Biomedical Informatics Commons^™

Semi-Parametric Bayes Regression With Network-Valued Covariates, Xin Ma, Suprateek Kundu, Jennifer Stevens

Faculty, Staff and Student Publications

Although there has been an explosive rise in network data in a variety of disciplines, there is very limited development of regression modeling approaches based on high-dimensional networks. The scarce literature in this area typically assume linear relationships between the outcome and the high-dimensional network edges that results in an inflated model plagued by the curse of dimensionality and these models are unable to accommodate non-linear relationships or higher order interactions. In order to overcome these limitations, we develop a novel two-stage Bayesian non-parametric regression modeling framework using high-dimensional networks as covariates, which first finds a lower dimensional node-specific representation …

T1 Signal Intensity Ratio Of The Pancreas As An Imaging Biomarker For The Staging Of Chronic Pancreatitis, Temel Tirkes, Anil K Dasyam, Zarine K Shah, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Stephanie T Chang, Carlos A Farinas, Joseph R Grajo, Kareem Mawad, Naoki Takahashi, Sudhakar K Venkatesh, Ashley Wachsman, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Stephen K Van Den Eeden, Yunlong Yang, Mark Topazian, Dana K Andersen, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.

Methods: The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their …

Discovery Of An Orally Active Benzoxaborole Prodrug Effective In The Treatment Of Chagas Disease In Non-Human Primates, Angel M Padilla, Wei Wang, Tsutomu Akama, David S Carter, Eric Easom, Yvonne Freund, Jason S Halladay, Yang Liu, Sarah A Hamer, Carolyn L Hodo, Gregory K Wilkerson, Dylan Orr, Brooke White, Arlene George, Huifeng Shen, Yiru Jin, Michael Zhuo Wang, Susanna Tse, Robert T Jacobs, Rick L Tarleton

Faculty, Staff and Student Publications

Trypanosoma cruzi, the agent of Chagas disease, probably infects tens of millions of people, primarily in Latin America, causing morbidity and mortality. The options for treatment and prevention of Chagas disease are limited and underutilized. Here we describe the discovery of a series of benzoxaborole compounds with nanomolar activity against extra- and intracellular stages of T. cruzi. Leveraging both ongoing drug discovery efforts in related kinetoplastids, and the exceptional models for rapid drug screening and optimization in T. cruzi, we have identified the prodrug AN15368 that is activated by parasite carboxypeptidases to yield a compound that targets the messenger RNA …

Brequinar And Dipyridamole In Combination Exhibits Synergistic Antiviral Activity Against Sars-Cov-2 In Vitro: Rationale For A Host-Acting Antiviral Treatment Strategy For Covid-19, James F Demarest, Maryline Kienle, Ruthmabel Boytz, Mary Ayres, Eun Jung Kim, J J Patten, Donghoon Chung, Varsha Gandhi, Robert A Davey, David B Sykes, Nadim Shohdy, John C Pottage, Vikram S Kumar

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in >400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet medical need for effective and convenient treatment options for SARS-CoV-2 infection. SARS-CoV-2 is an RNA virus that depends on host intracellular ribonucleotide pools for its replication. Dihydroorotate dehydrogenase (DHODH) is a ubiquitous host …

Effect Of Dexamethasone On Dyspnoea In Patients With Cancer (Abcd): A Parallel-Group, Double-Blind, Randomised, Controlled Trial, David Hui, Veronica Puac, Zeena Shelal, Rony Dev, Sandra K Hanneman, Kristofer Jennings, Hilary Ma, Diana L Urbauer, Sanjay Shete, Frank Fossella, Zhongxing Liao, George Blumenschein, Joe Y Chang, Michael O'Reilly, Saumil J Gandhi, Anne Tsao, Donald A Mahler, Eduardo Bruera

Faculty, Staff and Student Publications

BACKGROUND: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea.

METHODS: This double-blind, multi-site, parallel group randomized trial enrolled ambulatory patients with cancer, age ≥18, average dyspnea intensity over the past week ≥4/10 in a 0–10 point numeric rating scale and randomly assigned them to receive dexamethasone 8 mg orally every 12 hours for 7 days followed by 4 mg orally every 12 hours for 7 days or matching placebo capsules. Pharmacists conducted permuted block …

Adhering To Eat And Exercise Status During Radiotherapy For Oropharyngeal Cancer For Prevention And Mitigation Of Radiotherapy-Associated Dysphagia, Carly E A Barbon, Christine B Peterson, Amy C Moreno, Stephen Y Lai, Jay P Reddy, Ariana Sahli, Rosemary Martino, Faye M Johnson, Clifton David Fuller, Katherine A Hutcheson

Faculty, Staff and Student Publications

IMPORTANCE: Previously published work reported independent benefit of maintenance of oral intake (eat) and swallowing exercise adherence (exercise) during radiotherapy (RT) on diet and functional outcomes. The current study seeks to validate the authors' previously published findings in a large contemporary cohort of patients with oropharynx cancer (OPC) and address limitations of the prior retrospective study using prospective, validated outcome measures.

