Digital Commons Network^™

Comprehensive Prediction Analysis Of Novel Noncoding Regulatory Variants Identified In The Microrna Binding Regions In Complement System Genes, Anthony Shadid, Haydn E Rich, Kathryn D Hok, Marie-Francoise Doursout, Marcos I Restrepo, Nirmal K Banda, Lavanya Gunamalai, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

The complement system is a central component of innate immunity that coordinates host defense, immune surveillance, and inflammatory responses through tightly regulated proteolytic cascades. Genetic variation within complement genes contributes substantially to interindividual differences in complement activity and disease susceptibility. While coding variants directly alter complement protein structure and function, the microRNA (miRNA)-mediated control and post-transcriptional regulation is not fully understood in shaping complement gene expression across immune and inflammatory mechanisms. Complement pathway genes exhibit extensive and heterogeneous 3'-untranslated regions (3'UTRs), which serve as primary platforms for miRNA binding and RNA-binding protein interactions. Both common and rare single-nucleotide polymorphisms within …

Chemotherapeutic Induction Of Cytosolic Single-Stranded Dna Accumulation Sensitizes Triple-Negative Breast Cancer To Immunotherapy, Yong Du, Li Yang, Hui Dai, Jianli Zhou, Zhicheng Zhou, Ruoxi Yuan, Rui Ye, Anh Thai Quynh Nguyen, Kishor Bhatia, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Background: Despite the widespread adoption of chemoimmunotherapy in triple-negative breast cancer (TNBC), the mechanisms by which cytotoxic chemotherapy engages antitumor immunity remain poorly defined. Identifying tumor-intrinsic immunogenic programs that predict and enhance responsiveness to immune checkpoint blockade (ICB) is therefore of critical clinical importance.

Methods: Transcriptomic signatures of TREX1 deficiency were generated from CRISPR-engineered TNBC models and applied to multiple independent TNBC cohorts treated with chemoimmunotherapy. Cytosolic single-stranded DNA (ssDNA) accumulation was quantified using a flow cytometry-based assay to functionally screen chemotherapeutic agents. Immune activation and therapeutic efficacy were evaluated using in vitro assays, syngeneic mouse tumor models, flow cytometry, …

Letter To The Editor: Hemodynamic Role In Hepatic Encephalopathy Pathogenesis Following Transjugular Intrahepatic Portosystemic Shunt Placement, John Halphen, Yash S Dayal, Cameron Laurie, Mohadese Ahmadzade, David Wynne, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Hepatic encephalopathy (HE) is a common complication following transjugular intrahepatic portosystemic shunt (TIPS) placement and is thought to result from reduced hepatic detoxification of neurotoxins. However, Zhuang et al in the World Journal of Radiology demonstrate that this understanding may be incomplete through exploration of the pathophysiology from a hemodynamic perspective. They found significant changes in cerebral blood flow (CBF) and spontaneous brain activity following TIPS. Initially, CBF increased in specific areas within the first month, followed by a return to baseline at three months. These CBF changes coincided with increased spontaneous brain activity that persisted in some areas, suggesting …

Enhancing Research Communication With Visual Tools, Sonya Fogg

Library Class: Lunch & Learn

Understand the role of visual communication in medical research. Distinguish between data visualizations, infographics, and visual abstracts. Identify best practices and some resources and tools for creating effective visuals.

Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker

Faculty, Staff and Students Publications

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. …

Evaluating The Reproducibility And Verifiability Of Nutrition Research: A Case Study Of Studies Assessing The Relationship Between Potatoes And Colorectal Cancer, Yasaman Jamshidi-Naeini, Colby J Vorland, Pranav Kapoor, Bailey Ortyl, Jocelyn Mineo, Luke Still, Korlu Sorsor, Shelby Rodney, Xander Tooze, Brent Flickinger, Beate Henschel, Stephanie L Dickinson, David B Allison

Faculty, Staff and Students Publications

The credibility of nutritional research is dependent on the rigor with which studies are conducted and the ability for independent assessment to be performed. Despite the importance of these, more work is needed in the field of nutrition to buttress the trustworthiness of nutrition research. To develop and apply a process for evaluating the rigor, reproducibility, and verifiability of nutritional research, using the relationship between potato consumption and Colorectal Cancer (CRC) as a case study. We updated existing systematic reviews to include studies on potatoes and CRC, assessing their design, execution, and reporting quality. We attempted to reproduce and verify …

