Digital Commons Network^™

A Consensus Guide To Preclinical Indirect Calorimetry Experiments, Alexander S Banks, David B Allison, Thierry Alquier, Ansarullah, Steven N Austad, Johan Auwerx, Julio E Ayala, Joseph A Baur, Stefania Carobbio, Gary A Churchill, Morten Dall, Rafael De Cabo, Jose Donato, Nathalia R V Dragano, Carol F Elias, Anthony W Ferrante, Brian N Finck, Jose E Galgani, Zachary Gerhart-Hines, Laurie J Goodyear, Justin L Grobe, Rana K Gupta, Kirk M Habegger, Sean M Hartig, Andrea L Hevener, Steven B Heymsfield, Corey D Holman, Martin Hrabě De Angelis, David E James, Lawrence Kazak, Jae Bum Kim, Martin Klingenspor, Xingxing Kong, Sander Kooijman, Louise Lantier, K C Kent Lloyd, James C Lo, Irfan J Lodhi, Paul S Maclean, Owen P Mcguinness, Gema Medina-Gómez, Raghavendra G Mirmira, Christopher D Morrison, Gregory J Morton, Timo D Müller, Yoshihiro Ogawa, David Pajuelo-Reguera, Matthew J Potthoff, Nathan Qi, Marc L Reitman, Patrick C N Rensen, Jan Rozman, Jennifer M Rutkowsky, Kei Sakamoto, Philipp E Scherer, Gary J Schwartz, Radislav Sedlacek, Mohammed Selloum, Saame Raza Shaikh, Shuai Chen, Gerald I Shulman, Vojtěch Škop, Alexander A Soukas, John R Speakman, Bruce M Spiegelman, Gregory R Steinberg, Katrin J Svensson, John P Thyfault, Tony Tiganis, Paul M Titchenell, Nigel Turner, Licio A Velloso, Antonio Vidal-Puig, Christopher S Ward, Ashley S Williams, Christian Wolfrum, Allison W Xu, Ying Xu, Juleen R Zierath, International Indirect Calorimetry Consensus Committee (Iiccc)

Children’s Nutrition Research Center Staff Publications

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data …

A Fascination With Gastrointestinal Viruses, Mary Kolb Estes

Faculty, Staff and Students Publications

My arrival into this world came quickly, according to my mother, and it feels like my life has mirrored that rapid beginning. I have enjoyed a rich, varied, and stimulating life and career that have gone through several phases. I credit genetics, my family, technological advances, and many environmental factors for shaping my career. Being a virologist allowed me to be curious and creative and to make several unexpected discoveries. This has been a fun and rewarding journey, but it wasn't always easy. I am not accustomed to talking about myself, but I am happy to share some scientific achievements …

Acute Loss Of Tactile Input Leads To General Compensatory Changes In Eye-Hand Coordination During Object Manipulation, Kevin Ung, John F Magnotti, Brandon Kim, Jeffrey M Yau, Per F Nordmark

Faculty, Staff and Students Publications

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants …

Treatment Of Cutaneous Collagenous Vasculopathy With Pulsed Dye Laser, Hannah L Hanania, Isabella Camacho-Hubbard, Zeena Y Nawas

Faculty, Staff and Students Publications

Objectives: Cutaneous collagenous vasculopathy (CCV) is a rare, idiopathic microangiopathy marked by widespread telangiectasias and histologic vessel wall thickening. Due to its rarity and clinical overlap with other vascular conditions, CCV poses diagnostic and therapeutic challenges. This report highlights the successful use of pulsed dye laser (PDL) therapy in treating a case of extensive CCV.

Methods: A 40-year-old woman with a decade-long history of progressive telangiectasias involving the extremities, trunk, and forearms underwent treatment with a 595-nm PDL. Six treatment sessions were conducted over 14 months.

Results: The patient experienced significant improvement in erythema, telangiectasias, and associated discomfort, with sustained …

Spatial Omics Enters The Microscopic Realm: Opportunities And Challenges, Yichen Si, Joo Sang Lee, Goo Jun, Hyun Min Kang, Jun Hee Lee

Faculty, Staff and Students Publications

Spatial transcriptomics (ST) enables systematic profiling of whole-transcriptome gene expression in tissues while preserving spatial context. Recent advances in sequencing- and imaging-based ST technologies have ushered in the era of microscopic-resolution ST (μST), allowing transcriptome mapping at cellular and even subcellular scales with unprecedented precision. Despite these advances, μST faces substantial challenges, including sparse transcript discovery per submicron (or micron)-sized spatial units and data fragmentation across platforms, hindering integration and analysis. There is also a growing demand for scalable, segmentation-free, and universally applicable analysis methods, as well as strategies for 3D mapping, multi-omics integration, and artificial intelligence (AI)-driven spatial analysis. …

A Phase 2 Randomized Trial Of Nbi-1065846 (Tak-041) In Patients With Anhedonia Associated With Major Depressive Disorder: Results Of The Terpsis Study, Shannon R Benedetto, Adrian Ionescu, Tingting Ge, Maura Furey, Swan Lin, Manish K Jha, Andrew Krystal, Asim A Shah, David P Walling, Neel Shah, Sakina J Rizvi, Sidney Kennedy, Antonio Laurenza, Venkatesha Murthy, Eiry Roberts, Jaskaran B Singh

Faculty, Staff and Students Publications

Background: Anhedonia is a core symptom of major depressive disorder (MDD) that may result from aberrant lateral habenula hyperactivity. Targeting G-protein coupled receptor 139 (GPR139) may improve anhedonia by modulating lateral habenula activity. NBI-1065846 is an investigational GPR139 agonist that improved anhedonia, anxiety, and depression in rodent models.

Methods: TERPSIS was a phase 2, proof-of-concept clinical study. Adults with MDD experiencing a major depressive episode with anhedonia were randomized 1:1 to NBI-1065846 or placebo for 8 weeks. The primary endpoint was the change in the Dimensional Anhedonia Rating Scale (DARS) score. Secondary endpoints were change in total Montgomery Åsberg Depression …

Fluid Assessment Scoring Tool (Fast): Development Of A Novel Fluid Assessment Scoring Tool For Critically Ill Pediatric Patients-A Pilot Study, Mohammed Salameh, Pranali Awadhare, Jennifer Joiner, Michael Scheurer, Utpal Bhalala

Faculty, Staff and Students Publications

Introduction: Monitoring fluid balance (FB) is important yet challenging in the pediatric intensive care unit (PICU). Currently used, conventional methods of fluid assessment are either not feasible or unreliable. Also, there is a lack of composite scores or clinical algorithms that use different parameters of fluid status. We aim to develop a fluid assessment scoring tool (FAST) to clinically assess the fluid status of children in the PICU.

Methods: In this pilot study, we included critically ill patients aged 0-21 years who presented to our PICU between December 2020 and March 2021 and required invasive or non-invasive mechanical ventilation, inotropes, …

Validation Of An Assay For Ngal In A Pediatric Population, Nazmin Bithi, Ridwan B Ibrahim, Estella L Tam, Radwa Almamoun, Annette C Frenk Oquendo, Ayse Akcan-Arikan, Sridevi Devaraj

Faculty, Staff and Students Publications

Background and objectives: Acute kidney injury (AKI) poses a serious clinical challenge, particularly in high-risk environments, due to its association with increased morbidity and mortality. Traditional diagnostic markers, such as serum creatinine, often detect AKI only after significant kidney damage has occurred, limiting opportunities for early intervention. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising early biomarker due to its rapid upregulation following kidney ischemia. NGAL supports renal recovery by reducing toxicity and promoting tubular regeneration via heme oxygenase-1 activity. This study aimed to validate the BioPorto ProNephro AKI™ turbidimetric immunoassay for urinary NGAL on the Ortho Vitros XT7600 …

Corrigendum To "Validation Of An Assay For Ngal In A Pediatric Population" [Practical Laboratory Medicine, Plabm 486, E00486], Nazmin Bithi, Ridwan B Ibrahim, Estella Tam, Radwa Almamoun, Annett C Frenk Oquendo, Ayse Akcan-Arikan, Sridevi Devaraj

Faculty, Staff and Students Publications

This corrects the article "Validation of an assay for NGAL in a pediatric population", e00486.

