Digital Commons Network^™

Diagnostic Criteria And Management Of Melas And Stroke-Like Episodes: Consensus-Based Statements, Michelangelo Mancuso, Marcello Bellusci, Valerio Carelli, Irenaeus De Coo, Daria Diodato, Felix Distelmaier, Omar Hikmat, Michio Hirano, Rita Horvath, Amel Karaa, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Chiara La Morgia, Piervito Lopriore, Mika Henrik Martikainen, Robert Mcfarland, Olimpia Musumeci, Robert D S Pitceathly, Guido Primiano, Shamima Rahman, Fernando Scaglia, Andrew Schaefer, Manuel Schiff, Luisa Semmler, Costanza Lamperti, Serenella Servidei

Faculty, Staff and Student Publications

Background and purpose: Mitochondrial Encephalomyopathy, Lactic acidosis and Stroke-like episodes (MELAS) is a rare multisystem mitochondrial disorder with clinical heterogeneity. Diagnostic criteria and management strategies for MELAS and mitochondrial stroke-like episodes (SLE) remain inconsistent. This work provides international consensus recommendations on the definition, diagnosis, and management of MELAS and SLE in pediatric and adult populations.

Methods: An international Delphi consensus process was conducted within the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD), in collaboration with the US Mitochondrial Medicine Society, the ERN for Hereditary Metabolic Disorders (MetabERN), and patient representatives. Following a systematic literature review, 54 statements addressing diagnostic …

Functional And Structural Basis Of A Hypermorphic Trpc3 Variant, Briar Bell, Angela M Jaramillo-Granada, Luis O Romero, Irene A Gutierrez, Venkata K P S Mallampalli, Guizhen Fan, Sameer Varma, Matthew L Baker, Irina I Serysheva, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Cerebellar ataxias are characterized by impaired motor coordination resulting from neuronal dysfunction within the cerebellum. The mechanisms underlying this pathology and its cerebellar-specific neurodegeneration remain unknown. We uncover how a gain-of-function canonical transient receptor potential member 3 (TRPC3) mutation, coupled with a cerebellum-specific isoform, stabilizes the channel’s open state, resists the leading inhibitor Pyr3, and drives calcium-dependent cell death. Restoring calcium homeostasis by expressing a Purkinje cell calcium pump improves cell viability. Transgenic expression of the TRPC3 hypermorphic variant in Caenorhabditis elegans induces neurodegeneration, confirming its pathogenicity across species. Cryo–electron microscopy and molecular simulations reveal the structural basis for the …

Monitoring Relapse In Post-Transplant Acute Myeloid Leukemia Requires Integrated Assessment, With Flow Cytometry Showing The Highest Efficacy, Wei J Wang, Sa A Wang, Hong Fang, Qing Wei, Shimin Hu, Sanam Loghavi, Gheath Al-Atrash, Chenxuan Zang, Peng Wei, Jeffrey L Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

An Integrated Germline And Somatic Genomic Model For Coronary Artery Disease, Xiong Yang, Min Seo Kim, Xinyu Zhu, Md Mesbah Uddin, Tetsushi Nakao, So Mi Jemma Cho, Satoshi Koyama, Tingfeng Xu, Laurens F Reeskamp, Rufan Zhang, Zhaoqi Liu, Yunga A, Paul S De Vries, Ramachandran S Vasan, Eric Boerwinkle, Alanna C Morrison, Bruce M Psaty, Russell P Tracy, Susan R Heckbert, Michael H Cho, Jeong H Yun, Nicholette D Palmer, Donald W Bowden, Joanne M Murabito, Daniel Levy, Nancy L Heard-Costa, George T O'Connor, Lewis C Becker, Brian G Kral, Lisa R Yanek, Laura M Raffield, Bertha Hidalgo, Jerome I Rotter, Stephen S Rich, Kent D Taylor, Wendy S Post, Charles Kooperberg, Alexander P Reiner, Braxton D Mitchell, Sharon L R Kardia, Jennifer A Smith, Patricia A Peyser, Lawrence F Bielak, Dong Keon Yon, Hong-Hee Won, Donna K Arnett, Albert V Smith, Stacey B Gabriel, Patrick T Ellinor, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Pradeep Natarajan, Minxian Wang, Akl C Fahed

Faculty, Staff and Student Publications

Multiple germline and somatic genomic factors are associated with risk of coronary artery disease, but there is no single measure of risk that integrates all information from a DNA sample. To address this gap, we develop an integrated genomic model that includes six germline and somatic genetic drivers for coronary artery disease, including polygenic risk score, genetically-proxied proteomic/metabolomic risk scores, and clonal hematopoiesis of indeterminate potential. We evaluated its predictive power in the UK Biobank (N = 391,536), and validate it using data from the TOPMed program (N = 34,177). The 10-year coronary artery disease risk based on the integrated …

Nerandomilast In Progressive Pulmonary Fibrosis: Data From The Whole Follow-Up Period Of The Fibroneer-Ild Trial, Marlies S Wijsenbeek, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Toby M Maher, Fernando J Martinez, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Hui Gu, Ivana Ritter, Susanne Stowasser, Michael Kreuter

Faculty, Staff and Student Publications

Background: In the FIBRONEER-ILD trial in patients with progressive pulmonary fibrosis (PPF), nerandomilast 9 mg bid and 18 mg bid reduced the decline in forced vital capacity at week 52 compared with placebo (the primary endpoint). We assessed the effects of nerandomilast up to the final database lock.

Methods: Time to first acute exacerbation of ILD, hospitalisation for respiratory cause, or death (key secondary endpoint) and other time-to-event endpoints were assessed.

Results: 1176 patients, of whom 512 were taking background nintedanib, received nerandomilast or placebo. At final database lock, mean (sd) exposure to trial medication was 15.1 (5.7) months and …

Therapeutic Plasma Exchange For Uncontrollable Bleeding After Platelet Inhibition With Ticagrelor: A Report Of 2 Cases, Amanda Herrmann, Brenda Mai, Yu Bai, Brian Castillo, Biswajit Kar, Kimberly Klein, Ismael A Salas De Armas, Eric Salazar, Hlaing Tint, Igor D Gregoric

Faculty, Staff and Student Publications

Case series

Patients: Male, 52-year-old Male, 66-year-old

Final Diagnosis: Uncontrolled bleeding following ticagrelor associated with cardiac surgery

Symptoms: Bleeding

Clinical Procedure: —

Specialty: Cardiology Critical Care Medicine Pathology

Objective: Unusual clinical course

Background

Acute coronary syndrome is the most common cause of death in the United States. Successful intervention often requires a multi-therapeutic approach, including percutaneous coronary intervention (PCI) and antiplatelet agents such as ticagrelor. However, the use of antiplatelet agents can cause life-threatening bleeding, particularly during emergency procedures. Therapeutic plasma exchange (TPE) is a procedure that selectively removes the patient’s plasma to eliminate harmful substances. Here, we present 2 …

Fungal Meningitis In Us Patients Who Received Epidural Anesthesia In Matamoros, Mexico, Dallas J Smith, Elizabeth Misas, Jeremy A W Gold, Nicole Evert, Thi Dang, Emilie Prot, Simone Godwin, Julieanna Rivas, Jessica Pearson, Lori Koenecke, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Irma López-Martínez, Caitlyn Lutfy, Samantha Williams, Axel A Vazquez Deida, Katrina M Byrd, Julian A Villalba, Sarah Reagan-Steiner, Lindsay Parnell, Lalitha Gade, Romney M Humphries, Nathan P Wiederhold, Charles Y Chiu, Joshua A Lieberman, Anastasia P Litvintseva, Tom Chiller, Luis Ostrosky-Zeichner, Fungal Meningitis Response Team

Faculty, Staff and Student Publications

Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in US patients who received epidural anesthesia in Matamoros, Mexico.

Methods: Early epidemiological information suggested US patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in 2 Matamoros clinics. US patients known to have received surgery at these clinics during 1 January-13 May 2023 (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, …

Visdb 20: A Manually Curated Resource Of Viral Integration Sites And Their Regulatory Maps In Human Diseases, Citu Citu, Ajeet Singh, Xinyi Liu, Mounika Ashannagari, Rinki Ratnapriya, Zhongming Zhao

Faculty, Staff and Student Publications

The integration of viral sequence into the human genome plays critical role in the onset of various diseases, especially cancers. To facilitate systematic analysis of these events, we present VISDB 2.0, an expanded and updated database of human viral integration sites (VISs). The current release contains more than 270,000 manually curated VISs derived from 209 peer-reviewed publications, covering 11 viruses, including four retroviruses and seven DNA viruses. This represents a 3.5-fold increase in VIS entries compared with the previous version. Each VIS record includes standardized genomic coordinates and annotations describing local genomic context, CpG islands, repetitive elements, chromosomal fragile sites, …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

Uncovering Hidden Prognostic Patterns In Colorectal Cancer Histology Using Unsupervised Learning: A Computational Pathology Study, Wen-Tong Zhou, Yong Liu, Gang Yu, Kuan-Song Wang, Chao Xu, Jonathan Greenbaum, Chong Wu, Lin-Dong Jiang, Christopher J Papasian, Hong-Mei Xiao, Hong-Wen Deng

Faculty, Staff and Student Publications

Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, yet current histopathological diagnostics capture only limited features. This study aimed to discover subtle, prognostically significant histomorphological patterns in CRC tissues using unsupervised deep learning. We developed a framework integrating convolutional neural networks with deep clustering, trained on 23,341 image patches from 493 patients. We identified 30 distinct histomorphological clusters from CRC tissue images. Through univariate and multivariate survival analyses, three clusters (Cluster13, Cluster19, and Cluster24) were consistently associated with patient prognosis. These clusters were integrated with clinical factors (T stage, N stage, and differentiation degree) to construct a …

Penile Prosthetic Infections: What Can Be Learned From Orthopedics?, Kenneth B Mathis, Alisina Shahi

Faculty, Staff and Student Publications

No abstract provided.

Medial Pulvinar Nucleus As A Causal Hub For Heteromodal Naming, Oscar Woolnough, Tessy Thomas, Kathryn M Snyder, Ellery Wheeler, Jay Gavvala, Nitin Tandon

Faculty, Staff and Student Publications

Our ability to retrieve the names of objects in our environment is a fundamental aspect of everyday life. This process requires a complex, dynamic network of cortical and subcortical interactions. While the cortical constituents of this network have been extensively studied with intracranial recordings, the subcortical nodes of the naming network are unclear. We probed the role of the left medial pulvinar nucleus in naming with direct intracranial recordings and stimulation in eight humans (three male, five female) as they named objects using pictures and auditory and written descriptions. We found a spectrotemporal signature of naming in the left medial …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Surface Morphometrics Reveals Local Membrane Thickness Variation In Organellar Subcompartments, Michaela Medina, Ya-Ting Chang, Hamidreza Rahmani, Mark Frank, Zidan Khan, Daniel Fuentes, Frederick A Heberle, M Neal Waxham, Benjamin A Barad, Danielle A Grotjahn

Faculty, Staff and Student Publications

Lipid bilayers form the basis of organellar architecture, structure, and compartmentalization in the cell. Decades of biophysical, biochemical, and imaging studies on purified or in vitro-reconstituted liposomes have shown that variations in lipid composition influence the physical properties of membranes, such as thickness and curvature. However, similar studies characterizing these membrane properties within the native cellular context have remained technically challenging. Recent advancements in cellular cryo-electron tomography (cryo-ET) imaging enable high-resolution, three-dimensional views of native organellar membrane architecture preserved in near-native conditions. We previously developed a "Surface Morphometrics" pipeline that generates surface mesh reconstructions to model and quantify cellular membrane …

Consolidation Enfortumab Vedotin And Pembrolizumab After Cisplatin Induction In Metastatic Urothelial Cancer: Outcomes Of Complete Response And Bladder Preservation, Kok Hoe Chan, Putao Cen, Tung Shu, Steven Canfield, Hui Zhao, Anneliese Gonzalez, Julie Rowe, Varaha Tammisetti, Hajar Ayoub, Angel Blanco, Mark Amsbaugh, Nizar Tannir

Faculty, Staff and Student Publications

Bladder preservation remains a highly desirable therapeutic goal in urothelial carcinoma, particularly when durable survival can be achieved. Radical cystectomy is the standard treatment for muscle-invasive disease; however, it results in irreversible bladder loss and significant morbidity. Among patients with locally advanced or metastatic urothelial carcinoma, recurrence rates after standard therapy remain high. Consolidation therapy with enfortumab vedotin and pembrolizumab following cisplatin-based induction chemotherapy has demonstrated promising efficacy, with substantial complete response rates and improved bladder preservation. This single-center retrospective analysis evaluated the efficacy and safety of enfortumab vedotin plus pembrolizumab as consolidation therapy in 11 patients with metastatic urothelial …

Apoe And Plasma Ad Biomarkers: The Role Of Genetic Ancestry In Hispanics/Latinos, Caitlin Cheung, Natasha Z Anita, Paola Filigrana, Myriam Fornage, Kevin A Gonzalez, Linda C Gallo, Carmen R Isasi, Robert C Kaplan, Xihao Li, Freddie Márquez, Humberto Parada, Krista M Perreira, Alberto R Ramos, Tatjana Rundek, Wassim Tarraf, Fernando D Testai, Charles Decarli, Hector M González, Tamar Sofer

Faculty, Staff and Student Publications

Background: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

Methods: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

Results: ε4 was associated with lower Aβ42/40 and higher p-tau181and …

Early Behavioral And Cognitive Changes In Patients With Pathologically Confirmed Alzheimer Disease, Lewy Body Dementia, And Mixed Dementia, Ming Wang, Hongke Wu, Aaron Bonner-Jackson, Yiming Chen, Wen Tang, Hao Feng, Lijun Zhang, Chixiang Chen, James B Leverenz, Jagan A Pillai

Faculty, Staff and Student Publications

Background and objectives: Alzheimer's disease pathology (ADP) and Lewy body pathology (LBP) are traditionally associated with distinct cognitive profiles. However, growing evidence highlights the role of behavioral and psychological symptoms of dementia (BPSD) in shaping clinical presentations. The combined influence of cognitive and behavioral symptoms across neuropathologically confirmed ADP, LBP, and mixed AD-LBP has not been systematically examined. This study aimed to identify clinically meaningful subtypes by jointly analyzing cognitive performance and BPSD profiles in individuals with autopsy-confirmed dementia pathology.

Methods: This retrospective longitudinal cohort study used data from the National Alzheimer Coordinating Center (NACC), collected across multiple U.S. Alzheimer's …

Pharmacokinetic Modeling Strategies For Dynamic Hyperpolarized Urea Imaging, Keith A Michel, Collin J Harlan, Christopher M Walker, Matthew E Merritt, Yunyun Chen, Stephen Y Lai, James A Bankson

Faculty, Staff and Student Publications

Purpose: To evaluate pharmacokinetic modeling methods for quantification of tissue perfusion/permeability with hyperpolarized 13C urea.

Methods: Three models for quantitative analysis of dynamic HP urea imaging data were proposed and evaluated in numerical simulations and a thyroid cancer mouse model. A multicompartment model resembling the extended Tofts model for DCE-MRI (Model I) and two simplified models were used. The simplified models each eliminate a volume parameter representing vascular (Model II) or impermeable cellular space (Model III). Signal curves were generated from Model I, and models were fit to these synthetic data to quantify the effects of acquisition settings, bias in …

Real-World Effectiveness Of Second-Line Therapies In Advanced Non-Small Cell Lung Cancer: Insights From Propensity-Weighted Comparative Analyses Of Longitudinal Ehr Data, Gary C N Hettinger, Qi Long, Ravi B Parikh

Faculty, Staff and Student Publications

Background: While substantial research has focused on first-line (1L) therapies for advanced-stage non-small cell lung cancer (aNSCLC), less is known about the effectiveness of second-line (2L) treatments following disease progression on 1L. The poor prognosis after 1L progression, limited guidance for 2L treatment, and constraints of clinical trials in addressing these questions underscore the need for real-world comparative effectiveness research.

Methods: We conducted a retrospective analysis to compare real-world overall survival (rwOS) associated with 2L treatments among patients with disease progression during 1L. Eligible patients were selected from Flatiron Health's nationwide electronic health record (EHR)-derived de-identified database. 1L and 2L …

Information Extraction From Clinical Notes: Are We Ready To Switch To Large Language Models?, Yan Hu, Xu Zuo, Yujia Zhou, Xueqing Peng, Jimin Huang, Vipina K Keloth, Vincent J Zhang, Ruey-Ling Weng, Cathy Shyr, Qingyu Chen, Xiaoqian Jiang, Kirk E Roberts, Hua Xu

Faculty, Staff and Student Publications

Objectives: To assess the performance, generalizability, and computational efficiency of instruction-tuned Large Language Model Meta AI (LLaMA)-2 and LLaMA-3 models compared to bidirectional encoder representations from transformers (BERT) for clinical information extraction (IE) tasks, specifically named entity recognition (NER) and relation extraction (RE).

Materials and methods: We developed a comprehensive annotated corpus of 1588 clinical notes from 4 data sources-UT Physicians (UTP) (1342 notes), Transcribed Medical Transcription Sample Reports and Examples (MTSamples) (146), Medical Information Mart for Intensive Care (MIMIC)-III (50), and Informatics for Integrating Biology and the Bedside (i2b2) (50), capturing 4 clinical entities (problems, tests, medications, other treatments) …

Analysis Of Patients With Monocytic And Monocytic-Like Acute Myeloid Leukemia, Including Aml-M4 And Aml-M5, Treated With Venetoclax Plus Azacitidine, Marina Konopleva, Courtney D Dinardo, Yan Sun, Paul Jung, Sanam Loghavi, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Mutational Landscape And Burden On Rbc Transfusion Response In Patients With Lower-Risk Myelodysplastic Syndromes (Lr-Mds) In The Commands Study, Rami S Komrokji, Sheida Hayati, Manuel Ugidos, Guillermo Garcia-Manero, Matteo Giovanni Della Porta, Amer M Zeidan, Valeria Santini, Uwe Platzbecker, Anita K Gandhi, Rajasekhar N V S Suragani

Faculty, Staff and Student Publications

The COMMANDS trial established luspatercept as a first‐line treatment for anemia in transfusion‐dependent lower‐risk (LR) myelodysplastic syndromes (MDS). Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%–59%. Mutation profiles were similar in the treatment groups. Luspatercept …

Shiny-Magec: A Bayesian R Shiny Application For Meta-Analysis Of Censored Adverse Events, Zihan Zhou, Zizhong Tian, Christine Peterson, Le Bao, Shouhao Zhou

Faculty, Staff and Student Publications

Accurate assessment of adverse event (AE) incidence is critical in clinical research for drug safety. While meta-analysis serves as an essential tool to comprehensively synthesize the evidence across multiple studies, incomplete AE reporting in clinical trials remains a persistent challenge. In particular, AEs occurring below study-specific reporting thresholds are often omitted from publications, leading to left-censored data. Failure to account for these censored AE counts can result in biased AE incidence estimates. We present an R Shiny application that implements a Bayesian meta-analysis model specifically designed to incorporate censored AE data into the estimation process. This interactive tool provides a …

Large Language Models For Bioinformatics, Wei Ruan, Yanjun Lyu, Jing Zhang, Jiazhang Cai, Peng Shu, Yang Ge, Yao Lu, Shang Gao, Yue Wang, Peilong Wang, Lin Zhao, Tao Wang, Yufang Liu, Luyang Fang, Ziyu Liu, Zhengliang Liu, Yiwei Li, Zihao Wu, Junhao Chen, Hanqi Jiang, Yi Pan, Zhenyuan Yang, Jingyuan Chen, Shizhe Liang, Wei Zhang, Terry Ma, Yuan Dou, Jianli Zhang, Xinyu Gong, Qi Gan, Yusong Zou, Zebang Chen, Yuanxin Qian, Shuo Yu, Jin Lu, Kenan Song, Xianqiao Wang, Andrea Sikora, Gang Li, Xiang Li, Quanzheng Li, Yingfeng Wang, Lu Zhang, Yohannes Abate, Lifang He, Wenxuan Zhong, Rongjie Liu, Chao Huang, Wei Liu, Ye Shen, Ping Ma, Hongtu Zhu, Yajun Yan, Dajiang Zhu, Tianming Liu

Faculty, Staff and Student Publications

With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and …

Generalizability Analyses With A Partially Nested Trial Design: The Necrotizing Enterocolitis Surgery Trial, Sarah E Robertson, Matthew A Rysavy, Martin L Blakely, Jon A Steingrimsson, Issa J Dahabreh

Faculty, Staff and Student Publications

We discuss generalizability analyses under a partially nested trial design, where part of the trial is nested within a cohort of trial-eligible individuals, while the rest of the trial is not nested. This design arises, for example, when only some centers participating in a trial are able to collect data on non-randomized individuals, or when data on non-randomized individuals cannot be collected for the full duration of the trial. Our work is motivated by the Necrotizing Enterocolitis Surgery Trial (NEST), which compared initial laparotomy versus peritoneal drain for infants with necrotizing enterocolitis or spontaneous intestinal perforation. During the first phase …

Asymmetric Sacral Dysmorphism: Prevalence And Impact On Surgical Planning, Adeet Amin, Kathryn Barth, Colin Ward, Ryan Deangelis, Gregory Schimizzi, Connor Park, Milton L Routt, Stephen J Warner, Patrick Kellam, Mark R Adams, Jonathan G Eastman

Faculty, Staff and Student Publications

Objectives: To determine the prevalence and surgical relevance of asymmetry in patients with sacral dysmorphism.

Design: Retrospective review.

Setting: Level 1 academic trauma center.

Patient selection criteria: Included were patients between 16 and 85 years old with an operative pelvic ring injury (Orthopaedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen (OTA/AO) 61A-C) and a thin-cut pelvis computed tomography (≤2.0 mm) with 3D reformats. Sacral dysmorphism was defined by the inability to place a transiliac-transsacral screw in the upper sacral segment.

Outcome measures and comparisons: Asymmetry was assessed by evaluating side-to-side differences in neuroforaminal height, upper sacral segment pathway obliquity, and anterior-posterior pathway width. …

Influence Of Pullback Pressure Gradient On Residual Angina At One Year, Takuya Mizukami, Kazumasa Ikeda, Daniel Munhoz, Koshiro Sakai, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Antonio Maria Leone, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Tatyana Storozhenko, Frédéric Bouisset, Domenico Galante, Bruno R Da Costa, Gianluca Campo, Colin Berry, Damien Collison, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad A Ali, Ethan Korngold, Eric Wyffels, Adriaan Wilgenhof, Nico Pijls, Bernard De Bruyne, Nils P Johnson, Carlos Collet

Faculty, Staff and Student Publications

Background: The pullback pressure gradient (PPG) is a novel physiological metric that quantifies coronary artery disease patterns as focal or diffuse on a scale from 0 to 1. This study assessed the relationship between PPG and residual angina at 1 year.

Methods: PPG Global is a prospective, investigator-initiated, single-arm, multicenter study that enrolled patients with at least 1 lesion with a fractional flow reserve ≤0.80 intended to be treated with percutaneous coronary intervention. After the PPG calculation, physicians could revise treatment assignment to medical therapy or coronary artery bypass graft surgery instead of percutaneous coronary intervention. Focal and diffuse disease …

An Artificial Intelligence Model For Electrocardiogram Detection Of Occlusion Myocardial Infarction: A Retrospective Study To Reduce False-Positive Cath Lab Activations, Benjamin L Cooper, Evan A Genova, Carrie A Bakunas, Catherine E Reynolds, Benjamin Karfunkle, Nils P Johnson

Faculty, Staff and Student Publications

Aims: Existing ST-segment elevation myocardial infarction (STEMI) alert pathways that rely on traditional STEMI criteria perform suboptimally. We aimed to evaluate the diagnostic performance of an artificial intelligence (AI) model to detect acute occlusion myocardial infarction (OMI) from the routine 12-lead electrocardiogram (ECG) and, specifically, its potential to reduce false-positive activations.

Methods and results: Consecutive adults managed via the STEMI pathway were included from a tertiary academic medical centre between January 2022 and December 2023. Cases without an available ECG for review, death prior to catheterization, or alternative reasons for activation (i.e. electrical instability or urgent interventions) were excluded. Pre-coronary …

A Patient-Derived Organ-On-Chip Platform For Modeling The Tumor Microenvironment And Drug Responses In Pancreatic Cancer, Darbaz Adnan, Natan Roberto De Barros, Luca S Santovito, Xuhong Cheng, Kristi M Lawrence, Mariah K Barnett, Martine D Boetto, Neal Mehta, Ajaypal Singh, Lin Cheng, Xiangsheng Huang, Faraz Bishehsari

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient‐derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ‐on‐a‐chip (OoC) systems can …