Self-Perceived Burden And Mental Health Outcomes In Adults With Osteogenesis Imperfecta, Emily R Strouphauer, Camille Villar, Ryan J Mccarty, Danqi Li, Gianna M Colombo, Brendan Lee, Chaya N Murali, Dianne Nguyen, Sarah Sadek, Marie-Eve Robinson, Jocelyn Gomez, Michelle Fynan, V Reid Sutton, Andrew D Wiese, Eric A Storch

Faculty, Staff and Students Publications

Osteogenesis Imperfecta (OI) is a rare disorder causing bone fragility, pain, and functional impairment that causes substantial psychosocial burden. This study examined how self-perceived burden (SPB), or distress from feelings of dependence on caregivers, relates to depression, anxiety, and suicidality in adults with OI. A total of 208 adults (M age = 42.9, predominately White and female) with OI were recruited to complete a cross-sectional survey assessing SPB, psychological symptoms, health, and sociodemographics. Results indicated that SPB was significantly higher among younger individuals, those not living with a partner, those living with adult family members, lower-income groups, and individuals …

Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas

Faculty, Staff and Students Publications

Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of Uba3, which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle–stage Uba3 conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated …

Qeith: Quantifies Tumor Ecosystem Heterogeneity To Predict Cancer Progression And Treatment Benefit, Qiqi Liu, Jiangti Luo, Jiawei Wang, Bangqi Zhao, Xiaosheng Wang, Linjun You

Faculty, Staff and Student Publications

Intratumor heterogeneity (ITH) is a fundamental driver of therapeutic failure and disease progression. However, the complexity of the tumor ecosystem is a critical yet underexplored aspect, making its precise quantification essential for fully deciphering ITH and its clinical implications. To address this, we developed Quantifying Ecosystem Intratumor Heterogeneity (QeITH), a computational framework that applies Shannon entropy to quantify ecosystem heterogeneity by measuring the diversity and distributional entropy of cellular compositions and functional states across single-cell, bulk, and spatial transcriptomics. At the single-cell resolution, QeITH identifies elevated ITH as intrinsic markers of malignant transformation, yet enhanced sensitivity to therapy. Pan-cancer bulk …

Oral Cancer Numerical Index (Ocni): Development And Validation Of A Cytology-Based Risk Assessment For Oral Lesions, Michael P Mcrae, Nadarajah Vigneswaran, Alexander Ross Kerr, Spencer W Redding, Martin H Thornhill, Craig Murdoch, Paul M Speight, Rachelle Wolk, Kritika S Rajsri, Pooja Gaikwad, Nancy Ruel, Nicolaos J Christodoulides, John T Mcdevitt

Faculty, Staff and Student Publications

Background/Objectives: Oral potentially malignant disorders (OPMDs) require accurate risk stratification to identify patients at the highest risk for severe oral epithelial dysplasia (OED) or oral squamous cell carcinoma (OSCC). We developed and internally validated the oral cancer numerical index (OCNI), a quantitative risk score derived from clinical features and deep learning-based brush cytology measurements.

Methods: This retrospective model development and internal validation study was conducted using data from the multicenter Grand Opportunity study. Prospectively recruited subjects with OPMD with complete data were divided at the subject level into a training set (n = 384) and a holdout test set …

Placenta Accreta Spectrum Risk In Endometriosis: A Retrospective Cohort Study With Art Subanalysis, Madeline West, Amir Alsaidi, Michael A Belfort, Hendrik A Lombaard, Yamely H Mendez, Christina C Reed, Amir A Shamshirsaz, Jessian L Munoz

Faculty, Staff and Students Publications

No abstract provided.

Macropinocytosis Inhibition Attenuates Profibrotic Responses In Lung Fibroblasts And Pulmonary Fibrosis Models, Ivan O Rosas, Aaron K Mcdowell-Sanchez, Santiago Sanchez, Juan D Cala-Garcia, Alan R Waich Cohen, Elisa Ruiz-Echartea, Scott A Ochsner, Daniel C Kraushaar, Lindsay J Celada, Dandan Sun, Francesca Polverino, Cristian Coarfa, Neil J Mckenna, Konstantin Tsoyi

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stress conditions. Here, we studied the role of macropinocytosis in experimental pulmonary fibrosis models. We found that macropinocytosis is increased in human lung fibroblasts (HLFs) derived from patients with IPF. The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs and reduced pulmonary fibrosis in bleomycin-injured (Bleo-injured) mice. EIPA exerted its antifibrotic effects by regulating amino acid uptake, mammalian target of rapamycin complex 1 …

