Digital Commons Network^™

Systemic Carbonic Anhydrase Inhibitors In Common Ophthalmic Diseases: A Scoping Review From A Clinical Standpoint, Shahin Hallaj, Wesam S. Shalaby, Sapna Sinha, Jonathan S. Myers, Reza Razeghinejad

Wills Eye Hospital Papers

PURPOSE OF REVIEW: This paper provides a detailed overview of systemic carbonic anhydrase inhibitors (CAIs) and their application in managing ophthalmic conditions, including glaucoma, cystoid macular edema, and idiopathic intracranial hypertension. Despite their recognized clinical benefits, the potential for severe systemic adverse effects often discourages clinicians from prescribing these agents. By examining the pharmacology, pharmacokinetics, safety profile, and clinical indications of systemic CAIs, this review highlights strategies to mitigate treatment challenges, particularly in patients with comorbidities and complex medical backgrounds.

RECENT FINDINGS: New insights into the diverse roles and distribution of carbonic anhydrase (CA) isozymes have expanded our understanding of …

Food Noise: Definition, Measurement, And Future Research Directions, Emily J Dhurandhar, Kevin C Maki, Nikhil V Dhurandhar, Theodore K Kyle, Sydney Yurkow, Misty A W Hawkins, Jon Agley, Emily H Ho, Lawrence J Cheskin, Thorkild I A Sørensen, Xi Rita Wang, David B Allison

Children’s Nutrition Research Center Staff Publications

The term food noise has been recently popularized by individuals managing their weight or adhering to specific diets for health reasons. Anecdotal evidence from patients and clinical observations suggests that food noise involves constant preoccupation with food-related decisions-such as which foods to eat, caloric intake, macronutrient balance, and meal timing-which can become intrusive and unpleasant. Food noise also appears to affect cognitive burden and quality of life, and is being cited as one reason weight-loss attempts fail. The increase in public discourse about food noise has highlighted its potential significance, yet a formal clinical definition and method of measurement of …

Extracellular Vesicles In Cancer: From Isolation And Characterization To Metastasis, Drug Resistance, And Clinical Applications, Ancuta Jurj, Doru Paul, George A Calin

Faculty, Staff and Student Publications

Cancer progression, along with other hallmarks of cancer, is sustained through bidirectional cell-to-cell communication. This function is primarily facilitated by lipid-rich nanoparticles expelled into the extracellular matrix by stromal and/or malignant cells. These entities, known as extracellular vesicles, contain a vast repertoire of bioactive molecules and hold promise as potential biomarkers and nanovehicles for drug delivery. Intriguingly, the cellular and molecular mechanisms governing the functions of extracellular vesicles remain poorly understood. In the present manuscript, we highlight the intracellular and intercellular journey of extracellular vesicles, from their inception to the present day, their implications in various hallmarks of cancer, and …

Pi(4)P Recruits Cide Proteins To Promote The Formation Of Unilocular Lipid Droplets During Adipogenesis And Hepatic Steatosis, Jin Wu, Mingming Gao, Xiaoqin Wu, Yang Liu, Taiping Zhang, Yan Liang, Haixia Yang, Chengxin Ma, Youpi Ye, Chunmei Chang, Peng Li, Feng-Jung Chen, Hongyuan Yang

Faculty, Staff and Student Publications

Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. The composition of LD surface phospholipids and their impact on LD growth and function remain to be defined. Phosphoinositides mark cellular organelles and regulate organellar function. Here, we demonstrate that PI(4)P decorates a subset of LDs to recruit and activate CIDE proteins. Enhanced expression of ORP2 and ORP5, LD-associated lipid transfer proteins that remove PI(4)P from LDs, abolished the localization and function of CIDE proteins. Blocking the synthesis of PI(4)P on the LD surface …

Opposing Roles For Myeloid And Smooth Muscle Cell Sting In Pulmonary Hypertension, Ann T Pham, Shiza Virk, Aline C Oliveira, Matthew D Alves, Chunhua Fu, Yutao Zhang, Jimena Alvarez-Castanon, Brian B Lee, Keira L Lee, Radwan Mashina, Katherine E Ray, Patrick Donabedian, Elnaz Ebrahimi, Harsh Patel, Reeha Patel, Duncan Lewis, Zhiguang Huo, Harry Karmouty-Quintana, Li Chen, Lei Jin, Andrew J Bryant

