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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 …

Intestinal Oxygen Utilisation And Cellular Adaptation During Intestinal Ischaemia-Reperfusion Injury, Paraschos Archontakis-Barakakis, Theodoros Mavridis, David-Dimitris Chlorogiannis, Georgios Barakakis, Eleni Laou, Daniel I Sessler, George Gkiokas, Athanasios Chalkias

Faculty, Staff and Student Publications

The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia-reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia). Intestinal oxygen uptake usually remains constant over a wide range of blood flows and pressures, with cellular function being substantively compromised …

Rbd Amplicon Sequencing And Evolutionary Analysis Of Sars-Cov-2 Variants From Wastewater Samples, Xingwen Chen, Chunfu Zheng, Fuqing Wu

Faculty, Staff and Student Publications

The surveillance of SARS-CoV-2 is significantly limited by the presence of numerous variants with distinct behaviors driven by rapid evolution. Although the conventional clinical genome sequencing method provides comprehensive data, it has limitations in capturing the epidemiological dynamics of the variants circulating in the community. In this chapter, we describe a protocol using RBD amplicon sequencing of wastewater samples. We present the detailed experimental procedure for wastewater sample processing, robust nested-PCR-based amplification of the target RBD sequence, and library preparation. Moreover, we describe a general pipeline of sequencing data processing and interpretation, showing the epidemiological and evolutionary trends of SARS-CoV-2 …

Effects Of High-Intensity Interval Training On Biomarkers And Inflammatory Factors In Patients With Heart Failure: A Meta-Analysis Of Randomized Controlled Trials, Wanting Zhang, Jooyeon Hwang, Beibei Lu, Xin Xu

Faculty, Staff and Student Publications

Background: There is still controversy about the effect of high-intensity interval training (HIIT) on the levels of cardiac and inflammatory biomarkers in patients with heart failure compared with moderate-intensity continuous training (MCT) and conventional healthcare activities. This article is to systematically investigate the effects of HIIT on the levels of cardiac and inflammatory biomarkers in patients with heart failure compared with MCT and conventional healthcare activities.

Methods: A computerized search of databases was conducted with the search year from the establishment of the database, and the screened results were subjected to quality assessment and data extraction, and the data was …

Community Engagement Studios To Improve Racial Diversity And Health Equity In Parkinson’S, Eunyoung Kang, Dominique Woodhouse, Kandace Davis, Jane Q Yap, Peter S Myers, Meghan C Campbell, Yvonne D Hughes, Joyce E Balls-Berry, Erin R Foster

Faculty, Staff and Student Publications

Background: Black or African Americans (AA) with Parkinson's disease (PD) are underrepresented in both care and research and experience significant health disparities. The existing literature provides limited guidance on how to enhance the engagement of AA individuals in PD care and research, particularly from the perspectives of AA patients, care partners, and healthcare providers. This project aimed to (1) describe the use of Community Engagement (CE) Studios as a community-engaged research approach to inform culturally appropriate and inclusive research and (2) examine factors influencing AA engagement in PD-related activities.

Methods: We conducted three CE Studios: one with AA with PD …

A Directed Content Analysis For Greatest Problems Among People With And Without Traumatic Brain Injury, Emily Dudek, Michael W Williams, Chung Lin Novelle Kew, Annalyn Demello, Brittany Wright, Alexandra B Holland, Alyssa Day-Gorman, Alexa S Gonzalez, Luis Leon Novelo, Xiangyi Liu, Shannon B Juengst

Faculty, Staff and Student Publications

Objective: To characterize the greatest problem or need among individuals with a history of traumatic brain injury (TBI), as compared with individuals with a history of other neurologic conditions, mental health conditions, and no history of neurologic or mental health conditions.

Design: A directed content analysis of open-text responses to a single online survey question using a framework guided by the Mayo-Portland Adaptability Inventory-4.

Setting: Community.

Participants: A total of 2861 community-dwelling adults (n=274 with TBI; n=289 with other neurologic conditions besides TBI; n=454 with mental health conditions but no neurologic conditions; and n=1844 controls).