Ultrasound-Enabled Refreshable Electrochemical Sensors For Cardiac Biomarker Monitoring, Mayank Garg, Heng Guo, Myeong Namkoong, Elizabeth Zhanov, Connor Malone, Md Saifur Rahman, Ayse Akcan-Arikan, Limei Tian

Faculty, Staff and Students Publications

Cardiac troponin I (cTnI) is the gold-standard biomarker for acute myocardial infarction, yet current laboratory-based high-sensitivity assays require centralized infrastructure, trained personnel, and serial testing, limiting their suitability for real-time or continuous monitoring in resource-limited settings. Point-of-care electrochemical sensors have shown promise for rapid cTnI detection, but their reliance on antibodies as biorecognition elements and redox mediator solutions, and single-use operation restricts practical translation. Here, we report an ultrasound-enabled refreshable electrochemical biosensor for sensitive, stable, and repeatable cTnI monitoring. The device employs a cTnI-specific peptide as the biorecognition element, providing enhanced stability during storage, transport, and operation. Label-free electrochemical impedance …

Single-Nucleus Profiling Reveals A Core Disease Signature And Cell Type-Specific Vulnerabilities In Early Rett Syndrome, Yan Li, Ashley G Anderson, Guantong Qi, Sih-Rong Wu, Jean-Pierre Revelli, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is an X-linked neurological disorder caused by MECP2 mutations, creating distinct cellular environments in females (mosaic) versus males (nonmosaic). Despite female patients representing most cases, how mosaicism contributes molecularly to RTT pathogenesis, particularly in presymptomatic stages, remains poorly understood. To address this question, we profiled hippocampal transcriptomes of young female and male RTT mice using bulk and single-nucleus RNA sequencing. We identified a core disease signature of consistently dysregulated genes only in MeCP2− cells across RTT models. Moreover, we uncovered non–cell autonomous effects exclusively in female MeCP2+ excitatory neurons, suggesting that these circuits are more vulnerable early …

Artificial Intelligence In Biomedical Scientific Publishing, Tomasz J Guzik, Victor Aboyans, Stefan Agewall, Steven Bailey, Adrian Baranchuk, Magnus Bäck, Michael Böhm, Robert O Bonow, George W Booz, Giuseppe Boriani, Biykem Bozkurt, Nico Bruining, Davide Capodanno, Çetin Erol, Péter Ferdinandy, Alessia Gimelli, Gerd Heusch, Thomas Kahan, Chim Choy Lang, Gerald Maurer, Robert J Mentz, Marco Metra, Philip Moons, Daniel Piskorz, Massimo Piepoli, Piotr Ponikowski, Alexandra Popma, Bianca Rocca, Juan Sanchis Fores, Philipp Sommer, Rhian M Touyz, Zoltan Ungvari, Pascal Vranckx, Joseph A Hill, Thomas F Lüscher, Filippo Crea

Faculty, Staff and Students Publications

Artificial intelligence is now embedded across the scientific research and publishing ecosystem, influencing discovery, analysis, knowledge translation, authorship, peer review, and editorial workflows. In cardiovascular and biomedical sciences, these developments offer substantial opportunities to accelerate knowledge generation, integrate complex datasets, and improve efficiency and consistency. At the same time, they introduce new risks related to bias, transparency, data integrity, and authorship responsibility, potentially endangering trust in the scientific record. This commentary examines the evolving role of AI in biomedical publishing, with particular attention to generative models and machine learning tools. We review both benefits and limitations, highlight risks such as …

Targeted Next-Generation Sequencing Implementation In Eswatini Identifies Rifampicin And Bedaquiline Resistance Undetected By Routine Diagnostic Testing, Debrah Vambe, Alexander Kay, Mangaliso Ziyane, Mdigo Thunzini, Sein Sein Thi, Leonardo De Araujo, Viola Dreyer, Tanja Niemann, Busizwe Sibandze, Sijabu Masina, Andrea Maurizio Cabibbe, Jennifer Furin, Tafadzwa Mazuruse, Lindokuhle Dlamini, Thulani Jele, Bheki Mamba, Gugu Maphalala, Makhosazana Dlamini, Mbongeni Dube, Nomthandazo Lukhele, Daniela Maria Cirillo, Anna Mandalakas, Christoph Lange, Sphiwe Ngwenya, Christian Utpatel, Sindisiwe Dlamini, Stefan Niemann