The Role Of Serum Phosphate Control In Supporting Transplant Readiness In Patients On Dialysis, Laura A Williams, Stephen Z Fadem

Faculty, Staff and Students Publications

Chronic kidney disease affects over 36 million Americans, with more than 800,000 progressing to end-stage kidney disease (ESKD). Treatment with kidney transplantation offers superior survival, quality of life, and cost-effectiveness compared with dialysis, yet access remains limited. Hyperphosphatemia is a highly prevalent and modifiable complication of ESKD that contributes to cardiovascular disease, mineral bone disorder, and potential pulmonary dysfunction. Additionally, elevated serum phosphate has been linked to transplant graft failure and adverse post-transplant outcomes. Although normal phosphate levels are not formally required for transplant eligibility, they are frequently considered as part of transplant readiness assessments. Persistent gaps between clinical guideline …

Author Correction: Clonal Evolution Of Hematopoietic Stem Cells After Autologous Stem Cell Transplantation, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Linda Zhang, Jennifer Padilla, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi

Faculty, Staff and Student Publications

No abstract provided.

Current Controversies In Prenatal Diagnosis 2: Conventional Postmortem Examination Remains The Gold Standard For The Anatomical Examination Of Fetal Loss, J Ciaran Hutchinson, Lorraine Potocki, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. …

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

History Informing The Future Of Exercise Oncology, Daniel A. Galvão, Kerry S. Courneya, Alejandro Lucia, Anne M. May, Karen Mustian, Allison B. Warner, Wiskemann Joachim, Karen Wonders, Kathryn H. Schmitz, Robert U. Newton

Research outputs 2022 to 2026

Exercise is increasingly recognized by patients, clinicians, and allied health professionals globally as an important component of cancer care. In this paper, we provide a viewpoint on developments in exercise oncology over the past 4 decades leading up to the creation of the International Society of Exercise Oncology (ISEO). We briefly review research in adult and pediatric cancers from early foundation studies to larger randomized controlled trials published in mainstream oncology journals alongside critical work undertaken in exercise and cancer biological mechanisms. We also discuss potential strengths, weaknesses, opportunities, and threats facing ISEO in becoming a global forum for exercise …

Enhancing Patient Outcomes: Developing A Comprehensive Database For Tracking Post- Dural Puncture Headache Incidence And Contributing Factors, Meredith B. Auge, Brittany Bogonovich

Doctor of Nurse Anesthesia Practice (DNAP) Manuscripts

Post-dural puncture headache (PDPH) is a debilitating complication following labor analgesia, often resulting from unintentional dural puncture (UDP). While national incidence is approximately 1.5%, institutional rates may vary due to provider experience, documentation practices, and patient factors. This Doctor of Nurse Anesthesia Practice (DNAP) quality improvement project aimed to improve identification and monitoring of UDP and PDPH through a revised tracking tool, retrospective review of 2024 data, and planning for an electronic registry. A multidisciplinary team of anesthesiologists, Certified Registered Nurse Anesthetists (CRNAs), Student Registered Nurse Anesthetists (SRNAs), and IT and quality specialists revised an existing tracking tool to better …

Utilizing Simulation Training To Understand Maternal Cardiac Arrest Precipitated By Amniotic Fluid Embolism: A Quality Improvement Project, Erica L. Wright, Megan L. Tiernan, Michael W. Neft, Paige Spagiare, Erica Coffin

Doctor of Nurse Anesthesia Practice (DNAP) Manuscripts

Background and Problem: Maternal cardiac arrest precipitated by amniotic fluid embolism is among the leading direct causes of death among laboring women (Enomoto et al., 2022). Because it presents suddenly without any immediate apparent cause and lacks specific diagnostic tests, frontline obstetric caregivers must be vigilant, competent, and prepared to handle this potentially catastrophic emergency. Coordination among multiple disciplines is paramount since two lives, not just one, are at risk. Unfortunately, the rarity of maternal cardiac arrest significantly limits opportunities for staff to learn how to identify and manage these events successfully. Method: This quality improvement project established a simulation-based …

Auprc: A Metric For Evaluating The Performance Of In-Silico Perturbation Methods In Identifying Differentially Expressed Genes, Hongxu Zhu, Amir Asiaee, Leila Azinfar, Jun Li, Han Liang, Ehsan Irajizad, Kim-Anh Do, James P Long

Faculty, Staff and Student Publications

In silico perturbation models, computational methods that can predict cellular responses to perturbations, present an opportunity to reduce the need for costly and time-intensive in vitro experiments. Many recently proposed models predict high-dimensional cellular responses, such as gene or protein expression to perturbations such as gene knockout or drugs. However, evaluating in silico performance has largely relied on metrics such as $R^{2}$, which assess overall prediction accuracy but fail to capture biologically significant outcomes like the identification of differentially expressed (DE) genes. In this study, we present a novel evaluation framework that introduces the AUPRC metric to assess the precision …

Can Artificial Intelligence Models Provide Reliable Medical Counselling To Fertility Patients?, Idan Alcalay, Ariel Weissman, Hadas Ganer Herman, Avi Tsafrir, Matan Friedman, Eran Weiner, Raoul Orvieto, Nikolaos P. Polyzos, Michael H. Dahan, Alex Polyakov, Robert Fischer, Sandro C. Esteves, Baris Ata, Jason M. Franasiak, Yossi Mizrachi

Department of Obstetrics and Gynecology Faculty Papers

RESEARCH QUESTION: Can generative artificial intelligence (AI) models provide reliable counselling to fertility patients regarding real-world clinical questions?

DESIGN: In this cross-sectional study, 12 clinical questions were developed to reflect common, real-life dilemmas encountered during fertility workup and treatment. Responses to each question were generated by two experienced fertility specialists, and two AI models - ChatGPT and Gemini. Eight leading internationally recognized fertility experts, blinded to the source of each reply, independently rated all the responses on a scale from 1 (strongly disagree) to 10 (strongly agree). Ratings were compared across all four repliers using non-parametric statistical tests.

RESULTS: The …

Whole-Genome Sequence-Based Association Analysis Of African American Individuals With Bipolar Disorder And Schizophrenia, Runjia Li, Sarah A Gagliano Taliun, Kevin Liao, Matthew Flickinger, Janet L Sobell, Giulio Genovese, Adam E Locke, Rebeca Rothwell Chiu, Jonathon Lefaive, Jiongming Wang, Taylor Martins, Sinéad Chapman, Anna Neumann, Robert E Handsaker, Donna K Arnett, Kathleen C Barnes, Eric Boerwinkle, David Braff, Brian E Cade, Myriam Fornage, Richard A Gibbs, Karin F Hoth, Lifang Hou, Charles Kooperberg, Ruth J F Loos, Ginger A Metcalf, Courtney G Montgomery, Alanna C Morrison, Zhaohui S Qin, Susan Redline, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Karine A Viaud-Martinez, Tim B Bigdeli, Stacey Gabriel, Sebastian Zollner, Albert V Smith, Goncalo Abecasis, Steve A Mccarroll, Michele T Pato, Carlos N Pato, Michael Boehnke, James Knowles, Hyun Min Kang, Roel A Ophoff, Jason Ernst, Laura J Scott

Faculty, Staff and Student Publications

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole-genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of …

Iatrogenic Aortic Coarctation Physiology After Elephant Trunk Procedure For Type A Aortic Dissection, Khushie Matharoo, Emidio Germano Md, Animesh Rathore Md

Cardiovascular Research Symposium

Introduction: Surgical management of type A aortic dissections has evolved, with growing adoption of extended aortic repairs into the descending aorta. Despite accumulating experience in complex aortic repairs, morbidity and mortality remain high. We present a case of iatrogenic aortic coarctation post-elephant trunk procedure that was ultimately repaired via a thoracic endovascular aortic repair (TEVAR).

Methods: The patient is a 40-year-old male with a medical history of hypertension and cigarette smoking who presented with acute onset of dizziness, hypotension, acute kidney injury (AKI) (Cr 1.4, baseline 0.9) and type 2 myocardial infarction. Echocardiogram showed severe aortic insufficiency, and CTA evidenced …

C-C Motif Chemokine Receptor-Like 2 Promotes The Interferon-Γ Signaling Response In Myeloid Neoplasms With Erythroid Differentiation And Mutated Tp53, Nour Sabiha Naji, Sergiu Pasca, Theodora Chatzilygeroudi, Pablo Toledano-Sanz, Joseph Rimando, Yuju An, Yashvi Hemani, Brandy Perkins, Xinghan Zeng, Conover Talbot, Bogdan Paun, Abdulmuez Abdulmalik, Chen Lossos, Tatianna R Boronina, Ilias Sinanidis, Panagiotis Tsakiroglou, Priyanka Fernandes, Christopher Esteb, Alexander J Ambinder, Robert N Cole, Rena Xian, Ivana Gojo, Suman Paul, Mark J Levis, Amy E Dezern, Leo Luznik, Styliani Karanika, Linda S Resar, Richard J Jones, Frederick Bunz, Lukasz Gondek, Marios Arvanitis, Theodoros Karantanos

Faculty, Staff and Students Publications

Patients with myeloid neoplasms with loss-of-function TP53 mutations and erythroid differentiation have poor outcomes, and a better understanding of disease biology is required. Upregulation of interferon-γ (IFN-γ) signaling has been associated with acute myeloid leukemia (AML) progression, selection of TP53 mutated clones and chemotherapy resistance, but its drivers remain unclear. In this study, we found that the surface receptor C-C motif chemokine receptor-like 2 (CCRL2) is overexpressed in AML with erythroid differentiation and TP53 mutations compared to other AML subtypes and healthy hematopoietic cells. CCRL2 knockout (KO) suppressed erythroleukemia growth in vitro and in vivo. Further proteomics and transcriptomics analysis …

The Immunophenotypic And Genetic Characterization Of Pediatric T -L Ymphoblastic Leukemia With A Mature Immunophenotype, Mahsa Khanlari, Wei Wang, Parastou Tizro, Mohammad K Eldomery

Faculty, Staff and Student Publications

Not available.

Understanding The Why: Patient, Parent, And Oncologist Perspectives On Prognostic Communication Preferences In Advanced Childhood Cancer, Erin Batchelor, Rachel A Kentor, Calliope Reeves, Harmony Farner, Shoshana Mehler, Caroline Christianson, Erica C Kaye

Faculty, Staff and Students Publications

Background/objectives: High-quality prognostic communication in pediatric oncology is essential to support informed decision making, foster trust, and honor goals of care. While families differ in their preferences for how prognosis is discussed, clinicians often rely on assumptions rather than directly eliciting these preferences, risking misalignment and distress. To address this gap, we aimed to characterize patient, parent, and oncologist perspectives on key variables, experiences, and circumstances that influence their preferences for prognostic communication.

Methods: Semi-structured interviews were conducted with 85 participants (25 patients aged 12-25, 40 parents, and 20 oncologists) to elicit their preferences for prognostic communication and the reasons …

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …

The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry

Pharmacy Faculty Articles and Research

Lafora disease (LD) is a fatal childhood progressive myoclonus epilepsy and glycogen storage disease that is caused by recessive mutations in either EPM2A or EPM2B. The hallmarks of LD are cytoplasmic, aberrant glycogen-like aggregates, called Lafora bodies (LBs), that drive disease progression. The 9th Annual Lafora Science Symposium was held in San Diego, California and brought together over 70 researchers, clinicians, academic trainees, and friends and family members of patients with LD and 80 attendees joined virtually. This symposium focused primarily on international collaborations for therapeutic development and biomarker identification and strategies for preparing the Lafora community for upcoming …

Transcatheter Pulmonary Valve Replacement (Tpvr): A Saudi Consensus Statement, Khalid Alnajashi, Ahmed Al Zahrani, Atif Al Qabani, Mohamed Al Humaid, Mishael Binobaidan, Ahmed Krimley, Ahmed Al Omrani, Dhafer Al Shahrani, Ahmed Al Samman, Abdullah Al Quei, Khalid Al Twirqi, Wail Alkashkari, Adel Tash