Faculty, Staff and Student Publications

There is an emerging role for stimulator of interferon genes (STING) signaling in pulmonary hypertension (PH) development. Related to this, prior research has demonstrated the relevance of immune checkpoint protein programmed death ligand 1 (PD-L1) expression by immunoregulatory myeloid cells in PH. However, there remains a need to elucidate the cell-specific role of STING expression, and the STING/PD-L1 signaling axis in PH, before readily available disease-modifying therapies can be applied for patients with the disease. Here, through generation of bone marrow chimeric mice, we show that STING-/- mice receiving WT bone marrow were protected against PH secondary to chronic hypoxia. …

Nivolumab Plus Relatlimab For Patients With Relapsed Or Progressed B-Cell Malignancies In Relativity-022, Ajay K Gopal, Philippe Armand, Sattva S Neelapu, Nancy L Bartlett, Stephen E Spurgeon, John Kuruvilla, Kerry J Savage, John P Leonard, Arnold B Gelb, Nasir Ahmed, Shiqi Dong, Sai Praneeth Bathena, Rasika Suryawanshi, Jenny Qun Wu, Sheen Wang, Douglas E Gladstone

Faculty, Staff and Student Publications

Despite high response rates, anti-programmed death 1 (anti-PD-1) monotherapy eventually fails in most patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and is ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved in advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with R/R B-cell malignancies. We treated 106 patients and no dose-limiting toxicities were observed during …

Pulsed Field Ablation Of Persistent Atrial Fibrillation With Continuous Electrocardiographic Monitoring Follow-Up: Advantage Af Phase 2., Vivek Y Reddy, Edward P Gerstenfeld, Boris Schmidt, Jason G Andrade, Devi Nair, Andrea Natale, Walid Saliba, Philipp Sommer, Andreas Metzner, Atul Verma, Troy Hounshell, Anish Amin, Philip Gentlesk, Stanislav Weiner, Frank A Cuoco, Jamie Kim, Mohit K Turagam, Gery Tomassoni, Chinmay Patel, Ziad Issa, Michael Shehata, Allison M Anderson, Thomas J Stoltz, Jonathan D Raybuck, Torri Schwartz, Brad S Sutton, Moussa Mansour

Heart and Vascular Articles

BACKGROUND: There are sparse high-quality safety and effectiveness data for pulsed field ablation (PFA) of persistent atrial fibrillation (PerAF), in which lesions beyond pulmonary vein isolation (PVI) are often placed. In addition, no large trials have used insertable cardiac monitors for continuous rhythm monitoring after ablation in patients with PerAF or after PFA in any atrial fibrillation population. In Phase 2 of the ADVANTAGE AF study (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation), patients with PerAF underwent PFA for PVI and posterior wall ablation (PWA) and, in …