Faculty, Staff and Students Publications

In Eswatini, multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains harbouring the rifampicin-resistance (RR) rpoB I491F mutation are missed by routine diagnostics, including GeneXpert MTB/RIF Ultra (Xpert Ultra), line probe assays (LPA), and mycobacterium growth indicator tube (MGIT) phenotypic drug susceptibility testing (pDST). To address this diagnostic gap, Eswatini introduced targeted next-generation sequencing (tNGS) in 2019. We analysed 234 patient samples enrolled from June 2021 to December 2024 with isoniazid and/or rifampicin resistance detected by routine diagnostics, or suspected treatment failure, and obtained detailed clinical and outcome data from 59 patients. tNGS detected RR in 159 strains, of which 101 (64%) carried …

Microaxial Flow Device-Associated Electromagnetic Interference During Left Atrial Electroanatomic Mapping: A Case Report, Amit Koduri, Ellen Condoure, Ramesh Hariharan

Journal of Shock and Hemodynamics

Microaxial flow devices (MFDs) provide hemodynamic support in patients with severe left ventricular systolic dysfunction but may introduce electromagnetic interference (EMI) during electroanatomic mapping, limiting the accuracy of magnetic-based localization systems. Although catheter ablation for atrial fibrillation in advanced heart failure is increasingly recognized as beneficial, limited data exist on mapping feasibility in patients supported by contemporary MFDs. Even less is known regarding left atrial flutter ablation in this setting.

We present a case illustrating the technical challenges and procedural feasibility of left atrial flutter ablation in a patient with advanced heart failure supported by an Impella 5.5 (Abiomed). Magnetic-based …

Whole-Genome Variant Detection In Long-Read Sequencing Data From Ultra-Low Input Patient Samples, Katherine Wang, Cera J Aex, Hayan Lee, Lucas Finot, Kevin Zhu, Julianna R Chang, Aaron M Horning, William J Rowell, Philip Li, Sarah B Kingan, Michael P Snyder, Graham Scott Erwin

Faculty, Staff and Students Publications

Long-read sequencing provides a more complete view of the genome than short-read sequencing, with improved detection of structural variants, tandem repeats, and small variants (single nucleotide variants and insertions and deletions) in difficult-to-map regions. One limitation of long-read sequencing has been high input DNA requirements, with several micrograms required per sample. Here, we evaluate two methods of amplification-based long-read, whole-genome sequencing: ultra-low input HiFi (ULI-HiFi) sequencing and droplet multiple displacement amplification (dMDA) sequencing. When benchmarked against the Genome in a Bottle reference set (NA24385), we observe high precision and recall of single nucleotide variants (SNVs) with ULI-HiFi compared to the …

In Vivo Orf Overexpression Screening Identifies Ccn4 As A Regulator Of Glioblastoma Growth Validated Across Multiple Models, Pushan Dasgupta

Faculty, Staff and Students Publications

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive "hits" from …

Auricular Point Acupressure Self-Management (Apa-Sm) Program For Chronic Musculoskeletal Pain Among Rural Populations: A Protocol For A Pragmatic, Randomized Controlled Trial, Jennifer Kawi, Jane Bolin, Hulin Wu, Jungkyung Min, Rupsikha Bora, Sarah Pace, Idara N Akpan, Alee Lockman, Tonychris Nnaka

Faculty, Staff and Student Publications

Introduction: Chronic musculoskeletal pain (CMP) is a leading cause of incurred personal healthcare costs and disability in the USA. It disproportionately affects rural populations, who are more likely to be uninsured, lack access to a regular healthcare provider and experience a higher prevalence of CMP. As a result of reduced access to non-pharmacological care, there is greater reliance on opioids. The Auricular Point Acupressure - Self-Management (APA-SM) program is a simple, needleless, evidence-based therapy that empowers individuals to self-manage their pain. Preliminary studies, including a recent UG3 pilot testing, demonstrated feasibility, safety and significant improvements in pain and function. Guided …

Development And Preliminary Validation Of Orca-Pd, An Online Rapid Cognitive Assessment For Parkinson Disease: Mixed Methods Study, Avigail Lithwick Algon, Sarah Brisman, Chi-Ying R Lin, William Saban

Faculty, Staff and Students Publications

Background: Traditional in-person neuropsychological tests for Parkinson disease (PD) lack accessibility, scalability, and PD specificity. Mobility impairments hinder access to in-person assessments, and long waiting times for expert evaluation limit scalability. Common tools for cognitive screening, such as the Montreal Cognitive Assessment, are generic and not specific to PD.