Journal of the Saudi Heart Association

Objectives: To provide an expert consensus on the appropriate use of transcatheter pulmonary valve replacement (TPVR) in managing chronic pulmonary regurgitation (PR), particularly in patients with congenital heart defects such as Tetralogy of Fallot (TOF). The consensus aims to address current practices, patient selection criteria, procedural planning, and device-specific considerations to guide clinicians in optimizing outcomes. Methods: A multidisciplinary panel reviewed existing literature, clinical guidelines, and real-world practices. Key domains covered include epidemiology, anatomical and hemodynamic evaluation, pre- and post-procedural imaging, device characteristics, and patient selection. Imaging modalities such as echocardiography, cardiac magnetic resonance (CMR), and computed tomography (CT) were …

Aorto-Septal Angle As A Predictor Of Left Ventricular Outflow Tract Obstruction In Pediatric Patients With Subaortic Stenosis And Subaortic Membrane Development: A Study At Prince Sultan Cardiac Center, Buraydah, Saudi Arabia 2023, Rehab N. Alharbi, Ali A. Alakhfash, Abdullah M. Alqwaiee, Abdulrahman A. Almesned, Abdulrahman O. Alharbi

Journal of the Saudi Heart Association

Background: The angle between the interventricular septum and the anterior aortic wall is shallow and measured at 120 degrees in normal individuals. In patients with LVOT narrowing, aortic valve anomalies, and a subaortic membrane, this angle is more acute. This will change the flow hemodynamics and might lead to the formation or progression of the subaortic membrane. Objectives: This study aims to assess the IVS/Anterior Aortic wall angle in patients with abnormal aortic valves and/or LVOT obstruction and its association with SAM development. Methodology: A one-year prospective observational study (September 2022 to June 2023) at PSCC-Qassim's pediatric cardiology department included …

Suppression Of Cardiac Allograft Vasculopathy By A Macrophage Efferocytosis Receptor, Sahil Shah, Aparnaa Ananthakrishnan, Matthew Deberge, Kristofor Glinton, Rebecca T L Jones, Mallory Filipp, Ivana Shen, Joey Lockhart, Connor W Lantz, Edward B Thorp

Faculty, Staff and Student Publications

Cardiac allograft vasculopathy remains a major cause of late morbidity following heart transplantation. While accumulating evidence implicates innate macrophages in the inflammatory progression of CAV, the underlying mechanisms remain incompletely understood. In murine models of CAV, we identified proteolytic cleavage of MERTK, a key anti-inflammatory receptor on macrophages, as a contributing factor to CAV progression. In a model of CAV, MERTK deficiency accelerated allograft rejection and increased intimal leukocyte infiltration. In contrast, mice expressing a genetically cleavage-resistant form of MERTK (MertkCR/CR) exhibited prolonged graft survival, reduced intimal thickening, diminished immune cell infiltration, and decreased circulating effector T cells. …

Reproducibility Of Statistically Significant Phase Iii Oncology Trials: An In Silico Meta-Epidemiological Analysis, Alexander D Sherry, Pavlos Msaouel, Avital M Miller, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Adina H Passy, Tomer Meirson, Nikolaos Ignatiadis, Zachary R Mccaw, Erik Van Zwet, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: The conventional assumption that P values ≤ 0.05 imply reproducible effects has come under recent criticism. This concern is particularly relevant in oncology, as phase III oncology trials, which directly inform practice, are usually not repeated. Using advanced modeling techniques, we investigated the relationship between P values and reproducibility in oncology.

Methods: We obtained the signal-to-noise ratio distribution in phase III oncology using outcomes from 632 two-arm superiority trials enrolling 496,219 patients. With this distribution, we estimated successful replication probability as the probability that a replicate trial, having the same design, effect size, and standard error, would have a …

Mrna Vaccines Encoding Variant Forms Of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma Mansoni, Athos Silva Oliveira, Sevan Alwan, Philip T Loverde, Ramiz Shaheed, Pranav Mandyam, Rakesh Adhikari, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

Despite the global burden of helminth infections, no human vaccines have yet been licensed against these parasites. This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2), an antigen currently under evaluation as a protein vaccine. We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine challenge model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest of antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm …