Digital Commons Network^™

Gender Disparities Among General Surgeons: A Comprehensive Review, Julie Holihan, Devi Bavishi, Kush Brahmbhatt, Rebecca Franks, Zuhair Ali, Karla Bernardi, Christine Castillo, Mike Liang, Rachel Wong, Michele Loor

Faculty, Staff and Student Publications

Background: Unlike in-house call, the Accreditation Council for Graduate Medical Education (ACGME) does not require a postcall day for "home call" shifts. Despite this, we hypothesize that on-call residents are still in the hospital for the majority of their shift despite having the luxury of home call and, thus, are not protected by ACGME postcall duty hour regulations.

Methods: A prospective single center survey study was conducted by surveying junior and senior residents who completed overnight call shifts from January 2023 to April 2023 at one of the busiest level 1 trauma centers in the United States. Data include number …

Psychotropic Medications And Their Interactions With Subcortical Brain Volume In Bipolar Disorder: An Enigma Mega-Analysis, Sinead King, John O'Connor, Emma Corley, Giulia Tronchin, Elisa Fontana, Leila Nabulsi, Melody J Y Kang, Joaquim Radua, Brian Hallahan, Christoph Abé, Martin Alda, Dag Alnæs, Silvia Alonso-Lana, Silvia Amoretti, Jochen Bauer, Francesco Benedetti, Klaus Berger, Michael Berk, Erlend Bøen, Joscha Böhnlein, Birgitte Boye, Beatrice Bravi, Erick J Canales-Rodríguez, Udo Dannlowski, Caroline Demro, Annabella Di Giorgio, Ana M Diaz-Zuluaga, Torbjørn Elvsåshagen, Pauline Favre, Tracy Erwin-Grabner, María Florencia Forte, Janice M Fullerton, Lisa S Furlong, Susan L Rossell, David C Glahn, Benjamin I Goldstein, Ian H Gotlib, Roberto Goya-Maldonado, Melissa J Green, Dominik Grotegerd, Oliver Gruber, Bartholomeus C M Haarman, Tim Hahn, Tomas Hajek, Leonie Hater, Marco Hermesdorf, Josselin Houenou, Fleur M Howells, James A Karantonis, Kody G Kennedy, Tilo Kircher, Anna Luisa Klahn, Maximilian Konowski, Bernd Krämer, Elijah Lahud, Rayus Kuplicki, Mikael Landén, Carlos López-Jaramillo, Bradley J Macintosh, Hannah Meinert, Susanne Meinert, Elisa M T Melloni, Philip B Mitchell, Benson Mwangi, Igor Nenadić, Bronwyn J Overs, Nadine Parker, Godfrey Pearlson, Edith Pomarol-Clotet, James J Prisciandaro, Yann Quidé, Gloria Roberts, Amanda Rodrigue, Elena Rodríguez-Cano, Lisa Rauer, Matthew D Sacchet, Raymond Salvador, Fabio Sambataro, Theodore D Satterthwaite, Jonathan Savitz, Freda Scheffler, Navid Schürmeyer, Chen Shen, Kang Sim, Jair C Soares, Aleix Solanes, Márcio Gerhardt Soeiro-De-Souza, Scott R Sponheim, Dan J Stein, Frederike Stein, Henk S Temmingh, Lea Teutenberg, Sophia I Thomopoulos, Snezana Urosevic, Tamsyn E Van Rheenen, Eduard Vieta, Lars T Westlye, Daniel H Wolf, Mon-Ju Wu, Lakshmi N Yatham, Giovana B Zunta-Soares, Dara M Cannon, Paul M Thompson, Ole A Andreassen, Christopher R K Ching, Colm Mcdonald

Faculty, Staff and Student Publications

MRI studies in bipolar disorder (BD) have yielded inconsistent findings, partly due to the varied use of psychotropic medications. This study utilised a mega-analysis approach, accounting for concurrent medication status (syndrome-based and Neuroscience-based Nomenclature (NbN) classifications), in order to assess the association of medication status with subcortical brain volumes in BD. Data from 2,664 BD patients and 4,065 controls (CN) were pooled from 34 research groups as part of the ENIGMA Bipolar Disorder Working Group. Standardized ENIGMA protocols were used to measure subcortical brain volumes. Linear-mixed-effects regression evaluated the association between psychotropic medications and subcortical volumes, and moderation analyses explored …