Towards Fair Decentralized Benchmarking Of Healthcare Ai Algorithms With The Federated Tumor Segmentation (Fets) Challenge, Maximilian Zenk, Ujjwal Baid, Sarthak Pati, Akis Linardos, Brandon Edwards, Micah Sheller, Patrick Foley, Alejandro Aristizabal, David Zimmerer, Alexey Gruzdev, Jason Martin, Russell T Shinohara, Annika Reinke, Fabian Isensee, Santhosh Parampottupadam, Kaushal Parekh, Ralf Floca, Hasan Kassem, Bhakti Baheti, Siddhesh Thakur, Verena Chung, Kaisar Kushibar, Karim Lekadir, Meirui Jiang, Youtan Yin, Hongzheng Yang, Quande Liu, Cheng Chen, Qi Dou, Pheng-Ann Heng, Xiaofan Zhang, Shaoting Zhang, Muhammad Irfan Khan, Mohammad Ayyaz Azeem, Mojtaba Jafaritadi, Esa Alhoniemi, Elina Kontio, Suleiman A Khan, Leon Mächler, Ivan Ezhov, Florian Kofler, Suprosanna Shit, Johannes C Paetzold, Timo Loehr, Benedikt Wiestler, Himashi Peiris, Kamlesh Pawar, Shenjun Zhong, Zhaolin Chen, Munawar Hayat, Gary Egan, Mehrtash Harandi, Ece Isik Polat, Gorkem Polat, Altan Kocyigit, Alptekin Temizel, Anup Tuladhar, Lakshay Tyagi, Raissa Souza, Nils D Forkert, Pauline Mouches, Matthias Wilms, Vishruth Shambhat, Akansh Maurya, Shubham Subhas Danannavar, Rohit Kalla, Vikas Kumar Anand, Ganapathy Krishnamurthi, Sahil Nalawade, Chandan Ganesh, Ben Wagner, Divya Reddy, Yudhajit Das, Fang F Yu, Baowei Fei, Ananth J Madhuranthakam, Joseph Maldjian, Gaurav Singh, Jianxun Ren, Wei Zhang, Ning An, Qingyu Hu, Youjia Zhang, Ying Zhou, Vasilis Siomos, Giacomo Tarroni, Jonathan Passerrat-Palmbach, Ambrish Rawat, Giulio Zizzo, Swanand Ravindra Kadhe, Jonathan P Epperlein, Stefano Braghin, Yuan Wang, Renuga Kanagavelu, Qingsong Wei, Yechao Yang, Yong Liu, Krzysztof Kotowski, Szymon Adamski, Bartosz Machura, Wojciech Malara, Lukasz Zarudzki, Jakub Nalepa, Yaying Shi, Hongjian Gao, Salman Avestimehr, Yonghong Yan, Agus S Akbar, Ekaterina Kondrateva, Hua Yang, Zhaopei Li, Hung-Yu Wu, Johannes Roth, Camillo Saueressig, Alexandre Milesi, Quoc D Nguyen, Nathan J Gruenhagen, Tsung-Ming Huang, Jun Ma, Har Shwinder H Singh, Nai-Yu Pan, Dingwen Zhang, Ramy A Zeineldin, Michal Futrega, Yading Yuan, Gian Marco Conte, Xue Feng, Quan D Pham, Yong Xia, Zhifan Jiang, Huan Minh Luu, Mariia Dobko, Alexandre Carré, Bair Tuchinov, Hassan Mohy-Ud-Din, Saruar Alam, Anup Singh, Nameeta Shah, Weichung Wang, Chiharu Sako, Michel Bilello, Satyam Ghodasara, Suyash Mohan, Christos Davatzikos, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Christopher Hess, John Mongan, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, Raymond Y Huang, Ken Chang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Ker Kovský, Tereza Kopr Ivová, Marek Dostál, Václav Vybíhal, Marco C Pinho, James Holcomb, Marie Metz, Rajan Jain, Matthew D Lee, Yvonne W Lui, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Rivka R Colen, Aikaterini Kotrotsou, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J Preetha, Felix Sahm, Martin Bendszus, Wolfgang Wick, Abhishek Mahajan, Carmen Balaña, Jaume Capellades, Josep Puig, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Hassan F Shaykh, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Pamela Lamontagne, Daniel S Marcus, Mikhail Milchenko, Arash Nazeri, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B Chambless, Akshitkumar Mistry, Reid C Thompson, Ashok Srinivasan, J Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, John Garrett, Matthew Larson, Robert Jeraj, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Alexandre Xavier Falcão, Samuel B Martins, Bernardo C A Teixeira, Flávia Sprenger, David Menotti, Diego R Lucio, Simone P Niclou, Olivier Keunen, Ann-Christin Hau, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Richard Mckinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A Velastin, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M Buatti, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M Kardamakis, Bing Luo, Laila M Poisson, Ning Wen, Martin Vallières, Mahdi Ait Lhaj Loutfi, David Fortin, Martin Lepage, Fanny Morón, Jacob Mandel, Gaurav Shukla, Spencer Liem, Gregory S Alexandre, Joseph Lombardo, Joshua D Palmer, Adam E Flanders, Adam P Dicker, Godwin Ogbole, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu'aibu Hikima, Mayowa Soneye, Farouk Dako, Adeleye Dorcas, Derrick Murcia, Eric Fu, Rourke Haas, John A Thompson, David Ryan Ormond, Stuart Currie, Kavi Fatania, Russell Frood, Amber L Simpson, Jacob J Peoples, Ricky Hu, Danielle Cutler, Fabio Y Moraes, Anh Tran, Mohammad Hamghalam, Michael A Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Lisa Cimino, Cynthia Price, Brian Bialecki, Sailaja Marella, Charles Apgar, Andras Jakab, Marc-André Weber, Errol Colak, Jens Kleesiek, John B Freymann, Justin S Kirby, Lena Maier-Hein, Jake Albrecht, Peter Mattson, Alexandros Karargyris, Prashant Shah, Bjoern Menze, Klaus Maier-Hein, Spyridon Bakas