Interventions: Not applicable.

Main outcome …

Risk And Prognosis Of Hepatocellular Carcinoma In Mexican Americans With Type 2 Diabetes Mellitus, Rikita I Hatia, Lu-Yu Hwang, Ruosha Li, Catherine Troisi, Prasun K Jalal, Christopher I Amos, Henry F Gomez, Yun Shin Chun, Asif Rashid, Ahmed O Kaseb, Paul A Scheet, Manal M Hassan

Faculty, Staff and Student Publications

INTRODUCTION: Hepatocellular carcinoma (HCC) disproportionately affects Hispanic persons with higher age-specific incidence and increased mortality rates compared to non-Hispanic Whites. These high rates of incidence and mortality may be explained by the variation in risk factors. Given the high prevalence of type 2 diabetes mellitus (DM) among the Hispanic population, we aimed to assess the risk and prognosis of HCC in Mexican Americans with type 2 DM with consideration of treatment for DM.

METHODS: A case-control study of 241 Mexican American HCC patients and 500 healthy controls in Texas was conducted. Multivariable logistic regression analysis was performed to determine the …

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.

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 …

Privacy-Preserving Collaborative Population Stratification With Dynamic Algorithm And Hyperparameter Selection, Maryam Ghasemian, Lynette Hammond Gerido, Erman Ayday

Faculty, Staff and Student Publications

We present a privacy-preserving selection layer for collaborative population stratification under 𝜖-local differential privacy (LDP). Rather than fixing a single pipeline (e.g., PCA+K-Means with preset 𝐾), our framework lets parties choose among three DP pipelines: PCA→Noise, Noise→PCA, and Noise-Only, according to their resources, and has an honest-but-curious server aggregate only DP shares to automatically select the clustering algorithm (K-Means, GMM, or Hierarchical) and 𝐾 that maximize internal metrics (Silhouette, Calinski–Harabasz, Davies–Bouldin). Because selection operates on DP data, it adds no further privacy loss. On openSNP (942 samples, 28,396 SNPs), the PCA-augmented pipelines yield higher utility …

Safeguarding Privacy In Genome Research: A Comprehensive Framework For Authors, Maryam Ghasemian, Lynette Hammond Gerido, Erman Ayday

Faculty, Staff and Student Publications

As genomic research continues to advance, sharing of genomic data and research outcomes has become increasingly important for fostering collaboration and accelerating scientific discovery. However, such data sharing must be balanced with the need to protect the privacy of individuals whose genetic information is being utilized. This paper presents a bidirectional framework for evaluating privacy risks associated with data shared (both in terms of summary statistics and research datasets) in genomic research papers, particularly focusing on re-identification risks such as membership inference attacks (MIA). The framework consists of a structured workflow that begins with a questionnaire designed to capture researchers' …

Daily Movement Activities Are Associated With Within-Person Instability Of Cognitive Function In Older Adults: Evidence From An Ambulatory Assessment Study, Chih-Hsiang Yang, Donald Hedeker, Jongwon Lee, Halle Prine, Donna Coffman, Jingkai Wei, Jonathan George Hakun

Faculty, Staff and Student Publications

Background and objectives: Physical inactivity and excessive sedentary time (ST) are associated with poor cognitive health in older adults. However, current literature largely relies on cross-sectional designs or in-lab cognitive assessments, which do not adequately reflect cognitive function in naturalistic settings. Further, existing studies have largely overlooked the variability or the instability in daily cognitive function, which represents a critical marker of cognitive decline. This ambulatory assessment study examined the temporal associations of daily movement behaviors with the mean levels and the variability of cognition among older adults at risk of dementia.

