Digital Commons Network^™

Selecting Patients For Food Allergy Therapy, Aikaterini Anagnostou

Faculty, Staff and Students Publications

Background: Food allergies pose a significant burden on the daily life of individuals with food allergy, including dietary, psychosocial, and economic impact. The management of food allergy has shifted recently from previous passive avoidance approaches to current active therapeutic interventions.

Objective: This article aims to discuss selection of patients with food allergies for different therapies.

Methods: Published literature on risks and benefits of various therapies as well as articles on shared decision-making were reviewed for this article. Key papers are included.

Results and conclusion: In addition to the two U.S. Food and Drug Administration approved therapies currently available (for oral …

Developmental Delay Can Precede Neurologic Regression In Early Onset Metachromatic Leukodystrophy, Laura Ann Adang, Samuel Groeschel, Chloe Grzyb, Russell D'Aiello, Francesco Gavazzi, Omar Sherbini, Nowa Bronner, Akshilkumar Patel, Ariel Vincent, Anjana Sevagamoorthy, Sylvia Mutua, Kayla Muirhead, Johanna Schmidt, Amy Pizzino, Emily Yu, Danielle Jin, Florian Eichler, Jamie L Fraser, Lisa Emrick, Keith Van Haren, Jean-Martin Boulanger, Maura Ruzhnikov, Michel Sylvain, Cam-Tu Émilie Nguyen, Ana Potic, Stephanie Keller, Ali Fatemi, Eloise Uebergang, Michele Poe, Pouneh Amir Yazdani, John Bernat, Kristen Lindstrom, Joshua L Bonkowsky, Genevieve Bernard, Chloe A Stutterd, Paul Orchard, Ashish O Gupta, Merete Ljungberg, Sabine Groenborg, Alberto Zambon, Sara Locatelli, Francesca Fumagalli, Saskia Elguen, Christiane Kehrer, Ingeborg Krägeloh-Mann, Justine Shults, Adeline Vanderver, Maria L Escolar

Faculty, Staff and Students Publications

Objective: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau. With the advent of presymptomatic screening platforms and transformative therapies, it is essential to define the onset of neurologic disease.

Methods: The specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative …

Synaptic Fidelity For Drug Development: Is It Time To Move Beyond Glutamate Release And Receptors?, Chadi G Abdallah, Amanda J F Tamman

Faculty, Staff and Students Publications

No abstract provided.

Assessing The State Of Obesity Care: Quality, Access, Guidelines, And Standards, Lee M Kaplan, Caroline M Apovian, Jamy D Ard, David B Allison, Louis J Aronne, Rachel L Batterham, Luca Busetto, Dror Dicker, Deborah B Horn, Aaron S Kelly, Jeffrey I Mechanick, Jonathan Q Purnell, Ximena Ramos-Salas, Assessing The State Of Obesity Care Writing Group

Faculty, Staff and Student Publications

BACKGROUND: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence.

AIMS: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity.

METHODS: The panel was held in Leesburg, Virginia in September 2019.

RESULTS: The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice …

Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris

Faculty, Staff and Student Publications

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used …

The Role Of An Ultraconserved Long Non-Coding Rna In B-Cell Lymphomagenesis, Swati Mohapatra

Dissertations and Theses (Open Access)

Ultraconserved regions (UCRs) are genomic segments with perfect (100%) conservation between the orthologous regions of human, rat, and mouse genomes. UCRs can be transcribed into mono-exonic long non-coding RNAs (lncRNAs) known as transcribed ultraconserved regions (T-UCRs). These regions, despite lacking protein-coding potential, are increasingly recognized for their regulatory roles in gene expression, including the modulation of non-coding RNA (ncRNA) transcripts. NcRNAs play crucial roles in cellular processes, including oncogenic transformation, with emerging evidence revealing their ability to encode small peptides known as ncRNA-encoded peptides (ncPEPs). These peptides, originating from small open reading frames (smORFs), contribute to diverse cellular functions and …

Evaluation Of Myogenic Differentiation Potential Of Bmd Ipscs In Vitro And The Effect Of Ubiquitination Inhibitors On Dystrophin Stability In Vivo, Muchen Liu

Dissertations and Theses (Open Access)

Background: Muscular dystrophies are heterogeneous groups of inherited diseases leading to progressive muscular weakness and degeneration. In the case of Becker muscular dystrophy (BMD), non-disrupting mutations of the DMD gene reading frame is the causative defect. By the age of 30s, about 60 to 70% of BMD patients develop cardiomyopathy, which is often lethal. Unfortunately, there is currently no cure for BMD. Meanwhile, improvement of dystrophin stability by repressing polyubiquitination is a promising strategy. The application of human iPSCs in tissue regeneration also serves as a potential therapeutic strategy. This study aims to test the efficacy of selected drugs interfering …

In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations and Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

Mapping The Single-Cell Differentiation Landscape Of Osteosarcoma, Danh D Truong, Corey Weistuch, Kevin A Murgas, Prasad Admane, Bridgette L King, Jes Chauviere Lee, Salah-E Lamhamedi-Cherradi, Jyothishmathi Swaminathan, Najat C Daw, Nancy Gordon, Vidya Gopalakrishnan, Richard G Gorlick, Neeta Somaiah, Joseph O Deasy, Antonios G Mikos, Allen Tannenbaum, Joseph Ludwig

Faculty, Staff and Student Publications

Purpose: The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.

Experimental design: To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.

Results: This "roadmap" served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify …

Sequential Inhibition Of Parp And Bet As A Rational Therapeutic Strategy For Glioblastoma, Xin Peng, Xin Huang, Shaolu Zhang, Naixin Zhang, Shengfan Huang, Yingying Wang, Zhenxing Zhong, Shan Zhu, Haiwang Gao, Zixiang Yu, Xiaotong Yan, Zhennan Tao, Yuxiang Dai, Zhe Zhang, Xi Chen, Feng Wang, Francois X Claret, Moshe Elkabets, Ning Ji, Yuxu Zhong, Dexin Kong

Faculty, Staff and Student Publications

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient-derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can …

Smyd5 Methylation Of Rpl40 Links Ribosomal Output To Gastric Cancer, Juhyung Park, Jibo Wu, Krzysztof J Szkop, Jinho Jeong, Predrag Jovanovic, Dylan Husmann, Natasha M Flores, Joel W Francis, Ying-Jiun C Chen, Ana Morales Benitez, Emily Zahn, Shumei Song, Jaffer A Ajani, Linghua Wang, Kamini Singh, Ola Larsson, Benjamin A Garcia, Ivan Topisirovic, Or Gozani, Pawel K Mazur

Faculty, Staff and Student Publications

Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis1,2. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites. A biochemical-proteomics strategy identifies the monoubiquitin fusion protein partner rpL40 (ref. 3) as the principal physiological substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprogrammes …

Accelerated Tumor Progression After Covid-19 Infection In Patients With Glioblastoma: A Retrospective Case-Control Study, Timothy A Gregory, Stephanie R Knight, Ashley E Aaroe, Kaitlin N Highsmith, Zachary C Janatpour, Barbara J O'Brien, Nazanin K Majd, Monica E Loghin, Chirag B Patel, Shiao-Pei Weathers, Vinay K Puduvalli, Carlos Kamiya-Matsuoka

Faculty, Staff and Student Publications

Background: We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case-control study.

Methods: Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed. Hyperprogression was defined using modified response evaluation criteria in solid tumors criteria. Time to progression and overall survival were estimated using the Kaplan-Meier method.

Results: Thirty-two glioblastoma cases with positive COVID-19 testing were …

Variability In Performance Of Genetic-Enhanced Dxa-Bmd Prediction Models Across Diverse Ethnic And Geographic Populations: A Risk Prediction Study, Yong Liu, Xiang-He Meng, Chong Wu, Kuan-Jui Su, Anqi Liu, Qing Tian, Lan-Juan Zhao, Chuan Qiu, Zhe Luo, Martha I Gonzalez-Ramirez, Hui Shen, Hong-Mei Xiao, Hong-Wen Deng

Faculty, Staff and Student Publications

BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations.

METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both …

Antitumor Activity Of A Novel Lair1 Antagonist In Combination With Anti-Pd1 To Treat Collagen-Rich Solid Tumors, Bertha L Rodriguez, Jiawei Huang, Laura Gibson, Jared J Fradette, Hung-I H Chen, Kikuye Koyano, Czrina Cortez, Betty Li, Carmence Ho, Amir M Ashique, Vicky Y Lin, Suzanne Crawley, Julie M Roda, Peirong Chen, Bin Fan, Jeong Kim, James Sissons, Jonathan Sitrin, Daniel D Kaplan, Don L Gibbons, Lee B Rivera

Faculty, Staff and Student Publications

We recently reported that resistance to PD-1 blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1). Thus, we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. In this study, we report that LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer. Stroma-associated myeloid cells exhibit a suppressive phenotype and correlate with LAIR1 expression in human cancer. NGM438, a novel humanized LAIR1 antagonist mAb, elicits myeloid inflammation and allogeneic T-cell responses by binding …

A Randomised, Parallel-Group, Double-Blind, Placebo-Controlled Phase 3 Study To Determine The Effectiveness Of The Type I Interferon Receptor Antibody, Anifrolumab, In Systemic Sclerosis: Daisy Study Design And Rationale, Dinesh Khanna, Christopher P Denton, Shervin Assassi, Masataka Kuwana, Yannick Allanore, Robyn T Domsic, Christi Kleoudis, John Xu, Eszter Csomor, Caroline Seo, Marius Albulescu, Raj Tummala, Hussein Al-Mossawi, Rubana N Kalyani, Francesco Del Galdo

Faculty, Staff and Student Publications

Objectives: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY).

Methods: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, …

Ephb2 Receptor Promotes Dermal Fibrosis In Systemic Sclerosis, Erika S A Egal, Severin Donald Kamdem, Masaaki Yoshigi, Ching-Chu Yang, Sarah Pellizzari, Ernest M Kameni, My N Helms, Shervin Assassi, Mark Henkemeyer, Tracy M Frech, Patrice N Mimche

Faculty, Staff and Student Publications

Objective: Erythropoietin-producing hepatocellular (Eph)/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc).

Methods: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting EphB2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models of skin fibrosis. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward signaling in bleomycin-induced dermal fibrosis. In …

From Disorder Comes Function: Regulation Of Small Gtpase Function By Intrinsically Disordered Lipidated Membrane Anchor, Chase M Hutchins, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The intrinsically disordered, lipid-modified membrane anchor of small GTPases is emerging as a critical modulator of function through its ability to sort lipids in a conformation-dependent manner. We reviewed recent computational and experimental studies that have begun to shed light on the sequence-ensemble-function relationship in this unique class of lipidated intrinsically disordered regions (LIDRs).

Myeloablation Followed By Hematopoietic Stem Cell Transplantation And Long-Term Normalization Of Systemic Sclerosis Molecular Signatures, Nancy Wareing, Xuan Wang, Lynette Keyes-Elstein, Ellen A Goldmuntz, Marka A Lyons, Peter Mcsweeney, Daniel E Furst, Richard A Nash, Leslie J Crofford, Beverly Welch, Ashley Pinckney, Maureen D Mayes, Keith M Sullivan, Shervin Assassi

Faculty, Staff and Student Publications

Objective: In the randomized Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to the normalization of systemic sclerosis (SSc) peripheral blood cell (PBC) gene expression signature at the 26-month visit. Herein, we examined long-term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC).

Methods: Global PBC transcript studies were performed in study participants at pretreatment baseline and at 38 months and 54 months after randomization, as well as in healthy controls using Illumina HT-12 arrays.

Results: Thirty (HSCT = 19 and CYC = …

Assessment Of Gfr In Patients With Cancer: A Statement From The American Society Of Onco-Nephrology, Abhijat Kitchlu, Verônica T Costa E Silva, Shuchi Anand, Jaya Kala, Ala Abudayyeh, Lesley A Inker, Mitchell H Rosner, Sabine Karam, Prakash Gudsoorkar, Shruti Gupta, Sheldon Chen, Nattawat Klomjit, Nelson Leung, Tomaz Milanez, Shveta S Motwani, Sheikh B Khalid, Vinay Srinivasan, Rimda Wanchoo, Jan H Beumer, Geoffrey Liu, Nizar M Tannir, Ani Orchanian-Cheff, Yimin Geng, Sandra M Herrmann

Faculty, Staff and Student Publications

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and …

Electrical Stimulation Of The Dorsal Motor Nucleus Of The Vagus In Male Mice Can Regulate Inflammation Without Affecting The Heart Rate, Aidan Falvey, Santhoshi P Palandira, Sangeeta S Chavan, Michael Brines, Robert Dantzer, Kevin J Tracey, Valentin A Pavlov

Faculty, Staff and Student Publications

Background: The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide …

Collaborative Filtering For The Imputation Of Patient Reported Outcomes, Eric Ababio Anyimadu, Clifton David Fuller, Xinhua Zhang, G Elisabeta Marai, Guadalupe Canahuate

Faculty, Staff and Student Publications

This study addresses the prevalent issue of missing data in patient-reported outcome datasets, particularly focusing on head and neck cancer patient symptom ratings sourced from the MD Anderson Symptom Inventory. Given that many data mining and machine learning algorithms necessitate complete datasets, the accurate imputation of missing data as an initial step becomes crucial. In this study we propose, for the first time, the use of collaborative filtering for imputing missing head and neck cancer patient symptom ratings. Two configurations of collaborative filtering, namely patient-based and symptom-based, leverage known ratings to infer the missing ones. Additionally, this study compares the …

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation Of Refractory Erectile Dysfunction, Yang Xiong, Feng Qin, Shanzun Wei, Xingliang Yang, Jun Li, Changjing Wu, Fuxun Zhang, Jiuhong Yuan

Faculty, Staff and Student Publications

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, …

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 …

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 …

Shared Delusion: Impact On The Parent-Child Relationship, Ngozi Adaralegbe, Ayotomide Oyelakin, Omobusayo Omotayo

Faculty, Staff and Student Publications

Folie à famille, also known as shared psychotic disorder among family members, is a rare and underdiagnosed psychiatric condition. This disorder, seldom discussed in the literature, is particularly notable for its impact on clinical management and parent-child relationships. The few reported cases have predominantly focused on adult populations, leaving a significant gap in understanding how this condition manifests and affects younger individuals and family dynamics. One area that remains largely unexplored in the literature is the intersection between attachment patterns and shared psychosis, particularly in the context of parent-child relationships. Understanding this intersection is crucial, as it can provide insights …

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 …

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 …

Candida Albicans Natural Diversity: A Resource To Dissect Fungal Commensalism And Pathogenesis, Elena Lindemann-Perez, J Christian Perez

Faculty, Staff and Student Publications

Candida albicans is a ubiquitous fungus of humans. It is not only a component of the oral and intestinal microbiota of most healthy adults but also a major cause of mucosal disorders and life-threatening disseminated infections. Until recently, research on the biology and pathogenesis of the fungus was largely based on a single clinical isolate. We review investigations that have started to dissect a diverse set of C. albicans strains. Using different approaches to leverage the species' phenotypic and/or genetic diversity, these studies illuminate the wide range of interactions between fungus and host. While connecting genetic variants to phenotypes of …

Patient-Derived Organoids As Therapy Screening Platforms In Cancer Patients, Danial Khorsandi, Jia-Wei Yang, Samuel Foster, Safoora Khosravi, Negar Hosseinzadeh Kouchehbaghi, Fahimeh Zarei, Yun Bin Lee, Farhana Runa, Ankit Gangrade, Leon Voskanian, Darbaz Adnan, Yangzhi Zhu, Zhaohui Wang, Vadim Jucaud, Mehmet Remzi Dokmeci, Xiling Shen, Faraz Bishehsari, Jonathan A Kelber, Ali Khademhosseini, Natan Roberto De Barros

Faculty, Staff and Student Publications

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. …

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 …