Intravenous Buprenorphine Reversed Opioid-Induced Respiratory Depression Without Precipitating Withdrawal In Emergency Department Patients, Anthony Spadaro, Nicholas Imperato, Jaclyn Scalgione, Cynthia Santos

Faculty, Staff and Student Publications

Objective: Buprenorphine is a high-affinity partial agonist that can displace full opioid agonists and could be used to reverse opioid-induced respiratory depression. There is scant evidence to support the use of buprenorphine in an acute opioid overdose to reverse respiratory depression in the era of high fentanyl prevalence in the drug supply. This is a case series of four patients with signs and symptoms of an opioid overdose who showed clinical improvement after receiving intravenous buprenorphine.

Method: A case series of adult emergency department patients treated at a single urban academic medical center was reviewed by the authors, who determined …

Structural Brain Differences Associated With Panic Disorder: An Enigma-Anxiety Working Group Mega-Analysis Of 4924 Individuals Worldwide, Laura K M Han, Willem B Bruin, Janna Marie Bas-Hoogendam, Nynke A Groenewold, Kevin Hilbert, Anderson M Winkler, Andre Zugman, Takeshi Asami, Jacques P Barber, Francesco Benedetti, Robert J R Blair, Joscha Böhnlein, Paolo Brambilla, Fabian Breuer, Randy L Buckner, Robin Bülow, Monica E Calkins, Natalia Chechko, Udo Dannlowski, Katharina Dohm, Katharina Domschke, Thomas Dresler, Angelika Erhardt-Lehmann, Gregory A Fonzo, Andreas J Forstner, Hans J Grabe, Dominik Grotegerd, Raquel E Gur, Ruben C Gur, Catherine Harmer, David Hofmann, Odile A Van Den Heuvel, Neda Jahanshad, Tilo T J Kircher, Katharina Koch, Max A Laansma, Till Langhammer, Sang-Hyuk Lee, Elisabeth J Leehr, Eleonora Maggioni, Claire E Marino, Susanne Meinert, Hannah Meinert, Barbara Milrod, Benson Mwangi, Jared A Nielsen, Patricia Ohrmann, Spiro P Pantazatos, Martin P Paulus, Brenda W J H Penninx, Sara Poletti, Andrea Reinecke, Isabelle C Ridderbusch, Pavel Rjabtsenkov, Philipp G Sämann, Theodore D Satterthwaite, Lianne Schmaal, Elisabeth Schrammen, Jair C Soares, Nili Solomonov, Murray B Stein, Benjamin Straube, Thomas Straube, Benjamin Suarez-Jimenez, Jordan W Smoller, Ardesheer Talati, Sophia I Thomopoulos, Carlos E Vazquez, Henry Völzke, Katharina Wittfeld, Mon-Ju Wu, Yunbo Yang, Giovana B Zunta Soares, Ulrike Lueken, Paul M Thompson, Daniel S Pine, Dan J Stein, Nic J A Van Der Wee, Dick J Veltman, Moji Aghajani

Faculty, Staff and Student Publications

Neuroanatomical findings on panic disorder (PD) are typically difficult to replicate, with inconsistent effects. These concerns prompted a paradigm shift towards large-scale collaborations, focused on harmonized data extraction and processing for robust examination of PD brain correlates. Hence, leveraging the largest-ever multi-site neuroimaging database on PD (Age: 10–66 years; global sites: 28), compiled by the ENIGMA-Anxiety Working Group, we report on cortical and subcortical differences in individuals with PD (N = 1146) versus healthy controls (HC: N = 3778). The analyses revealed lower thickness and smaller cortical surface area within fronto-temporo-parietal regions in PD (Cohen’s ds: −0.08–0.13), along with lower …

Vo: The Vaccine Ontology, Jie Zheng, Asiyah Yu Lin, Anthony Huffman, Anna Maria Masci, Rebecca Racz, Guanming Wu, Kallan Roan, Edison Ong, Sirarat Sarntivijai, Joy Hu, Eliyas Asfaw, Hayleigh Kahn, Xingxian Li, Xumeng Zhang, Joshua Monickaraj, Nilufer Kosar, Jianfu Li, Warren Manuel, Rashmie Abeysinghe, Hasin Rehana, Benu Bansal, Yuanyi Pan, Jinjing Guo, Virginia He, Justin Song, Andrey I Seleznev, Katelyn Hur, Anna He, Alexander Davydov, Qi Yang, Anna Ostropolets, Randi Vita, Bjoern Peters, Alan Ruttenberg, Alexander D Diehl, Charles Tapley Hoyt, Paola Roncaglia, Rachael P Huntley, Richard H Scheuermann, Melanie Courtot, Thomas Todd, Samantha Sayers, Fang Chen, Xinna Li, Feng-Yu Yeh, Zuoshuang Xiang, Arzucan Ozgur, Patricia L Whetzel, Mark A Musen, Christopher J Mungall, Wolfgang W Leitner, Licong Cui, Lesley A Colby, Harry L T Mobley, Brian D Athey, Gilbert S Omenn, Lindsay G Cowell, Cui Tao, Junguk Hur, Barry Smith, Yongqun He

Faculty, Staff and Student Publications

Vaccines are widely used in both research and clinical settings. To facilitate FAIR data practices, we urgently need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO ontologically models vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as …

Admixture-Informed Polygenic Risk Reporting Using The Eprs Framework, Yu-Jyun Huang, Nuzulul Kurniansyah, Matthew O Goodman, Brian W Spitzer, Jiongming Wang, Adrienne Stilp, Cecelia Laurie, Paul S De Vries, Han Chen, Yuan-I Min, Mario Sims, Gina M Peloso, Xiuqing Guo, Joshua C Bis, Jennifer A Brody, Laura M Raffield, Jennifer A Smith, Wei Zhao, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Robert Kaplan, Nora Franceschini, Daniel Levy, Alanna C Morrison, Eric Boerwinkle, Nicholas L Smith, Charles Kooperberg, Bruce M Psaty, Sebastian Zöllner, Tamar Sofer

Faculty, Staff and Student Publications

Polygenic risk score values vary with genetic ancestry due to differences in population-specific allele frequencies and linkage disequilibrium patterns. We present a framework to calibrate polygenic risk scores based on ancestral makeup. We propose the "expected polygenic risk score" or ePRS, defined as the expected value of a polygenic risk score based on one's global or local admixture patterns. We further define the "residual polygenic risk score" or rPRS as measuring the deviation of the polygenic risk score from the ePRS. The ePRS reflects the baseline ancestry-driven component of genetic risk, whereas the rPRS isolates an ancestry-agnostic measure of genetic …

Hyperdynamic Microtubule-Based Structural Changes In Monocyte-Derived-Neuronal-Like Cells From Patients With Schizophrenia, Alfredo Bellon, Alonso Cortez-Resendiz, Lauren N Forrest, Omar Elmarasi, Janani Iyer, Anjali Iyer, Chachrit Khunsriraksakul, Dajiang Liu, L Elliot Hong, Therese M Jay, Marie-Odile Krebs, Anne Hosmalin

Faculty, Staff and Student Publications

A consistent postmortem finding in schizophrenia (SCZ) is reduction in dendrites' size. However, neurons with larger dendritic trees have also been encountered. In vitro experiments with neurons and neuronal-like cells coming directly from patients with SCZ showed similar results, evidencing at times more extensions and at others less arborizations. The process of extending and retracting neuronal outgrowths depends on microtubules polymerization and depolymerization. The possibility that microtubule polymerization/depolymerization is related to defects in the neuronal structure comes from several microtubular anomalies reported in SCZ such as its abnormal distribution in the cytoplasm, irregular shape of microtubules and even absence of …

The Right Time For A Synapse To Change: Windows And Mechanisms Of Multiday Training Trials, Rong-Yu Liu, Yili Zhang, Roberta Calvo, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Although learning over multiple days is more effective than a single day of training, the underlying cellular mechanisms of repeated training trials remain poorly understood. With a combination of empirical and computational approaches, we determined a critical time window for a second stimulus block of a multiday training protocol to augment long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse and long-term enhancement of neuronal excitability (LTEE), two cellular correlates of learning and memory. A second stimulus block delivered 24 h after the first block significantly enhanced LTF and LTEE, but was without effect at 18 or 32 h. This …

