Medicine and Health Sciences Commons^™

Evaluating Large Language Model Performance To Support The Diagnosis And Management Of Patients With Primary Immune Disorders, Nicholas L Rider, Yingya Li, Aaron T Chin, Daniel V Digiacomo, Cullen Dutmer, Jocelyn R Farmer, Kirk Roberts, Guergana Savova, Mei-Sing Ong

Faculty, Staff and Student Publications

Background: Generative artificial intelligence (GAI) is transforming health care in a variety of ways; however, the present utility of GAI for supporting clinicians who treat rare disease such as primary immune disorders (PIs) is not well studied. We evaluated the ability of 6 state-of-the-art large language models (LLMs) for providing clinical guidance about PIs.

Objective: To quantitatively and qualitatively measure the utility of current, open-source LLMs for diagnosing and providing helpful clinical decision support about PIs.

Methods: Five expert clinical immunologists each provided 5 real-world, anonymized PI case vignettes via multi-turn prompting to 6 LLMs (OpenAI GPT-4o, Llama-3.1-8B-Instruct, Llama-3.1-70B-Instruct, Mistral-7B-Instruct-v0.3, …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …

Genome-Wide Association Meta-Analysis Of Human Olfactory Identification Discovers Sex-Specific And Sex-Differential Genetic Variants, Franz Förster, David Emmert, Katrin Horn, Janne Pott, Johannes Frasnelli, Mohammed Aslam Imtiaz, Konstantinos Melas, Valentina Talevi, Honglei Chen, Christoph Engel, Michele Filosi, Myriam Fornage, Martin Gögele, Markus Löffler, Thomas H Mosley, Cristian Pattaro, Peter Pramstaller, Srishti Shrestha, N Ahmad Aziz, Monique M B Breteler, Kerstin Wirkner, Markus Scholz, Christian Fuchsberger

Faculty, Staff and Student Publications

Smelling is a human sense, expressing strong sexual dimorphisms. We aim to improve the knowledge of the genetics of human olfactory perception by performing an exploratory genome-wide association meta-analysis of up to 21,495 individuals of European ancestry. By sex-stratified and overall analysis of the identification of twelve odours and an identification score, we discovered ten independent loci, seven of them novel, with trait-wise genome-wide significance (p <  5 × 10−8) involving five odours. Seven of these loci, including four novel ones, are also significant using a stricter study-wide significance threshold (p <  3.85 × 10−9). Loci were predominantly located within clusters of olfactory receptors. Two loci were female-specific while one was sex-differential with respective candidate genes containing androgen response elements. Two-sample Mendelian randomization was applied to search for causal relationships between sex hormones, odour identification and neurodegenerative diseases. A causal negative effect was detected for Alzheimer’s disease on the identification score. These findings deepen our understanding of the genetic basis of olfactory perception and its interaction with sex, prioritizing mechanisms for further molecular research.

Dietary Patterns, Serum Metabolites, And Risk Of Cardiovascular Disease In United States Hispanic/Latino Adults: A Prospective Analysis Of The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Hongbo Yang, Yi Wang, Kai Luo, Yasmin Mossavar-Rahmani, Christina Cordero, Robert J Ostfeld, Claudia Martinez, Luis Maldonado, Amber Pirzada, Martha Daviglus, Bing Yu, Frank B Hu, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Background: Healthy dietary patterns are recommended to prevent cardiovascular disease (CVD), yet the relationships among healthy dietary patterns, blood metabolite profile, and incident CVD are not well understood.

Objectives: This study aimed to assess the associations of healthy dietary patterns and related serum metabolite profiles with incident CVD in United States Hispanic/Latino adults.

Methods: The study included 13,922 participants aged 18-74 y from the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores, including Healthy Eating Index (HEI)-2020, healthful Plant-based Diet Index (hPDI), and alternate Mediterranean diet score (aMED), were constructed at baseline (2008-2011) based on 2 24-h dietary recalls. …

Pulmonary Complications Associated With Sugammadex Or Neostigmine In Patients Recovering From Advanced Diagnostic Or Interventional Bronchoscopy: A Retrospective Two-Centre Analysis, Ehab Farag, Karan Shah, Maged Argalious, Basem Abdelmalak, Thomas Gildea, John Seif, Shuyi Li, Edward J Mascha, Daniel I Sessler

Faculty, Staff and Student Publications

Background: Many diagnostic and interventional procedures are performed in bronchoscopy suites in high-risk patients. Minor impairment in respiratory muscle function caused by incomplete reversal of neuromuscular block can contribute to postoperative pulmonary complications (PPCs). We assessed whether there are fewer serious PPCs after diagnostic or therapeutic bronchoscopy when neuromuscular block is reversed with sugammadex rather than neostigmine.

