Medicine and Health Sciences Commons^™

Estimating The Direct Effects Of The Genetic Liabilities To Bipolar Disorder, Schizophrenia, And Behavioral Traits On Suicide Attempt Using A Multivariable Mendelian Randomization Approach, Brenda Cabrera-Mendoza, Necla Aydin, Gabriel R Fries, Anna R Docherty, Consuelo Walss-Bass, Renato Polimanti

Faculty, Staff and Student Publications

Bipolar disorder (BD) and schizophrenia (SZ) are associated with higher odds of suicide attempt (SA). In this study, we aimed to explore the effect of BD and SZ genetic liabilities on SA, also considering the contribution of behavioral traits, socioeconomic factors, and substance use disorders. Leveraging large-scale genome-wide association data from the Psychiatric Genomics Consortium (PGC) and the UK Biobank (UKB), we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the putative causal effect of BD (41,917 cases, 371,549 controls) and SZ (53,386 cases, 77,258 controls) on SA (26,590 cases, 492,022 controls). Then, we assessed the putative causal effect …

Markov Models For Clinical Decision-Making In Radiation Oncology: A Systematic Review, Lucas B Mccullum, Aysenur Karagoz, Cem Dede, Raul Garcia, Fatemeh Nosrat, Mehdi Hemmati, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

The intrinsic stochasticity of patients' response to treatment is a major consideration for clinical decision-making in radiation therapy. Markov models are powerful tools to capture this stochasticity and render effective treatment decisions. This paper provides an overview of the Markov models for clinical decision analysis in radiation oncology. A comprehensive literature search was conducted within MEDLINE using PubMed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies published from 2000 to 2023 were considered. Selected publications were summarized in two categories: (i) studies that compare two (or more) fixed treatment policies using Monte Carlo simulation …

Pb-05204, A Supercritical Co2 Extract Of Nerium Oleander, Suppresses Glioblastoma Stem Cells By Inhibiting Grp78 And Inducing Programmed Necroptotic Cell Death, Sharmistha Chakraborty, Daoyan Wei, Megan Tran, Frederick F Lang, Robert A Newman, Peiying Yang

Faculty, Staff and Student Publications

Successful treatment of glioblastoma multiforme (GBM), an aggressive form of primary brain neoplasm, mandates the need to develop new therapeutic strategies. In this study, we investigated the potential of PBI-05204 in targeting GBM stem cells (GSCs) and the underlying mechanisms. Treatment with PBI-05204 significantly reduced both the number and size of tumor spheres derived from patient-derived GSCs (GBM9, GSC28 and TS543), and suppressed the tumorigenesis of GBM9 xenografts. Moreover, PBI-05204 treatment led to a significant decrease in the expression of CD44 and NANOG, crucial markers of progenitor stem cells, in GBM9 and GSC28 GSCs. This treatment also down-regulated GRP78 expression …

Pharmacodynamic Activity Of [18f]-Fluorthanatrace Poly(Adp-Ribose) Polymerase Positron Emission Tomography In Patients With Brca1/2-Mutated Breast Cancer Receiving Talazoparib, Lilie L Lin, Franklin Wong, Ruitao Lin, Timothy Yap, Jennifer K Litton

Faculty, Staff and Student Publications

Purpose: We tested the ability of [18F] fluorthanatrace (FTT), a radiolabeled analog of poly(ADP-ribose) polymerase (PARP)-1 inhibitors, to demonstrate target engagement on positron emission tomography (PET) scans from patients with newly diagnosed primary breast cancer receiving the PARP inhibitor (PARPi) talazoparib.

Methods: Seven patients with germline BRCA1/2 pathogenic variants underwent [18F]FTT PET-computed tomography scanning at baseline, and five underwent repeat scanning 14 days after talazoparib initiation. Maximum uptake on PET was quantified in the primary tumor, involved nodes, contralateral pectoralis muscle, and lumbar vertebra body level 3, and compared between the two time points.