Objective: The goal of this study was to address these challenges by leveraging the internet. This study aimed to develop a sensitive tool to detect cognitive impairments in early- to mid-stage PD in an accessible and scalable manner.

Methods: We developed the Online Rapid Cognitive Assessment for Parkinson's Disease (ORCA-PD), a …

Otologic Manifestations Of Temporomandibular Disorders, Fatemeh Ebrahimi, Ali Akbar, Vivian Jin, Vivian F Kaul, Craig B Pearl

Faculty, Staff and Student Publications

Background/Objectives: Temporomandibular disorder (TMD) affects a third of the adult population and has been associated with otologic symptoms. These symptoms are frequently misattributed to primary otologic diseases, leading to delays in diagnosis and treatment. This review aims to summarize the reported prevalence, proposed pathophysiologic mechanisms, and management strategies of otologic manifestations in patients with TMD.

Methods: A literature review was conducted using the MeSH terms "temporomandibular joint disease" and "otologic symptoms." Five additional searches were performed using "temporomandibular disease/dysfunction" combined with each of the five most common otologic symptoms. Meta-analyses, randomized controlled trials, reviews, and systematic reviews were …

Behavioural Activation For The Prevention Of Poststroke Depression In Low-Income Older Stroke Survivors (Live Wel): Protocol For A Randomised Controlled Trial, Jennifer E S Beauchamp, Sean I Savitz, Anjail Sharrief, Belinda M Reininger, Ronald Acierno, Robert Suchting, Jason Burnett, Lauren Rosales, Jenan Ahmed Albaqali, Rinitha Rajan, Namkee G Choi

Faculty, Staff and Student Publications

Introduction: Poststroke depression (PSD) affects approximately 33% of stroke survivors and is associated with worse outcomes, poor quality of life (QOL) and mortality. Despite its prevalence and consequences, there is no consensus on the most effective strategy for PSD prevention. Behavioural activation (BA) is an effective intervention for depression across diverse populations and is considered safer, better tolerated and a longer-lasting alternative to antidepressant medications. This study aims to test the effectiveness of a remotely delivered BA intervention to prevent PSD (Tele-BA-S).

Methods and analysis: We will conduct a randomised effectiveness trial of 350 low-income adults (≥ 55 years) within …

Decoding Growth Hormone Actions On Human Growth Plate Stem Cells, Shion Orikasa, Noriaki Ono

Faculty, Staff and Student Publications

The epiphyseal growth plate is the key target of growth hormone (GH) therapy. Although growth plate stem cells are well defined in mice, their presence in humans was unclear. Using rare surgical specimens, the study by Chu et al. reveals conserved, GH-responsive stem cells in the human pubertal growth plate.

Recommendations For Disclosure Of Artificial Intelligence In Scientific Writing And Publishing: A Regional Anesthesia And Pain Medicine Modified Delphi Study, Michael R Fettiplace, Anuj Bhatia, Yian Chen, Steven L Orebaugh, Michael Gofeld, Rodney A Gabriel, Daniel I Sessler, Hannah Lonsdale, Brittani Bungart, Christopher P Cheng, Garrett W Burnett, Lichy Han, Matthew Wiles, Steve Coppens, Thomas Joseph, Kristin L Schreiber, Thomas Volk, Richard D Urman, Vesela P Kovacheva, Christopher L Wu, Edward R Mariano, Vivian H Y Ip

Faculty, Staff and Student Publications

Introduction: The use of artificial intelligence (AI) in the scientific process is advancing at a remarkable speed, thanks to continued innovations in large language models. While AI provides widespread benefits, including editing for fluency and clarity, it also has drawbacks, including fabricated content, perpetuation of bias, and lack of accountability. The editorial board of Regional Anesthesia & Pain Medicine (RAPM) therefore sought to develop best practices for AI usage and disclosure.

Methods: A steering committee from the American Society of Regional Anesthesia and Pain Medicine used a modified Delphi process to address definitions, disclosure requirements, authorship standards, and editorial oversight …

Monoclonal Antibodies Targeting Pcdh7 Inhibit Tumor Growth And Enhance Immune Responses In Kras-Mutant Non-Small Cell Lung Cancer, Nicole Novaresi, Poorva Ghosh, Shayna Thomas-Jardin, Hui Deng, Xuejun Fan, Zhiqiang Ku, Wei Xiong, Xiaorong Zhou, Jingfei Zhu, Huiyu Li, Mahesh S Padanad, Bethany Smith, Chul Ahn, John D Minna, Zhiqiang An, Ningyan Zhang, Kathryn A O'Donnell

The Brown Foundation: Institute of Molecular Medicine

We identified an important oncogenic role for protocadherin 7 (PCDH7), a cell surface protein frequently overexpressed in lung adenocarcinoma and associated with poor clinical outcome. Pcdh7 depletion reduces tumor burden and prolongs survival in KrasLSL-G12D; Tp53fl/fl mice. These findings nominate this cell surface protein as an actionable therapeutic target and highlight the therapeutic potential of PCDH7 inhibition for non–small cell lung cancer. We report the development and characterization of high-affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream mitogen-activated protein kinase (MAPK) pathway activation and suppress tumor growth in multiple mutant KRAS–driven models. A lead mAb (mAb7) sensitized tumors …

Targeted Reflex Rna Sequencing For Enhanced Variant Classification On Exome And Genome Sequencing Improves Patient Outcomes, Xiaonan Zhao, Robert Rigobello, Morgan Driver, Sydney Lau, Mei Ling Chong, Jason Chibuk, Hongzheng Dai, Wilson C W Wu, Christina Peroutka, Laura Famularo, Alexander Y Kim, Bailey Hummel, Sarah Dugan, Tinsley Douglas, Linyan Meng, Fan Xia, Christine M Eng

Faculty, Staff and Students Publications

RNA sequencing (RNA-seq) has been utilized to provide functional evidence regarding the impact of splicing variants. This study explores the utility of targeted reflex RNA-seq to inform classification of predicted splicing variants identified through clinical exome sequencing (ES) and genome sequencing (GS). A retrospective analysis was conducted on consecutive ES/GS cases completed at a single center in which targeted reflex RNA-seq was performed following identification of eligible variants. There were 131 cases (4.1%) that had at least one RNA-seq eligible variant reported, with eight of these cases having two unique eligible variants. Of the 139 eligible variants, 125 were classified …

Safety And Synergy Of Finerenone And Empagliflozin In Lowering Blood Pressure, Rajiv Agarwal, Ricardo Correa-Rotter, Sankar D Navaneethan, Hiddo J L Heerspink, Matthew R Weir, Janet B Mcgill, Amy K Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Charlie Scott, Li Li, Meike Brinker, Csaba P Kovesdy, Jennifer B Green, Johannes F E Mann

Faculty, Staff and Students Publications

Background: This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions.

Methods: Participants (n=800) were stratified by baseline SBP (< 130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction.

Results: At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) …

The Aggregated Latent Profile Index: Measuring Person Profile Differentiation Within A Bootstrap-Validated Latent Profile Space, Se-Kang Kim

Faculty, Staff and Students Publications

Multivariate assessment profiles contain two conceptually distinct sources of variation: overall level and profile shape. Existing approaches recover some aspects of this structure, but none jointly establishes the replicability of latent pattern dimensions and provides a principled, population-referenced summary of person profile differentiation independent of overall level. We introduce the Aggregated Latent Profile Index (ALPI), a variance-weighted Euclidean distance that quantifies the degree to which an individual’s profile departs from a flat population reference within a bootstrap-validated latent profile space. ALPI is derived from the Aggregated Latent Profile Space (ALPS), a framework that combines parallel analysis with bootstrap stability diagnostics …

Global Burden Of Drug-Resistant Tuberculosis In Children: A Systematic Analysis For The Global Burden Of Disease Study, Xuhui Liu, Peierdun Mijiti, Lu Xia, Sylvia M Lacourse, Wulan Talafuhan, Alexander W Kay, Yang Yang, Huarui Liu, Dan Ye, Leonardo Martinez, Shuihua Lu, Adong Shen, Anna M Mandalakas, Feng Li, Christoph Lange, Zhen Huang

Faculty, Staff and Students Publications

Background: Paediatric tuberculosis (TB), particularly drug-resistant TB (DR-TB), is associated with significant mortality. However, the global burden of childhood TB remains poorly understood.

Methods: We analysed incident cases, deaths, and age-standardised incidence and mortality rates among children (0-14 years) with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) using the Global Burden of Disease (GBD) 2021 database. Data were stratified by age, sex, region, country, and HIV/AIDS status. Annual and average annual percentage changes were assessed using joinpoint regression analysis. Secondary analyses compared adult and paediatric TB trends in the End TB era and evaluated the potential impact of the …