Methods: This is a retrospective cohort study for bronchoscopy under general anaesthesia with the use of neuromuscular blockers between July 2016 and June 2022. The primary outcome was a composite of PPCs. The secondary outcome was hypoxaemia. We used inverse probability of treatment …

Investigation Of A Pathogenic Inversion In Unc13d And Comprehensive Analysis Of Chromosomal Inversions Across Diverse Datasets, Tugce Bozkurt-Yozgatli, Ming Yin Lun, Jesse D Bengtsson, Ugur Sezerman, Ivan K Chinn, Zeynep Coban-Akdemir, Claudia M B Carvalho

Faculty, Staff and Student Publications

Inversions are known contributors to the pathogenesis of genetic diseases. Identifying inversions poses significant challenges, making it one of the most demanding structural variants (SVs) to detect and interpret. Recent advancements in sequencing technologies and the development of publicly available SV datasets have substantially enhanced our capability to explore inversions. However, a cross-comparison in those datasets remains unexplored. In this study, we reported a proband with familial hemophagocytic lymphohistiocytosis type-3 carrying a splicing variant (c.1389+1G>A) in trans with an inversion present in 0.006345% of individuals in gnomAD (v4.0) that disrupts UNC13D. Based on this result, we investigate the features …

The Impact Of Household Dysfunction On Dating Violence Perpetration Among Adolescents In The United States: A Scoping Review, Sumaita Choudhury, Melissa F Peskin, Timothy J Walker, Emily T Hébert, Nivedhitha Parthasarathy, Kaitlyn L Zajack-Garcia, Lea Sacca, Christine M Markham

Faculty, Staff and Student Publications

Adverse childhood experiences, such as household dysfunction (HD), play a central role in how adolescents establish, experience, and navigate the challenges of relationship formation, maintenance, and dissolution. HD exposures have been independently associated with dating violence (DV) perpetration in both adolescents and adults. However, research examining the association between the concurrent effect of HD on DV perpetration, especially among adolescents remains scarce. Thus, we conducted a scoping review to accumulate and summarize existing research regarding the impact of HD on DV perpetration among adolescents aged 10 to 17 years in the United States. We used three electronic databases, Medline (Ovid), …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

Restoring Calibration For Aligned Large Language Models: A Calibration-Aware Fine-Tuning Approach, Jiancong Xiao, Bojian Hou, Zhanliang Wang, Ruochen Jin, Qi Long, Weijie J Su, Li Shen

Faculty, Staff and Student Publications

One of the key technologies for the success of Large Language Models (LLMs) is preference alignment. However, a notable side effect of preference alignment is poor calibration: while the pre-trained models are typically well-calibrated, LLMs tend to become poorly calibrated after alignment with human preferences. In this paper, we investigate why preference alignment affects calibration and how to address this issue. For the first question, we observe that the preference collapse issue in alignment undesirably generalizes to the calibration scenario, causing LLMs to exhibit overconfidence and poor calibration. To address this, we demonstrate the importance of fine-tuning with domain-specific knowledge …

High-Impact Chronic Pain And Cognitive Decline Among Mexicans Aged 60 And Older From 2012 To 2018, Sadaf Arefi Milani, Sirena Gutierrez, Brandon O'Grady, Rebeca Wong, Rafael Samper-Ternent, Brian Downer

Faculty, Staff and Student Publications

Pain is associated with cognitive decline, but prior research has not considered differences between high- and low-impact chronic pain or low-and middle-income countries, such as Mexico. Our objective was to evaluate the association between high-impact chronic pain and cognitive decline among older adults in Mexico. We used data from the 2012-2018 Mexican Health and Aging Study (MHAS), a nationally representative study of older Mexican adults (60+). Pain, measured at each wave, was categorized as high-impact chronic pain (pain that limits daily activities), low-impact chronic pain (pain that did not limit daily activities), and no chronic pain. Cognition was measured at …

Diet, Gut Microbiota, And Histidine Metabolism Toward Imidazole Propionate Production In Relation To Type 2 Diabetes, Hongbo Yang, Kai Luo, Brandilyn A Peters, Yi Wang, Yanbo Zhang, Martha Daviglus, Amber Pirzada, Christina Cordero, Bing Yu, Robert D Burk, Robert Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Objective: To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people.

Research design and methods: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake. …

Mtap Immunohistochemistry As A Surrogate Marker Of Cdkn2a Loss In Brain Tumors: A Meta-Analysis And Literature Review, Antonio Dono, Diego Pichardo-Rojas, Leonardo Mendoza Mora, Pavel S Pichardo-Rojas, Luis A Marin-Castañeda, Abril Carrillo, Adrian Coria Medrano, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted …

I2moe: Interpretable Multimodal Interaction-Aware Mixture-Of-Experts, Jiayi Xin, Sukwon Yun, Jie Peng, Inyoung Choi, Jenna L Ballard, Tianlong Chen, Qi Long

Faculty, Staff and Student Publications

Modality fusion is a cornerstone of multimodal learning, enabling information integration from diverse data sources. However, vanilla fusion methods are limited by

It Is Time We Include Leadership Education And Experiences In Mfm Training And Lifelong Learning, Cheryl A Moyer, Timothy R B Johnson

Faculty, Staff and Student Publications

No abstract provided.

Federated Target Trial Emulation Using Distributed Observational Data For Treatment Effect Estimation, Haoyang Li, Chengxi Zang, Zhenxing Xu, Weishen Pan, Suraj Rajendran, Yong Chen, Fei Wang

Faculty, Staff and Student Publications

Target trial emulation (TTE) aims to estimate treatment effects by simulating randomized controlled trials using real-world observational data. Applying TTE across distributed datasets shows great promise in improving generalizability and power but is always infeasible due to privacy and data-sharing constraints. Here we propose a Federated Learning-based TTE framework, FL-TTE, that enables TTE across multiple sites without sharing patient-level data. FL-TTE incorporates federated protocol design, federated inverse probability of treatment weighting, and a federated Cox proportional hazards model to estimate time-to-event outcomes across heterogeneous data. We validated FL-TTE by emulating Sepsis trials using eICU and MIMIC-IV data from 192 hospitals, …

Dynamic Few-Shot Prompting For Clinical Note Section Classification Using Lightweight, Open-Source Large Language Models, Kurt Miller, Steven Bedrick, Qiuhao Lu, Andrew Wen, William Hersh, Kirk Roberts, Hongfang Liu

Faculty, Staff and Student Publications

Objective: Unlocking clinical information embedded in clinical notes has been hindered to a significant degree by domain-specific and context-sensitive language. Identification of note sections and structural document elements has been shown to improve information extraction and dependent downstream clinical natural language processing (NLP) tasks and applications. This study investigates the viability of a dynamic example selection prompting method to section classification using lightweight, open-source large language models (LLMs) as a practical solution for real-world healthcare clinical NLP systems.

Materials and methods: We develop a dynamic few-shot prompting approach to classifying sections where section samples are first embedded using a transformer-based …

A Recipe For Disaster - Sodium Bicarbonate Overdose, Adeola A Kosoko, Amara Ogoke, Kyle Vogt

Faculty, Staff and Student Publications

Audience: Emergency medicine residents post-graduate years 1-4.

Introduction: Sodium bicarbonate is a compound found commonplace in many households and in many products. It lends itself to countless everyday uses including cooking and cleaning. Physicians prescribe sodium bicarbonate regularly both on- and off-label regularly for various ailments.1 Due to the ubiquitous way both emergency physicians and the general public use and are exposed to sodium bicarbonate, we wanted to prepare learners to identify and appropriately manage sodium bicarbonate toxicity.Obtaining a thorough history not just of medications prescribed but of significant ingestions or infusions is critical in diagnosing this toxicity. Furthermore, acute …

Empirical Tuberculosis Treatment In Human Immunodeficiency Virus (Hiv)-Associated Fever Of Unknown Origin: A Case-Based Rationale, Matthew Antonioli, Samantha H Antonioli, Gabriel M Aisenberg

Faculty, Staff and Student Publications

Fever of unknown origin (FUO) in people living with human immunodeficiency virus (PLHIV) is clinically defined as recurrent fever lasting more than four weeks in the outpatient setting or more than three days during hospitalization, despite a thorough diagnostic evaluation. This evaluation typically includes a comprehensive medical history, physical examination, imaging studies (such as chest radiography), and an extensive range of laboratory tests, including complete blood counts, blood and urine cultures, and metabolic panels. Among the many possible causes, tuberculosis (TB) stands out as a leading concern, given its disproportionate burden in PLHIV. However, whether to initiate empirical anti-tubercular therapy …

Venoarterial Extracorporeal Membrane Oxygenation Is A Feasible Option For Patients With Pregnancy-Associated Diagnoses Who Require Mechanical Circulatory Support, Trishna Parikh, Sabiha Armin, Saad Afzal Khan, Adishwar Rao, Akriti Agrawal, Dev Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used in patients with cardiopulmonary collapse, but data regarding its use in pregnancy is limited. We aimed to identify the clinical characteristics and predictors of in-hospital mortality in female patients requiring VA-ECMO, including evaluating the role of pregnancy.

