Kaya, Shekhar D Khanpara, Kristofer Nyman, Stephen Y Lai, Miriam Lango, Kim O Learned, Anna Lee, Carol M Lewis, Anastasios Maniakas, Amy C Moreno, Jeffrey N Myers, Jack Phan, Kristen B Pytynia, David I Rosenthal, Vlad C Sandulache, Dawid Schellingerhout, Shalin J Shah, Andrew G Sikora, Abdallah S R Mohamed, Melissa M Chen, Clifton D Fuller, Multidisciplinary Oropharyngeal Cancer Extra‐Nodal Extension (Opc Ene) Assessment Working Group

Faculty, Staff and Students Publications

Background: Pathologic extranodal extension (pENE) is a crucial prognostic factor in oropharyngeal cancer (OPC), but determining pENE from imaging has high inter-observer variability. The role of clinician specialty in the accuracy of imaging-detected extranodal extension (iENE) remains unclear. The purpose of this study is to assess the influence of clinician specialty on the accuracy of preoperative iENE detection in human papillomavirus (HPV)-positive OPC using computed tomography (CT) imaging.

Methods: This prospective observational study evaluated pretherapy CT images from 24 HPV-positive OPC patients (30 scans, including duplicates). Thirty-four expert observers (11 radiologists, 12 surgeons, 11 radiation oncologists) assessed iENE and reported …

Recent Advances In The Management Of Pediatric Cholestatic Liver Diseases, Krupa R Mysore, Katherine Cheng, Lakshmi Anandini Suri, Rima Fawaz, Alisha M Mavis, Debora Kogan-Liberman, Saeed Mohammad, Sarah A Taylor

Faculty, Staff and Students Publications

Pediatric cholestatic liver diseases are rare conditions that can result from multiple specific underlying etiologies. Among the most common etiologies of pediatric cholestatic liver diseases are biliary atresia, Alagille syndrome (ALGS), and inherited disorders of bile acid transport. These diseases are characterized by episodic or chronic unremitting cholestasis. Due to the chronicity of these conditions, it is imperative to optimize medical management to improve patient quality of life, provide nutritional support, and reduce bile acid toxicity in efforts to slow disease progression. Cholestatic liver diseases remain the leading cause of pediatric liver transplantation, as many underlying disease etiologies have no …

Uric Acid Stroke Cerebroprotection Transcended Sex, Age, And Comorbidities In A Multicenter Preclinical Trial, Rakesh B Patel, Mariia Kumskova, Hanish Kodali, Ivan Budnik, Vitalii Kuznetsov, Aditi Jain, Abhishek Jha, Daniel Thedens, Nirav Dhanesha, Brijesh Sutariya, Karisma A Nagarkatti, Jessica Lamb, Pradip Kamat, Yanrong Shi, Brooklyn Avery, Takahiko Imai, Xuyan Jin, Anjali Chauhan, Ligia S B Boisserand, Mohammad B Khan, Krishnan Dhandapani, Basavaraju G Sanganahalli, Lauren H Sansing, David C Hess, Raymond C Koehler, Louise D Mccullough, Jaroslaw Aronowski, Cenk Ayata, Márcio A Diniz, Patrick D Lyden, Anna M Planas, Angel Chamorro, Anil K Chauhan, Enrique C Leira, Span Investigators

Faculty, Staff and Student Publications

Background: Past failures in translating stroke cerebroprotection provoked calls for a more rigorous methodological approach, leading to the stroke preclinical assessment network SPAN (Stroke Preclinical Assessment Network), where uric acid (UA) treatment exceeded a prespecified efficacy boundary for the primary functional outcome. Still, successful translation to humans requires confirmation of the effect of UA across key biological variables relevant to patients with stroke.

Methods: We measured the effects of intravenous UA treatment (16 mg/kg) versus intravenous saline in groups of animals enrolled in the SPAN network with diverse comorbidities, sex, and age. The masked study drug or placebo was administered …

Opportunities In Stroke Care At Safety Net Hospitals: A Socioecological Perspective, Anjail Sharrief, Joshua Wollen, Maha Almohamad, M Carter Denny, Erica Jones, Aardhra M Venkatachalam, Digvijaya Navalkele, Shivika Chandra, Mariam Ahmed, Robert Pratt, Bradley D Shy, John Mcmenamy, Chigozirim Izeogu, Lesli E Skolarus, Nneka L Ifejika, Nicole R Gonzales

Faculty, Staff and Student Publications

Safety net hospitals (SNHs) provide care to patients regardless of their insurance status or ability to pay, serving populations at the highest risk for poor stroke outcomes. These include historically marginalized racial and ethnic groups, and individuals disproportionately affected by adverse social drivers of health, including lower socioeconomic status, housing instability, and limited access to preventive care. Improving stroke care at SNHs presents a critical opportunity to strengthen care delivery for individuals with the greatest need. However, such efforts require a clear understanding of the barriers across all levels of the healthcare system. In this Perspective, the authors adopt a …