OBJECTIVE: To examine the longitudinal association of oral intake and swallowing exercise using validated, clinician-graded and patient-reported outcomes.

DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a prospective OPC registry including patients who underwent primary RT/chemoradiotherapy (CRT) or primary transoral …

An Elisa-Based Platform For Rapid Identification Of Structure-Dependent Nucleic Acid-Protein Interactions Detects Novel Dna Triplex Interactors, Nicholas G Economos, Upasna Thapar, Nanda Balasubramanian, Georgios I Karras, Peter M Glazer

Faculty, Staff and Student Publications

Unusual nucleic acid structures play vital roles as intermediates in many cellular processes and, in the case of peptide nucleic acid (PNA)-mediated triplexes, are leveraged as tools for therapeutic gene editing. However, due to their transient nature, an understanding of the factors that interact with and process dynamic nucleic acid structures remains limited. Here, we developed snapELISA (structure-specific nucleic acid-binding protein ELISA), a rapid high-throughput platform to interrogate and compare up to 2688 parallel nucleic acid structure-protein interactions in vitro. We applied this system to both triplex-forming oligonucleotide-induced DNA triplexes and DNA-bound PNA heterotriplexes to describe the identification of previously …

Detecting Förster Resonance Energy Transfer In Living Cells By Conventional And Spectral Flow Cytometry, Jared Henderson, Ondrej Havranek, Man Chun John Ma, Vaclav Herman, Kristyna Kupcova, Tereza Chrbolkova, Mariana Pacheco-Blanco, Zhiqiang Wang, Justin M Comer, Tomasz Zal, Richard Eric Davis

Faculty, Staff and Student Publications

Assays based on Förster resonance energy transfer (FRET) can be used to study many processes in cell biology. Although this is most often done with microscopy for fluorescence detection, we report two ways to measure FRET in living cells by flow cytometry. Using a conventional flow cytometer and the "3-cube method" for intensity-based calculation of FRET efficiency, we measured the enzymatic activity of specific kinases in cells expressing a genetically-encoded reporter. For both AKT and protein kinase A, the method measured kinase activity in time-course, dose-response, and kinetic assays. Using the Cytek Aurora spectral flow cytometer, which applies linear unmixing …

Revisiting The Multisite Phosphorylation That Produces The M-Phase Supershift Of Key Mitotic Regulators, Tan Tan, Chuanfen Wu, Boye Liu, Bih-Fang Pan, David H Hawke, Zehao Su, Shuaishuai Liu, Wei Zhang, Ruoning Wang, Sue-Hwa Lin, Jian Kuang

Faculty, Staff and Student Publications

The term M-phase supershift denotes the phosphorylation-dependent substantial increase in the apparent molecular weight of numerous proteins of varied biological functions during M-phase induction. Although the M-phase supershift of multiple key mitotic regulators has been attributed to the multisite phosphorylation catalyzed by the Cdk1/cyclin B/Cks complex, this view is challenged by multiple lines of paradoxical observations. To solve this problem, we reconstituted the M-phase supershift of Xenopus Cdc25C, Myt1, Wee1A, APC3, and Greatwall in Xenopus egg extracts and characterized the supershift-producing phosphorylations. Our results demonstrate that their M-phase supershifts are each due to simultaneous phosphorylation of a considerable portion of …

223ra Induces Transient Functional Bone Marrow Toxicity, Maria Parlani, Francesco Boccalatte, Anna Yeaton, Feng Wang, Jianhua Zhang, Iannis Aifantis, Eleonora Dondossola

Faculty, Staff and Student Publications

223Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of 223Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. Methods: In this study, we investigated the consequences of 223Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Results: 223Ra accumulated in bones and induced zonal radiation damage confined to …

Netbce: An Interpretable Deep Neural Network For Accurate Prediction Of Linear B-Cell Epitopes, Haodong Xu, Zhongming Zhao

Faculty, Staff and Student Publications

Identification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines and immuno-diagnostic reagents, as well as antibody design and production. In this work, we generated a large benchmark dataset comprising 124,879 experimentally supported linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while all sequence-derived and structural features were informative. To search more efficient and interpretive feature representations, a ten-layer deep learning framework …

Artificial Intelligence For Radiation Oncology Applications Using Public Datasets, Kareem A Wahid, Enrico Glerean, Jaakko Sahlsten, Joel Jaskari, Kimmo Kaski, Mohamed A Naser, Renjie He, Abdallah S R Mohamed, Clifton D Fuller

Faculty, Staff and Student Publications

Artificial intelligence (AI) has exceptional potential to positively impact the field of radiation oncology. However, large curated datasets - often involving imaging data and corresponding annotations - are required to develop radiation oncology AI models. Importantly, the recent establishment of Findable, Accessible, Interoperable, Reusable (FAIR) principles for scientific data management have enabled an increasing number of radiation oncology related datasets to be disseminated through data repositories, thereby acting as a rich source of data for AI model building. This manuscript reviews the current and future state of radiation oncology data dissemination, with a particular emphasis on published imaging datasets, AI …

Gpu Accelerated Estimation Of A Shared Random Effect Joint Model For Dynamic Prediction, Shikun Wang, Zhao Li, Lan Lan, Jieyi Zhao, W Jim Zheng, Liang Li

Faculty, Staff and Student Publications

In longitudinal cohort studies, it is often of interest to predict the risk of a terminal clinical event using longitudinal predictor data among subjects at risk by the time of the prediction. The at-risk population changes over time; so does the association between predictors and the outcome, as well as the accumulating longitudinal predictor history. The dynamic nature of this prediction problem has received increasing interest in the literature, but computation often poses a challenge. The widely used joint model of longitudinal and survival data often comes with intensive computation and excessive model fitting time, due to numerical optimization and …

Loss Of Lamp5 Interneurons Drives Neuronal Network Dysfunction In Alzheimer’S Disease, Yuanyuan Deng, Mian Bi, Fabien Delerue, Shelley L Forrest, Gabriella Chan, Julia Van Der Hoven, Annika Van Hummel, Astrid F Feiten, Seojin Lee, Ivan Martinez-Valbuena, Tim Karl, Gabor G Kovacs, Grant Morahan, Yazi D Ke, Lars M Ittner

Faculty, Staff and Student Publications

In Alzheimer's disease (AD), where amyloid-β (Aβ) and tau deposits in the brain, hyperexcitation of neuronal networks is an underlying disease mechanism, but its cause remains unclear. Here, we used the Collaborative Cross (CC) forward genetics mouse platform to identify modifier genes of neuronal hyperexcitation. We found LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations. Interestingly, synaptic LAMP5 was lost in AD brains and LAMP5 interneurons degenerated in different AD mouse models. Genetic reduction of LAMP5 augmented functional deficits and neuronal network hypersynchronicity in both Aβ- and tau-driven AD mouse models. …

Aapm Report 373: The Content, Structure, And Value Of The Professional Doctorate In Medical Physics (Dmp), Jay W Burmeister, Charles W Coffey, John D Hazle, Neil Kirby, Yu Kuang, Michael A Lamba, Brian Loughery, Niko Papanikolaou

Faculty, Staff and Student Publications

The Professional Doctorate in Medical Physics (DMP) was originally conceived as a solution to the shortage of medical physics residency training positions. While this shortage has now been largely satisfied through conventional residency training positions, the DMP has expanded to multiple institutions and grown into an educational pathway that provides specialized clinical training and extends well beyond the creation of additional training spots. As such, it is important to reevaluate the purpose and the value of the DMP. Additionally, it is important to outline the defining characteristics of the DMP to assure that all existing and future programs provide this …

Targeting Hemoglobin To Reduce Delayed Cerebral Ischemia After Subarachnoid Hemorrhage, Hussein A Zeineddine, Pedram Honarpisheh, Devin Mcbride, Peeyush Kumar Thankamani Pandit, Ari Dienel, Sung-Ha Hong, James Grotta, Spiros Blackburn

Faculty, Staff and Student Publications

Delayed cerebral ischemia (DCI) continues to be a sequela of aneurysmal subarachnoid hemorrhage (aSAH) that carries significant morbidity and mortality. Aside from nimodipine, no therapeutic agents are available to reduce the incidence of DCI. Pathophysiologic mechanisms contributing to DCI are poorly understood, but accumulating evidence over the years implicates several factors. Those have included microvessel vasoconstriction, microthrombosis, oxidative tissue damage, and cortical spreading depolarization as well as large vessel vasospasm. Common to these processes is red blood cell leakage into the cerebrospinal fluids (CSF) and subsequent lysis which releases hemoglobin, a central instigator in these events. This has led to …

Handling Informative Premature Treatment Or Study Discontinuation For Assessing Between-Group Differences In A Comparative Oncology Trial, Bo Huang, Ryan Sun, Brian Claggett, Lu Tian, Ethan B Ludmir, Lee-Jen Wei

Faculty, Staff and Student Publications

This decision analytical model study examines premature treatment discontinuation in clinical trials for patients with advanced renal cell carcinoma.

Monkeypox: What Do Dental Professionals Need To Know?, Charifa Zemouri, Edgar O Beltrán, Richard Holliday, Nicholas S Jakubovics, James R Allison

Faculty, Staff and Student Publications

Infection control is critical for the safe delivery of dental care. Infection control practices must be responsive to emerging and re-emerging infectious diseases and outbreaks, as was clearly seen during the peak of the COVID-19 pandemic. An emerging global outbreak of the monkeypox virus has again raised potential challenges for infection control in dentistry. Monkeypox is an infectious disease, characterised by a rash affecting the skin and soft tissues, including the oral cavity. Previously, cases were mostly seen following contact with infected animals in Central and West Africa, with limited human-to-human transmission within and outside of these areas. However, since …

Targeted Inhibition Of Dna-Pkcs, Atm, Atr, Parp, And Rad51 Modulate Response To X Rays And Protons, Scott J Bright, David B Flint, David K J Martinus, Broderick X Turner, Mandira Manandhar, Mariam Ben Kacem, Conor H Mcfadden, Timothy A Yap, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects. In this study we screened the response to X-ray or proton radiation in cell lines treated with DDR inhibitors (DDRis) targeting ATM, ATR, DNA-PKcs, Rad51, …

A Retrospective Analysis Of Ebv-Dna Status With The Prognosis Of Lymphoma, Lihua Qiu, Junqi Si, Junnan Kang, Zehui Chen, Rexidan Nuermaimaiti, Zhengzi Qian, Lanfang Li, Shiyong Zhou, Mingjian James You, Huilai Zhang, Chen Tian

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) infection is proved to be associated with clinicopathology of lymphoma. However, little is known about the relationship between EBV-DNA status after treatment and prognosis. In this study, real-time polymerase chain reaction (PCR) was used for quantitative detection of EBV-DNA load in peripheral blood of all 26,527 patients with lymphoma, and the clinical characteristics and prognosis of 202 patients were retrospectively analysed, including 100 patients with positive EBV-DNA and 102 randomly selected patients with negative EBV-DNA. We found that the average rate of EBV-DNA positivity in lymphomas was 0.376%, and EBV-DNA-positive patients presented higher risk with elevated lactate …

Lurbinectedin, A Selective Inhibitor Of Oncogenic Transcription, In Patients With Pretreated Germline Brca1/2 Metastatic Breast Cancer: Results From A Phase Ii Basket Study, V Boni, B Pistilli, I Braña, G I Shapiro, J Trigo, V Moreno, D Castellano, C Fernández, C Kahatt, V Alfaro, M Siguero, A Zeaiter, F Longo, K Zaman, A Antón, A Paredes, G Huidobro, V Subbiah

Faculty, Staff and Student Publications

Background: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer.

Patients and methods: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival …

Gpu Accelerated Estimation Of A Shared Random Effect Joint Model For Dynamic Prediction, Shikun Wang, Zhao Li, Lan Lan, Jieyi Zhao, W Jim Zheng, Liang Li

Faculty, Staff and Student Publications

In longitudinal cohort studies, it is often of interest to predict the risk of a terminal clinical event using longitudinal predictor data among subjects at risk by the time of the prediction. The at-risk population changes over time; so does the association between predictors and the outcome, as well as the accumulating longitudinal predictor history. The dynamic nature of this prediction problem has received increasing interest in the literature, but computation often poses a challenge. The widely used joint model of longitudinal and survival data often comes with intensive computation and excessive model fitting time, due to numerical optimization and …

Association Of Pd-L1 Expression And Other Variables With Benefit From Immune Checkpoint Inhibition In Advanced Gastroesophageal Cancer: Systematic Review And Meta-Analysis Of 17 Phase 3 Randomized Clinical Trials, Harry H Yoon, Zhaohui Jin, Oudom Kour, Lionel Aurelien Kankeu Fonkoua, Kohei Shitara, Michael K Gibson, Larry J Prokop, Markus Moehler, Yoon-Koo Kang, Qian Shi, Jaffer A Ajani

Faculty, Staff and Student Publications

Importance: Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.

Objective: To systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.

Data sources: MEDLINE, Embase, Scopus, Web of Science, Cochrane …

Characteristics Of Community-Acquired Carbapenem-Resistant Enterobacterales, Rima Shrestha, Courtney L Luterbach, Weixiao Dai, Lauren Komarow, Michelle Earley, Gregory Weston, Erica Herc, Jesse T Jacob, Robert Salata, Darren Wong, Deverick Anderson, Kirsten B Rydell, Cesar A Arias, Liang Chen, David Van Duin, Mdro Investigators

Faculty, Staff and Student Publications

BACKGROUND: Community-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.

METHODS: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.

RESULTS: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was …

Pin-Pointing The Key Hubs In The Ifn-Γ Pathway Responding To Sars-Cov-2 Infection, Ayelen Toro, Sofia Lage-Vickers, Juan Bizzotto, Felipe Vilicich, Agustina Sabater, Gaston Pascual, Sabrina Ledesma-Bazan, Pablo Sanchis, Maria Sol Ruiz, Ana Paula Arevalo, Jorge L Porfido, Mercedes Abbate, Rocio Seniuk, Estefania Labanca, Nicolas Anselmino, Nora M Navone, Daniel F Alonso, Elba Vazquez, Martina Crispo, Javier Cotignola, Geraldine Gueron

Faculty, Staff and Student Publications

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient's viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) …

Identifying Candidate Genes And Drug Targets For Alzheimer’S Disease By An Integrative Network Approach Using Genetic And Brain Region-Specific Proteomic Data, Andi Liu, Astrid M Manuel, Yulin Dai, Brisa S Fernandes, Nitesh Enduru, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

Genome-wide association studies (GWAS) have identified more than 75 genetic variants associated with Alzheimer's disease (ad). However, how these variants function and impact protein expression in brain regions remain elusive. Large-scale proteomic datasets of ad postmortem brain tissues have become available recently. In this study, we used these datasets to investigate brain region-specific molecular pathways underlying ad pathogenesis and explore their potential drug targets. We applied our new network-based tool, Edge-Weighted Dense Module Search of GWAS (EW_dmGWAS), to integrate ad GWAS statistics of 472 868 individuals with proteomic profiles from two brain regions from two large-scale ad cohorts [parahippocampal gyrus …

Video-Urodynamics Efficacy Of Sacral Neuromodulation For Neurogenic Bladder Guided By Three-Dimensional Imaging Ct And C-Arm Fluoroscopy: A Single-Center Prospective Study, Shuaishuai Shan, Wen Zhu, Guoxian Zhang, Qinyong Zhang, Yingyu Che, Jianguo Wen, Qingwei Wang

Faculty, Staff and Student Publications

To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the …

Prognostic Molecular Biomarkers In Chordomas: A Systematic Review And Identification Of Clinically Usable Biomarker Panels, Franco Rubino, Christopher Alvarez-Breckenridge, Kadir Akdemir, Anthony P Conley, Andrew J Bishop, Wei-Lien Wang, Alexander J Lazar, Laurence D Rhines, Franco Demonte, Shaan M Raza

Faculty, Staff and Student Publications

INTRODUCTION AND OBJECTIVE: Despite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis.

METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) …

Mucus-Degrading Bacteroides Link Carbapenems To Aggravated Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Mohamed A Jamal, Takahiko Miyama, Chia-Chi Chang, Miriam R Ortega, Saira S Ahmed, Jennifer L Karmouch, Christopher A Sanchez, Alexandria N Brown, Rawan K El-Himri, Ivonne I Flores, Lauren K Mcdaniel, Dung Pham, Taylor Halsey, Annette C Frenk, Valerie A Chapa, Brooke E Heckel, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Lin Tan, Lucas Veillon, Nadim J Ajami, Jennifer A Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F Chemaly, Lauren Davey, Robert W P Glowacki, Chen Liu, Gabriela Rondon, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Raphael H Valdivia, Eric C Martens, Philip L Lorenzi, Robert R Jenq

Faculty, Staff and Student Publications

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic …

Integration Of Mouse Ovary Morphogenesis With Developmental Dynamics Of The Oviduct, Ovarian Ligaments, And Rete Ovarii, Jennifer Mckey, Dilara N Anbarci, Corey Bunce, Alejandra E Ontiveros, Richard R Behringer, Blanche Capel

Faculty, Staff and Student Publications

Morphogenetic events during the development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii (RO) elaborated into a convoluted tubular structure extending …