Results: Blocking of [18F]FTT was observed …

Patient Education Practices And Preferences Of Radiation Oncologists And Interprofessional Radiation Therapy Care Teams: A Mixed-Methods Study Exploring Strategies For Effective Patient Education Delivery, Jie Jane Chen, Anna M Brown, Allison E Garda, Ellen Kim, Sarah A Mcavoy, Subha Perni, Michael K Rooney, Kevin Shiue, Kristi L Tonning, Laura E Warren, Daniel W Golden, Jennifer M Croke

Faculty, Staff and Student Publications

Purpose: Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE.

Methods and materials: An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE …

A First-In-Class Selective Inhibitor Of Egfr And Pi3k Offers A Single-Molecule Approach To Targeting Adaptive Resistance, Christopher E Whitehead, Elizabeth K Ziemke, Christy L Frankowski-Mcgregor, Rachel A Mumby, June Chung, Jinju Li, Nathaniel Osher, Oluwadara Coker, Veerabhadran Baladandayuthapani, Scott Kopetz, Judith S Sebolt-Leopold

Faculty, Staff and Student Publications

Despite tremendous progress in precision oncology, adaptive resistance mechanisms limit the long-term effectiveness of molecularly targeted agents. Here we evaluated the pharmacological profile of MTX-531 that was computationally designed to selectively target two key resistance drivers, epidermal growth factor receptor and phosphatidylinositol 3-OH kinase (PI3K). MTX-531 exhibits low-nanomolar potency against both targets with a high degree of specificity predicted by cocrystal structural analyses. MTX-531 monotherapy uniformly resulted in tumor regressions of squamous head and neck patient-derived xenograft (PDX) models. The combination of MTX-531 with mitogen-activated protein kinase kinase or KRAS-G12C inhibitors led to durable regressions of BRAF-mutant or KRAS-mutant colorectal …

Perioperative Nivolumab Versus Observation In Patients With Renal Cell Carcinoma Undergoing Nephrectomy (Prosper Ecog-Acrin Ea8143): An Open-Label, Randomised, Phase 3 Study, Mohamad E Allaf, Se-Eun Kim, Viraj Master, David F Mcdermott, Lauren C Harshman, Suzanne M Cole, Charles G Drake, Sabina Signoretti, Mahmut Akgul, Nicholas Baniak, Elsa Li-Ning, Matthew B Palmer, Hamid Emamekhoo, Nabil Adra, Hristos Kaimakliotis, Yasser Ged, Phillip M Pierorazio, E Jason Abel, Mehmet A Bilen, Kenneth Ogan, Helen H Moon, Krishna A Ramaswamy, Eric A Singer, Tina M Mayer, Jay Lohrey, Vitaly Margulis, Jessie Gills, Scott E Delacroix, Mark J Waples, Andrew C James, Peng Wang, Toni Choueiri, M Dror Michaelson, Anil Kapoor, Daniel Y Heng, Brian Shuch, Bradley C Leibovich, Primo N Lara, Judith Manola, Deborah Maskens, Dena Battle, Robert Uzzo, Gennady Bratslavsky, Naomi B Haas, Michael A Carducci

Faculty, Staff and Student Publications

Background: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only.

Methods: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or …

Updated Understanding Of The Protein-Dna Recognition Code Used By C2h2 Zinc Finger Proteins, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

C2H2 zinc-finger (ZF) proteins form the largest family of DNA-binding transcription factors coded by mammalian genomes. In a typical DNA-binding ZF module, there are twelve residues (numbered from -1 to -12) between the last zinc-coordinating cysteine and the first zinc-coordinating histidine. The established C2H2-ZF "recognition code" suggests that residues at positions -1, -4, and -7 recognize the 5', central, and 3' bases of a DNA base-pair triplet, respectively. Structural studies have highlighted that additional residues at positions -5 and -8 also play roles in specific DNA recognition. The presence of bulky and either charged or polar residues at these five …