Faculty, Staff and Student Publications

Computational competitions are the standard for benchmarking medical image analysis algorithms, but they typically use small curated test datasets acquired at a few centers, leaving a gap to the reality of diverse multicentric patient data. To this end, the Federated Tumor Segmentation (FeTS) Challenge represents the paradigm for real-world algorithmic performance evaluation. The FeTS challenge is a competition to benchmark (i) federated learning aggregation algorithms and (ii) state-of-the-art segmentation algorithms, across multiple international sites. Weight aggregation and client selection techniques were compared using a multicentric brain tumor dataset in realistic federated learning simulations, yielding benefits for adaptive weight aggregation, and …

Younger Haplo-Donors Improve Older Patient Survival Outcomes, Ahmad Ghorab, Leo Luznik

Faculty, Staff and Students Publications

No abstract provided.

Psilocybin Treatment Extends Cellular Lifespan And Improves Survival Of Aged Mice, Kosuke Kato, Jennifer M Kleinhenz, Yoon-Joo Shin, Cristian Coarfa, Ali J Zarrabi, Louise Hecker

Faculty, Staff and Students Publications

Psilocybin, the naturally occurring psychedelic compound produced by hallucinogenic mushrooms, has received attention due to considerable clinical evidence for its therapeutic potential to treat various psychiatric and neurodegenerative indications. However, the underlying molecular mechanisms remain enigmatic, and few studies have explored its systemic impacts. We provide the first experimental evidence that psilocin (the active metabolite of psilocybin) treatment extends cellular lifespan and psilocybin treatment promotes increased longevity in aged mice, suggesting that psilocybin may be a potent geroprotective agent.

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

The Benefits Of Exercise Training In Combination With Weight Loss Therapies, Bryan C Jiang, Dennis T Villareal

Faculty, Staff and Students Publications

The primary treatment for obesity involves calorie restriction (CR) to promote dietary weight loss achieved through interventions including behavioral modification, bariatric surgery, and antiobesity medications. In adults with obesity, CR-induced weight loss enhances physical function and improves quality of life, while also reducing the burden of various obesity-related chronic conditions, including hypertension, diabetes, obstructive sleep apnea, and atherosclerotic heart disease. However, it is also associated with a decline in lean mass and bone mineral density, which increases the risk of sarcopenia and osteoporosis. When performed alongside CR, progressive resistance training (RT) attenuates this loss of lean mass and bone mass, …

Infantile Pyknocytosis Revisited: Possible Familial Trend In A Study Of 9 Patients, Aileen Y Hu, Amy M Coffey, Jyotinder N Punia, Andrea N Marcogliese, Choladda V Curry, M Tarek Elghetany

Faculty, Staff and Students Publications

Context.—: Infantile pyknocytosis (IP) is an uncommon cause of transient neonatal hemolytic anemia and hyperbilirubinemia occurring in approximately 10% of cases of unexplained neonatal hemolytic anemia.

Objective.—: To study cases of IP with focus on long-term follow-up, perinatal events, and family history.

Design.—: Cases were prospectively identified during review of peripheral blood smears for neonatal hyperbilirubinemia during an 11-year period. Clinical and laboratory parameters, follow-up data, and family history were recorded.