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Guan-Yu Xiao, Lenka Koudelková, Chao Wu, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2-modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component of …

Clinical And Genetic Delineation Of Autosomal Recessive And Dominant Actl6b-Related Developmental Brain Disorders., Elisa Cali, Tania Quirin, Clarissa Rocca, Stephanie Efthymiou, Antonella Riva, Dana Marafi, Maha S. Zaki, Mohnish Suri, Roberto Dominguez, Hasnaa M. Elbendary, Shahryar Alavi, Mohamed S. Abdel-Hamid, Heba Morsy, Frederic Tran Mau-Them, Mathilde Nizon, Pavel Tesner, Lukáš Ryba, Faisal Zafar, Nuzhat Rana, Nebal W. Saadi, Zahra Firoozfar, Pinar Gencpinar, Bulent Unay, Canan Ustun, Ange-Line Bruel, Christine Coubes, Jennifer Stefanich, Ozlem Sezer, Emanuele Agolini, Antonio Novelli, Gessica Vasco, Donatella Lettori, Mathieu Milh, Laurent Villard, Shimriet Zeidler, Henry Opperman, Vincent Strehlow, Mahmoud Y Issa, Hebatallah El Khassab, Prem Chand, Shahnaz Ibrahim, Ali Rashidi-Nezhad, Mohammad Miryounesi, Pegah Larki, Jennifer Morrison, Ingrid Cristian, Isabelle Thiffault, Nicole L. Bertsch, Grace J. Noh, John Pappas, Ellen Moran, Nikolaos M. Marinakis, Joanne Traeger-Synodinos, Susan Hosseini, Mohammad Reza Abbaszadegan, Roseline Caumes, Lisenka E L M Vissers, Maedeh Neshatdoust, Mostafa Montazer Zohour, Elmostafa El Fahime, Christina Canavati, Lara Kamal, Moien Kanaan, Omar Askander, Victoria Voinova, Olga Levchenko, Shahzhad Haider, Sara S. Halbach, Rayana Elias Maia, Salehi Mansoor, Vivek Jain, Sanjukta Tawde, Viveka Santhosh R. Challa, Vykuntaraju K. Gowda, Varunvenkat M. Srinivasan, Lucas Alves Victor, Benito Pinero-Banos, Jennifer Hague, Heba Ahmed Elawady, Adelia Maria De Miranda Henriques-Souza, Huma Arshad Cheema, Muhammad Nadeem Anjum, Sara Idkaidak, Firas Alqarajeh, Osama Atawneh, Hagar Mor-Shaked, Tamar Harel, Giovanni Zifarelli, Peter Bauer, Fernando Kok, Joao Paulo Kitajima, Fabiola Monteiro, Juliana Josahkian, Gaetan Lesca, Nicolas Chatron, Dorothe Ville, David Murphy, Jeffrey L. Neul, Sureni V. Mullegama, Amber Begtrup, Isabella Herman, Tadahiro Mitani, Jennifer E. Posey, Chee Geap Tay, Iram Javed, Lucinda Carr, Farah Kanani, Fiona Beecroft, Lee Hane, Elsayed Abdelkreem, Milan Macek, Luciana Bispo, Marwa Abd Elmaksoud, Farzad Hashemi-Gorji, Davut Pehlivan, David J. Amor, Rami Abou Jamra, Wendy K. Chung, Eshan Ghayoor Karimiani, Philippe M. Campeau, Fowzan S. Alkuraya, Alistair T. Pagnamenta, Joseph G. Gleeson, James R. Lupski, Pasquale Striano, Andres Moreno-De-Luca, Denis L J Lafontaine, Henry Houlden, Reza Maroofian

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

METHODS: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.

RESULTS: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, …

Methylation Patterns Of The Nasal Epigenome Of Hospitalized Sars-Cov-2 Positive Patients Reveal Insights Into Molecular Mechanisms Of Covid-19., Benjamin L. Spector, Boryana Koseva, Rebecca Mclennan, Dithi Banerjee, Kamani Lankachandra, Todd Bradley, Rangaraj Selvarangan, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts to identify factors responsible for differential COVID-19 severity include but are not limited to genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links to disease severity. However, whole epigenome analysis of the respiratory tract, the target tissue of SARS-CoV-2, remains ill-defined.

RESULTS: We interrogated the nasal methylome to identify pathophysiologic drivers in COVID-19 severity through whole genome bisulfite sequencing (WGBS) of nasal samples from COVID-19 positive individuals …

Acute Pain Trajectories In Elderly Patients With Fragility Hip Fractures, Paul Potnuru, Christina Goehl, Katherine S Becker, Alejandro Juul, Madison Aycock, Johanna Blair De Haan, Sudipta Sen, Michelle Ge, Stephen J Warner, Nadia Hernandez

Faculty, Staff and Student Publications

Background: Pain management for hospitalized elderly patients with fragility hip fractures (FHF) remains challenging. This study aims to distinguish acute pain trajectories in FHF patients that can inform personalized analgesia management.

Methods: We conducted a prospective observational study of patients aged 65 and older with FHF at a Level I trauma center. The primary outcome was daily average pain assessed for five days post-injury using the Brief Pain Inventory (BPI). We used group-based trajectory modeling (GBTM) to distinguish acute pain trajectories. Then, factors and secondary outcomes (opioid use and hospital length of stay [LOS]) associated with more severe pain trajectories …

Role Of Peripheral Amyloid-Β Aggregates In Alzheimer's Disease: Mechanistic, Diagnostic, And Therapeutic Implications, Nazaret Gamez, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Amanda Nash, Jonathon Debonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …

Single-Nucleus Transcriptional Profiling Of The Placenta Reveals The Syncytiotrophoblast Stress Response To Covid-19, Rachel A Keuls, Scott A Ochsner, Mary B O'Neill, Diana R O'Day, Akihiko Miyauchi, Kadeshia M Campbell, Natalie Lanners, Jeffery A Goldstein, Connor Yee, Neil J Mckenna, Ronald J Parchem, Jacqueline G Parchem

Faculty, Staff and Students Publications

Background: COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology and function is unclear.

Objective: This study aimed to determine the effects of maternal COVID-19 on placental syncytiotrophoblasts using single-nucleus transcriptional profiling and to compare placental stress responses in COVID-19 and preeclampsia.

Study design: For transcriptional characterization of syncytiotrophoblasts, we used the single-nucleus RNA sequencing platform, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3), to profile placental villi and fetal membranes from unvaccinated patients with symptomatic COVID-19 at birth (n = 4), gestational age-matched controls (n = 4), and a case of …

Clinical And Genetic Delineation Of Autosomal Recessive And Dominant Actl6b-Related Developmental Brain Disorders, Elisa Cali, Tania Quirin, Clarissa Rocca, Stephanie Efthymiou, Antonella Riva, Dana Marafi, Maha S Zaki, Mohnish Suri, Roberto Dominguez, Hasnaa M Elbendary, Shahryar Alavi, Mohamed S Abdel-Hamid, Heba Morsy, Frederic Tran Mau-Them, Mathilde Nizon, Pavel Tesner, Lukáš Ryba, Faisal Zafar, Nuzhat Rana, Nebal W Saadi, Zahra Firoozfar, Pinar Gencpinar, Bulent Unay, Canan Ustun, Ange-Line Bruel, Christine Coubes, Jennifer Stefanich, Ozlem Sezer, Emanuele Agolini, Antonio Novelli, Gessica Vasco, Donatella Lettori, Mathieu Milh, Laurent Villard, Shimriet Zeidler, Henry Opperman, Vincent Strehlow, Mahmoud Y Issa, Hebatallah El Khassab, Prem Chand, Shahnaz Ibrahim, Ali Rashidi-Nezhad, Mohammad Miryounesi, Pegah Larki, Jennifer Morrison, Ingrid Cristian, Isabelle Thiffault, Nicole L Bertsch, Grace J Noh, John Pappas, Ellen Moran, Nikolaos M Marinakis, Joanne Traeger-Synodinos, Susan Hosseini, Mohammad Reza Abbaszadegan, Roseline Caumes, Lisenka E L M Vissers, Maedeh Neshatdoust, Mostafa Montazer Zohour, Elmostafa El Fahime, Christina Canavati, Lara Kamal, Moien Kanaan, Omar Askander, Victoria Voinova, Olga Levchenko, Shahzhad Haider, Sara S Halbach, Rayana Elias Maia, Salehi Mansoor, Vivek Jain, Sanjukta Tawde, Viveka Santhosh R Challa, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Lucas Alves Victor, Benito Pinero-Banos, Jennifer Hague, Heba Ahmed Elawady, Adelia Maria De Miranda Henriques-Souza, Huma Arshad Cheema, Muhammad Nadeem Anjum, Sara Idkaidak, Firas Alqarajeh, Osama Atawneh, Hagar Mor-Shaked, Tamar Harel, Giovanni Zifarelli, Peter Bauer, Fernando Kok, Joao Paulo Kitajima, Fabiola Monteiro, Juliana Josahkian, Gaetan Lesca, Nicolas Chatron, Dorothe Ville, David Murphy, Jeffrey L Neul, Sureni V Mullegama, Amber Begtrup, Isabella Herman, Tadahiro Mitani, Jennifer E Posey, Chee Geap Tay, Iram Javed, Lucinda Carr, Farah Kanani, Fiona Beecroft, Lee Hane, Elsayed Abdelkreem, Milan Macek, Luciana Bispo, Marwa Abd Elmaksoud, Farzad Hashemi-Gorji, Davut Pehlivan, David J Amor, Rami Abou Jamra, Wendy K Chung, Eshan Ghayoor Karimiani, Philippe M Campeau, Fowzan S Alkuraya, Alistair T Pagnamenta, Joseph G Gleeson, James R Lupski, Pasquale Striano, Andres Moreno-De-Luca, Denis L J Lafontaine, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.

Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, …