Digital Commons Network^™

Complement Activation In Maternal And Placental Pathology Of Preeclampsia, Manu T Banadakoppa, Madhulatha S Chauhan, Moises J Tacam, Allyson W Nevins, Antonio H Ruano, Simone H Ruano, Jon A Fuson, Chandra Yallampalli

Faculty, Staff and Students Publications

Background: Preeclampsia is a multifactorial, pregnancy-related disorder characterized by new-onset hypertension and proteinuria, with distinct early- and late-onset forms. Although complement dysregulation has been implicated in the pathogenesis of preeclampsia, its causal role remains unclear. In mice, Crry (complement receptor 1-related protein Y) functions as a critical complement regulator at the fetal-maternal interface. Because complete Crry deficiency is embryonically lethal, direct in vivo investigation of complement activation in pregnancy has been challenging.

Methods: We generated a placenta-specific, doxycycline-inducible short hairpin RNA mouse model in which Crry expression can be downregulated in a dose-dependent manner. This system employs Cyp19-driven Cre recombinase …

Cytosine Base Editing Of Lpa In Transgenic Mice Averts Large Deletions, Marcel A Chuecos, So Hyun Park, Madhvi M Bhakta, Usosa Too-Chiobi, Daniel Betancourth, Mingming Cao, Marco De Giorgi, Christopher J Walkey, Anjana Tiwari, Biana Godin, Julia M Assini, Donna J Palmer, Philip Ng, Michael B Boffa, Marlys L Koschinsky, Gang Bao, William R Lagor

Faculty, Staff and Students Publications

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease, with approximately 20% of the population exhibiting elevated levels. While there are promising drugs in development, there are currently no approved therapies specifically designed to lower Lp(a) levels. For high-risk individuals with extreme levels of Lp(a), liver-directed genome editing could be an effective one-time solution. Genome editing approaches such as CRISPR and TALENs can reduce Lp(a) in LPA-transgenic mouse models, but they frequently induce large and potentially harmful genomic deletions. Here, we report the first application of TadA-derived cytosine base editing (CBE), delivered via helper-dependent adenovirus (HDAdV) and …

Vitamin D–Amp Axis In Host Defense Against Fungal Infections, Nuraly S. Akimbekov, Ilya Digel, Svetlana K. Sakhanova, Kuanysh Tastambek, Dinara K. Sherelkhan, Mohammed S. Razzaque

School of Medicine Publications

Vitamin D–mediated regulation of antimicrobial peptides (AMPs) is an important focus in innate immunology and is aimed at elucidating the role of vitamin D in enhancing antimicrobial defense. AMPs are short protein chains that serve as a first line of defense against invading pathogens, including fungi, bacteria and viruses. Unlike conventional antibiotics, AMPs are produced endogenously and are less likely to induce antimicrobial resistance, making them promising candidates for treating infections caused by drug-resistant pathogens. Studies indicate that optimal vitamin D levels are essential for activating antimicrobial pathways and regulating AMPs that target multiple fungal pathogens. This article summarizes recent …

Molecular And Histologic Studies Of The Amygdala And Reward Circuits In Rhesus Macaques (Macaca Mulatta) With Self-Injurious Behavior (Sib), Jackie Barua

Doctoral Dissertations

Self-injurious behavior (SIB), also known as non-suicidal self-injury (NSSI), is characterized by deliberate infliction of harming one’s own body tissues without committing suicide, and persists in a group of captive rhesus macaques despite an enhanced enrichment program and pharmacological intervention with diazepam. The aim of this dissertation was to identify the neurobiological underpinnings of SIB by combining RNA-seq guided transcriptomic discovery and targeted candidate gene validation with unbiased histological and imaging analysis. The secondary aim was to employ a complementary mouse model to investigate the endogenous opioid system in response to diazepam. The amygdala transcriptome of primates with SIB (n …

Activated Dorsomedial Hypothalamic Astrocytes Regulate Feeding Behavior, Bella M. Lisenby

Honors Projects

The dorsomedial hypothalamus (DMH) region of the brain has been shown to be important for anticipatory feeding activity and play a role in restricting excessive food intake. In obese animals that overconsume calories, astrocytes within the DMH exhibit intracellular signaling changes indicative of cellular activation. Because astrocytes are known to influence neuronal function, we hypothesize that activated astrocytes regulate behavior. In the current study, we use chemogenetics combined with stereotaxic surgery to assess the contribution of astrocyte activity in the DMH towards metabolic behaviors.

Fentanyl Mediated Distortions Of Phasic Dopamine Release Dynamics Encoding Natural Reward And Aversive Processing In The Mammalian Mesolimbic Circuit, Oliver P. Culver Iv

MUSC Theses and Dissertations

Mu opioid receptor (MOR) agonists are recognized to disinhibit tonic dopamine (DA) in the ventral striatum (VS), contributing to opioid addiction and euphoria. However, MOR agonists can also inhibit non-drug reward-seeking, and disrupt conditioned responding to aversive stimuli, a phenomenon not readily explained by tonic DA disinhibition. We hypothesized that this effect could be due in part to disruption of phasic DA responses to conditioned stimuli (CS) which critically shape and maintain behaviors during naturalistic reward and aversive processing. Because MOR effects on CS-evoked phasic DA are largely unexamined, we conducted in vivo fiber photometric recordings in water-deprived male and …

Nursing Students Applying Active Teaching And Learning To Develop Clinical Judgment Skills, Charlene Lindsay Jones

Walden Dissertations and Doctoral Studies

No abstract provided.

Garlic-Derived Metabolite Activates Lkb1, Promotes Adipose Enampt Secretion, And Improves Age-Related Muscle Function Via Hypothalamic Signaling, Jun-Ichiro Suzuki, Kiyoshi Yoshioka, Masahiro Kurita, Takumi Sugimoto, Takahiro Eguchi, Naoki Ito, Aoi Kodama, Yasutomi Kamei, Masahiro Ohtani, Toshiaki Matsutomo, Shin-Ichiro Imai

2020-Current year OA Pubs

Garlic (Allium sativum L.) and its aged extract contain many bioactive compounds that can bring health benefits to humans. Among them, S-1-propenyl-L-cysteine (S1PC) has recently drawn significant attention in the field of nutriceutical research. However, the mechanism of its molecular action has remained poorly understood. Here, we show that S1PC significantly activates liver kinase B1 (LKB1) through enhancing its tertiary complex formation with STRAD and MO25, leading to stimulating the phosphorylation of a mammalian NAD

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the

Reducing Cardiovascular Disease Risk In Obesity: An Unexpected But Welcome Fourier Transformation, Layla A Abushamat, Arsalan Hamid, Vijay Nambi, Huaizhu Wu, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Effect Of Exercise On Modifying Progression Of Physical Symptoms In Parkinson’S Disease: A Systematic Review And Meta-Analysis, Ruiping Xia, Mitchell Stanford, Robert S. Phillips

Internet Journal of Allied Health Sciences and Practice

Purpose: Parkinson’s disease (PD) is a progressive neurodegenerative disease. Emerging evidence suggests a promising treatment of combining exercise with medication. This systematic review with meta-analysis examined effect of exercise on modifying PD progression of physical symptoms. Methods: E-databases were searched to date. Randomized trials were included if they compared effect of exercise with no exercise/other exercise, and measured motor function for >=12 months. Results: Ten trials were included with eight eligible for meta-analyses. The pooled effect of exercise on UPDRS-III was a standard mean difference of 0.327 (95% CI: -0.052 to 0.707; p < 0.091). Mean difference in off-medication exceeded minimal clinically important difference. The pooled effects were 0.927 (95% CI: 0.015 to 1.839, p = 0.046) for Timed Up-and-Go, and 0.338 (95% CI: 0.022 to 0.654, p < 0.036) for PD Questionnaire-39. All findings were in favor of exercise intervention to improve patients’ motor severity and function/participation for at least 12 months. Conclusions: This study suggests that physical therapy …

Correlation Of Oxidative Stress Markers Between Serum And Colostrum And Their Association With Production Performance In Lactating Sows From A Prrs-Unstable Herd, Supasit Sopin, Yonlayong Woonwoong, Pichai Jirawattanapong, Prapassorn Boonsoongnern, Wirod Lakkanasombat, Alongkot Boonsoongnern

The Thai Journal of Veterinary Medicine

Oxidative stress occurs when the production of reactive oxygen species exceeds the antioxidant defense capacity of living organisms. Oxidative stress is commonly assessed using serum samples; however, blood sampling in pigs is often avoided on commercial farms because of disease transmission concerns and animal welfare considerations. This study aimed to evaluate the correlation between oxidative stress markers in serum and colostrum samples and to determine their association with production performance in lactating sows. A total of 34 Landrace × Large White sows from a commercial farrow-to-finish farm were included in the study. Blood and colostrum samples were collected immediately after …

Articulator Volume 32, Issue 2

Metro Denver Dental Society Articulator Magazine

The 2nd Quarter 2026 issue of The Articulator explores the growing intersection between oral health and whole-body wellness, with a focus on oral-systemic health, interdisciplinary collaboration and the role of dentistry in preventive medicine. Articles include:

• A perspective from Dr. Brett Kessler examining what true medical-dental integration would require, including reimbursement reform, collaborative care models and expanded recognition of dentistry’s role in systemic health.
• An evidence-based article from Ms. Anne O. Rice exploring the connection between periodontal disease, inflammation and Alzheimer’s disease, including the role of dentistry in dementia risk reduction and preventive healthcare.
• Insights from Ms. Lani McBeth on …

Calcium Signaling And Postsynaptic Density Dynamics: The Roles Of Calmodulin In Synaptic Protein Regulation, Keyaa Dilip Shah, Yonghong Zhang

School of Integrative Biological & Chemical Sciences Faculty Publications

Calcium signaling in neuronal cells is the principal mechanism underlying learning and synaptic plasticity, whereas the postsynaptic density (PSD) is an important center where calcium-dependent processes are organized and regulated. This review explores the roles of calmodulin (CaM) in facilitating calcium-dependent modulation of the activities of synaptic proteins in the PSD. We focus on the molecular processes through which CaM interacts with calcium signals to regulate the function, localization, and interactions of central synaptic proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), membrane-associated guanylate kinases (MAGUKs), and N-methyl-D-aspartate (NMDA) receptors. We aim to summarize recent advances in structural, biochemical, and imaging …

Social Media Is A Juggernaut: Lagged Correlation Analysis Using Ngram Data On “Internet” And “Social Media” With Amplification By The Advent Of The “Iphone”, William Zywiak, Gao Niu, Nicolas Petrell, Victoria Nichele, Kirsten Hokeness

Mathematics and Economics Faculty Journal Articles

The amount of new information transmitted per day can be overwhelming. The data available through Ngram Viewer allows statistical examination to determine the most salient topics, as well as lagged correlation and lagged variance to support possible causal connections between concepts. Using this database, we determined that COVID, crypto, microplastics, and especially social media are important topics of the last few years. We also present results that suggest the development of the internet and the iPhone fueled the prominence of social media, and the access of the iPhone also increased access to the internet.

Increasing Lead (Pb) Screening Participation Rates In The Pediatric Patient Population At The Philadelphia College Of Osteopathic Medicine Lancaster Avenue Community Healthcare Center, Jacob Varrato

PCOM Biomedical Studies Student Scholarship

Elevated blood lead levels (EBLLs) are an ongoing public health crisis predominantly affecting children under six in low-income communities located in major cities across the United States (Zartarian et al. 2024). Chronic lead exposure due to outdated housing, polluted water, and contaminated soil is especially harmful in early childhood. Frequent hand to mouth contact at this age increases the risk of ingesting particulate matter containing lead (CDC). EBLLs can predispose children to neurocognitive deficits, cardiovascular disease, and epigenetic modifications to gene expression patterns (Collin et al. 2022). While precautionary measures and timely screening protocols greatly reduce the risk of developing …

Effects Of Mitoquinone On Doxorubicin-Induced Cytotoxicity In H9c2 Cardiac Myoblasts And 22rv1 Prostate Cancer Cells, Tia Patrick

PCOM Biomedical Studies Student Scholarship

Introduction:

Although Doxorubicin (DOX) is a widely prescribed chemotherapeutic agent, its clinical use is limited by cardiotoxicity (DIC) caused by oxidative stress, mitochondrial dysfunction, and cardiac apoptosis. Dexrazoxane (DEX) is the only FDA-approved cardioprotective agent to prevent DIC. However, DEX may induce secondary malignancy. Mitochondria-targeted antioxidants (MTAs), such as mitoquinone (MitoQ) and 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SKQ1), selectively accumulate within mitochondria to scavenge reactive oxygen species (ROS) at their primary site of production. Our previous findings demonstrated that MitoQ and SKQ1 prevented the reduction in cell viability caused by DOX treatment in H9c2 myoblasts. However, it remains unclear whether MitoQ can selectively …

Adjunctive Psychosocial Interventions And Opioid Abstinence Among Patients Receiving Buprenorphine: A Randomized Clinical Trial., Michelle R. Lent, Emily E Hurstak, Kevin G Lynch, Emily Loscalzo, Kimberly Mazur, Helen L Lugo, Karen L Dugosh

PCOM Scholarly Works

IMPORTANCE: Adjunctive psychosocial treatments are recommended for many using medications for opioid use disorder (MOUD), but it is unclear which approaches can best enhance treatment outcomes.

OBJECTIVES: To evaluate the comparative effectiveness of 2 psychosocial treatments, peer recovery support (PRS) and cognitive-behavioral therapy (CBT), on opioid abstinence when used as adjunctive therapies to office-based buprenorphine treatment in adults with opioid use disorder (OUD).

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included US adults diagnosed with OUD referred for care at 5 federally qualified health centers with office-based addiction treatment programs by their clinicians from 2020 to 2024. Participants were …

Radiotheranostics For Gynecological Pathologies, Joni Sebastiano

Dissertations, Theses, and Capstone Projects

Molecular imaging, specifically positron emission tomography (PET), is vital for detecting disease and understanding its biological makeup. The exploitation of radiolabeled antibodies for PET imaging has proven to be indispensable to the field of molecular imaging over the last several decades. The development of radioimmunoconjugates for use in immunoPET has not only allowed for the sensitive, specific, and high-resolution detection of disease, but has also enabled a deeper understanding of the disease biology, ultimately guiding more personalized therapeutic strategies. Most typically, this technology is harnessed for the diagnosis and treatment of cancer, however more recently, the field has explored the …

Wayfindr: Investigating Feedback In Biological Pathways, Polina Bombina, Reginald L Mcgee Ii, Jake Reed, Zachary B Abrams, Lynne V Abruzzo, Kevin R Coombes

2020-Current year OA Pubs

Understanding biological pathways requires more than static diagrams. We present WayFindR, an R package that converts pathway data from WikiPathways and KEGG into graph structures using igraph, enabling computational analysis of regulatory features such as negative feedback loops. Rooted in control theory, negative feedback is essential for system stability, yet it is often underrepresented in curated pathway data. In this study, we systematically analyzed pathway information from both databases across multiple species and found that feedback loops-particularly negative ones-are rarely captured. This gap likely reflects both biological and technical challenges. Biologically, feedback mechanisms are inherently complex and often remain uncharted …

Clinical Presentations Of Pemphigus Vulgaris In Patients With Skin Of Color: A Systematic Literature Review, Haya Alkiswani, Simona Alomary, Jared Boetes, Nicole J. Baker, Susan C. Taylor

SKMC Student Presentations and Publications

Background: Pemphigus vulgaris (PV) is a rare, often severe autoimmune disease affecting skin and mucous membranes. Despite the scarce literature on PV in skin of color (SOC) populations (Fitzpatrick III-VI), existing studies suggest that there are misdiagnosis, delayed treatment, and recurrence of symptoms in SOC patients with PV. Objective: This review explores the clinical presentations of PV reported in patients with SOC, diagnostic challenges and delays, treatments, and patient outcomes to allow for an improved understanding of how PV manifests clinically in darker skin. Methods: A systematic literature review was conducted using articles found in PubMed and Embase. Two independent …

Neuroinflammation And Neuropathology In A Novel Tau, Amyloid-Beta And Alpha-Synuclein Co-Pathology Model, Jhodi Mickayla Webster

ETDs from 2020-2029

Neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson disease (PD) often present with overlapping proteinopathies rather than aggregated proteins in isolation. Amyloid-β (Aβ) and phosphorylated tau are found in a substantial proportion of idiopathic PD cases, while α-synuclein (α-syn) pathology is present in over half of AD cases. The presence of these co-pathologies is associated with accelerated cognitive decline and increase mortality in these patients. In parallel, neurodegenerative diseases are increasingly recognized as being shaped by interactions between central nervous system (CNS) pathology and the immune system. Despite this, most experimental animal models of neurodegenerative disease examine single pathologies in …

Robotic-Assisted Pedicle Screw Placement Achieves High Accuracy And Narrows The Experience Gap: A Preclinical Evaluation, Anna T. Reza, Matthias Walper, Mitchell K. Ng, Paul G. Mastrokostas, Andrew S. Lee, Rafael G. Rafael, Kornelis A. Poelstra, Ratliff K. John, Rajiv K. Sethi, Michael A. Mont

Rothman Institute Papers

To assess a robotic-assisted system versus open manual techniques to: (1) compare pedicle screw accuracy between fellows and attendings with and without robotic assistance, and (2) evaluate executed versus planned trajectory fidelity relative to prior reports. Robotic-assisted spine systems aim to improve the accuracy, reproducibility, and safety of pedicle screw placement. Limited evidence compares outcomes across differing surgeon experience levels. A total of 255 thoracolumbar pedicle screws were placed in synthetic torsos simulating adult degenerative anatomy. Four surgeons (two fellows, two attendings) each placed half their screws using open fluoroscopy-guided techniques and half using a minimally invasive percutaneous approach with …

Dementia, Advance Directives, And Second-Order Volitions, Rand Hirmiz

Research Collection School of Social Sciences

This paper contributes to the ongoing debate over the authority of advance directives in cases where patients with dementia express desires that conflict with their earlier wishes. Drawing on Harry Frankfurt’s concept of second-order volitions, I argue that the preferences of the pre-dementia self (the “then-self”) should, in most cases, take precedence over those of the post-dementia self (the “now-self”) –  particularly in instances where the now-self has lost the capacity to form second-order volitions and is no longer able to meaningfully repudiate prior values and commitments.

Artelon Graft Augmentation In Revision Anterior Cruciate Ligament Reconstruction: Surgical Technique Guide., Taylor Manes, Morgan Turnow, Trent Davis, Anthony Perugini, Michael Anderson, Benjamin Taylor

Surgery Articles

INTRODUCTION: Revision anterior cruciate ligament (ACL) procedures are becoming more prevalent. Variable grafts for ACL reconstruction are available, including autograft, allograft, and synthetic graft options. Various augmentation techniques are also available and typically consist of synthetic material such as Artelon graft. This type of synthetic material has been used and shown to produce safe and reliable augmentation in ligament injuries. The purpose of this study was to describe our unique revision ACL reconstruction technique utilizing Artelon graft augmentation and report our short-term results.

MATERIALS AND METHODS: We retrospectively reviewed patients undergoing revision ACL reconstruction with Artelon graft augmentation, a Flexband …

The Effects Of Bone Health And Variation On Saw Mark Signatures, Lily Ambrose

PCOM Biomedical Studies Student Scholarship

Bone health and structural variation are multifactorial. Population, environment, age, diet, and health influence the overall functional morphology of bone and its response to stressors. Reduced cortical porosity, trabecular thinning, and low bone mass are common indicators of age-related and pathological changes, affecting a significant portion of the population. Because of this, bones encountered in medicolegal investigations often differ from what is considered “normal.” The structural integrity of bone needs to be considered because density influences mechanical strength and response to external forces. In criminal dismemberment cases, forensic scientists analyze saw marks to identify tool class and reconstruct events. While …

The Effect Of Bai1 Deficiency On Cell Survival During The Critical Period Of Retinal Development, Nicholas Mirmanesh

PCOM Biomedical Studies Student Scholarship

The postnatal retina undergoes further development during the critical period, during which excess neurons are culled, and synapses are refined to shape the mature retinal circuitry. Brain-specific angiogenesis inhibitor-1 (BAI1) has been implicated in synaptic development, phagocytosis, the regulation of angiogenesis, and inflammatory signaling, suggesting it may play an important role in retinal maturation. The goal of this project was to determine how BAI1 deficiency affects retinal cell survival and layer morphology during the critical period. Mice were divided into three genotype groups: BAI1 +/+ Wild Type (WT), +/- (Het), and -/- (KO). Apoptotic cells were quantified using TUNEL staining …

Lingo4 Coordinates Ilc3-Intrinsic Il-22 Production And Microbiota-Mediated Ilc3 Homeostasis, José L Fachi, Tihana Trsan, Cristiane Sécca, Sarah De Oliveira, Vinícius R Rodovalho, Patrick Fernandes Rodrigues, Wandy L Beatty, Raki Sudan, Shitong Wu, Bishan Bhattarai, Santosh K Panda, Marina Cella, Susan Gilfillan, Marco Colonna

2020-Current year OA Pubs

LINGO4 is a leucine-rich repeat and immunoglobulin-like domain-containing transmembrane protein encoded immediately adjacent to Rorc, the gene for RORγt, raising the possibility that it contributes to the biology of RORγt+ lymphocytes. However, its impact on these cells and resistance to enteric infections has remained unknown. Here, we identify LINGO4 as a critical regulator of group 3 innate lymphoid cells (ILC3s). Lingo4-/- ILC3s exhibit a profound, cell-intrinsic defect in IL-22 production linked to impaired STAT3 activation, mitochondrial dysfunction, elevated ROS, and increased apoptosis. In vivo, Lingo4 deficiency also drives a dysbiotic gut microbiota, resulting in an additional, microbiota-dependent loss of ILC3s. …

Activation Of The Human Β3 Gabaa Receptor By Combinations Of Receptor Protonation With Chemical Agonists And Gain-Of-Function Mutations, Allison L Germann, Spencer R Pierce, Joe Henry Steinbach, Gustav Akk

2020-Current year OA Pubs

Native GABA

Human Stem Cell-Based Embryo Models: Innovation, Ethics, And Policy, Alfonso Martinez Arias, Thorold Theunissen, Et Al.

2020-Current year OA Pubs

The aim of this White Paper is to establish a foundational framework for research, technological development, and regulation in the emerging field of stem cell-based embryo models (SCBEMs). These models, generated from Pluripotent Stem Cells, are designed to recapitulate essential events in early stages of human development. They have the potential to illuminate the early stages of embryo development and implantation and hold promise as an avenue to address global health challenges, including infertility and pregnancy loss, congenital, neonatal and adult conditions, and the need for organ transplants. While SCBEMs are not a substitute for human embryos, their tractability for …