Research design and methods: 96 older adults from …

Oral Microbiome Brain Axis And Cognitive Performance In Older Adults, Darbaz Adnan, Phillip A Engen, Michelle Villanueva, Shohreh Raeisi, Vivian Ramirez, Ankur Naqib, Stefan J Green, Faraz Bishehsari, Lisa L Barnes, Ali Keshavarzian, Klodian Dhana, Robin M Voigt

Faculty, Staff and Student Publications

The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer’s disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria …

Giant Cell Tumor Of The Bone With Fatal Pulmonary Metastasis: A Case Report, Mohamad Taha, Saadia A Faiz, Pushan Jani, Jing Liu, Yasir D Ali, Mohammad Asim Amjad

Faculty, Staff and Student Publications

Giant cell tumors of the bone are typically benign, locally aggressive lesions that rarely metastasize. In this report, we describe the case of a 48-year-old woman presenting with a giant cell tumor of the bone of the hip joint, which demonstrated aggressive histological features and recurrent behavior. The patient developed multiple unresectable pulmonary metastases despite several wide local excisions. Although pulmonary metastases from giant cell tumors of the bone are usually associated with a relatively favorable prognosis, guidelines for the optimal treatment of metastatic giant cell tumors of the bone remain limited. This case highlights the unpredictable nature of giant …

Esomeprazole Inhibits Proliferation Of Scleroderma Fibroblasts Via Cell Cycle Regulation, Mohammad A Khan, Shaheer Koniyan, Manisha Ahir, Anil G Jegga, Maureen D Mayes, David Gius, Justin Leung, Mark D Bonnen, Sydney B Montesi, Yohannes T Ghebre

Faculty, Staff and Student Publications

Background: Scleroderma is a complex autoimmune disease characterized by abnormal fibroblast proliferation and excessive collagen deposits in the skin and internal organs. We previously showed that esomeprazole, an FDA-approved drug for gastric disorders, may prevent dermal fibrosis.

Methods: To test this, we evaluated the antiproliferative effect of esomeprazole and the underlying molecular mechanisms using primary fibroblasts derived from patients with scleroderma. BrdU incorporation, flow cytometry, immunofluorescence, Western blot analysis, RNA sequencing, and functional enrichment analysis were performed.

Results: Esomeprazole inhibited the proliferation of scleroderma fibroblasts in a dose-dependent manner, as measured by BrdU incorporation and Ki-67 marker. Intriguingly, esomeprazole arrested …

Long-Term Dynamic Profiles Of Cognitive Kinases Induced By Different Learning Protocols, Yili Zhang, Rong-Yu Liu, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Learning is associated with activation of multiple protein kinases, but few details are known about the activation dynamics in response to different learning protocols. We addressed this issue by examining the long-term dynamics of kinases critical for long term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse. Three serotonin (5-HT) protocols have been found to induce LTF with distinct effectiveness: the five-pulse regular-spaced Standard protocol; the five-pulse irregular-spaced Enhanced protocol; and the two-pulse protocol with an interval of 45 min. We previously compared long-term dynamics of the mitogen-activated protein kinase (MAPK) isoform ERK after these protocols. Here we examined the …

Polygenic Scores Contribution To Parkinson’S Disease Comorbidities, Carlos F Hernández, Camilo Villaman, Cristian Tejos, Gabriela M Repetto, Costin Leu, Dennis Lal, Ignacio F Mata, Andrés D Klein, Eduardo Pérez-Palma

Faculty, Staff and Student Publications

Comorbidities are common in Parkinson’s disease and significantly impact the disease progression and management. While polygenic scores have been widely used to assess genetic risk for complex diseases, their role in comorbidity presentation in Parkinson’s disease remains unclear. This study investigates whether genetic predisposition to comorbidities, as measured by polygenic scores, differs between individuals with Parkinson’s disease and the general population and explores how genetic risk influences disease onset and sex-related differences. We analysed data from 4144 individuals with Parkinson’s disease and 370 480 individuals from the general population in the UK Biobank, focusing on four comorbidities with high-quality genome-wide …

Editorial: Understanding The Mechanism Of Dynamic Cell Communications: A Much Needed Angle For Cell Motility And Barrier Functions, Virag Vas, Zhen Xu, Pasquale Cervero

Faculty, Staff and Student Publications

No abstract provided.