Methods: In this cross-sectional study, a cohort of female patients aged 19-45 years who required VA-ECMO were identified from the National Inpatient Sample from 2018 to 2021 and further stratified according to presence of pregnancy-associated diagnoses. Baseline characteristics were compared using Pearson chi-square test and Wilcoxon rank-sum test for categorical and continuous variables, respectively. Multivariate …

Ten Practical Tips For A Successful Presentation At An Infectious Disease Clinical Case Conference, Takahiro Matsuo, Pablo C Okhuysen, Ben J Barnett

Faculty, Staff and Student Publications

This mini-review provides 10 practical tips for infectious disease trainees presenting at clinical case conferences. These tips, grounded in principles from education theory, aim to enhance the effectiveness of case presentations.

An Ectopic Pancreatic Mass Inducing Gastric Outlet Obstruction, Rohan Ahuja, Samir Mehta, Nakia Armendariz, Jimmy Q Pham, Madhav Desai

Faculty, Staff and Student Publications

Gastric outlet obstruction (GOO) is a clinical diagnosis characterized by early satiety, abdominal pain, post-prandial vomiting, and weight loss. Here, we present a rare case of an ectopic pancreatic cyst inducing GOO, highlighting the importance of a thorough diagnostic workup. A 40-year-old man with no prior medical or surgical history presented with a six-month history of intermittent epigastric pain, nausea, and vomiting with an inability to tolerate oral intake for a week. CT of the abdomen and pelvis revealed a 4.5 × 3.0 × 2.9 cm, well-circumscribed, peripherally enhancing cystic lesion in the distal pylorus. Initial esophagogastroduodenoscopy (EGD) revealed an …

Encephalitis In Immunocompromised Vs Immunocompetent Patients: A Comparative Study, Anna Kolchinski, Margaret Li, Ralph Habis, Paris Bean, Ashley N Heck, John C Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Background: Encephalitis is characterized by brain parenchymal inflammation caused by infection or autoimmunity. There are limited recent data on how immunocompromised patients with encephalitis differ from the general encephalitis population.

Methods: This retrospective study of 2 large medical institutions compares clinical characteristics and outcomes of immunocompromised and immunocompetent patients with all-cause encephalitis.

Results: Of the 657 patients, 151 (23%) were immunocompromised. Immunocompromised patients were more likely to have an infectious etiology, comorbidities, inflammatory cerebrospinal fluid (CSF) profile, abnormal neuroimaging, and worse clinical outcomes as assessed by discharge Glasgow Outcome Scale (GOS) and in-hospital mortality (all P < .05). The most commonly identified etiologies in immunocompromised patients were herpes simplex virus (HSV) and varicella zoster virus. HSV accounted for similar proportions in the immunocompromised (18%) and immunocompetent (14%) groups, though it was more commonly associated with a CSF neutrophilia in the immunocompromised group (P = .001). Strikingly, …

Evolving Hemodynamics In Fontan Circulation: Age-Driven Insights In Patients With Interrupted Inferior Vena Cava And Hepatoazygos Shunt, Vikas Kannojiya, Akshita Sahni, Emily Eickhoff, Neha Zacharia, Nicole St Clair, Noah Schulz, Peter E Hammer, Pedro J Del Nido, Rahul H Rathod, David M Hoganson, Vijay Govindarajan

Faculty, Staff and Student Publications

Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 patients with I-IVC showed a nonlinear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ∼3, ∼10, and ∼20, respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery, with median splits of …

Prevalence, Treatment Patterns, Burden, And Factors Related To Treatment Failure With Sodium-Glucose Cotransporter 2 Inhibitor In Adults With Type 2 Diabetes In The United States, Xi Tan, Yiwen Cao, Yan Wang, Joanna Boland, Mico Guevarra, Lin Xie, Yan Song, Min Ji Kwak

Faculty, Staff and Student Publications

Aims: To evaluate treatment failure of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among adults with type 2 diabetes (T2D) and assess associated risk factors and clinical and economic outcomes in the real-world setting.

