Digital Commons Network^™

Higher Amyloid Is Associated With Greater Loneliness Among Cognitively Normal Older Adults During The Covid-19 Pandemic [Version 2; Peer Review: 2 Approved], Abigail Kehrer-Dunlap, Rebecca Bollinger, Szu-Wei Chen, Audrey Keleman, Regina Thompson, Anne Fagan, Beau Ances, Susan Stark

2020-Current year OA Pubs

BACKGROUND: Loneliness has been associated with several consequences, including increased risk of developing Alzheimer disease (AD). Loneliness may arise during the preclinical phase of AD, but little is known about the relationship between loneliness and amyloid accumulation consistent with preclinical AD. Therefore, the purpose of this study was to examine the relationship between amyloid accumulation and subjective experiences of loneliness among cognitively normal older adults during the COVID-19 pandemic.

METHODS: A global Clinical Dementia Rating

RESULTS: The 108 participants had a mean age of 75.0 and an average amyloid accumulation of 22.2 ± 31.9. Mean UCLA Loneliness Scale scores were …

Neonatal Motor Functional Connectivity And Motor Outcomes At Age Two Years In Very Preterm Children With And Without High-Grade Brain Injury, Peppar E P Cyr, Rachel E Lean, Jeanette K Kenley, Sydney Kaplan, Dominique E Meyer, Jeffery J Neil, Dimitrios Alexopoulos, Rebecca G Brady, Joshua S Shimony, Thomas L Rodebaugh, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.

The First 20 Months Of The Covid-19 Pandemic: Mortality, Intubation And Icu Rates Among 104,590 Patients Hospitalized At 21 United States Health Systems, Michael C. Fiore, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.

STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR …

Temporal Cohort Logic, Guo-Qiang Zhang, Xiaojin Li, Yan Huang, Licong Cui

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

Interleukin-1Β Secretion Induced By Mucosa-Associated Gut Commensal Bacteria Promotes Intestinal Barrier Repair, Wan-Jung H Wu, Myunghoo Kim, Lin-Chun Chang, Adrien Assie, Fatima B Saldana-Morales, Daniel F Zegarra-Ruiz, Kendra Norwood, Buck S Samuel, Gretchen E Diehl

Faculty, Staff and Students Publications

The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX3CR1+ mononuclear phagocytes, including CX3CR1+ macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro …

Identification Of Serum Mirna Signature And Establishment Of A Nomogram For Risk Stratification In Patients With Pancreatic Ductal Adenocarcinoma, Raju Kandimalla, Tadanobu Shimura, Saurav Mallik, Fuminori Sonohara, Susan Tsai, Douglas B Evans, Song Cheol Kim, Hideo Baba, Yasuhiro Kodera, Daniel Von Hoff, Xi Chen, Ajay Goel

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging.

METHODS: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. …

Hypermethylation Of Pi3k-Akt Signalling Pathway Genes Is Associated With Human Neural Tube Defects, Tian Tian, Xinyuan Lai, Kuanhui Xiang, Xiao Han, Shengju Yin, Robert M Cabrera, John W Steele, Yunping Lei, Xuanye Cao, Richard H Finnell, Linlin Wang, Aiguo Ren

Faculty, Staff and Students Publications

Neural tube defects (NTDs) are a group of common and severe congenital malformations. The PI3K-AKT signalling pathway plays a crucial role in the neural tube development. There is limited evidence concerning any possible association between aberrant methylation in PI3K-AKT signalling pathway genes and NTDs. Therefore, we aimed to investigate potential associations between aberrant methylation of PI3K-AKT pathway genes and NTDs. Methylation studies of PI3K-AKT pathway genes utilizing microarray genome-methylation data derived from neural tissues of ten NTD cases and eight non-malformed controls were performed. Targeted DNA methylation analysis was subsequently performed in an independent cohort of 73 NTD cases and …

The Third International Hackathon For Applying Insights Into Large-Scale Genomic Composition To Use Cases In A Wide Range Of Organisms, Kimberly Walker, Divya Kalra, Rebecca Lowdon, Guangyi Chen, David Molik, Daniela C Soto, Fawaz Dabbaghie, Ahmad Al Khleifat, Medhat Mahmoud, Luis F Paulin, Muhammad Sohail Raza, Susanne P Pfeifer, Daniel Paiva Agustinho, Elbay Aliyev, Pavel Avdeyev, Enrico R Barrozo, Sairam Behera, Kimberley Billingsley, Li Chuin Chong, Deepak Choubey, Wouter De Coster, Yilei Fu, Alejandro R Gener, Timothy Hefferon, David Morgan Henke, Wolfram Höps, Anastasia Illarionova, Michael D Jochum, Maria Jose, Rupesh K Kesharwani, Sree Rohit Raj Kolora, Jędrzej Kubica, Priya Lakra, Damaris Lattimer, Chia-Sin Liew, Bai-Wei Lo, Chunhsuan Lo, Anneri Lötter, Sina Majidian, Suresh Kumar Mendem, Rajarshi Mondal, Hiroko Ohmiya, Nasrin Parvin, Carolina Peralta, Chi-Lam Poon, Ramanandan Prabhakaran, Marie Saitou, Aditi Sammi, Philippe Sanio, Nicolae Sapoval, Najeeb Syed, Todd Treangen, Gaojianyong Wang, Tiancheng Xu, Jianzhi Yang, Shangzhe Zhang, Weiyu Zhou, Fritz J Sedlazeck, Ben Busby

Faculty, Staff and Students Publications

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov

Faculty, Staff and Students Publications

Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance. To identify genes with an excess of potentially functional missense or nonsense mutations one needs to compare the observed and expected numbers of mutations in the gene. We estimated the expected numbers of missense and nonsense mutations in individual human genes using (i) the …

Screening For Balance In Children And Adults In A Community Science Education Setting: Normative Data, Influence Of Age, Sex, And Body Mass Index, And Feasibility, Phyllis Friello, Nathan Silver, Haleh Sangi-Haghpeykar, Helen S Cohen

Faculty, Staff and Students Publications

BACKGROUND: Screening standing and walking balance is useful for people suspected of having vestibular disorders, a variety of neurologic and musculoskeletal disorders, and for screening astronauts returning after exposure to microgravity. Visitors to a community science education center children and adults, aged 4 to 85, were tested on tandem walking with eyes closed and the modified Romberg test on compliant foam. They were then asked about their experience participating in research, many people for the first time.

METHODS: Subjects performed 10 steps of tandem walking with eyes closed, and three trials of the modified Romberg, or Clinical Test of Sensory …

Subjective Versus Objective Tests Of Dizziness And Vestibular Function In Epidemiologic Screening Research, Helen S Cohen, Haleh Sangi-Haghpeykar, Michael W Plankey

Faculty, Staff and Students Publications

BACKGROUND: Many epidemiologic studies of vestibular disorders are based on responses to questionnaires which have not been tested against objective tests of the vestibular system.

OBJECTIVE: The goal was to determine if the dizziness and balance questions used in the National Health Interview Survey (NHIS) are valid and predict performance on objective tests of the vestibular system (VNG).

METHODS: Data from 367 participants recruited from the community, aged 21.4 to 87.6 years, were collected in the Otolaryngology department at a tertiary care center. They were asked the eight NHIS questions twice, at least 30 minutes apart and were tested on …

Crispr/Cas9-Mediated Genome Editing Reveals 12 Testis-Enriched Genes Dispensable For Male Fertility In Mice, Yuki Oyama, Haruhiko Miyata, Keisuke Shimada, Yoshitaka Fujihara, Keizo Tokuhiro, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Gene expression analyses suggest that more than 1000-2000 genes are expressed predominantly in mouse and human testes. Although functional analyses of hundreds of these genes have been performed, there are still many testis-enriched genes whose functions remain unexplored. Analyzing gene function using knockout (KO) mice is a powerful tool to discern if the gene of interest is essential for sperm formation, function, and male fertility in vivo. In this study, we generated KO mice for 12 testis-enriched genes, 1700057G04Rik, 4921539E11Rik, 4930558C23Rik, Cby2, Ldhal6b, Rasef, Slc25a2, Slc25a41, Smim8, Smim9, Tmem210, and Tomm20l, using the clustered regularly interspaced short palindromic repeats /CRISPR-associated …

Facilitating Federated Genomic Data Analysis By Identifying Record Correlations While Ensuring Privacy, Leonard Dervishi, Xinyue Wang, Wentao Li, Anisa Halimi, Jaideep Vaidya, Xiaoqian Jiang, Erman Ayday

Faculty, Staff and Student Publications

With the reduction of sequencing costs and the pervasiveness of computing devices, genomic data collection is continually growing. However, data collection is highly fragmented and the data is still siloed across different repositories. Analyzing all of this data would be transformative for genomics research. However, the data is sensitive, and therefore cannot be easily centralized. Furthermore, there may be correlations in the data, which if not detected, can impact the analysis. In this paper, we take the first step towards identifying correlated records across multiple data repositories in a privacy-preserving manner. The proposed framework, based on random shuffling, synthetic record …

Caries Risk Documentation And Prevention: Emeasures For Dental Electronic Health Records, Suhasini Bangar, Ana Neumann, Joel M White, Alfa Yansane, Todd R Johnson, Gregory W Olson, Shwetha V Kumar, Krishna K Kookal, Aram Kim, Enihomo Obadan-Udoh, Elizabeth Mertz, Kristen Simmons, Joanna Mullins, Ryan Brandon, Muhammad F Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

BACKGROUND: Longitudinal patient level data available in the electronic health record (EHR) allows for the development, implementation, and validations of dental quality measures (eMeasures).

OBJECTIVE: We report the feasibility and validity of implementing two eMeasures. The eMeasures determined the proportion of patients receiving a caries risk assessment (eCRA) and corresponding appropriate risk-based preventative treatments for patients at elevated risk of caries (appropriateness of care [eAoC]) in two academic institutions and one accountable care organization, in the 2019 reporting year.

METHODS: Both eMeasures define the numerator and denominator beginning at the patient level, populations' specifications, and validated the automated queries. For …

Enhancing Diagnosis Through Technology: Decision Support, Artificial Intelligence, And Beyond, Robert El-Kareh, Dean F Sittig

Faculty, Staff and Student Publications

Patient care in intensive care environments is complex, time-sensitive, and data-rich, factors that make these settings particularly well-suited to clinical decision support (CDS). A wide range of CDS interventions have been used in intensive care unit environments. The field needs well-designed studies to identify the most effective CDS approaches. Evolving artificial intelligence and machine learning models may reduce information-overload and enable teams to take better advantage of the large volume of patient data available to them. It is vital to effectively integrate new CDS into clinical workflows and to align closely with the cognitive processes of frontline clinicians.

Prediction Of Fluid Intelligence From T1-W Mri Images: A Precise Two-Step Deep Learning Framework, Mingliang Li, Mingfeng Jiang, Guangming Zhang, Yujun Liu, Xiaobo Zhou

Faculty, Staff and Student Publications

The Adolescent Brain Cognitive Development (ABCD) Neurocognitive Prediction Challenge (ABCD-NP-Challenge) is a community-driven competition that challenges competitors to develop algorithms to predict fluid intelligence scores from T1-w MRI images. In this work, a two-step deep learning pipeline is proposed to improve the prediction accuracy of fluid intelligence scores. In terms of the first step, the main contributions of this study include the following: (1) the concepts of the residual network (ResNet) and the squeeze-and-excitation network (SENet) are utilized to improve the original 3D U-Net; (2) in the segmentation process, the pixels in symmetrical brain regions are assigned the same label; …

Flow Dynamics In Anomalous Aortic Origin Of A Coronary Artery In Children: Importance Of The Intramural Segment, Hoda Hatoum, Rajesh Krishnamurthy, Jayanthi Parthasarathy, Dorma C Flemister, Carly M Krull, Benjamin A Walter, Carlos M Mery, Silvana Molossi, Lakshmi Prasad Dasi

Faculty, Staff and Students Publications

This study aims to assess the differences in pressure, fractional flow reserve (FFR) and coronary flow (with increasing pressure) of the proximal coronary artery in patients with anomalous aortic origin of a coronary artery with a confirmed ischemic event, without ischemic events, and before and after unroofing surgery, and compare to a patient with normal coronary arteries. Patient-specific flow models were 3D printed for 3 subjects with anomalous right coronary arteries with intramural course, 2 of them had documented ischemia, and compared with a patient with normal coronaries. The models were placed in the aortic position of a pulse duplicator …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

Rac-Maninoff And Rho-Vel: The Symphony Of Rho-Gtpase Signaling At Excitatory Synapses, Joseph G Duman, Francisco A Blanco, Christopher A Cronkite, Qin Ru, Kelly C Erikson, Shalaka Mulherkar, Ali Bin Saifullah, Karen Firozi, Kimberley F Tolias

Faculty, Staff and Students Publications

Synaptic connections between neurons are essential for every facet of human cognition and are thus regulated with extreme precision. Rho-family GTPases, molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state, comprise a critical feature of synaptic regulation. Rho-GTPases are exquisitely controlled by an extensive suite of activators (GEFs) and inhibitors (GAPs and GDIs) and interact with many different signalling pathways to fulfill their roles in orchestrating the development, maintenance, and plasticity of excitatory synapses of the central nervous system. Among the mechanisms that control Rho-GTPase activity and signalling are cell surface receptors, GEF/GAP complexes that …

Adult Memory T Cell Responses To The Respiratory Syncytial Virus Fusion Protein During A Single Rsv Season (2018-2019), Brittani N Blunck, Laura S Angelo, David Henke, Vasanthi Avadhanula, Matthew Cusick, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is ubiquitous and re-infection with both subtypes (RSV/A and RSV/B) is common. The fusion (F) protein of RSV is antigenically conserved, induces neutralizing antibodies, and is a primary target of vaccine development. Insight into the breadth and durability of RSV-specific adaptive immune response, particularly to the F protein, may shed light on susceptibility to re-infection. We prospectively enrolled healthy adult subjects (n = 19) and collected serum and peripheral blood mononuclear cells (PBMCs) during the 2018–2019 RSV season. Previously, we described their RSV-specific antibody responses and identified three distinct antibody kinetic profiles associated with infection …

An Introductory Point-Of-Care Ultrasound Curriculum For An Anesthesiology Residency Program, Susan C Lee, Edward C Yang, Jovany Cruz Navarro, Charles G Minard, Xiaofan Huang, Yi Deng

Faculty, Staff and Students Publications

INTRODUCTION: The use of point-of-care ultrasound (POCUS) is a growing trend in the field of anesthesiology. However, formal POCUS curriculums are still not widely implemented in residency programs. As the Accreditation Council for Graduate Medical Education and the American Board of Anesthesiology have both incorporated POCUS into their educational aims and expectations for graduates, we recognized the need for a formal POCUS curriculum for our residency program. We developed and implemented a comprehensive 3-week POCUS curriculum for our first-year anesthesiology residents (CA1s) in the latter half of their academic year.

METHODS: Twenty CA1s participated in this educational activity. The POCUS …

How Do Digital Lives Affect Resident Mental Health In The Digital Era? Empirical Evidence Based On Chinese General Social Survey, Yan Chen, Mengyang Wei, Jaime Ortiz

Faculty, Staff and Students Publications

Having good mental health means we are better able to connect, function, cope and thrive. The widespread application of digital technology in daily life provides new ways and promising tools for residents to maintain their mental health. Given the importance of mental health for everyone, and the fact that mental health problems are prevalent worldwide, this study discusses how digital lives affects the mental health of residents. The results suggest that digital lives are significantly and positively associated with mental health. Mechanisms analysis identifies personal perceptions (self-rated physical exercise and subjective wellbeing) as the important paths for digital lives to …

Effect Of Acute Postsurgical Pain Trajectories On 30-Day And 1-Year Pain, Saria S Awadalla, Victoria Winslow, Michael S. Avidan, Simon Haroutounian, Thomas G. Kannampallil

2020-Current year OA Pubs

Untreated pain after surgery leads to poor patient satisfaction, longer hospital length of stay, lower health-related quality of life, and non-compliance with rehabilitation regimens. The aim of this study is to characterize the structure of acute pain trajectories during the postsurgical hospitalization period and quantify their association with pain at 30-days and 1-year after surgery. This cohort study included 2106 adult (≥18 years) surgical patients who consented to participate in the SATISFY-SOS registry (February 1, 2015 to September 30, 2017). Patients were excluded if they did not undergo invasive surgeries, were classified as outpatients, failed to complete follow up assessments …

Voting Behavior During Fda Medical Device Advisory Committee Panel Meetings, Amanda Maisel-Campbell, Daniel I Schlessinger, Arianna F. Yanes, Emir Veledar, Kelly A. Reynolds, Sarah A. Ibrahim, Bianca Y. Kang, Noor Anvery, Emily Poon, Murad Alam

2020-Current year OA Pubs

OBJECTIVES: During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations.

METHODS: This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to …

Subtyping Of Common Complex Diseases And Disorders By Integrating Heterogeneous Data. Identifying Clusters Among Women With Lower Urinary Tract Symptoms In The Lurn Study, Victor P. Andreev, H Henry Lai, Et Al

2020-Current year OA Pubs

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data …

Tourette Syndrome Research Highlights From 2021, Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Marinette Debes, Natalia Szejko, Keisuke Ueda, Kevin J. Black

2020-Current year OA Pubs

We summarize selected research reports from 2021 relevant to Tourette syndrome that the authors consider most important or interesting. The authors welcome article suggestions and thoughtful feedback from readers.

Urinary T Cells Are Detected In Patients With Immune Checkpoint Inhibitor-Associated Immune Nephritis That Are Clonotypically Identical To Kidney T Cell Infiltrates, Shailbala Singh, Leticia C Clemente, Edwin R Parra, Amanda Tchakarov, Chao Yang, Yisheng Li, James P Long, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune …

Update On Mri In Evaluation And Treatment Of Endometrial Cancer, Ekta Maheshwari, Stephanie Nougaret, Erica B Stein, Gaiane M Rauch, Ken-Pin Hwang, R Jason Stafford, Ann H Klopp, Pamela T Soliman, Katherine E Maturen, Andrea G Rockall, Susanna I Lee, Elizabeth A Sadowski, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and