Rosai-Dorfman Disease In A Rare Cardiac Presentation: Left Ventricular Mass Causing Ventricular Tachycardia, Motaz Al Yafi, Swetha Pasala, Valentina Robila, Cory Trankle, Bharadhwaj Kolipakkam, Patricia Nicolato

Faculty, Staff and Student Publications

Background: Rosai-Dorfman disease (RDD) is a rare, benign histiocytic disorder that most often presents with nodal involvement. Cardiac involvement is exceedingly uncommon and poses significant diagnostic and therapeutic challenges.

Case summary: A 51-year-old woman presented with shortness of breath and palpitations and was found to have monomorphic ventricular tachycardia. Imaging revealed a left ventricular mass, and biopsy confirmed RDD. The lesion was surgically excised with cryoablation and CorMatrix reinforcement. The patient recovered uneventfully and remains disease free 25 months postoperatively.

Discussion: RDD with cardiac involvement has been reported in only approximately 25 cases, with very few affecting the left ventricle. …

Cross-Sectional Associations Of Metabolically Healthy Obesity, Lifestyle Factors, And Steatotic Liver Disease In Adults From The Fels Longitudinal Study, Ariana L Garza, Audrey C Choh, John Blangero, Cici X Bauer, Stefan A Czerwinski, Miryoung Lee

Faculty, Staff and Student Publications

Objective: To examine the associations of metabolic health and obesity phenotypes with liver fat accumulation and hepatic steatosis in adults.

Methods: We analyzed 676 non-Hispanic white adults (18-95 years; 55.8% female) from the Fels Longitudinal Study using a cross-sectional design. Participants were classified into metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO) phenotypes. Metabolically unhealthy status was defined as the presence of ≥1 metabolic dysfunction, consistent with prior epidemiological definitions; secondary analyses using ≥2 were also performed. Obesity was defined using DXA-derived body fat percentage. Liver fat (%) was …

Serum Metabolites Associated With Depression And Anxiety In The Hispanic Community Health Study/Study Of Latinos, Xinye Qiu, Yu Zhang, Yogesh Purushotham, Qibin Qi, Bing Yu, Jan Bressler, Krista M Perreira, Humberto Parada, Martha L Daviglus, Alejandra Cid Vega, Carmen R Isasi, Linda C Gallo, Tamar Sofer

Faculty, Staff and Student Publications

Omics signatures for psychiatric conditions have been under-investigated. In this study, we used data from a representative observational cohort study of Hispanic/Latino adults to identify serum metabolites associated with symptoms of depression or anxiety and to develop and assess metabolite risk scores (MRSs) of these phenotypes. We conducted a metabolome-wide association study of 768 metabolites with depression and anxiety symptoms, using two separate assay batches measured from baseline samples collected between June 2008 and July 2011 for discovery (batch 1: n = 4002 adults) and replication (batch 2: n = 2178 adults). We estimated the associations via survey-based generalized linear …

Risk Of Alzheimer Dementia After High-Dose Vs Standard-Dose Influenza Vaccination, Avram Samuel Bukhbinder, Yaobin Ling, Lauren Jhin, Elizabeth He, Kristofer Harris, Mya Rodriguez, Jenna Thomas, Gabriela Cruz, Kamal Phelps, Yejin Kim, Luyao Chen, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

Background and objectives: Previous studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.

Methods: This retrospective cohort study analyzed data spanning 2014-2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic …

Vestibular Schwannoma Microsurgery In The Era Of Multimodal Treatment: Advances In Technique And Patient Selection, Ibrahem Albalkhi, Basel Musmar, Nimer Adeeb, Hussam Abou-Al-Shaar, Jacques J Morcos

Faculty, Staff and Student Publications

Background: The management of vestibular schwannoma (VS) has traditionally prioritized gross total resection to achieve high tumor control, often at the cost of cranial nerve injuries and quality of life impairment. However, advances in surgical approaches and intraoperative technologies, coupled with active surveillance and/or adjuvant treatment, have shifted the management paradigm towards prioritizing patient-centered outcomes, which are as critical as oncological control.

Content: The authors reviewed the technical advances driving this paradigm shift, including endoscopic assistance in the different microsurgical approaches (retrosigmoid, translabyrinthine, and middle cranial fossa approaches) of VS resection and advanced neuromonitoring (facial nerve electromyography and cochlear/auditory evoked …

Breathing-Controlled Electrical Stimulation (Breestim) Selectively Modulates Affective And Cognitive Components Of Pain-An Eeg Study, Ahmad Z Rao, Michael Houston, Hao Meng, Shengai Li, Yingchun Zhang, Sheng Li

Faculty, Staff and Student Publications

Breathing-controlled electrical stimulation (BreEStim) is an innovative neuromodulation intervention that synchronizes deep voluntary breathing with peripheral electrical stimulation. Prior studies have shown its analgesic effects in healthy adults and spinal cord injury patients with neuropathic pain. The present study used EEG to examine BreEStim's neural effects on sensory, affective, and cognitive components of pain. Fourteen healthy participants (7 M, 7 F) completed 30 min of BreEStim and conventional electrical stimulation (EStim) interventions in a randomized, crossover within-subject design. Electrical pain thresholds (EPT) and EEG were recorded pre- and post-intervention. Event-related potentials (ERPs) at pre-EPT-level stimuli before and immediately after each …

Modeling Early Human Heart Development Using An Ipsc-Based 3d Bioprinted Model Of Embryonic Heart Tube, Linqi Jin, Christian Park, Sunder Neelakantan, Shweta Karnik, Arnab Dey, Sarah Fineman, Roshni Nandwani, Carmen J Gil, Boeun Hwang, Melissa A Cadena, Vani Sridhar, Jing Wang, Yuxiao Wu, Connor J Evans, Lan Li, Sarah Rezapourdamanab, Mehdi Salar Amoli, Martin L Tomov, Ryan K Roeder, Reza Avazmohammadi, Lakshmi Prasad Dasi, Hanjoong Jo, Eric Weeks, Holly D Bauser-Heaton, Sean M Wu, Vahid Serpooshan

Faculty, Staff and Student Publications

Human heart development depends on tightly coordinated genetic programs and biomechanical cues, yet the underlying cell-microenvironment interactions remain poorly understood because the developing heart is difficult to study in utero and accurate experimental models are lacking. Recent advances in stem cell biology and three-dimensional (3D) bioprinting now allow the construction of human tissue analogues with defined structure and function. Here we show a perfusable 3D bioprinted model of the human embryonic heart tube composed of layered myocardium, cardiac jelly, and endocardium. Human induced pluripotent stem cell-derived cardiomyocytes and endothelial cells are cultured under controlled flow conditions, producing constructs with high …

Engineering Function In Lung Biology: Integrating Imaging, Regenerative Constructs, And Functional Biodesign, Rene A Girard, Jamie Tran, Yuqing Cai, Mary C Farach-Carson, Hadi T Nia, Allison M Greaney, Laura E Niklason, Killian Hurley, Elvin Blanco, Sinem Koc-Günel, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The lung is a uniquely demanding target for regeneration because function depends on the coordinated integration of cellular diversity, three-dimensional architecture, cyclic mechanical forces, vascular perfusion, immune surveillance, and extracellular matrix remodeling. While single-cell and spatial profiling, lineage tracing, and iPSC-derived models have transformed our understanding of lung cell states and developmental potential, these descriptive approaches have also highlighted a central bottleneck: the field still lacks broadly adopted platforms to test whether engineered tissues and regenerative interventions restore function under physiologic load. In this review, we focus on emerging technologies that enable functional biodesign in lung biology by coupling engineered …

Latent Class Patterns Of Medication Attitudes And Their Correlates Among Older Adults In The United States, Jiaming Liang, Min Ji Kwak, Mona Shirvani, Alexander Testa, Rafael Samper-Ternent, Zhigang Xie, Jack Tsai

Faculty, Staff and Student Publications

No abstract provided.

Development Of A Multiplex Assay For Early Detection Of Pancreatic Cancer In High-Risk Groups, Sheng Pan, Ramesh Karki, Lisa A Lai, Chad J Creighton, Teresa A Brentnall, Randall E Brand, Ru Chen

Faculty, Staff and Student Publications

No abstract provided.

Perceived Inadequate Neighborhood Food Shopping And Cardiovascular Disease Risk: The Multi-Ethnic Study Of Atherosclerosis, Amier Haidar, Ghadi Ghanem, Rishi Rikhi, Karol E Watson, Shreela V Sharma, Michael D Shapiro

Faculty, Staff and Student Publications

Background: Individuals with access to healthy food have healthier diets, improved cardiometabolic risk profiles, and decreased cardiovascular disease (CVD). However, previous studies have focused on the neighborhood food environment as distance to and density of food retailers. Our study examines the association between an individual's perceived adequacy of neighborhood food shopping and incident CVD.

Methods: We analyzed data from 6814 participants in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals aged 45 to 84 who were enrolled in the study between 2000 and 2002 and followed longitudinally. Cox proportional hazards models estimated hazard ratios (HRs) for …

There Is Strength In Numbers: The Case For Another Model Of Cardiometabolic Hfpef, Sadia Ashraf, Hunter A Hidalgo, Romain Harmancey

Faculty, Staff and Student Publications

No abstract provided.

Changes In Internet Search Term Popularity In Elder Mistreatment (2018-2023): Infodemiology Study Of Google Trends Data, Nicholas Sevey, Melvin Livingston, Kristin Lees-Haggerty, Olanike Ojelabi, Randi Campetti, Jason Burnett, Carolyn E Z Pickering, David Hancock, Rachit Sabharwal, Michael Brad Cannell

Faculty, Staff and Student Publications

Background: Elder mistreatment (EM) is a significant public health problem that is frequently underdetected and underreported. Insufficient public recognition and engagement have been hypothesized as one contributor to this underreporting; however, few data sources exist to quantify public awareness or engagement with EM at the population level.

Objective: This study examined relative internet search interest in EM compared with other forms of abuse (child abuse and domestic violence) in the United States using Google Trends data.

Methods: We analyzed Google Trends data to compare the Relative Search Index (RSI) for the terms "elder abuse," "child abuse," and "domestic violence" in …

Diagnostic Potential For Igm Antibody Detection By The Dpp Syphilis Tnt Assay In Neonates At Risk For Congenital Syphilis, Irene A Stafford, Lierni Ugartemendia Ugalde, Laura M Goetzl, Analuisa Mosqueda, Sabrina Dacosta, Dhammika Gunasekera, Mark Rivieccio, Javan Esfandiari, Konstantin P Lyashchenko

Faculty, Staff and Student Publications

Neonatal IgM antibodies reflect an in utero immune response to Treponema pallidum and may offer added diagnostic value. This study evaluated the test performance of treponemal IgM levels measured by the research-use-only (RUO) Dual Path Platform (DPP) Syphilis TnT point-of-care (POC) assay for congenital syphilis (CS) risk stratification. Conducted from May 2023 to May 2025, this study tested neonatal serum samples from infants born to mothers with syphilis using the DPP Syphilis TnT RUO POC assay, which reports treponemal and nontreponemal IgM levels as relative light units (RLU). Neonates were classified as confirmed proven or highly probable CS, possible …

Genome-Wide Association Study Of Copy Number Variations In Parkinson’S Disease, Zied Landoulsi, Ashwin Ashok Kumar Sreelatha, Nicole Kuznetsov, Claudia Schulte, Dheeraj Reddy Bobbili, Ludovica Montanucci, Costin Leu, Lisa-Marie Niestroj, Emadeldin Hassanin, Cloé Domenighetti, Pierre-Emmanuel Sugier, Milena Radivojkov-Blagojevic, Peter Lichtner, Berta Portugal, Connor Edsall, Jens Krüger, Dena G Hernandez, Cornelis Blauwendraat, George D Mellick, Alexander Zimprich, Walter Pirker, Manuela Tan, Ekaterina Rogaeva, Anthony Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B Deutschländer, Georges M Hadjigeorgiou, Efthimos Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Lena F Burbulla, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Lukas Pavelka, Pierre Kolber, Bart Pc Van De Warrenburg, Bastiaan R Bloem, Andrew B Singleton, Dan Vitale, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Karin Wirdefeldt, Nancy L Pedersen, Caroline Ran, Andrea C Belin, Andreas Puschmann, Carl E Clarke, Karen E Morrison, Dimitri Krainc, Matt J Farrer, Dennis Lal, Alexis Elbaz, Thomas Gasser, Rejko Krüger, Manu Sharma, Patrick May

Faculty, Staff and Student Publications

We investigated the role of copy number variations (CNVs) in Parkinson's disease (PD) using genotyping data from 10,815 patients (2731 early-onset PD, EOPD) and 8901 controls from the COURAGE-PD consortium. CNVs were analyzed using a sliding window genome-wide association and burden approach. No genome-wide significant CNVs were detected in the overall cohort, but a robust deletion spanning exons 2-6 of PRKN was identified in EOPD cases, validated by MLPA, and replicated in the GP2 dataset (23,089 cases, 18,824 controls). CNV burden was significantly enriched in PD-related genes, primarily driven by PRKN, with the strongest effect observed in EOPD. PRKN CNV …

Predicting Clinically Significant Prostate Cancer With Or Without Digital Rectal Exam And Mri Data Using Claritydx Prostate Models, Robert J Paproski, Adam Kinnaird, M Eric Hyndman, Adrian Fairey, Leonard Marks, Christian P Pavlovich, Sean A Fletcher, Roman Zachoval, Vanda Adamcova, Jiri Stejskal, Armen Aprikian, Christopher J D Wallis, Desmond Pink, Catalina Vasquez, Perrin H Beatty, John D Lewis

Faculty, Staff and Student Publications

This prognostic study created optimized ensembles of calibrated random forest models to predict clinically significant prostate cancer (csPCa, grade group ≥2 PCa) using total prostate-specific antigen (PSA), free PSA, negative biopsy status, and age, with or without DRE and MRI data. Observational data were aggregated from cohorts in six organizations in Canada, the USA, and Czechia. Prostate biopsies were performed between 2009 and 2024. Risk models (ClarityDX Prostate + DRE, ClarityDX Prostate + MRI, and ClarityDX Prostate + MRI + DRE) were derived (training cohorts n = 1626 to 2191) and validated (validation cohorts n = 378 to 1318) from …

Neuropathological Hallmarks During The Chronic Phase Of Ischemic Stroke In Mice And Humans, Romeesa Khan, Gary Guzman, Trang Do, Patrick Devlin, John Ahn, Chunfeng Tan, Venugopal Reddy Venna, Sean P Marrelli, Haniyeh Koochak, Claudia M Di Gesù, Anthony Flores, Louise D Mccullough, Rodney M Ritzel

Faculty, Staff and Student Publications

Background: Advances in acute stroke care, including endovascular thrombectomy and improved neurocritical management, have increased survival after ischemic stroke. However, stroke remains a leading cause of long-term disability, with many survivors experiencing persistent neurological and cognitive impairments. The chronic neurological consequences of stroke, particularly its potential to accelerate brain aging, remain poorly understood.

Methods: We examined chronic neurobehavioral changes at 2 and 6 months after middle cerebral artery occlusion in male C57Bl/6 mice. Behavioral assessments included the open field test (OFT), novel object recognition test (NORT), fear conditioning (FC), nesting activity, and tail suspension testing. Transcriptomic profiling was performed using …

Decoding Immunotherapy Response Through Computational Modeling, Bingrui Li, Ruihan Luo, Kexin Huang, Jiajia Liu, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Immunotherapy has seen success in treating patients with cancer, but variable responses underscore the need for effective patient stratification and therapy planning. Computational tools integrating multi-omics, imaging and machine learning have advanced, yet reliable personalized predictions remain challenging. This review analyzes the field through four converging paradigms: classical machine learning, deep learning, graph and network modeling, and mechanistic systems biology. We examine the evolution from correlational features to representation learning, relational inference, and causal simulation of tumor-immune dynamics, highlighting the shift towards multi-modal fusion and interpretable, clinically deployable models. By providing an integrated review of these computational tools, we hope …

Ftsz Forms Biomolecular Condensates In A Polar-Growing Alphaproteobacterium, Todd A Cameron, Miguel Ángel Robles-Ramos, Lorenzo Suigo, Silvia Zorrilla, William Margolin

Faculty, Staff and Student Publications

The conserved tubulin homolog FtsZ assembles into GTP-dependent protofilaments that organize the bacterial cell division machinery. Purified Escherichia coli FtsZ (FtsZEc) can form biomolecular condensates in the absence of GTP in macromolecular crowding conditions, but FtsZ condensates have not yet been confirmed in vivo. FtsZ from the Alphaproteobacterium Agrobacterium tumefaciens (FtsZAt) localizes to distinct polar foci during growth and contains an intrinsically disordered region much longer than FtsZEc, suggesting a greater tendency to form condensates. Here, we show that purified FtsZAt readily formed dynamic condensates in vitro under molecular crowding conditions, and the addition of GTP induced the formation …

Single-Nucleus Brain Transcriptomics Reveals Microglia Dysfunction In Multiple System Atrophy, Rasmus Rydbirk, Frederik Nørby Friis Sørensen, Jonas Folke, Henriette Haukedal, Andrea Asenjo Martinez, Irene Lisa Vargas, Simone Mcgarry, Oline Chantell Hollmann, Camila Gherardelli, Sofia Sepulveda, Adam T Szafran, Michael A Mancini, Sanne Simone Kaalund, Tomasz Brudek, Lisette Salvesen, Sara Bech, Justyna Okarmus, Peter Kharchenko, Morten Meyer, Claudio Soto, Kristine Freude, Abhisek Mukherjee, Susana Aznar, Konstantin Khodosevich

Faculty, Staff and Student Publications

Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson's disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while oligodendroglia and neurons are comparable. PD brains show abundant microglia expressing MHC class II HLA haplotypes, indicative of a proinflammatory state, alongside more homeostatic astrocytes. In contrast, MSA lack activated microglia but has more …

Sex-Specific Autosomal Susceptibility Loci In Systemic Sclerosis: A Genome-Wide Association Study, Inmaculada Rodriguez-Martin, Martin Kerick, Carlos Rangel-Peláez, Carlos Rosa-Baez, Gonzalo Borrego-Yaniz, Lourdes Ortiz-Fernández, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José Luis Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcón-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Background: Systemic sclerosis is an immune-mediated inflammatory disease with marked sex differences in prevalence and severity. Although genome-wide association studies (GWAS) have advanced the understanding of systemic sclerosis genetics, sex-aware approaches remain scarce. We aimed to address this gap by examining autosomal sex-specific genetic factors in systemic sclerosis.

Methods: Based on a chromosomal definition of sex, we conducted a sex-stratified autosomal meta-analysis of GWAS in systemic sclerosis. We retrieved patient-level and control data from a previous GWAS for systemic sclerosis and newly recruited participants from an international multicentre collaboration (data cutoff June 1, 2024). Adult patients (aged ≥18 years) were …

Engineering Of Genetically Encoded Programmable Calcium Channel Inhibitory Binders, Xiaoxuan Liu, Sher Ali, Tien-Hung Lan, Decheng Wang, Brendan Mckee, Tatsuki Nonomura, Siyao Liu, Feng Zhao, Michael X Zhu, Yun Huang, Qing Deng, Guolin Ma, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated Ca2+ release-activated Ca2+ (CRAC) channels, composed of STIM and ORAI, are essential for immune and developmental processes, and their dysregulation underlies channelopathies such as Stormorken syndrome. Here, we report the engineering of genetically encoded CRAC channel inhibitory binders (CRABs) derived from the ORAI C-terminal tail. Guided by deep mutational scanning, we optimize a membrane-anchored CRAB variant that potently inhibits Ca2+ influx and NFAT signaling, and rescues thrombocytopenia-like phenotypes in a zebrafish model of Stormorken syndrome. To enable tunable inhibition, we further design oligomeric, optogenetic (Opto-CRAB), and chemogenetic (Chemo-CRAB) variants, providing graded and real-time control of CRAC activity. Chemo-CRAB further …