Results.—: Nine cases of IP were identified from the morphologic recognition of pyknocytes and clinical and laboratory evidence of hemolysis, and included 6 males and 3 females. Age at …

The Co-Occurrence Of Autism Spectrum Disorder And Aarskog-Scott Syndrome In An Accomplished Young Man, Raisa S Romanova, Oksana I Talantseva, Katerina V Lind, Victoria A Manasevich, Julia E Kuznetsova, Elena L Grigorenko

Faculty, Staff and Students Publications

Objectives/Background: Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia, is a rare X-linked genetic disorder primarily characterized by its diverse physical manifestations. Previous evidence suggests a potential association between AAS and neurodevelopmental disorders, including autism spectrum disorder (ASD).

Methods: This case study presents a male adolescent with ASD and a novel genetic variant in FGD1 underlying AAS. We conducted comprehensive clinical, genetic, and behavioral assessments to characterize the neurodevelopmental presentation. Moreover, we examined the existing literature on AAS and comorbid neurodevelopmental disorders.

Results: The patient demonstrated features consistent with both AAS and ASD, presenting with characteristic physical features of AAS …

Rapid Access Chest Pain Assessment Clinic: An Australian Virtual Care Experience, Marwan Shawki, Thalys Sampaio Rodrigues, Hussein Al-Fiadh, Karen Sanders Mnursing, Ali H. Al-Fiadh

Journal of the Saudi Heart Association

Background: The Rapid Access Chest Pain Assessment Clinic (RACPAC) streamlines the evaluation of low to intermediate-risk chest pain patients, reducing hospitalisation and healthcare costs. However, there is limited data on the virtual model of care for RACPAC.

Aim: We sought to evaluate the structure, cost-effectiveness, and imaging modalities performance of face-to-face and virtual RACPAC in an Australian setting.

Methods:A retrospective analysis of patients attending the RACPAC within a large Australian quaternary hospital between 2012 and 2021. We described the clinic parameters and imaging modality utilisation with parametric and non-parametric descriptive statics. Patterns of diagnostic modality utilisation were assessed with …

Enhancing Diagnostic Reliability Through Centrifuge Validation And Staff Education: Quality Management Initiative In A Clinical Laboratory, Chris Agoki

MSMLS Capstone Projects

Abstract

This capstone project aims to enhance diagnostic reliability in a clinical laboratory by validating centrifuge performance and implementing an adult education-based training program within a quality management framework. Twenty archived, de-identified whole blood samples were analyzed to compare the performance of a new centrifuge with an existing model, focusing on plasma volume, hemolysis index, and Tacrolimus concentration.

The study demonstrated statistical and clinical equivalence between the devices, supporting the implementation of the new centrifuge. A staff training program, grounded in andragogical principles and guided by transformational leadership and Kotter’s 8-Step Change Model, was developed to integrate validation practices into …

Being Well: Stories Of Coping And Resilience, Simiao Li-Sauerwine, Abbas Husain, Al'ai Alvarez, Gillian Baty, Manish Garg, Ryan Bodkin, Andy Grock, Marc Borenstein, Pamela Dyne

Journal of Wellness

Introduction: The approach to physician well-being has transformed from a focus on identification of distress to embracing a comprehensive model that values vulnerability, growth, self-compassion, and a sense of purpose and community in the profession. This manuscript, a collaborative effort by the Council of Residency Directors in Emergency Medicine Well-being Committee and the Society for Academic Emergency Medicine Wellness Committee, presents the personal narratives of academic emergency physicians during which they faced challenges and stressors, as well as supportive resources they found helpful. The scenarios are written by the individuals themselves as they experienced them.

Discussion: Through these shared and …

Leveraging A Randomized Trial To Assess Relationships Between Transeptal Puncture, Brain Emboli, And Migraine Symptoms, Adi Elias, Roderick Tung, Edward P Gerstenfeld, Trisha F Hue, Feng Lin, Jing Cheng, J Peter Weiss, Wendy S Tzou, Henry Hsia, Ashkan Ehdaie, Daniel H Cooper, T Jared Bunch, Jeffrey Arkles, Babak Nazer, Adam Lee, Alexios Hadjis, Duy T Nguyen, Mihail G Chelu, Joshua D Moss, Jonathan C Hsu, Miguel Valderrábano, Prashant D Bhave, Gabrielle Montenegro, Anthony S Kim, William P Dillon, Gregory M Marcus

Faculty, Staff and Students Publications

Background: Catheter ablation procedures with transseptal punctures (usually for atrial fibrillation) are often associated with migraine-related visual auras, but the mechanism remains unknown. Whether this phenomenon is mediated by the creation of an atrial septal defect from transseptal puncture or by silent acute brain emboli detected on magnetic resonance imaging related to the procedure remains to be investigated.

Objective: This study aimed to evaluate whether randomization to a transseptal puncture during catheter ablation for ventricular arrhythmias is associated with postprocedural visual auras and assess the relationship between occipital and parietal lobes acute brain emboli and migraine-related visual auras.

Methods: In …

From Imaging To Computational Domains For Physics-Driven Molecular Biology Simulations: Hindered Diffusion In Platelet Masses, Catherine House, Ziyi Huang, Kaushik Shankar, Sandra Young, Meghan Roberts, Scott Diamond, Maurizio Tomaiuolo, Timothy Stalker, Lu Lu, Talid Sinno

Cardeza Foundation for Hematologic Research

When formed in vivo, murine hemostatic thrombi exhibit a heterogeneous architecture comprised of distinct regions of densely and sparsely packed platelets. In this study, we utilize high-resolution electron microscopy alongside machine learning and physics-based simulations to investigate how such clot microstructure impacts molecular diffusivity. We used Serial Block Face - Scanning Electron Microscopy (SBF-SEM) to image select volumes of hemostatic masses formed in a mouse jugular vein, producing high-resolution 2D images. Images were segmented using machine learning software (Cellpose), whose training was augmented by manually segmented images. The segmented images were then utilized as 2D computational domains for Lattice Kinetic …

Convergent Reduction Of Olfactory Genes And Olfactory Bulb Size In Mammalian Species At Altitude, Allie M Graham, Elysia Saputra, Bogdan Kirilenko, Jason S Presnell, Arianna Harrington, Chad Huff, Michael Hiller, Nathan Clark

Faculty, Staff and Student Publications

The invasion of specialized ecological niches can cause drastic changes to selection regimes, resulting in genomic and phenotypic transformation.

Risk Of Pancreatic Cancer In Glycemically Defined New-Onset Diabetes: A Prospective Cohort Study, Suresh T Chari, Bechien Wu, Camden Lopez, Eva Lustigova, Qiaoling Chen, Stephen K Van Den Eeden, Amethyst D Leimpeter, William Fisher, Amy Wood, Ashley S Alexander, John Valenta, Santhi Swaroop Vege, Erin E Carlson, Kari G Rabe, Phil A Hart, Lu Qian, Ying-Qi Zhao, Nadia Yosuf, Lynn Matrisian, Barbara Kenner, Jo Ann Rinaudo, Anirban Maitra, Ziding Feng

Faculty, Staff and Student Publications

Background & aims: The increased 3-year incidence of pancreatic cancer after new-onset diabetes observed in retrospective studies needs prospective validation. It is unknown whether incidence varies by race and ethnicity.

Methods: In a prospective, observational study using active real-time surveillance of electronic health records, we identified 18,838 adults 50 years or older with glycemically defined new-onset diabetes (GNOD). In this interim analysis, we report 3-year Kaplan-Meier estimates of the proportion diagnosed with pancreatic cancer after GNOD (absolute incidence [95% CI]) and associated standardized incidence ratio (SIR) by race and ethnicity, overall 3-year incidence of pancreatic cancer adjusting for racial distribution …

Accounting For Competing Risks In The Assessment Of Prognostic Biomarkers' Discriminative Accuracy, Xinran Huang, Xinyang Jiang, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

The discriminative performance of biomarkers often changes over time and exhibits heterogeneity across subgroups defined by patient characteristics. Assessing how this performance varies with these factors is crucial for a comprehensive evaluation of biomarkers and to identify areas for improvement in sub-populations with poor performance. Additionally, the presence of competing risks complicates the assessment of discriminative performance. Ignoring competing risks can lead to misleading conclusions, as the biomarker's performance for the event of interest, such as disease onset, may be confounded by its performance for competing events, such as death. To address these challenges, we develop a regression model to …

Alpha-Synuclein Dysregulation In Systemic Pathophysiology Of Synucleinopathies, Hallie H. Dolin, Bowen Zhou, Robert W. Maitta

Faculty Scholarship

Alpha-synuclein (α-syn) has long been identified as the etiologic agent of multiple neurodegenerative diseases, the most common and well-known of which are Parkinson's disease (PD) and Lewy body dementia (LBD). While it is known that the pathophysiology of these synucleinopathies involves aggregation of improperly-folded α-syn, the mechanisms leading to its accumulation have not been fully identified. However, multiple pathways have been proposed, any or all of which may contribute to synucleinopathies. The role of α-syn in normal homeostasis and in other organ systems, especially the hematopoietic system, has been reported recently. Research within the last decade has shown that α-syn …

Development And Validation Of A Novel Clinical Risk Score To Predict Hypoxaemia In Children With Pneumonia Using The Who Prepare Dataset, Rainer Tan, Arjun Chandna, Tim Colbourn, Shubhada Hooli, Carina King, Norman Lufesi, Eric D Mccollum, Charles Mwansambo, Joseph L Mathew, Clare L Cutland, Shabir A Madhi, Marta Nunes, Sudha Basnet, Tor A Strand, Kerry-Ann F O'Grady, Brad Gessner, Emmanuel Addo-Yobo, Noel Chisaka, Patricia Hibberd, Prakash M Jeena, Juan M Lozano, William B Maleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Marilla Lucero, Syed Mohammad Akram Uz Zaman, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Mathuram Santosham, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean William Pape, Glaucia Paranhos-Baccala, Valentina S Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Romina Libster, Alexey W Clara, Fenella Beynon, Gillian Levine, Chris A Rees, Mark I Neuman, Shamim Qazi, Yasir Bin Nisar, World Health Organization Prepare Study Group

Faculty, Staff and Students Publications

Background: Hypoxaemia predicts mortality at all levels of care, and appropriate management can reduce preventable deaths. However, pulse oximetry and oxygen therapy remain inaccessible in many primary care health facilities. We aimed to develop and validate a simple risk score comprising commonly evaluated clinical features to predict hypoxaemia in 2-59-month-old children with pneumonia.

Methods: Data from seven studies conducted in five countries from the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) dataset were included. Readily available clinical features and demographic variables were used to develop a multivariable logistic regression model to predict hypoxemia (oxygen saturation < 90%) at presentation to care. The adjusted log coefficients were transformed to derive the PREPARE hypoxemia risk score and its diagnostic value was assessed in a held-out, temporal validation dataset. The model and risk score were analysed by evaluating the area under the receiver operating characteristic curve (AUC), sensitivity and specificity.

Results: We included 14 …

Consideration Of Patient Phenotypes In Geographic Atrophy Due To Age-Related Macular Degeneration, Rishi P Singh, Christina Y Weng, John W Kitchens, Jaclyn Quilantan, Roy Schwartz, Caroline R Baumal, Roger A Goldberg

Faculty, Staff and Students Publications

Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) affecting approximately 1 million people in the USA and 5 million globally. In this review, retinal imaging techniques used for diagnosis and monitoring progression of GA in AMD, and the risk factors associated with the development and progression of GA are summarised. To familiarise clinicians with common phenotypes of patients with GA, the clinical and imaging features that may lead to rapid progression of GA in various phenotypes are highlighted. With the recent US Food and Drug Administration approval of new GA treatments that reduce lesion growth, understanding …

Psychopharmacological Therapy Positively Modulates Disease Activity In Inflammatory Bowel Disease: A Systematic Review, Federica Di Vincenzo, Antonio Maria D'Onofrio, Angelo Del Gaudio, Elena Chiera, Gaspare Filippo Ferrajoli, Francesco Pesaresi, Alessio Simonetti, Marianna Mazza, Georgios Demetrios Kotzalidis, Mauro Pettorruso, Giovanni Martinotti, Loris Riccardo Lopetuso, Antonio Gasbarrini, Gabriele Sani, Gionata Fiorino, Franco Scaldaferri, Giovanni Camardese

Faculty, Staff and Students Publications

Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut-brain axis and frequent use of psychotropic medications in IBD patients, limited evidence exists regarding the effects of psychiatric treatments on gastrointestinal disease activity. Therefore, the aim of this systematic review is to evaluate the effectiveness of psychiatric therapies on gastrointestinal symptoms and disease activity in patients with IBD. The work was conducted in accordance with PRISMA guidelines. Searches …

The Articularis Genu As A Surrogate For Structural Determinants Of Peri-Articular Myopenia In Osteoarthritis, Davis Martin, José A.Cruz Ayala, Mary C. Gatterer, Tara Soria, Ryan Schroeder, Vinod Dasa, Luis Marrero

School of Medicine Faculty Publications

The functional limitations associated with the painful stiffness of knee osteoarthritis (kOA) can affect the muscles of the knee, such as the quadriceps femoris (QF) and articularis genu (AG). The vastus medialis oblique (VMO) of the QF complex is particularly sensitive to kOA. The AG, which can be sampled during total knee arthroplasty (TKA) for kOA, can provide information about the condition of the QF when affected by patient-reported disuse, helping to identify indicators of muscle weakness in the synovial fluid. This study compares the structural and gene expression changes between the VMO and the AG collected from patients with …

A Rare Cause Of Severe Bleeding In Neonate: Congenital Afibrogenemia Case Report, Abdul Azeem Hulkoti, Qudsiya Ansari, Kailas Randad, Akash Dnyandeo Sarkate Dr

Digital Journal of Clinical Medicine

Background- Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of fibrinogen, a critical factor for clot formation in the blood. This deficiency leads to significant bleeding tendencies from birth. Patients typically present with severe haemorrhagic symptoms early in the neonatal period.

Case presentation- We describe a case of a neonate presenting with umbilical bleeding diagnosed with congenital afibrinogenemia. Initial clinical manifestations included active umbilical bleeding and pallor, while hematological workup revealed a lack of detectable fibrinogen. The diagnosis was confirmed by coagulation assays and genetic testing. The infant was managed with Fresh Frozen Plasma (FFP) …

Dopamine Partial Agonists In Pregnancy And Lactation: A Systematic Review, Alexia Koukopoulos, Delfina Janiri, Miriam Milintenda, Sara Barbonetti, Georgios D Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Marianna Mazza, Lucio Rinaldi, Alessio Simonetti, Mario Pinto, Giovanni Camardese, Gabriele Sani

Faculty, Staff and Students Publications

Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. It is debated whether patients with psychiatric disorders becoming pregnant should discontinue or continue their antipsychotic treatment despite some risks for the fetus, i.e., whether it is worse to have an untreated disorder or treating it with drugs. The safety of drugs for mother and baby extend from pregnancy to the postpartum, when …

Preliminary Investigation Of The Association Between Epigenetic Aging Acceleration And Amyloid Biomarkers In Bipolar Disorder, Gabriel R Fries, Steven De La Garza, Ning O Zhao, Andres W Bass, Camila N C Lima, Nobuhide Kobori, Tatiana Barichello, Gustavo Turecki, Paul E Schulz, Breno S Diniz, Jair C Soares

Faculty, Staff and Student Publications

Objectives: Bipolar disorder (BD) has been associated with an elevated risk of Alzheimer's Disease (AD). We assessed AD biomarkers in BD and tested whether epigenetic aging (EA) acceleration is associated with changes in these markers.

Design, setting, participants: Cross-sectional study of n = 58 living individuals with BD and n = 20 age- and sex-matched control participants, as well as analyses of postmortem brain samples (Brodmann area 9/46) from n = 46 individuals with BD.

Measurements: Amyloid beta (Aβ)40, Aβ42, and total Tau levels were measured in plasma from individuals with BD and controls, and Aβ42 levels were measured in …