Digital Commons Network^™

Rare Variant Analysis Of Electronic Health Record-Defined Major Depressive Disorder In The All Of Us Research Program, Stephen Emil Vieno

Theses and Dissertations

The underlying pathogenesis of MDD remains poorly understood, with multiple competing hypotheses regarding its exact etiology. As a heterogeneous disorder with relatively low heritability, large-scale genome-wide association studies of MDD have relied on increasingly large sample sizes to identify common genetic variants associated with the disorder. However, the rare variant genetic architecture of MDD is still largely unknown. The aim of the present analysis was to use the AoU—a United States-based biobank that integrates healthcare records from over 50 healthcare systems and possesses whole genome sequencing data for participants—to perform a gene set–based analysis of MDD. This analysis presented several …

Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran

Theses and Dissertations

Major depressive disorder (MDD) affects over 350 million individuals worldwide and is characterized by profound dysregulation of serotonin (5-HT) and dopamine (DA) systems that govern mood, reward processing, and motivation. The serotonin transporter (SERT) and dopamine transporter (DAT), both dynamically regulated through phosphorylation, serve as critical determinants of synaptic monoamine signaling. Despite decades of therapeutic development, current antidepressants require 4-6 weeks to achieve efficacy, and approximately one-third to half of patients develop treatment-resistant depression. The emergence of rapid-acting antidepressants like ketamine represents a paradigmatic shift, demonstrating symptom relief within hours; however, ketamine's therapeutic potential remains constrained by abuse liability, dissociative …

Establishing A Conventional Linac-Based Electron Flash Beam, Justin Defrancisco

Theses and Dissertations

Problems: A rediscovered radiotherapy technique, FLASH, involves increasing the dose rate to >40 Gy/s. For a given dose, FLASH is shown to decrease the normal tissue complication probability without affecting the tumor control probability. More preclinical studies are necessary to confirm and enable these desirable properties on humans. Current preclinical investigations have diverse constraints, requiring FLASH apparatuses with flexible parameters and accurate control. However, there are limited FLASH platforms available, the existing ones are costly. Our institution is not in possession of any such infrastructure. Even if available, dosimetry and beam control in FLASH are extremely lacking. There is …

Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior

Faculty, Staff and Student Publications

No abstract provided.

Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

Background: Transcranial direct current stimulation is a non-invasive neuromodulation technique with emerging therapeutic potential in neurodevelopmental conditions. While childhood-onset stroke survivors frequently experience long-term motor impairment, there are very few studies examining the safety and feasibility of transcranial direct current stimulation in this population.

Objective: To evaluate the safety, feasibility, and tolerability of bihemispheric transcranial direct current stimulation paired with occupational therapy in children and adolescents with chronic hemiparesis following childhood-onset arterial ischemic stroke or intracranial hemorrhage.

Methods: In this single-arm, open-label pilot study, five participants aged 6-19 years of age received five daily sessions of transcranial direct current stimulation …

Smoking Habit And Long-Term Colorectal Cancer Incidence By Exome-Wide Mutational And Neoantigen Loads: Evidence Based On The Prospective Cohort Incident-Tumour Biobank Method, Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino

Faculty, Staff and Student Publications

Objective: To test the hypothesis that the association of smoking with long-term colorectal cancer incidence may be stronger for tumours with higher mutational and neoantigen loads.

Methods and analysis: In the Nurses' Health Study (1980-2012) and the Health Professionals Follow-up Study (1986-2012), our novel prospective cohort incident-tumour biobank method (PCIBM) used 3053 incident colorectal carcinoma cases including 752 cases with whole-exome sequencing data. Using the multivariable duplication-method Cox regression model with the inverse probability weighting to adjust for the selection bias due to tissue availability, we assessed a differential association of cigarette smoking with colorectal carcinoma incidence by an exome-wide …

A Comparison Of Two Motivational Tasks In Male And Female Rats Under Acute Stress, Stephanie M. Muscott

Graduate Research Theses & Dissertations

Motivation is a complex concept that contributes to or is embedded within many different behaviors. As such, it can be difficult to assess motivation directly, but many researchers have attempted to measure motivation to understand its role in behavior and in diseases associated with a dysregulation of motivation, such as drug addiction or depression. To better understand motivation, behavioral tests frequently use palatable foods to measure motivation as defined by the amount of effort a rat will demonstrate to achieve the reward. Much of research has focused on highly controlled experimental settings, such as lever pressing in an operant box …

Multimodal Approach In Distinguishing And Managing Uterine Arteriovenous Malformation: A Case Report, Sajeev Sridhar, Roman Sukhovershin, John A Hancock

The Brown Foundation: Institute of Molecular Medicine

Arteriovenous malformations (AVMs) are abnormal vascular connections bypassing the capillary system, categorized as acquired or congenital. Acquired uterine AVMs, often resulting from uterine trauma due to procedures like dilatation and curettage, can be life threatening, necessitating prompt diagnosis and management. Here we present a 34-year-old woman with a history of missed abortion and dilatation and curettage presenting with abnormal uterine bleeding 2 months postprocedure. Although initial transvaginal ultrasound suggested retained products of conception, several modalities were required to accurately diagnose uterine AVM with invasive angiography revealing the culprit vessel. Multimodal imaging approaches are crucial for accurate diagnosis and treatment. This …

Type 2 Diabetes Polygenic Risk Score Interactions With Lifestyle Risk Factors In Black Americans, Ashley W Scadden, Aastha Kakar, Elizabeth M Litkowski, Mariah C Meyer, Nicole D Armstrong, Steven Buyske, Yanwei Cai, Iona Cheng, Burcu F Darst, Myriam Fornage, Mariaelisa Graff, Boya Guo, Christopher A Haiman, Heather M Highland, Charles Kooperberg, Loïc Le Marchand, Kari North, Ulrike Peters, Stephen S Rich, Jerome I Rotter, Vinodh Srinivasasainagendra, Hemant K Tiwari, Stephanie Waldrop, Kristin Young, Sridharan Raghavan, Ethan M Lange, Leslie A Lange, Marguerite R Irvin, Maggie A Stanislawski

The Brown Foundation: Institute of Molecular Medicine

Introduction: Prior work in predominantly European ancestry populations has explained how the risk associated with demographic, lifestyle, and health factors differs with underlying genetic susceptibility to type 2 diabetes (T2D), but less is known about these relationships in Black Americans.

Methods: We used covariate-adjusted logistic regression models of T2D to examine interactions between a published trans-ancestry derived T2D polygenic risk score (PRS) and various demographic, lifestyle, and health-related factors among 28,251 self-identified Black Americans from six cohort studies.

Results: The results are generally consistent with prior work in White populations. The PRS showed a significant interaction with body mass index, …

Enhanced Anticancer Activity Of Novel Pyrimidine Nucleoside Analog In Pancreatic Cancer, Raviteja Bulusu, Joy Okoro, Esther Frimpong, Sunil Krishnan, Saunjoo Yoon, Bo Han, Xue Zhu, Edward Agyare

The Brown Foundation: Institute of Molecular Medicine

This study explores the synthesis, characterization, and therapeutic efficacy of AGY1, AGY2, AGY3, AGY4, and AGY5, which are novel 5-FU analogs designed to improve metabolic stability, prolong half-life, and anti-tumor activity against pancreatic cancer. The 5-FU molecule was chemically modified to bypass dihydropyrimidine dehydrogenase (DPD)-mediated inactivation, enhancing drug retention and increasing lipophilicity for improved cellular uptake. The analog cytotoxic activity was evaluated in 2D monolayer cultures and 3D pancreatic cancer spheroids and organoid models derived from MiaPaCa-2 and PANC-1 cells to simulate a more complex tumor environment. In the 2D model, AGY1, AGY2, AGY3, AGY4, and AGY5 displayed significantly higher …

Rezafungin For Suppressive Therapy Of Candida Auris In A Patient With A Left Ventricular Assist Device (Lvad), Matthew A Stack, Luis Ostrosky-Zeichner, Rodrigo Hasbun, Sun O Park, Jessica Babic, Mona Kapadia

The Brown Foundation: Institute of Molecular Medicine

Introduction: Invasive candidiasis is a common healthcare-associated infection with significant morbidity and mortality. Candida auris in particular has emerged as a problematic and challenging healthcare-associated infection, especially with regards to infections involving left ventricular assist devices (LVADs). There is a paucity of evidence on the best management of these particular types of infections. Rezafungin is a newly-approved echinocandin and an important new tool in the management of invasive candidiasis. We report the novel use of rezafungin for suppressive therapy in a patient with an LVAD-associated C. auris infection.

Case: The patient is a 57-year-old male with a past medical history …

Mechanisms And Environmental Factors Shaping The Ecosystem Of Brain Macrophages, Silvia Penati, Simone Brioschi, Zhangying Cai, Claudia Z Han, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Brain macrophages encompass two major populations: microglia in the parenchyma and border-associated macrophages (BAMs) in the extra-parenchymal compartments. These cells play crucial roles in maintaining brain homeostasis and immune surveillance. Microglia and BAMs are phenotypically and epigenetically distinct and exhibit highly specialized functions tailored to their environmental niches. Intriguingly, recent studies have shown that both microglia and BAMs originate from the same myeloid progenitor during yolk sac hematopoiesis, but their developmental fates diverge within the brain. Several works have partially unveiled the mechanisms orchestrating the development of microglia and BAMs in both mice and humans; however, many questions remain unanswered. …

A Systematic Review And Evaluation Of Mobile Health Apps Designed For Parents Who Are Preparing Or Caring For Medically Complex Infants, Anne Chevalier Mckechnie, Nellie Munn Swanson, Ratchada Jantraporn, Kristin M Elgersma, Taylor Iwaszko Wagner, Suhyun Park, Anna Trebilcock

The Brown Foundation: Institute of Molecular Medicine

Background: Parents learning about their children with medical complexity often use numerous health-related resources, including mobile health applications (mHealth apps). mHealth apps could provide broad access to key information and support, lower healthcare costs, and improve care. The quality of mHealth apps for this population has been a concern, but is currently unknown. The objective of this systematic review was to identify and evaluate the quality of publicly available mHealth apps designed for parents who are preparing or caring for medically complex infants.

Methods: A systematic search strategy was applied to identify mHealth apps in the Apple and Google Play …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno

School of Medical Diagnostics & Translational Sciences Publications

The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells …

Defining Spine Cancer Pain Syndromes: A Systematic Review And Proposed Terminology, Markian Pahuta, Ilya Laufer, Sheng-Fu Larry Lo, Stefano Boriani, Charles Fisher, Nicolas Dea, Michael H Weber, Dean Chou, Arjun Sahgal, Laurence Rhines, Jeremy Reynolds, Aron Lazary, Alessandro Gasbarrinni, Jorrit-Jan Verlaan, Ziya Gokaslan, Chetan Bettegowda, Mohamed Sarraj, Ori Barzilai, Ao Spine Knowledge Forum Tumor

Faculty, Staff and Student Publications

STUDY DESIGN: Systematic Review.

OBJECTIVES: Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive. Misdiagnosed spinal pain may lead to ineffective treatment recommendations for cancer patients.

METHODS: We conducted a systematic review of pain terminology that may be relevant to spinal oncology patients. We provide a comprehensive and unbiased summary of the existing evidence, not limited to the spine surgery literature, and subsequently consolidate these data into a practical, clinically relevant nomenclature for spine oncologists.

RESULTS: Our literature search identified 3515 unique citations. Through …

The Influence Of The Microbiome On Radiotherapy And Dna Damage Responses, Aadil Sheikh, Michael A Curran

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is one of the most prevalent cancers in terms of diagnosis and mortality. Radiotherapy (RT) remains a mainstay of CRC therapy. As RT relies on DNA damage to promote tumor cell death, the activity of cellular DNA damage repair pathways can modulate cancer sensitivity to therapy. The gut microbiome has been shown to influence intestinal health and is independently associated with CRC development, treatment responses and outcomes. The microbiome can also modulate responses to CRC RT through various mechanisms such as community structure, toxins and metabolites. In this review we explore the use of RT in the …

Reproducibility And Repeatability Of 18f-(2s, 4r)-4-Fluoroglutamine Pet Imaging In Preclinical Oncology Models, Gregory D Ayers, Allison S Cohen, Seong-Woo Bae, Xiaoxia Wen, Alyssa Pollard, Shilpa Sharma, Trey Claus, Adria Payne, Ling Geng, Ping Zhao, Mohammed Noor Tantawy, Seth T Gammon, H Charles Manning

Faculty, Staff and Student Publications

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.

Methods: Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, Leticia G Hamana Zorrilla, T Kris Eckols, Moses M Kasembeli, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Dedifferentiated Liposarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Experience, Madeline B Torres, Cheuk Hong Leung, Marianne Zoghbi, Rossana Lazcano, Davis Ingram, Khalida Wani, Emily Z Keung, M Alejandra Zarzour, Christopher P Scally, Kelly K Hunt, Anthony Conley, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan Farooqi, Devarati Mitra, Alison K Yoder, Michael S Nakazawa, Dejka Araujo, Andrew Livingston, Ravin Ratan, Shreyaskumar Patel, Vinod Ravi, Alexander J Lazar, Christina L Roland, Neeta Somaiah, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center.

Methods: We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between …

A Plain Language Summary Of The Final Analysis Of The Griffin Study Of Daratumumab Plus Lenalidomide, Bortezomib, And Dexamethasone For People With Newly Diagnosed Multiple Myeloma, Peter M Voorhees, Douglas W Sborov, Jacob Laubach, Jonathan L Kaufman, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Yvonne A Efebera, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Shira Dinner, Katharine S Gries, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

No abstract provided.

Grape-Pi: Graph-Based Neural Networks For Enhanced Protein Identification In Proteomics Pipelines, Chunhui Gu, Seyyed Mahmood Ghasemi, Yining Cai, Johannes F Fahrmann, James P Long, Hiroyuki Katayama, Chong Wu, Jody Vykoukal, Jennifer B Dennison, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Motivation: Protein identification via mass spectrometry (MS) is the primary method for untargeted protein detection. However, the identification process is challenging due to data complexity and the need to control false discovery rates (FDR) of protein identification. To address these challenges, we developed a graph neural network (GNN)-based model, Graph Neural Network using Protein-Protein Interaction for Enhancing Protein Identification (Grape-Pi), which is applicable to all proteomics pipelines. This model leverages protein-protein interaction (PPI) data and employs two types of message-passing layers to integrate evidence from both the target protein and its interactors, thereby improving identification accuracy.

Results: Grape-Pi achieved significant …

Disentangling Effects Of The Dr And Dq Isomers Encoded By The Hla Class Ii Haplotype Drb1*15:01/Dqb1*06:02 To Help Establish The True Risk Allele For Fviii Inhibitor Development In Hemophilia A, Vincent P Diego, Bernadette W Luu, Marcio A Almeida, Raja Rajalingam, Marco Hofmann, Jacob A Galan, Eron G Manusov, Jerry S Powell, Long V Dinh, Henry Mead, Huy Huynh, Anne M Verhagen, Juan M Peralta, Paul V Lehmann, Satish Kumar, Eli J Fine, Joanne E Curran, Harald H Goring, Miguel A Escobar, Sarah Williams-Blangero, Eugene Maraskovsky, John Blangero, Tom E Howard

Faculty, Staff and Student Publications

Introduction: Hemophilia A (HA) patients (HAPs) with the human leukocyte antigen (HLA)-class-II (HLAII) haplotype DRB1*15:01/DQB1*06:02, and thus antigen presenting cells which express HLAII β-polypeptide chains that form heterodimers of DR15- and DQ6-serotypes, respectively, have an increased risk of developing factor (F)VIII inhibitors (FEIs)-neutralizing antibodies against the therapeutic-FVIII-proteins (tFVIIIs) infused to prevent/arrest bleeding. As DRB1*15:01 and DQB1*06:02 exist in strong linkage disequilibrium, association analysis cannot determine which is the actual risk allele.

Methods: To establish the true risk allele of this haplotype, we analyzed the tFVIII-derived peptides (tFVIII-dPs) bound to either the DR or DQ molecules that comprise the individual HLAII …

Inhibition Of Nitric Oxide Synthase Transforms Carotid Occlusion-Mediated Benign Oligemia Into De Novo Large Cerebral Infarction, Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim

Faculty, Staff and Student Publications

No abstract provided.

Investigating Potential Therapeutic Vulnerabilities And Elucidating Molecular Mechanisms For The Tumor Suppressors Nfkbia And Anxa7 In Diffuse Gliomas, Aran Merati

All ETDs from UAB

Gliomas, and especially diffuse gliomas, can be a devastating disease when attempting treatment in the clinic. Diffuse gliomas are typically malignant and pose definitive problems with respect to patient care predominantly due to their ability to exist outside of the bulk tumor by invading into the surrounding brain parenchyma. Consequently, not every cancerous cell can be fully removed by surgical resection and therapeutic resistance, so the stem-like population left behind can repopulate a recurrent tumor from a single cell. There is a desperate need for pinpointing novel therapeutic vulnerabilities in diffuse gliomas, which could potentially involve the targeting of key …

Maternal Immune Activation Causes Oligodendrocyte Deficits In The Hypothalamus, Kate Miller

All ETDs from UAB

Maternal immune activation (MIA) refers to the occurrence of an inflammatory immune response during any stage of pregnancy. This manifests as the upregulation of proinflammatory cytokines and can be caused by air pollution, obesity, or viral infection. When this occurs during the first trimester in humans, it increases the offspring’s susceptibility to developing neuropsychiatric disorders such as autism (ASD) and schizophrenia (SZ), in males more commonly than females. In addition to behavioral manifestations of neuropsychiatric disorders, metabolic syndrome (MetS) is a common comorbidity, defined as the co-occurrence of three or more symptoms including but not limited to hyperlipidemia, hypertension, and …

Parsing Clinical And Neurobiological Heterogeneity In First-Episode Psychosis Patients With And Without Features Of The Deficit Syndrome Of Schizophrenia, Matheus Teles Gomes De Araujo

All ETDs from UAB

Schizophrenia is highly heterogeneous in its neurobiological and clinical presentations, which hinders attempts to understand its pathophysiology, limits efforts to identify biomarkers, and deters optimal patient care. A way to parse clinical heterogeneity is to subtype patients based on clinical presentations. The deficit syndrome (DS) is a possible subtype, characterized by primary and enduring negative symptoms. Evidence for neurobiological abnormalities dissociating DS from other forms of schizophrenia is inconsistent as most studies do not account for heterogeneity within patient groups due to limitations of group-level comparisons. The question remains whether DS presents a unique and less heterogeneous neurobiological phenotype. The …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

The Bacterial Sensing Nuclear-Oligomerization Domain 2 Receptor In The Brain: Location And Potential Function, Julia Smyth

Dissertations

Nucleotide-binding oligomerization domain-2 (NOD2) is a cytosolic receptor, activated by bacterial peptides that initiates innate immune responses through nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Caspase-1 pathways. While the role of NOD2 in inflammation outside the central nervous system (CNS) is well-established, especially in the gastrointestinal system, its expression and function in the brain remain poorly defined. Previous genetic studies suggest a link between NOD2 and neurological and psychiatric conditions, including stroke, Parkinson’s disease, and schizophrenia. However, information regarding NOD2 expression, localization, and function in the CNS is limited. In this work, we investigated NOD2 expression, localization, and regulation …

Havana Syndrome: A Scientific Review Of An Unresolved Medical Mystery, Aishik Dutta

Digital Journal of Clinical Medicine

Background

Since 2016, U.S. and Canadian officials have reported Anomalous Health Incidents (AHIs), or "Havana Syndrome," characterised by a strange sensory experience followed by chronic neurological, cognitive, and vestibular issues. The cause is intensely debated, with primary hypotheses pointing to either psychosocial factors or a directed-energy weapon, creating a significant medical and geopolitical puzzle.

Methods

This review critically assesses the current evidence by analysing peer-reviewed clinical studies and major institutional reports.

Results

The findings are deeply contradictory. A 2020 NASEM report identified directed, pulsed radiofrequency energy as the most plausible mechanism for a core set of symptoms. Conversely, comprehensive 2024 …

Upregulation Of Delta Opioid Receptor By Meningeal Interleukin-10 Prevents Relapsing Pain, Kufreobong E Inyang, Jaewon Sim, Kimberly B Clark, Matan Geron, Karli Monahan, Christine Evans, Patrick O'Connell, Sophie Laumet, Bo Peng, Jiacheng Ma, Cobi J Heijnen, Robert Dantzer, Grégory Scherrer, Annemieke Kavelaars, Matthew Bernard, Yasser A Aldhamen, Joseph K Folger, Alexis Bavencoffe, Geoffroy Laumet

Faculty, Staff and Student Publications

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological …