Medical Specialties Commons^™

Training Clinicians To Facilitate Diabetes Group Visits, Moe Ameri, Layla Abdul Jabbar, Stephanie Kim, Mukaila Raji, Susan L Samson, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Introduction: Managing diabetes in community clinics often presents substantial challenges. Diabetes group visits, shared medical appointments involving a clinician, offer a potential solution to these challenges. However, there is a need for training clinicians to effectively lead and facilitate these group visits.

Aim: The aim of this study is to develop and assess a training program designed to equip clinician learners with the skills to facilitate diabetes group visits.

Methods: Using the ADDIE model (Analysis, Design, Development, Implementation, Evaluation) as a guiding framework, we developed a 3-hour virtual training program for clinician learners at two community clinics. The training covered …

Mapping Snorna-Target Rna Interactions In An Rna-Binding Protein-Dependent Manner With Chimeric Eclip, Zhuoyi Song, Bongmin Bae, Simon Schnabl, Fei Yuan, Thareendra De Zoysa, Maureen V Akinyi, Charlotte A Le Roux, Karine Choquet, Amanda J Whipple, Eric L Van Nostrand

Faculty, Staff and Students Publications

Background: Small nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited.

Results: We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA-binding proteins as baits. Using core snoRNA-binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While …

Conformational Flexibility Is A Critical Factor In Designing Broad-Spectrum Human Norovirus Protease Inhibitors, Son Pham, Boyang Zhao, Neetu Neetu, Banumathi Sankaran, Ketki Patil, Sasirekha Ramani, Yongcheng Song, Mary K Estes, Timothy Palzkill, B V Venkataram Prasad

Faculty, Staff and Students Publications

UNLABELLED: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein. Thus, it is an ideal target for developing antiviral small-molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. …

Clostridioides Difficile Colonization Is Not Mediated By Bile Salts And Utilizes Stickland Fermentation Of Proline In An In Vitro Model, Xiaoyun Huang, April E Johnson, Joshua N Brehm, Thi Van Thanh Do, Thomas A Auchtung, Hugh C Mccullough, Armando I Lerma, Sigmund J Haidacher, Kathleen M Hoch, Thomas D Horvath, Joseph A Sorg, Anthony M Haag, Jennifer M Auchtung

Faculty, Staff and Students Publications

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; …

Associations Of Long-Term Exposure To Temperature With Coronary Artery Calcification Risk Among Middle-Aged Adults: The Coronary Artery Risk Development In Young Adults (Cardia) Study, Dandan Zhao, Jie Yao, Yuanfei Li, David R Jacobs, Yinan Zheng, Chunyu Liu, Yingbin Fu, Margaret M Deangelis, Donald Lloyd-Jones, Lifang Hou, Kai Zhang

Faculty, Staff and Students Publications

BACKGROUND: The impact of ambient temperature on population health has drawn increasing attention as climate change drives more extreme temperatures globally. However, little research has investigated its connection to subclinical cardiovascular diseases. This study aims to examine the impact of long-term exposure to temperature on coronary artery calcification (CAC) among middle-aged Black and White adults in four U.S. areas with varying climate and weather conditions.

METHODS: This study compiled long-term environmental temperature data and individual coronary artery Agatston score (0 vs. >0) from the Coronary Artery Risk Development in Young Adults study. It employed logistic regression and examined the influences …

Integration Of Metabolomic And Transcriptomic Analyses Reveals Regulatory Functions Of The Chrebp Transcription Factor In Energy Metabolism, Jie An, Inna Astapova, Guofang Zhang, Andrew L Cangelosi, Olga Ilkayeva, Hannah Marchuk, Michael J Muehlbauer, Tabitha George, Joseph Brozinick, Mark A Herman, Christopher B Newgard

Faculty, Staff and Students Publications

The transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP expression in liver reveal other ChREBP functions. GalNac-siChREBP treatment reduces expression of genes involved in coenzyme A (CoA) biosynthesis, with lowering of CoA and short-chain acyl-CoA levels. Despite suppression of pyruvate kinase, pyruvate levels are maintained, possibly via increased expression of pyruvate and amino acid transporters. In addition, expression of multiple anaplerotic enzymes is decreased by GalNac-siChREBP treatment, affecting TCA cycle intermediates. Finally, GalNAc-siChREBP treatment suppresses …

2′-Fucosyllactose Inhibits Human Norovirus Replication In Human Intestinal Enteroids, Ketki Patil, B Vijayalakshmi Ayyar, Nicole M Hayes, Frederick H Neill, Lars Bode, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2′-fucosyllactose …

Author Correction: Assessment Of Human Leukocyte Antigen-Based Neoantigen Presentation To Determine Pan-Cancer Response To Immunotherapy, Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng, Jie Wang, Zhijie Wang

Faculty, Staff and Students Publications

No abstract provided.

Ultra-Low Extracorporeal Volume Microfluidic Leukapheresis Is Safe And Effective In A Rat Model, Mubasher Iqbal, Alexandra L Mclennan, Anton Mukhamedshin, Mai T P Dinh, Qisheng Liu, Jacob J Junco, Arvind Mohan, Poyyapakkam R Srivaths, Karen R Rabin, Thomas P Fogarty, Sean C Gifford, Sergey S Shevkoplyas, Fong W Lam

Faculty, Staff and Students Publications

Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to …

Pitavastatin Is Well-Tolerated With No Detrimental Effects On Physical Function, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Jennifer A Schrack, Edgar T Overton, Carl J Fichtenbaum, Kathleen V Fitch, Jhoanna C Roa, Marissa R Diggs, Kenneth Wood, Markella V Zanni, Gerald S Bloomfield, Carlos Malvestutto, Judith A Aberg, Maria C Rodriguez-Barradas, Rosalba Gomez Morones, Katherine Breaux, Pamela S Douglas, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Little is known about the potential benefits or harms of statins on physical function among people with human immunodeficiency virus (PWH).

Methods: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH. Time to complete 10 chair rises, 4-m gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models.

Findings: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female …

Invasion And Metastasis In Cancer: Molecular Insights And Therapeutic Targets, Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H-F Zhang, Ji Zheng

Faculty, Staff and Students Publications

The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is …

Characterization Of Rationally Designed Crispr/Cas9-Based Dna Methyltransferases With Distinct Methyltransferase And Gene Silencing Activities In Human Cell Lines And Primary Human T Cells, Rosa Selenia Guerra-Resendez, Samantha Legoff Lydon, Alex J Ma, Guy C Bedford, Daniel R Reed, Sunghwan Kim, Erik R Terán, Tomoki Nishiguchi, Mario Escobar, Andrew R Dinardo, Isaac B Hilton

Faculty, Staff and Students Publications

Nuclease-deactivated Cas (dCas) proteins can be used to recruit epigenetic effectors, and this class of epigenetic editing technologies has revolutionized the ability to synthetically control the mammalian epigenome and transcriptome. DNA methylation is one of the most important and well-characterized epigenetic modifications in mammals, and while many different forms of dCas-based DNA methyltransferases (dCas-DNMTs) have been developed for programmable DNA methylation, these tools are frequently poorly tolerated and/or lowly expressed in mammalian cell types. Further, the use of dCas-DNMTs has largely been restricted to cell lines, which limits mechanistic insights in karyotypically normal contexts and hampers translational utility in the …

Pharmacological Interventions For Negative Symptoms In Schizophrenia: A Systematic Review Of Randomised Control Trials, Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini, Sara Barbonetti, Georgios D Kotzalidis, Sara Rossi, Romina Caso, Flavia Grisoni, Giuseppe Mandracchia, Stella Margoni, Tommaso Callovini, Delfina Janiri, Marianna Mazza, Alessio Simonetti, Silvia Montanari, Gianna Autullo, Giovanni Camardese, Maria Pepe, Marco Di Nicola, Vassilij Di Giorgio, Fabio Conti, Gabriele Sani, On Behalf Of The Gemelli Repsy Study Group

Faculty, Staff and Students Publications

Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative symptoms are difficult to treat, persisting despite treatment. Different strategies have been devised to deal with this problem. We aimed to review drug treatment for negative symptoms of schizophrenia in controlled trials of marketed drugs.

Methods: We searched the PubMed database and the resulting records' reference lists to identify eligible trials using schizophrenia[ti] AND "negative symptom*"[ti] as a search strategy. We determined eligibility through Delphi rounds among all authors.

Results: On 11 February 2025, we identified 1485 records on PubMed and 3 more from reference lists. Eligible were 95 …

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV

Oral Inflammation And Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease, Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

Faculty, Staff and Students Publications

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated …

Assessing The Contribution Of Rare Protein-Coding Germline Variants To Prostate Cancer Risk And Severity In 37,184 Cases, Jonathan Mitchell, Niedzica Camacho, Patrick Shea, Konrad H Stopsack, Vijai Joseph, Oliver S Burren, Ryan S Dhindsa, Abhishek Nag, Jacob E Berchuck, Amanda O'Neill, Ali Abbasi, Anthony W Zoghbi, Jesus Alegre-Díaz, Pablo Kuri-Morales, Jaime Berumen, Roberto Tapia-Conyer, Jonathan Emberson, Jason M Torres, Rory Collins, Quanli Wang, David Goldstein, Athena Matakidou, Carolina Haefliger, Lauren Anderson-Dring, Ruth March, Vaidehi Jobanputra, Brian Dougherty, Keren Carss, Slavé Petrovski, Philip W Kantoff, Kenneth Offit, Lorelei A Mucci, Mark Pomerantz, Margarete A Fabre

Faculty, Staff and Students Publications

To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis of 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline whole exome or genome sequencing data, and one cohort with imputed array data. At the gene level, our case-control collapsing analysis confirms associations between rare damaging variants in four genes and increased prostate cancer risk: SAMHD1, BRCA2 and ATM at the study-wide significance level (P <  1×10−8), and CHEK2 at the suggestive threshold (P <  2.6×10−6). Our case-only analysis, reveals that rare damaging variants in AOX1 are associated with more aggressive disease (OR = 2.60 [1.75–3.83], …

Development And Implementation Of A Personal Virtual Assistant For Patient Engagement And Communication In Postsurgical Cancer Care: Feasibility Cohort Study, Miguel Bargas-Ochoa, Alejandro Zulbaran-Rojas, M G Finco, Anthony B Costales, Areli Flores-Camargo, Rasha O Bara, Manuel Pacheco, Tina Phan, Aleena Khichi, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer-care complexity heightens communication challenges between health care providers and patients, impacting their treatment adherence. This is especially evident upon hospital discharge in patients undergoing surgical procedures. Digital health tools offer potential solutions to address communication challenges seen in current discharge protocols. We aim to explore the usability and acceptability of an interactive health platform among discharged patients who underwent oncology-related procedures.

METHODS: A 4-week exploratory cohort study was conducted. Following hospital discharge, a tablet equipped with an integrated Personal Virtual Assistant (PVA) system was provided to patients who underwent oncology-related procedures. The PVA encompasses automated features that provide …

The Potential Of Using Screening Tools For Bipolar Disorder To Predict Lithium Response, Delfina Janiri, Mario Pinto, Silvia Montanari, Ester Maria Marzo, Greta Sfratta, Guglielmo Donofrio, Alexia Koukopoulos, Giovanni Camardese, Alessio Simonetti, Lorenzo Moccia, Gianna Autullo, Gabriele Sani

Faculty, Staff and Students Publications

Background/Objectives: Lithium is the gold standard for treating Bipolar Disorder (BD), but its effectiveness varies widely. While clinical and environmental factors may influence response, it remains unclear if screening tools can reliably predict lithium response outcomes. This study explores this potential using two widely used screening instruments for BD.

Methods: A total of 146 patients with BD were evaluated. Lithium response was assessed using the Alda Scale, while hypomanic and manic symptoms were characterized through the Hypomania Checklist-32 (HCL-32) and the Mood Disorder Questionnaire (MDQ). Group differences in HCL-32 and MDQ scores were analyzed using ANOVA, and a multivariate model …

Machine Learning-Enhanced Surface-Enhanced Spectroscopic Detection Of Polycyclic Aromatic Hydrocarbons In The Human Placenta, Oara Neumann, Yilong Ju, Andres B Sanchez-Alvarado, Guodong Zhou, Weiwu Jiang, Bhagavatula Moorthy, Melissa A Suter, Ankit Patel, Peter Nordlander, Naomi J Halas

Faculty, Staff and Students Publications

The detection and identification of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, polycyclic aromatic compounds (PACs), are essential for environmental and health monitoring, for assessing toxicological exposure and their associated health risks. PAHs/PACs are the most dangerous chemicals found in tobacco smoke, and cigarette use during pregnancy can convey these molecules to the developing fetus through the placenta. This exposure is associated with many negative health outcomes, from premature birth to sudden infant death syndrome and adverse neurodevelopmental disorders. This study demonstrates the use of surface-enhanced Raman and surface-enhanced infrared absorption spectroscopies for direct detection of PAHs/PACs in human placental …

Biguanides Antithetically Regulate Tumor Properties By The Dose-Dependent Mitochondrial Reprogramming-Driven C-Src Pathway, Jun Hyoung Park, Kwang Hwa Jung, Dongya Jia, Sukjin Yang, Kuldeep S Attri, Songyeon Ahn, Divya Murthy, Tagari Samanta, Debasmita Dutta, Meron Ghidey, Somik Chatterjee, Seung Yeop Han, Diego A Pedroza, Abha Tiwari, Joyce V Lee, Caitlin Davis, Shuting Li, Vasanta Putluri, Chad J Creighton, Nagireddy Putluri, Lacey E Dobrolecki, Michael T Lewis, Jeffrey M Rosen, José N Onuchic, Andrei Goga, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

The biguanide metformin attenuates mitochondrial oxidation and is proposed as an anti-cancer therapy. However, recent clinical studies suggest increased proliferation and fatty acid β-oxidation (FAO) in a subgroup of patients with breast cancer (BC) after metformin therapy. Considering that FAO can activate Src kinase in aggressive triple-negative BC (TNBC), we postulate that low-dose biguanide-driven AMPK-ACC-FAO signaling may activate the Src pathway in TNBC. The low bioavailability of metformin in TNBC xenografts mimics metformin's in vitro low-dose effect. Pharmacological or genetic inhibition of FAO significantly enhances the anti-tumor properties of biguanides. Lower doses of biguanides induce and higher doses suppress Src …

Rna Methyltransferase Spout1/Cenp-32 Links Mitotic Spindle Organization With The Neurodevelopmental Disorder Spadmiss, Avinash V Dharmadhikari, Maria Alba Abad, Sheraz Khan, Reza Maroofian, Tristan T Sands, Farid Ullah, Itaru Samejima, Yanwen Shen, Martin A Wear, Kiara E Moore, Elena Kondakova, Natalia Mitina, Theres Schaub, Grace K Lee, Christine H Umandap, Sara M Berger, Alejandro D Iglesias, Bernt Popp, Rami Abou Jamra, Heinz Gabriel, Stefan Rentas, Alyssa L Rippert, Christopher Gray, Kosuke Izumi, Laura K Conlin, Daniel C Koboldt, Theresa Mihalic Mosher, Scott E Hickey, Dara V F Albert, Haley Norwood, Amy Feldman Lewanda, Hongzheng Dai, Pengfei Liu, Tadahiro Mitani, Dana Marafi, Hatice Koçak Eker, Davut Pehlivan, Jennifer E Posey, Natalie C Lippa, Natalie Vena, Erin L Heinzen, David B Goldstein, Cyril Mignot, Jean-Madeleine De Sainte Agathe, Nouriya Abbas Al-Sannaa, Mina Zamani, Saeid Sadeghian, Reza Azizimalamiri, Tahere Seifia, Maha S Zaki, Ghada M H Abdel-Salam, Mohamed S Abdel-Hamid, Lama Alabdi, Fowzan Sami Alkuraya, Heba Dawoud, Aya Lofty, Peter Bauer, Giovanni Zifarelli, Erum Afzal, Faisal Zafar, Stephanie Efthymiou, Daniel Gossett, Meghan C Towne, Raey Yeneabat, Belen Perez-Duenas, Ana Cazurro-Gutierrez, Edgard Verdura, Veronica Cantarin-Extremera, Ana Do Vale Marques, Aleksandra Helwak, David Tollervey, Sandeep N Wontakal, Vimla S Aggarwal, Jill A Rosenfeld, Victor Tarabykin, Shinya Ohta, James R Lupski, Henry Houlden, William C Earnshaw, Erica E Davis, A Arockia Jeyaprakash, Jun Liao

Faculty, Staff and Students Publications

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays from 21 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants show reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicate that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 reveals that most disease-associated missense variants are …

Genetic And Environmental Contribution To Phenotypic Resemblance Between Iranian Couples: Tehran Cardiometabolic And Genetic Study (Tcgs), Parisa Riahi, Amir Hossein Saeidian, Albert Tenesa, Carolyn T Hogan, Michael March, Kamran Guity, Mahmoud Amiri Roudbar, Asieh Zahedi, Maryam Zarkesh, Farideh Neshati, Mehdi Hedayati, Fereidoun Azizi, Hakon Hakonarson, Maryam S Daneshpour, Mahdi Akbarzadeh

Faculty, Staff and Students Publications

Objective: To provide an applied framework for assessing the genetic contribution to assortative mating (AM) using height as a model trait and disclose the trace of certain pieces of evidence of AM in the form of the shared environmental effects from long-term cohabitation on spouses' anthropometric traits and lipid serum levels.

Methods: 2315 genotyped couples were extracted from the Tehran Cardiometabolic Genetic Study (TCGS). Pearson correlation analysis was used to assess the relationship between spouses' height. The GCTA-GREML was used to assess the SNP-based heritability of individual and spousal heights with AM adjustments. We used a recent GWAS meta-analysis of …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Multimodal Objective Assessment Of Impulsivity In Healthy And Mood Disorder Participants, Bishal Lamichhane, Nidal Moukaddam, Ramiro Salas, Wayne Goodman, Ashutosh Sabharwal

Faculty, Staff and Students Publications

Impulsivity represents an individual's tendency to act on urges without sufficient forethought. Heightened impulsivity is a hallmark of many mental health disorders. Objective impulsivity assessments could improve risk evaluation, diagnosis, and behavioral outcome monitoring in impulsivity-related health disorders. Towards objective impulsivity assessment, in this work, we identify impulsivity correlates in objective measurements, investigate their complementarity, and contrast impulsivity mechanisms across health conditions. We analyzed behavioral tests, heart rate variability (HRV), and fMRI-based brain connectivity in 227 healthy participants and 34 participants with mood disorders. Impulsivity dimensions had complementary correlates in objective measurements, with fMRI providing the strongest correlates. Multimodal assessment …

Divergence In Cellular Markers Observed In Single-Cell Transcriptomics Datasets Between Cultured Primary Trabecular Meshwork Cells And Tissues, Alice Tian, Sangbae Kim, Hasna Baidouri, Jin Li, Xuesen Cheng, Janice Vranka, Yumei Li, Rui Chen, Vijaykrishna Raghunathan

Faculty, Staff and Students Publications

The trabecular meshwork within the outflow apparatus is critical in maintaining intraocular pressure homeostasis. In vitro studies employing primary cell cultures of the human trabecular meshwork (hTM) have conventionally served as surrogates for investigating the pathobiology of TM dysfunction. Despite its abundant use, translation of outcomes from in vitro studies to ex vivo and/or in vivo studies remains a challenge. Given the cell heterogeneity, performing single-cell RNA sequencing comparing primary hTM cell cultures to hTM tissue may provide important insights on cellular identity and translatability, as such an approach has not been reported before. In this study, we assembled a …

Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu

Faculty, Staff and Students Publications

Background: Early diagnosis and accurate prognosis of cognitive decline in Alzheimer's disease (AD) is important to timely assignment to optimal treatment modes. We aimed to develop a deep learning model to predict cognitive conversion to guide re-assignment decisions to more intensive therapies where needed.

Methods: Longitudinal data including five variable sets, i.e. demographics, medical history, neuropsychological outcomes, laboratory and neuroimaging results, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. We first developed a deep learning model to predicted cognitive conversion using all five variable sets. We then gradually removed variable sets to obtained parsimonious models for four different …

Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …

Designing Patient-Centered Interventions For Emergency Care: Participatory Design Study, Woosuk Seo, Shruti Jain, Vivian Le, Jiaqi Li, Zhan Zhang, Hardeep Singh, Kalyan Pasupathy, Prashant Mahajan, Sun Young Park

Faculty, Staff and Students Publications

Background: Emergency departments (EDs) are high-pressure environments where clinicians diagnose patients under significant constraints, including limited medical histories, severe time pressures, and frequent interruptions. Current ED care practices often inadequately support meaningful patient participation. Most interventions prioritize clinical workflow and health care provider communication, inadvertently overlooking patients' needs. Additionally, patient-facing technologies in EDs are typically developed without meaningful patient input, leading to solutions that may not effectively address patients' specific challenges. To enhance both patient-centered care practices and the diagnosis process in EDs, patient involvement in technology design is essential to ensure their needs during emergency care are understood and …

Mbnl Overexpression Rescues Cardiac Phenotypes In A Myotonic Dystrophy Type 1 Heart Mouse Model, Rong-Chi Hu, Yi Zhang, Larissa Nitschke, Sara J Johnson, Ayrea E Hurley, William R Lagor, Zheng Xia, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the dystrophia myotonica protein kinase (DMPK) gene. The expanded CUG repeat RNA (CUGexp RNA) transcribed from the mutant allele sequesters the muscleblind-like (MBNL) family of RNA-binding proteins, causing their loss of function and disrupting regulated pre-mRNA processing. We used a DM1 heart mouse model that inducibly expresses CUGexp RNA to test the contribution of MBNL loss to DM1 cardiac abnormalities and explored MBNL restoration as a potential therapy. AAV9-mediated overexpression of MBNL1 and/or MBNL2 significantly rescued DM1 cardiac phenotypes including conduction delays, contractile …