P53r172h And P53r245w Hotspot Mutations Drive Distinct Transcriptomes In Mouse Mammary Tumors Through A Convergent Transcriptional Mediator, Joy M Mcdaniel, Rhiannon L Morrissey, Denada Dibra, Lalit R Patel, Shunbin Xiong, Yun Zhang, Gilda P Chau, Xiaoping Su, Yuan Qi, Adel K El-Naggar, Guillermina Lozano

Faculty, Staff and Student Publications

Aggressive breast cancers harbor TP53 missense mutations. Tumor cells with TP53 missense mutations exhibit enhanced growth and survival through transcriptional rewiring. To delineate how TP53 mutations in breast cancer contribute to tumorigenesis and progression in vivo, we created a somatic mouse model driven by mammary epithelial cell-specific expression of Trp53 mutations. Mice developed primary mammary tumors reflecting the human molecular subtypes of luminal A, luminal B, HER2-enriched, and triple-negative breast cancer with metastases. Transcriptomic analyses comparing MaPR172H/− or MaPR245W/− mammary tumors to MaP−/− tumors revealed (1) differences in cancer-associated pathways activated in both p53 …

A Qualitative Exploration To Inform An Oral Health Training For Disability Care Workers In Burkina Faso, Ave Põld, Dan Filwendé Kientega, Jocelyne Valérie Garé, Michael Lorenz

Faculty, Staff and Student Publications

AIM: To explore enablers and barriers to the creation of an oral health training for care workers at specialized centres for children with disabilities in Ouagadougou.

DESIGN: This was a formative study informed by the Theoretical Domains Framework using qualitative methods.

METHODS: Qualitative observations and 14 semi-structured interviews were conducted with care workers from six specialized centres for disability.

RESULTS: Carer workers emphasized that a successful oral health training must account for available resources and competencies in each specific centre. Part of the training must be dedicated to oral hygiene targeted for people with disabilities and provide knowledge about risk …

Sotatercept For Anemia Of Myelofibrosis: A Phase Ii Investigator-Initiated Study, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Sharon D Bledsoe, Naval G Daver, Elias J Jabbour, Tapan M Kadia, Zeev Estrov, Steven M Kornblau, Michael Andreeff, Nitin Jain, Jorge E Cortes, Gautam Borthakur, Yesid Alvarado, Mary Ann Richie, Mackenzie H Dobbins, Selene A Mccrackin, Lingsha Zhou, Sherry A Pierce, Xuemei Wang, Allison M Pike, Guillermo Garcia-Manero, Hagop M Kantarjian, Srdan Verstovsek

Faculty, Staff and Student Publications

No abstract provided.

Structural Dynamics In Α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid Receptor Gating, Cuauhtemoc U Gonzalez, Vasanthi Jayaraman

Faculty, Staff and Student Publications

The ionotropic glutamate receptors (iGluRs) are comprised of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), N-methyl-d-aspartate receptor, kainate, and delta subtypes and are pivotal in neuronal plasticity. Recent structural studies on AMPA receptors reveal intricate conformational changes during activation and desensitization elucidating the steps from agonist binding to channel opening and desensitization. Additionally, interactions with auxiliary subunits, including transmembrane AMPA-receptor regulatory proteins, germ-cell-specific gene 1-like protein, and cornichon homologs, intricately modulate AMPA receptors. We discuss the recent high-resolution structures of these complexes that unveil stoichiometry, subunit positioning, and differences in specific side-chain interactions that influence these functional modulations.

Stratifying Heart Failure Patients With Graph Neural Network And Transformer Using Electronic Health Records To Optimize Drug Response Prediction, Shaika Chowdhury, Yongbin Chen, Pengyang Li, Sivaraman Rajaganapathy, Andrew Wen, Xiao Ma, Qiying Dai, Yue Yu, Sunyang Fu, Xiaoqian Jiang, Zhe He, Sunghwan Sohn, Xiaoke Liu, Suzette J Bielinski, Alanna M Chamberlain, James R Cerhan, Nansu Zong

Faculty, Staff and Student Publications

Objectives: Heart failure (HF) impacts millions of patients worldwide, yet the variability in treatment responses remains a major challenge for healthcare professionals. The current treatment strategies, largely derived from population based evidence, often fail to consider the unique characteristics of individual patients, resulting in suboptimal outcomes. This study aims to develop computational models that are patient-specific in predicting treatment outcomes, by utilizing a large Electronic Health Records (EHR) database. The goal is to improve drug response predictions by identifying specific HF patient subgroups that are likely to benefit from existing HF medications.

Materials and methods: A novel, graph-based model capable …

Assessing The Reproducibility Of Research Based On The Food And Drug Administration Manufacturer And User Facility Device Experience Data, Xinyu Li, Yubo Feng, Yang Gong, You Chen

Faculty, Staff and Student Publications

Objective: This article aims to assess the reproducibility of Manufacturer and User Facility Device Experience (MAUDE) data-driven studies by analyzing the data queries used in their research processes.

Methods: Studies using MAUDE data were sourced from PubMed by searching for "MAUDE" or "Manufacturer and User Facility Device Experience" in titles or abstracts. We manually chose articles with executable queries. The reproducibility of each query was assessed by replicating it in the MAUDE Application Programming Interface. The reproducibility of a query is determined by a reproducibility coefficient that ranges from 0.95 to 1.05. This coefficient is calculated by comparing the number …

Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants That Confer Risk For Breast Cancer, Xiaohui Sun, Shiv P Verma, Guochong Jia, Xinjun Wang, Jie Ping, Xingyi Guo, Xiao-Ou Shu, Jianhong Chen, Andriy Derkach, Qiuyin Cai, Xiaolin Liang, Jirong Long, Kenneth Offit, Jung H Oh, Anne S Reiner, Gordon P Watt, Meghan Woods, Yaohua Yang, Christine B Ambrosone, Stefan Ambs, Yu Chen, Patrick Concannon, Montserrat Garcia-Closas, Jian Gu, Christopher A Haiman, Jennifer J Hu, Dezheng Huo, Esther M John, Julia A Knight, Christopher I Li, Charles F Lynch, Lene Mellemkjær, Katherine L Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Andrew F Olshan, Tuya Pal, Julie R Palmer, Michael F Press, Maureen Sanderson, Dale P Sandler, Melissa A Troester, Wei Zheng, Jonine L Bernstein, Matthew F Buas, Xiang Shu

Faculty, Staff and Student Publications

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead …

Why Do Patients With Cancer Die?, Adrienne Boire, Katy Burke, Thomas R Cox, Theresa Guise, Mariam Jamal-Hanjani, Tobias Janowitz, Rosandra Kaplan, Rebecca Lee, Charles Swanton, Matthew G Vander Heiden, Erik Sahai

Faculty, Staff and Student Publications

Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier deployment of existing strategies to prolong quality of life is highly desirable. In this …

A Cell Cycle-Aware Network For Data Integration And Label Transferring Of Single-Cell Rna-Seq And Atac-Seq, Jiajia Liu, Jian Ma, Jianguo Wen, Xiaobo Zhou

Faculty, Staff and Student Publications

In recent years, the integration of single-cell multi-omics data has provided a more comprehensive understanding of cell functions and internal regulatory mechanisms from a non-single omics perspective, but it still suffers many challenges, such as omics-variance, sparsity, cell heterogeneity, and confounding factors. As it is known, the cell cycle is regarded as a confounder when analyzing other factors in single-cell RNA-seq data, but it is not clear how it will work on the integrated single-cell multi-omics data. Here, a cell cycle-aware network (CCAN) is developed to remove cell cycle effects from the integrated single-cell multi-omics data while keeping the cell …

The Surgical Infection Society Guidelines On The Management Of Intra-Abdominal Infection: 2024 Update, Jared M Huston, Philip S Barie, E Patchen Dellinger, Joseph D Forrester, Therese M Duane, Jeffrey M Tessier, Robert G Sawyer, Miguel A Cainzos, Kemal Rasa, Jeffrey G Chipman, Lillian S Kao, Frederic M Pieracci, Kristin P Colling, Daithi S Heffernan, Janice Lester

Faculty, Staff and Student Publications

Background: The Surgical Infection Society (SIS) published evidence-based guidelines for the management of intra-abdominal infection (IAI) in 1992, 2002, 2010, and 2017. Here, we present the most recent guideline update based on a systematic review of current literature.