Methods: Adults with T2D who initiated SGLT2i were selected from the Komodo's Healthcare Map, an administrative claims database (2016-2024). Treatment failure was defined as discontinuation, add-on/switching, or uncontrolled glycated hemoglobin (HbA1c) without action. Risk factors, treatment patterns, and clinical and economic burden were assessed.

Results: Among 237,295 eligible adults, the overall rate of treatment failure with SGLT2i was 77.3 %, with a median time to failure of 9.14 …

Efficacy And Safety Of Mechanical Thrombectomy In Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients On Low-Dose Aspirin, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and …

Endovascular Therapy For Late-Window M2-Segment Middle Cerebral Artery Occlusion: Analysis Of The Clear Study, Simon Winzer, Daniel P O Kaiser, Muhammad M Qureshi, Alicia C Castonguay, Daniel Strbian, Raul G Nogueira, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Hiroshi Yamagami, Kanta Tanaka, Sunil A Sheth, Anne Dusart, Patrik Michel, Marta Olive Gadea, Marc Ribo, Osama O Zaidat, Diogo C Haussen, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, James E Siegler, Ajit S Puri, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Milagros Galecio-Castillo, Sergio Salazar-Marioni, Pekka Virtanen, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Abiya Qureshi, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Mikko Sillanpää, Wei Hu, Eugene Lin, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Urs Fischer, Santiago Ortega-Gutierrez, Robin Lemmens, Peter A Ringleb, Thanh N Nguyen, Volker Puetz

Faculty, Staff and Student Publications

Background: There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6-24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The …

Non-Invasive Tools For Analysis Of Plasma Membrane Protein Topology In Living Cells, Daria Savenkova, Leysan Bulatova, Vera Skripova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane protein topology studies offer guidance to membrane protein structure, folding, and function, serving as a credible scaffold for designing site-directed mutagenesis and biochemical experiments, helping to identify functionally significant extracellular and intracellular regions, modeling three-dimensional structures, and building reliable mechanistic models. Membrane protein structure as a function of given lipid composition and physiological state of the cell is best probed in whole intact cells. A described simple and advanced immunofluorescence protocol applied to the transmembrane orientation of extramembrane domains permits a topology analysis of plasma membrane proteins in their native state in living unperturbed eucaryotic cells. The accessibility of …

Long Akap18 Isoforms Anchor Ubiquitin Specific Proteinases And Coordinate Calcium Reuptake At The Sarcoplasmic Reticulum, Taeyeop Park, Katherine Forbush, Yong Li, Oscar Vivas, Kacey J Rosenthal, Jerome Falcone, Cassandra J Wong, James E Bruce, Claudia Moreno, Carmen W Dessauer, John D Scott

Faculty, Staff and Student Publications

Subcellular targeting of signaling enzymes influences where and when various modes of intracellular communication operate. Macromolecular complexes of signal transduction and signal termination elements favor reversible control of repetitive processes. This includes adrenergic stimulation of excitation–contraction coupling in the heart. Long isoforms of A-kinase anchoring protein 18 (AKAP18γ and δ) modulate this process via regulation of calcium uptake into the sarcoplasmic reticulum through the Ca2+ATPase 2a (SERCA2a). AKAP18 proximity-proteomic screening in cardiomyocytes identifies networks for protein kinase A (PKA) and ubiquitin-specific proteinases (USPs). A 2′phosphoesterase domain on AKAP18 interfaces with the USP4 isoform at the Z bands of sarcomeres. PKA …

Bridging Cell Morphological Behaviors And Molecular Dynamics In Multi-Modal Spatial Omics With Morphlink, Jing Huang, Chenyang Yuan, Jiahui Jiang, Jianfeng Chen, Sunil S Badve, Yesim Gokmen-Polar, Rossana L Segura, Xinmiao Yan, Alexander Lazar, Jianjun Gao, Bing Yao, Michael Epstein, Linghua Wang, Jian Hu

Faculty, Staff and Student Publications

Multi-modal spatial omics data are invaluable for exploring complex cellular behaviors in diseases from both morphological and molecular perspectives. Current analytical methods primarily focus on clustering and classification, and do not adequately examine the relationship between cell morphology and molecular dynamics. Here, we present MorphLink, a framework designed to systematically identify disease-related morphological-molecular interplays. MorphLink has been evaluated across a wide array of datasets, showcasing its effectiveness in extracting and linking interpretable morphological features with various molecular measurements in spatial omics analyses. These linkages provide a transparent view of cellular behavior heterogeneity within tissue regions with similar cell type compositions, …