Medicine and Health Sciences Commons^™

Fastk Post-Transcriptional Regulators – A ‘Fast-Track’ In Mitochondrial Gene Expression, Justin Van Riper, Bridget J Corsaro, Monica C Pillon

Faculty, Staff and Students Publications

Fas-activated serine/threonine kinase (FASTK) proteins comprise one of the largest families of mitochondrial post-transcriptional regulators. Members are classified based on their conserved C-terminus, which shows homology with the PD-(D/E)XK superfamily of endoribonucleases. However, it is still uncertain which of these FASTK members are catalytic. The six human FASTK homologs rely on their RNA-binding activity to regulate distinct stages of mitochondrial gene expression, including early processing of nascent RNA, 3'-end messenger RNA (mRNA) maturation, ribosomal RNA (rRNA) modification, mRNA stability, and translation. Genetic and genomic studies have highlighted the crucial role of FASTK proteins in balancing the mitochondrial transcriptome and controlling …

Insights Into Spheroid Formation: Interaction Of Ovarian Cancer Cells With Macrophage Populations In The Tumor Microenvironment, Simone Pisano, Yajaira Sofia Jimenez, Paul Rees, Jing Xiao, Deyarina Gonzalez, Robert Steven Conlan, Bruna Corradetti

Faculty, Staff and Students Publications

Background: Treating advanced ovarian cancer (OC) is challenging due to the immunosuppressive tumor microenvironment. This study investigates tumor-immune cell interactions using organotypic spheroid models that simulate the in vivo microenvironment.

Methods: A dual-model spheroid system was established combining serous adenocarcinoma SKOV-3 cells with monocytes, pro-inflammatory (MΦ1) or anti-inflammatory (MΦ2) macrophages, or their derived exosomes (EXOs). In Model A, immune cells or EXOs were co-seeded with tumor cells to replicate early heterotypic aggregation. In Model B, immune cells or EXOs were introduced 24 h post-spheroid formation to simulate immune infiltration into established spheroids. Spheroid morphology was quantified by diameter and circularity, …

Short Term Hemodynamic Effects Of Atrial Fibrillation In A Closed-Loop Human Cardiac-Baroreflex System, Oluwasanmi Adeodu, Michelle Gee, Babak Mahmoudi, Rajanikanth Vadigepalli, Mayuresh V. Kothare

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Atrial fibrillation (AF) remains the leading cardiac cause of stroke and AF-related death rate in the United States has been increasing for over twenty years. While the effect of standalone AF on heart rate is well established, there is a lack of clarity on its impact on other critical hemodynamic metrics. This is ostensibly due to interaction with other common comorbidities, especially hypertension. In addition, AF has a complex relationship with the state of the baroreflex. Evidence indicates that baroreflex sensitivity (BRS), the ability of the intrinsic cardiac control system to initiate parasympathetic response, is suppressed during AF. Therefore, a …

Brca2 Deficiency And Replication Stress Drive Apobec3-Mediated Genomic Instability, Kathy Situ, Abby M Green, Et Al.

2020-Current year OA Pubs

BRCA2 plays a critical role in stabilizing stalled replication forks, yet critical gaps remain in understanding how BRCA2 deficiency triggers fork collapse and drives genomic instability. Here, we identify cytidine deaminase APOBEC3B as a key driver of this process. Using a unique uracil-in-DNA probe, we show that BRCA2 loss promotes APOBEC3B-mediated uracil accumulation in single-stranded DNA (U-ssDNA) at stalled forks. These lesions when processed by UNG2 and APE1, trigger fork collapse and release ssDNA fragments into the cytoplasm, activating NF-κB signaling. This in turn upregulates APOBEC3B expression, establishing a self-reinforcing loop that amplifies cytidine deamination at stalled forks and exacerbates …

Nasal Microbionts Differentially Colonize And Elicit Cytokines In Human Nasal Epithelial Organoids, Andrea I Boyd, Leah A Kafer, Isabel F Escapa, Amal Kambal, Hira Tariq, Susan G Hilsenbeck, Hoa Nguyen-Phuc, Anubama Rajan, Joshua M Lensmire, Kathryn A Patras, Pedro A Piedra, Sarah E Blutt, Katherine P Lemon

Faculty, Staff and Students Publications

Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae is associated with an increased risk of infection by these pathobionts, whereas nasal colonization by Dolosigranulum species is associated with health. Human nasal epithelial organoids (HNOs) differentiated at air-liquid interface (ALI) physiologically recapitulate human nasal respiratory epithelium with a robust mucociliary blanket. Due to their natural stem-like properties, HNO lines are a long-term experimental resource that offers genetic diversity based on the different donors. To develop HNOs as a new model system for bacterial nasal colonization, we reproducibly monocolonized HNOs differentiated at ALI with S. aureus, S. pneumoniae, or Dolosigranulum …

Effect Of Valemetostat On The Pharmacokinetics Of Midazolam And Digoxin: A Phase 1 Drug-Drug Interaction Study In Patients With Non-Hodgkin Lymphoma, Masaya Tachibana, Steven Horwitz, Eric Jacobsen, Francine Foss, Pamela Allen, Pierluigi Porcu, Tatyana Feldman, Jia Ruan, Jonathan Brammer, Jie Wang, Shinichi Inaba, Yuka Iko, Keiko Nakajima, Yasuyuki Kakurai, Noriaki Kitami, Yang Chen, Yvonne Lau

Department of Medicine Faculty Papers

Valemetostat tosylate (valemetostat) is an oral, potent, dual inhibitor of enhancer of zeste homolog (EZH)2/1, under investigation in non-Hodgkin lymphomas (NHLs) and solid tumors. In vitro, it inhibits cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) when combined with sensitive CYP3A or P-gp substrates. This drug–drug interaction (DDI) sub-study is part of the phase 1 trial of valemetostat monotherapy (DS3201-A-J101; NCT02732275), assessing the effect of valemetostat on the pharmacokinetics (PK) of sensitive CYP3A and P-gp substrates midazolam and digoxin, respectively, in patients with relapsed or refractory NHL, and its safety and efficacy. Patients received two simultaneous single doses of midazolam and …

Adherence To Integrative Care, Oncology Healthcare Utilization, Opioid Use And Hospitalization, Eran Ben-Arye, Dan Greenberg, Noah Samuels, Ana Maria Lopez, Tzahit Simon-Tuval

Kimmel Cancer Center Faculty Papers

Research on the relationship between integrative oncology (IO) programs and dispensing of chemotherapy agents and supportive care drugs, and hospitalization rates is limited. The present study examined these outcomes in chemotherapy-treated patients with cancer, comparing patients highly adherent to integrative care (high-AIC) to those with low adherence (low-AIC). Data from patients with cancer treated with taxane and/or platinum-based agents participating in an ongoing prospective, controlled pragmatic trial were examined retrospectively. Patients were referred to an IO consultation and weekly treatments at 3 medical centers in Northern Israel, with high-AIC defined as attending ≥4 sessions at 6 weeks; low-AIC, 0-3 sessions. …

Nuclear Poly(A)-Binding Protein And Nucleolin Utilize Their Rna Recognition Motifs To Read Par Chains, Leilei Shi, Morgan Dasovich, John R Horton, Hongrui Liu, Qiansheng Zhan, Swarnalatha Manickavinayaham, Collene R Jeter, Isaiah J Mixon, Nicholas M Zehrbach, Charles A Ishak, Je-Hyun Yoon, Xiaodong Cheng, Anthony K L Leung, Mark T Bedford

Faculty, Staff and Student Publications

Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification mediated by ADP-ribosyltransferases, known as PARPs, which attach ADP-ribose units onto proteins, forming negatively charged multimeric chains. This modification relaxes chromatin at DNA damage sites, facilitating repair machinery access. Additionally, PAR polymers serve as docking platforms for effector proteins, termed PAR "readers", commonly involved in DNA repair. The recruitment of these proteins is mediated through conserved protein domains, including RNA recognition motifs (RRMs). Using an array of hundreds of recombinant RNA-binding domains, we systematically examined RRM interactions with PAR chains of varying lengths. Despite their chemical similarity to RNA, only a small subset of …

Long-Term Results From The Agile Study Of Azacitidine Plus Ivosidenib Vs Placebo In Newly Diagnosed Idh1-Mutated Aml, Pau Montesinos, Dylan M Marchione, Christian Recher, Michael Heuser, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Marta Riva, Rodrigo T Calado, Andre C Schuh, Su-Peng Yeh, Adriana E Tron, Jianan Hui, Diego A Gianolio, Sung Choe, Prapti Patel, Stéphane De Botton, Courtney D Dinardo, Hartmut Döhner

Faculty, Staff and Student Publications

In the phase 3 AGILE study, after a 12.4-month median follow-up, ivosidenib, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, combined with azacitidine significantly improved event-free survival, overall survival (OS), and complete remission rates compared with placebo-azacitidine in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML), who were unfit for intensive chemotherapy. This post hoc analysis reports long-term follow-up results from AGILE after a median follow-up of 28.6 months. Overall, 148 patients were randomized to receive ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75). Median OS was significantly longer with ivosidenib (29.3 months; 95% confidence interval …

Early Intratracheal Budesonide To Reduce Bronchopulmonary Dysplasia In Extremely Preterm Infants: The Budesonide In Babies (Bib) Randomized Clinical Trial, Namasivayam Ambalavanan, Waldemar A Carlo, Kayla J Nowak, Laura Elizabeth Wiener, Shirley S Cosby, Abhay J Bhatt, Kristi L Watterberg, Brenda B Poindexter, Martin Keszler, Carl T D'Angio, Luc P Brion, Vivek Narendran, Carrie A Rau, C Michael Cotten, Matthew M Laughon, Abhik Das, Matthew A Rysavy, Anna Maria Hibbs, Janell Fuller, Karen M Puopolo, Anup Katheria, Ravi M Patel, Jennifer R Bermick, Abbot R Laptook, Irina Prelipcean, Myra H Wyckoff, Ryan Moore, Stephanie L Merhar, Robin K Ohls, Bradley A Yoder, Marta Perez, Sarvin Ghavam, Lauritz R Meyer, Valerie Y Chock, Sara B Demauro, Wesley M Jackson, Deepali Handa, Michele C Walsh

Faculty, Staff and Student Publications

Importance: Extremely preterm infants are at high risk for bronchopulmonary dysplasia (BPD) and death. Multiple small randomized clinical trials showed that a combination of budesonide with surfactant compared with surfactant alone reduced BPD or death.

Objective: To determine if early intratracheal administration of a combination of budesonide (0.25 mg/kg) mixed with surfactant, compared with surfactant alone, reduces physiologic BPD or death by 36 weeks' postmenstrual age in extremely preterm infants.

Design, setting, and participants: This double-masked randomized clinical trial was conducted from April 2021 to June 2024 in the 17 centers of the United States Neonatal Research Network. Infants 22 …

Cd7 Regulates The Persistence Of Terminally Exhausted Cd8 T Cells During Chronic Infection, Sean Hyslop, Colby J Hofferek, Maria V Stegantseva, Emerald Kan, Kelli A Mccord, Victor M Alvarez, Amanda Y Xia, Jacob P Conarty, Andreas Wieland, William H Hudson

Faculty, Staff and Students Publications

CD8+ T cell exhaustion limits immune responses during cancer and chronic infection. We identify CD7 as a tissue-specific regulator of terminally exhausted CD8+ T cells during chronic infection. CD7 expression progressively increases during exhaustion, reaching its highest levels on a subset of CD101+Tim3low terminally exhausted cells that arise in the liver. Transcriptomic analysis revealed that CD7-deficient terminally exhausted cells display altered expression of co-stimulatory, translational, and effector genes, correlating with markedly reduced persistence and increased apoptotic susceptibility. Importantly, CD7 is preferentially upregulated on PD-1+CD39+ tumor-infiltrating lymphocytes (TILs) in human head and neck squamous cell carcinoma (HNSCC), suggesting CD7 may play …

Impact Of Transplant Conditioning, Npm1 Mutations, And Measurable Residual Disease In Flt3-Itd Acute Myeloid Leukemia, Mark J Levis, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in …

Management Of Stone Disease In The Spina Bifida Patient, Meghan F. Davis, Kyle L. Yu, Arun K. Srinivasan

Department of Medicine Faculty Papers

PURPOSE OF THE REVIEW: This review provides a detailed overview of the specifics of presentation, diagnosis, and management of upper and lower urinary tract stone disease for individuals with spina bifida.

RECENT FINDINGS: Recent studies highlight the significant burden of stone disease for spina bifida patients. Individuals with spina bifida require lifelong urologic care. They are more likely to have stone disease and have complications from management. This is a particularly salient issue for patients who have undergone bladder augmentation. Given the frequency and severity of these issues, it is critical that urologists be familiar with the nuances of stone …

Cd5 Expression In Ctcl And Its Implications For Anti-Cd5 Car T-Cell Therapy, Leena Wardeh, Madeline Williams, Courtney Prestwood, Zachary Wolner, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous T-Cell Lymphomas (CTCL) are a heterogenous group of T-cell malignancies in the skin and have poor treatment outcomes in advanced stages. CD5, a surface glycoprotein expressed on most mature T cells, has emerged as a promising target for chimeric antigen receptor (CAR) T-cell therapy in systemic T-cell lymphomas. However, its expression profile in CTCL and relevance for targeted therapy remain unclear. Notably, in CTCL, the cell surface expression of receptors, such as CD7 and CD26, tends to become downregulated on the surfaces of malignant T cells In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from patients at …

Signs, Symptoms, And Health-Related Quality Of Life In Melas: Measuring What’S Important From The Patient And Clinician Perspectives, Paolo Medrano, Benjamin Banderas, Marisa Brimmer, Lily Settel, Sari Berger, Alan Shields, Amy Goldstein, Amel Karaa, Austin Larson, Sumit Parikh, Fernando Scaglia, Karra Danyelle Harrington, Chris James Edgar, Pamela Ventola, Matthew Webster, Jennifer Chickering, Chad Gwaltney, Phebe Wilson, Chad Glasser

Faculty, Staff and Students Publications

Background and objectives: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare genetic syndrome mostly associated with pathogenic variants in mitochondrial DNA. As there is limited research on the life experience of patients with MELAS, this study aimed to develop an understanding of the patient experience of MELAS through qualitative interviews to identify, describe, and substantiate important and relevant signs, symptoms, and health-related quality-of-life (HRQoL) impact (S/S/I) concepts.

Methods: Clinician and patient interviews were conducted virtually using semi-structured interview guides. During 60-minute interviews with five experts in the United States, clinicians were asked for their perspective on …

A Novel Approach To Calculating Expected Total Fetal Lung Volume In Fetuses With Isolated Congenital Diaphragmatic Hernia And Fetal Growth Restriction: A Theoretical Computational Simulation, Morcos Hanna, Jonathan Davies, Amaryllis Fernandes, Pamela M Ketwaroo, Amy R Mehollin-Ray, Roopali Donepudi, Alice King, Joseph Hagan, Sundeep G Keswani, Sharada H Gowda, Caraciolo J Fernandes

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …

Associations Of Early-Adulthood Adiposity With Breast Parenchymal Tissue Complexity Within Premenopausal Women, Sneha Das Gupta, Kayla Getz, Juanita Hernandez Lopez, Debbie L Bennett, Adetunji T Toriola, Aimilia Gastounioti

2020-Current year OA Pubs

BACKGROUND: Early-adulthood adiposity is associated with breast cancer risk. This study aims to evaluate the associations of early-adulthood adiposity with an emerging biomarker of breast cancer risk, breast parenchymal complexity, within premenopausal women.

METHODS: We retrospectively analyzed early-adulthood adiposity data and screening digital mammograms (DMs) of 326 premenopausal women (age in years; median: 48; range: 34-58) recruited at our institution. Adiposity measures were either assessed by trained personnel or self-reported by participants. DMs were analyzed using a well-validated computational imaging pipeline consisting of automated breast segmentation and radiomic feature extraction modules. The extracted radiomic features were fused into woman-specific breast …

Using The Electronic Health Record To Facilitate Drug Allergy Delabeling., Matthew J Molloy, Adam P Yan, Averi E Wilson, Jonathan Beus, Lauren M Hess

Faculty, Staff and Students Publications

Purpose of review: There is a growing number of allergy delabeling programs across diverse clinical specialties and care settings. The electronic health record (EHR) can be leveraged to facilitate allergy delabeling. The purpose of this review is to describe EHR tools that have been used in allergy delabeling programs. We also provide recommendations for organizations considering EHR-based allergy delabeling workflows that incorporate clinical informatics best practices.

Recent findings: Recent literature describes several EHR tools used in delabeling. These tools can be organized around the steps of the allergy delabeling workflow: 1. Identify eligible patients, 2. Risk stratify, 3. Evaluation and …

Branch Retinal Artery Occlusion After Covid-19, Danielle Kalberer Od, Mba, Grace Tan Od

Optometric Clinical Practice

Background: A healthy, 39-year-old male patient presented with sudden onset, painless vision loss of the right eye’s superior visual field two months after a mild case of COVID-19.

Case Report: The patient was diagnosed with an acute branch retinal artery occlusion and referred to the emergency department for prompt evaluation. When the emergency workup was unremarkable the patient was referred to cardiology and hematology and follow up with a retinal specialist. The exhaustive systemic work-up was unremarkable other than recent COVID-19. Retinal perfusion to the affected area resumed in the weeks after the incident but irreversible vision loss occurred.

Conclusion: …

Ocular Myasthenia Gravis: A Case Report, Erica Vanderpool Od, Carla Gilbertson Kuiken Od

Optometric Clinical Practice

Background: Myasthenia gravis (MG) is an autoimmune disease caused by faulty transmission at the neuromuscular junction leading to fatigable muscular weakness. Ocular MG is distressing in that it can cause visual difficulties, but generalized MG can be life-threatening. MG is an acquired disorder that can easily be overlooked in clinic and is commonly misdiagnosed. Providers should be aware of the clinical features of this condition, as well as the critical testing needed to confirm the diagnosis so the appropriate management course can be implemented.

Case Report: This case features a 67-year-old Caucasian male diagnosed with ocular myasthenia gravis …

Treatment Considerations For Early Primary Open Angle Glaucoma In Active-Duty Military, Ridwan Carim-Sanni Od, Danielle Kalberer Od, Mba

Optometric Clinical Practice

Background: Glaucoma is one of the leading causes of blindness in the United States. The tools available to treat glaucoma via intraocular pressure (IOP) reduction include pharmacological therapy or surgical intervention.

Case Report: This case study explores these tools in the context of glaucoma in active-duty military personnel. It involves an active-duty army patient diagnosed with early Primary Open Angle Glaucoma (POAG) who was initially prescribed IOP-lowering medication. Barriers in treatment compliance occurred while the patient was deployed that led to significant glaucomatous changes detected when the patient returned stateside.

Conclusion: This report suggests a shift from the traditional pharmacological …

Cryopreserved Amniotic Membrane For Corneal Epithelial Abrasions: Case Series, Laura Goldberg Od

Optometric Clinical Practice

Background: Corneal abrasions are one of the most frequent ocular conditions encountered in the emergency department and can lead to significant morbidity and visual impairment. Amniotic membrane has inherent anti-inflammatory and anti-scarring properties that help accelerate epithelialization and help prevent the complications known to be associated with corneal injuries. Herein we assessed the time till complete epithelialization after in-office application of cryopreserved amniotic membrane in cases of traumatic corneal abrasions in the acute setting.

Case Reports: A total of ten eyes (5 right eye; 5 left eye) of ten consecutive patients (8 Male; 2 Female; average age 40.9 ± 17.8 …

The Art Of Prescribing Low Amounts Of Prism: Optimizing Outcomes, Leonard J. Press Od

Optometric Clinical Practice

Expanding the Box

Learning From Our Future Colleagues, One Case At A Time, Paul B. Freeman Od

Optometric Clinical Practice

Editorial

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …

Positron Emission Tomography Reveals Increased Myocardial Glucose Uptake In A Subset Of Friedreich Ataxia Patients, R Mark Payne, Thomas M O'Connell, P Melanie Pride, Gregg R Wagner, George J Eckert, Tiffany R Johnson, Weinian Shou, Gary D Hutchins

Faculty, Staff and Student Publications

Why some but not all patients with the rare disease Friedreich ataxia (FRDA) are at increased risk of poor cardiovascular outcome and death is unclear and unpredictable. We investigated the hypothesis that mitochondrial dysfunction in FRDA leads to altered patterns of myocardial metabolic substrate utilization. We recruited 5 healthy controls (Ctl) and 11 FRDA participants. All underwent fasting myocardial positron emission tomography (PET scan) with 15O–H2O, 18F-FDG, and 11C-Palmitate. We conducted cardiac transcriptomics on mice with ablation of the Frda gene in heart to explore mechanisms of fuel substrate utilization. Five (45%) FRDA participants had an LV mass index (LVMi) …

Transdiagnostic Alterations In White Matter Microstructure Associated With Suicidal Thoughts And Behaviours In The Enigma Suicidal Thoughts And Behaviours Consortium, Laura S Van Velzen, Lejla Colic, Zuriel Ceja, Maria R Dauvermann, Luca M Villa, Hannah S Savage, Yara J Toenders, Niousha Dehestani, Alyssa H Zhu, Adrian I Campos, Lauren E Salminen, Martin Alda, Ingrid Agartz, Nina Alexander, Rosa Ayesa-Arriola, Elizabeth D Ballard, Nerisa Banaj, Carlotta Barkhau, Zeynep Başgöze, Jochen Bauer, Francesco Benedetti, Klaus Berger, Bianca Besteher, Katharina Brosch, Manuel Canal-Rivero, Simon Cervenka, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Philippe Courtet, Baptiste Couvy-Duchesne, Benedicto Crespo-Facorro, Kathryn R Cullen, Udo Dannlowski, Jeremy Deverdun, Ana M Diaz-Zuluaga, Lorielle M F Dietze, Jennifer W Evans, Negar Fani, Kira Flinkenflügel, Naomi P Friedman, Ian H Gotlib, Nynke A Groenewold, Dominik Grotegerd, Tomas Hajek, Alexander S Hatoum, Marco Hermesdorf, Ian B Hickie, Yoshiyuki Hirano, Tiffany C Ho, Yuki Ikemizu, Frank Iorfino, Jonathan C Ipser, Yuko Isobe, Andrea P Jackowski, Fabrice Jollant, Tilo Kircher, Melissa Klug, Sheri-Michelle Koopowitz, Anna Kraus, Axel Krug, Emmanuelle Le Bars, Elisabeth J Leehr, Meng Li, Elizabeth T C Lippard, Carlos Lopez-Jaramillo, Ivan I Maximov, Andrew M Mcintosh, Katie A Mclaughlin, Sean R Mcwhinney, Susanne Meinert, Elisa Melloni, Philip B Mitchell, Benson Mwangi, Igor Nenadić, Stener Nerland, Emilie Olie, Victor Ortiz-García De La Foz, Pedro M Pan, Fabricio Pereira, Fabrizio Piras, Federica Piras, Sara Poletti, Andrew E Reineberg, Gloria Roberts, Rafael Romero-García, Matthew D Sacchet, Giovanni A Salum, Anca-Larisa Sandu, Carl M Sellgren, Eiji Shimizu, Harry R Smolker, Jair C Soares, J Douglas Steele, Frederike Stein, Dan J Stein, Benjamin Straube, Lea Teutenberg, Florian Thomas-Odenthal, Paula Usemann, Romain Valabregue, Johanna Valencia-Echeverry, Gerd Wagner, Gordon Waiter, Martin Walter, Heather C Whalley, Mon-Ju Wu, Tony T Yang, Carlos A Zarate, Andre Zugman, Giovana B Zunta-Soares, Kees Van Heeringen, Sanne J H Van Rooij, Nic Van Der Wee, Steven Van Der Werff, Paul M Thompson, Hilary P Blumberg, Anne-Laura Van Harmelen, Miguel E Rentería, Neda Jahanshad, Enigma Suicidal Thoughts And Behaviours Consortium, Lianne Schmaal

Faculty, Staff and Student Publications

Previous studies have suggested that alterations in white matter (WM) microstructure are implicated in suicidal thoughts and behaviours (STBs). However, findings of diffusion tensor imaging (DTI) studies have been inconsistent. In this large-scale mega-analysis conducted by the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium, we examined WM alterations associated with STBs. Data processing was standardised across sites, and resulting WM microstructure measures (fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity and radial diffusivity) for 24 WM tracts and one global measure were pooled across 40 cohorts. We compared these measures among individuals with a psychiatric diagnosis and lifetime history of …

Distinct Spatiotemporal Patterns Of White Matter Hyperintensity Progression, Jinyong Chung, Gilsoon Park, Wi-Sun Ryu, Dawid Schellingerhout, Hang-Rai Kim, Dong-Seok Gwak, Elizabeth Haddad, Neda Jahanshad, Beom Joon Kim, Keun-Sik Hong, Hyerin Oh, Sang-Wuk Jeong, Joon-Tae Kim, Man Seok Park, Kang-Ho Choi, Kyungbok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Yong-Jin Cho, Byung-Chul Lee, Philip M Bath, Joanna M Wardlaw, Hee-Joon Bae, Hosung Kim, Dong-Eog Kim

Faculty, Staff and Student Publications

White matter hyperintensity, a key imaging biomarker for brain health, has prognostic implications for stroke. Using a multicenter MRI dataset of 9179 stroke patients plus the UK Biobank (n = 36,210 low/high risk controls), we employ Subtype and Stage Inference modeling and identify three distinct white matter hyperintensity progression subtypes: fronto-parietal, radial, and temporo-occipital. Longitudinal validation confirms classification stability. The fronto-parietal subtype shows delayed onset and more hypertension, while the temporo-occipital subtype has more atrial fibrillation and coronary heart disease. The fronto-parietal and radial subtypes are linked to small vessel stroke, while the temporo-occipital subtype is linked to cardioembolism. The …

Leptin As A Key Driver For Organ Fibrogenesis, Xue-Nan Sun, Shiuhwei Chen, Shangang Zhao, Jan-Bernd Funcke, Megan Virostek, Line Pedersen, Chao Li, Chanmin Joung, Qian Lin, Yan Li, Ayanna Cobb, May-Yun Wang, Kyounghee Min, Lisandro Maya-Ramos, Giovanna Degasperi, Junquan Liu, Ningyan Zhang, Zhiqiang An, Diana R Tomchick, R Max Wynn, Da Young Oh, Philipp E Scherer

Faculty, Staff and Student Publications

Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis of tissue fibrosis. Here, we report the x-ray crystal structures of a leptin-neutralizing antibody (hLep3) in the unbound and leptin-bound states. The interaction of this antibody with leptin mimics the interaction of the LEPR with leptin, providing direct insights into the mechanism by which the antibody disrupts leptin signaling. We furthermore evaluate the therapeutic potential of neutralizing leptin with this antibody across distinct mouse models of fibrosis affecting …

Whole-Genome Sequencing Reveals Individual And Cohort Level Insights Into Chromosome 9p Syndromes., Yingxi Wang, Eleanor I Sams, Rachel Slaugh, Sandra Crocker, Emily Cordova Hurtado, Sophia Tracy, Ying-Chen Claire Hou, Christopher Markovic, Kostandin Valle, Victoria Tate, Khadija Belhassan, Elizabeth Appelbaum, Titilope Akinwe, Rodrigo T Starosta, Yang Cao, Amber Neilson, Yu Liu, Nathaniel Jensen, Reza Ghasemi, Tina Lindsay, Juana Manuel, Sophia Couteranis, Milinn Kremitzki, Jack Ustanik, Thomas Antonacci, Jeffrey K Ng, Andrew Emory, Laura Metz, Tracie Deluca, Katherine N Lyons, Toni Sinnwell, Brianne Thomeczek, Katherine A King, Christina A Gurnett, Susan K Dutcher, Catherine Gooch, Yang E Li, Amjad Horani, Michael Heinz, Richard Head, Robert Fulton, Lucinda Antonacci-Fulton, Xiaoxia Cui, Robi D Mitra, F Sessions Cole, Julie Neidich, Patricia I Dickson, Jeffrey Milbrandt, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous genomic efforts on chromosome 9p deletion and duplication syndromes have utilized low-resolution strategies (i.e., karyotypes, chromosome microarrays). These studies have provided important initial insights into these syndromes. This current study is the first large-scale whole-genome sequencing (WGS) study of 100 individuals from families with chromosome 9p syndromes.

METHODS: Through the newly formed 9P-ARCH (Advanced Research in Chromosomal Health: Genomic, Phenotypic, and Functional Aspects of 9p-Related syndromes) research network, we assembled a cohort of individuals from families with chromosome 9p syndromes. WGS was applied to 100 individuals, and other genomic technologies were applied to a subset of individuals. To …