Methods: The writing group, including current and former members of the SIS Therapeutics and Guidelines Committee and other individuals with content or guideline expertise within the SIS, working with a professional librarian, performed a systematic review using PubMed/Medline, the Cochrane Library, Embase, and Web of Science from 2016 until February 2024. Keyword descriptors combined "surgical site infections" or "intra-abdominal infections" in adults …

Assessment Of Thrombectomy Versus Combined Thrombolysis And Thrombectomy In Patients With Acute Ischemic Stroke And Medium Vessel Occlusion, Adam A Dmytriw, Sherief Ghozy, Hamza Adel Salim, Basel Musmar, James E Siegler, Hassan Kobeissi, Hamza Shaikh, Jane Khalife, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Jeremy J Heit, Robert W Regenhardt, Nicole M Cancelliere, Kareem El Naamani, Abdelaziz Amllay, Lukas Meyer, Anne Dusart, Flavio Bellante, Géraud Forestier, Aymeric Rouchaud, Suzana Saleme, Charbel Mounayer, Jens Fiehler, Anna Luisa Kühn, Ajit S Puri, Christian Dyzmann, Peter T Kan, Marco Colasurdo, Gaultier Marnat, Jérôme Berge, Xavier Barreau, Igor Sibon, Simona Nedelcu, Nils Henninger, Thomas R Marotta, Christopher J Stapleton, James D Rabinov, Takahiro Ota, Shogo Dofuku, Leonard L L Yeo, Benjamin Y Q Tan, Juan Carlos Martinez-Gutierrez, Sergio Salazar-Marioni, Sunil Sheth, Leonardo Renieri, Carolina Capirossi, Ashkan Mowla, Nimer Adeeb, Hugo H Cuellar-Saenz, Stavropoula I Tjoumakaris, Pascal Jabbour, Priyank Khandelwal, Arundhati Biswas, Frédéric Clarençon, Mahmoud Elhorany, Kevin Premat, Iacopo Valente, Alessandro Pedicelli, João Pedro Filipe, Ricardo Varela, Miguel Quintero-Consuegra, Nestor R Gonzalez, Markus A Möhlenbruch, Jessica Jesser, Vincent Costalat, Adrien Ter Schiphorst, Vivek Yedavalli, Pablo Harker, Lina M Chervak, Yasmin Aziz, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Ramanathan Kadirvel, Monika Killer-Oberpfalzer, Christoph J Griessenauer, Ajith J Thomas, Cheng-Yang Hsieh, David S Liebeskind, Răzvan Alexandru Radu, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Robert Fahed, Charlotte S Weyland, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Mad-Mt Consortium

Faculty, Staff and Student Publications

Background

The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion.

Purpose

To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion.

Materials and Methods

This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and …

Contributions Of Capsular Releases To Femoral Exposure In Total Hip Arthroplasty Via The Direct Anterior Approach, Shuyang Han, Zackary Byrd, Sabir K Ismaily, Luis E Delgadillo, Adam M Freedhand, David Rodriguze-Quintana, Philip C Noble

Faculty, Staff and Student Publications

Background: In total hip arthroplasty via the direct anterior approach, appropriate exposure is critical to allow preparation of the femur. The objective of this study was to explore the optimal soft tissue releases needed to allow broaching of the femur through a combination of experimental tests and computer simulations.

Methods: Fourteen full-body cadaveric specimens were included in this study. Total hip arthroplasty was performed via the direct anterior approach with the femur at 20° adduction and 20°extension. Soft tissue releases were performed sequentially, namely, the transverse iliofemoral ligament, descending iliofemoral ligament, ischio-femoral ligament, conjoint tendon, and obturator externus. After each …

African American Patients Have A Higher Probability Of Cognitive Impairment After Incident Stroke: An Analysis Of National Electronic Health Record Data, Alicia Zha, Chenguang Zhang, Gen Zhu, Xinran Huang, Sahar Anjum, Yashar Talebi, Sean Savitz, Hulin Wu

Faculty, Staff and Student Publications

Background: Cognitive impairment (CI) and stroke are diseases with significant disparities in race and geography. Post stroke cognitive impairment (PSCI) can be as high as 15-70 % but few studies have utilized large administrative or electronic health records (EHR) to evaluate trends in PSCI. We utilized an EHR database to evaluate for disparities in PSCI in a large sample of patients after first recorded stroke to evaluate for disparities in race.

Methods: This is a retrospective cohort analysis of Cerner Health Facts® EHR database, which is comprised of EHR data from hundreds of hospitals/clinics in the US from 2009-2018. We …

Practice Patterns And Barriers To Vascular Genetic Testing Among Vascular Surgeons, James M Dittman, Siddharth K Prakash, Prem Chand Gupta, Wojciech Wiszniewski, Niten Singh, Matthew R Smeds, Sherene Shalhub

Faculty, Staff and Student Publications

Introduction: Engaging patients living with or at risk of aortic dissection via the Aortic Dissection Collaborative, physician education in vascular genetics was identified as a research priority. We surveyed vascular surgeons to characterize practice patterns, motivations, and barriers regarding aortopathy genetic testing.

Methods: An anonymous 27-question survey was distributed on social media platforms between November and December 2022. Domains included demographics, vascular genetic education, testing attitudes and utilization, and experience in treating patients with genetic vascular aortopathies. The analysis included summary statistics and unpaired t-test to compare responses by interest in incorporating testing and practice type.

Results: A total of …

4d Dynamic Spatial Brain Networks At Rest Linked To Cognition Show Atypical Variability And Coupling In Schizophrenia, Krishna Pusuluri, Zening Fu, Robyn Miller, Godfrey Pearlson, Peter Kochunov, Theo G M Van Erp, Armin Iraji, Vince D Calhoun

Faculty, Staff and Student Publications

Despite increasing interest in the dynamics of functional brain networks, most studies focus on the changing relationships over time between spatially static networks or regions. Here we propose an approach to study dynamic spatial brain networks in human resting state functional magnetic resonance imaging (rsfMRI) data and evaluate the temporal changes in the volumes of these 4D networks. Our results show significant volumetric coupling (i.e., synchronized shrinkage and growth) between networks during the scan, that we refer to as dynamic spatial network connectivity (dSNC). We find that several features of such dynamic spatial brain networks are associated with cognition, with …

Knowledge Representation And Management: 2023 Highlights And The Rise Of Knowledge Graph Embeddings, Jean Charlet, Licong Cui, Section Editors For The Imia Yearbook Section On Knowledge Representation And Management

Faculty, Staff and Student Publications

Objectives: We aim to identify, select, and summarize the best papers published in 2023 for the Knowledge Representation and Management (KRM) section of the International Medical Informatics Association (IMIA) Yearbook.

Methods: We performed PubMed queries and adhered to the IMIA Yearbook guidelines for conducting biomedical informatics literature review to select the best papers in KRM published in 2023.

Results: Our search yielded a total of 1,666 publications from PubMed. From these, we identified 15 papers as potential candidates for the best papers, and three of them were finally selected as the best papers in the KRM section. The candidate best …

Endotrophin As A Biomarker For Severe Acute Kidney Injury And Major Adverse Kidney Events, Alexander H Flannery, Dawei Bu, Madison Botkins, Fabiola Gianella, Ningyan Zhang, Zhiqiang An, Orson W Moe, Philipp E Scherer, Javier A Neyra

Faculty, Staff and Student Publications

Key Points:

• Endotrophin (ETP), a circulating marker of fibroinflammation, is elevated in critically ill patients with AKI.
• ETP is independently associated with major adverse kidney events at hospital discharge.
• Sustained elevations of ETP at 5–7 days are associated with major adverse kidney events.

Background: The search for novel biomarkers in AKI continues, both for being able to predict adverse events in AKI but also for confirming pathogenic pathways as potential therapeutic targets. Endotrophin (ETP) is an emerging biomarker in a number of fibroinflammatory diseases. We sought to test the association of ETP with the development of a major adverse kidney …

Effect Of Semaglutide On Regression And Progression Of Glycemia In People With Overweight Or Obesity But Without Diabetes In The Select Trial, Steven E Kahn, John E Deanfield, Ole Kleist Jeppesen, Scott S Emerson, Trine Welløv Boesgaard, Helen M Colhoun, Robert F Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos, Deborah Bade Horn, Irene M Hramiak, Ania M Jastreboff, Alexander Kokkinos, Michael Maeng, Ana Laura S A Matos, Francisco J Tinahones, A Michael Lincoff, Donna H Ryan, Select Trial Investigators

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.

RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c

RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference …

Structure And Function Are Not The Same: The Case For Restoring Mechanoreceptor Continuity Following Anterior Cruciate Ligament Injury, Jillian E Beveridge, Payam Zandiyeh, Brett D Owens, Ata M Kiapour, Braden C Fleming

Faculty, Staff and Student Publications

Anterior cruciate ligament (ACL) injury, particularly in increasingly young and active adolescents, continues to pose a clinical challenge with re-injury rates reported as high as 30%. Evidence also suggests that current standard-of-care ACL reconstruction (ACLR) does not mitigate post-traumatic osteoarthritis (PTOA) risk. Bridge- enhanced ACL restoration (BEAR) is a recently developed and tested ACL surgery that promotes primary healing of the native ACL with excellent early results. BEAR has shown to reduce signs of early PTOA compared to ACLR in an animal model. Here, we describe a theoretical framework related to re-innervation that can clarify why the outcomes of ACLR …

Consensus Statement On The Management Of Nonthrombotic Iliac Vein Lesions From The Viva Foundation, The American Venous Forum, And The American Vein And Lymphatic Society., Kush R Desai, Saher S Sabri, Steve Elias, Paul J Gagne, Mark J Garcia, Kathleen Gibson, Misaki M Kiguchi, Santhosh J Mathews, Erin H Murphy, Eric A Secemsky, Windsor Ting, Raghu Kolluri

Heart and Vascular Articles

A nonthrombotic iliac vein lesion is defined as the extrinsic compression of the iliac vein. Symptoms of lower extremity chronic venous insufficiency or pelvic venous disease can develop secondary to nonthrombotic iliac vein lesion. Anatomic compression has been observed in both symptomatic and asymptomatic patients. Causative factors that lead to symptomatic manifestations remain unclear. To provide guidance for providers treating patients with nonthrombotic iliac vein lesion, the VIVA Foundation convened a multidisciplinary group of leaders in venous disease management with representatives from the American Venous Forum and the American Vein and Lymphatic Society. Consensus statements regarding nonthrombotic iliac vein lesions …

Association Between Intravenous Fluids During Labor And Primary Postpartum Hemorrhage: A Retrospective Cohort Study, Belinda R Bruce, Heather L Shepherd, Saleem Ahmed Khan, Charlotte R Haunton, Julie Leask, Bradley S De Vries

Faculty, Staff and Student Publications

INTRODUCTION: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high-volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labor (<2500 >mL).

MATERIAL AND METHODS: A retrospective cohort study was conducted at a …

Vertebrate And Invertebrate Animal Infection Models Of Candida Auris Pathogenicity, Melissa Martinez, Danielle A Garsin, Michael C Lorenz

Faculty, Staff and Student Publications

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies …