Digital Commons Network^™

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

A Reinforcement Learning (Rl)-Motivated Simulation Framework For Evaluating Vancomycin Dosing Strategies, Bingyu Mao, Ziqian Xie, Laila Rasmy, Masayuki Nigo, Degui Zhi

Faculty, Staff and Student Publications

Achieving and maintaining the therapeutic range in vancomycin treatment is important for optimal outcomes. While guidelines and best practices based on empirical studies exist, the theoretical best dosing strategies under various conditions remain illusive. We developed an RL-based simulation framework using a deep learning two-compartment pharmacokinetic model (PK-RNN-2CM) and introduced the area under the time-concentration curve (AUC) reward score, which translates clinical guidelines into an RL reward. Ground truth time-concentration curves were generated from patient-specific data, and simulated curves were produced under different dosing strategies with optional noise perturbations to mimic real-world settings. Evaluation metrics included 24-hour AUC assessments and …

Microbiota Restoration Therapies For Recurrent Clostridioides Difficile Infection Reach An Important New Milestone, Herbert L Dupont, Andrew W Dupont, Glenn S Tillotson

Faculty, Staff and Student Publications

Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce …

Editorial: Immunological Aspects Of Emerging And Re-Emerging Zoonoses, Wei Wang, Jingxin Li, Yuejin Liang, Wenping Gong

Faculty, Staff and Student Publications

No abstract provided.

Unicentric Castleman Disease: Illustration Of Its Morphologic Spectrum And Review Of The Differential Diagnosis, Siba El Hussein, Andrew G Evans, Hong Fang, Wei Wang, L Jeffrey Medeiros

Faculty, Staff and Student Publications

Context: Unicentric Castleman disease (UCD) is a dynamic entity with a wide spectrum of morphologic findings. UCD can be further subdivided into hyaline-vascular and mixed/plasmacytic variants. Hyaline-vascular UCD has both follicular and interfollicular (stromal) changes, and occasionally these lesions show a skewed representation of either the follicular or stromal compartments. Plasmacytosis is usually minimal in the hyaline-vascular variant. The mixed/plasmacytic variant of UCD is composed of sheets of plasma cells often associated with a variable number of follicles with regressive changes.

Objective: To illustrate the differential diagnosis of UCD, as it is quite broad and includes lymphomas, plasma cell neoplasms, …

Highly Variable Timing Renders Immunotherapy Efficacy And Toxicity Impractical Biomarkers Of One Another In Clinical Practice, Mitchell S Von Itzstein, Yuqiu Yang, Yiqing Wang, David Hsiehchen, Thomas Y Sheffield, Farjana Fattah, Vinita Popat, Murtaza Ahmed, Jade Homsi, Jonathan E Dowell, Sawsan Rashdan, Jay Lohrey, Hans J Hammers, Randall S Hughes, Tao Wang, Yang Xie, David E Gerber

Faculty, Staff and Student Publications

Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI.

Methods: Using …

Innovations In Molecular Biomarkers And Biomaterial-Based Immunotherapies For Head & Neck Cancer, Sarah Anne Wong, Victoria A Manon, Simon Young, Chi T Viet

Faculty, Staff and Student Publications

Purpose of review: Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy.

Recent findings: Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease …

Accelerate Vaccine Development Using Seamless Phase 2/3 Trial Designs, Jia-Ying Yang, Guo-Chun Li, Ying Yuan

Faculty, Staff and Student Publications

Background: Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines.

Research design and methods: This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, …

Nontuberculosis Mycobacteria (Ntm) Infections In Patients With Leukemia: A Single Center Case Series, Jennifer Marvin-Peek, Koji Sasaki, Dimitrios P Kontoyiannis, Javier Adachi, Maro Ohanian, Koichi Takahashi, Ghayas C Issa, Steven Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with …

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …

Influence Of Oral Microbiome On Longitudinal Patterns Of Oral Mucositis Severity In Patients With Squamous Cell Carcinoma Of The Head And Neck, Liangliang Zhang, Erin Marie D San Valentin, Teny M John, Robert R Jenq, Kim-Anh Do, Ehab Y Hanna, Christine B Peterson, Cielito C Reyes-Gibby

Faculty, Staff and Student Publications

Background: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck.

Methods: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit …

Sample Multiplexing In Cytof: Path To Optimize Single-Cell Proteomic Profiling, Muharrem Muftuoglu, Michael Andreeff

Faculty, Staff and Student Publications

Sample multiplexing significantly enhanced the depth of single-cell proteomic analysis in CyTOF (Cytometry by Time-Of-Flight). New polymer-based chelators have broadened the utility of metal isotopes, enabling improved tagging and simultaneous analysis of multiple samples. These approaches minimize batch effects, streamline experiments, conserve valuable samples, reduce costs, enhance throughput, and increase the accuracy of biological data, thereby facilitating novel discoveries.

Endovascular Interventions In Cancer Patients With Compromise Of The Mediastinal Vasculature: A Review, Steven Yevich, Nicolas Cardenas, Rahul Sheth, Joshua Kuban, Milan Patel, Ketan Shah, Koustav Pal, Stephen R Chen, Alda Tam

Faculty, Staff and Student Publications

The mediastinal vasculature can be affected by various etiologies in cancer patients. Both direct and indirect sequela of cancer may result in life-threatening clinical presentations. Tumor growth may cause vessel narrowing and decreased blood flow from either extrinsic mass effect, invasion into the vascular wall, or tumor thrombus within the lumen. In addition, cancer patients are predisposed to indirect sequela to the mediastinal vasculature from an increased risk of benign thromboembolic events, tumor thrombus, or iatrogenic complications during cancer treatments. Benign thrombus may result in partial or complete occlusion of the superior vena cava (SVC) or pulmonary artery. Vascular damage …

Incidence And Impact Of Fungal Infections In Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis And Haploidentical Hematopoietic Cell Transplantation: A Center For International Blood And Marrow Transplant Research Analysis, Genovefa A Papanicolaou, Min Chen, Naya He, Michael J Martens, Soyoung Kim, Marjorie V Batista, Neel S Bhatt, Peiman Hematti, Joshua A Hill, Hongtao Liu, Sunita Nathan, Matthew D Seftel, Akshay Sharma, Edmund K Waller, John R Wingard, Jo-Anne H Young, Christopher E Dandoy, Miguel-Angel Perales, Roy F Chemaly, Marcie Riches, Celalettin Ustun

Faculty, Staff and Student Publications

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.

Methods: Patients who underwent their first …

The Association Of Mirnas As Biomarkers For Severe Liver Dysfunction In Severe Dengue Infection, Napat Pas-Arj

Chulalongkorn University Theses and Dissertations (Chula ETD)

Identification early biomarkers for severe liver dysfunction in severe dengue patients is essential. Currently, there is no any data on circulating miRNAs to predict this important complication, Therefore, this study aimed to explore the role of circulating miRNAs in severe liver dysfunction in dengue infection. On the initial day of admission, serum samples were gathered from patients with dengue infection. These patients were monitored for 14 days post-admission to ascertain their final diagnosis. Following the WHO 2009 criteria, participants were categorized into severe liver dysfunction and non-severe liver dysfunction group. To conduct a transcriptomic analysis of circulating miRNAs used the …

Gene Expression By Nanostring Rna Profiling Of Monocytic Myeloid-Derived Suppressor Cells In Knee Osteoarthritis, Varote Shotelersuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

Osteoarthritis (OA) is a widespread degenerative joint disease marked by cartilage destruction. This study investigates the role of monocytic myeloid-derived suppressor cells (M-MDSCs) in OA, focusing on their gene expression profiles and their relationship with body mass index (BMI) in knee OA patients. Previous research has shown a positive correlation between M-MDSCs and BMI in OA. We explored the role of M-MDSCs derived from the infrapatellar fat pad (IPFP) in OA patients.Using NanoString technology, we examined the transcriptional profile of M-MDSCs from the IPFP of knee OA patients undergoing total knee replacement surgery, categorized into different BMI groups. Flow cytometry …

Benign Disorders Of The Mediastinum: A Narrative Review, Saad Farooq, Sabiha Armin, Daniel Ocazionez, Rosa M Estrada-Y-Martin, Sujith V Cherian

Faculty, Staff and Student Publications

Background and objective: There are several benign processes that affect the mediastinum with considerable morbidity that may range from reactive entities to neoplastic disorders. This review article will focus on non-neoplastic benign mediastinal diseases which include large vessel vasculitis such as Takayasu and giant cell arteritis, mediastinal granulomas, fibrosing mediastinitis and mediastinal infections. These diseases can cause significant morbidity and mortality; therefore, we aim to familiarize readers with the pathophysiology, epidemiology and diagnosis of these mediastinal diseases and provide an update on the treatment options available.

Methods: We searched various databases such as PubMed and Google Scholar from August 2023 …

In Silico Study Of Bioactive Compounds Derived From Indonesian Marine Invertebrates As Novel Antituberculosis Agent, Ayu Masyita, Eri̇s Septiana, Asep Bayu, Bustanussalam Bustanussalam, Jonathan A. Panggabean, Fi̇rdayani̇ Firdayani, Tuti̇k Murniasih

Turkish Journal of Medical Sciences

Background/aim: Tuberculosis has still become the most deadly disease globally. The problem of finding an effective therapeutic is one of the obstacles in the treatment of patients. Marine invertebrates were a treasure since they produced many active compounds. Following up on this issue, screening active compounds is very important. This study will explain the result of anti-tuberculosis screening of compounds derived from marine invertebrates using in silico and confirmed to the in vitro-data.Materials and methods: Three-dimensional (3D) structures of pantothenate kinase (MtPanK type 1, PDB ID: 4BFT), Mycobacterium tuberculosis InhA (MtInhA, PDB ID: 2X23), protein kinase B (PDB ID: 5U94), …

Tracking The Footsteps Of Burkholderia Mallei: Determination Of The Molecular Differences And Potential Resistance Genes, Dilek Dülger, Seda Eki̇ci̇, Mehmet Demi̇rci̇, Akın Yi̇ği̇n, Orkun Babacan

Turkish Journal of Medical Sciences

Chemical biological radiological nuclear threats are at an important point in the agenda of world health today, as theycan cause mass deaths. B. mallei attracts attention as a potential biological warfare agent due to its features such as multidrug resistance,a rapid transmission mechanism via aerosol, the absence of a complete treatment protocol for the infection it causes, and the absence ofan approved vaccine for protection against the bacteria. B. mallei suspect samples must be studied by experienced personnel in biosafetylevel III laboratories. B mallei is a difficult and troublesome pathogen to diagnose and many unknowns about B. mallei today. Therefore,the …

Clinical Characteristics And Disease Course Before And After Sars-Cov-2 Infection In A Large Cohort Of Systemic Sclerosis Patients, Aslıhan Avanoğlu Güler, Büşra Özçi̇men, Mesude Seda Aydoğdu, Alper Sari, Aliyeva Numune, Nazife Tüzün Ersan, Seda Çolak, Hazan Karadeni̇z, İbrahim Vasi̇, Hamit Küçük, Yasemin Yalçinkaya, Abdulsamet Erden, Mehmet Kayaalp, Mehmet Akif Öztürk, Berna Göker, Ahmet Omma, Sedat Yilmaz, Süleyman Serdar Koca, Murat İnanç, Ali Akdoğan, Abdurrahman Tufan

Turkish Journal of Medical Sciences

The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19.Materials and methods: In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews.Results: The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory …

Identifying Missing Is-A Relations In Snomed Ct With Fine-Tuned Pre-Trained Language Models And Non-Lattice Subgraphs, Xubing Hao, Rashmie Abeysinghe, Jay Shi, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Ensuring the completeness of IS-A relations in SNOMED CT is crucial for maintaining its accuracy in clinical applications. In this study, we propose a hybrid approach leveraging non-lattice subgraphs and pre-trained language models (PLMs) to identify missing IS-A relations in SNOMED CT. We fine-tuned four BERT-based models: BERT, DistillBERT, DeBERTa, and BioClinicalBERT, and four generative large language models (LLMs): BioMistral, Llama3, Gemma2, and Phi-4. Missing IS-A relations were identified through consensus predictions by all eight models. De-BERTa achieved the best performance (precision: 0.96, recall: 0.97, F1-score: 0.965) for IS-A relation prediction. Our approach identified 678 potential missing IS-A relations in …

Epidemiology Of Invasive Candidiasis, Derek J Bays, Emily N Jenkins, Meghan Lyman, Tom Chiller, Nora Strong, Luis Ostrosky-Zeichner, Martin Hoenigl, Peter G Pappas, George R Thompson Iii

Faculty, Staff and Student Publications

Invasive candidiasis (IC) is an increasingly prevalent, costly, and potentially fatal infection brought on by the opportunistic yeast, Candida. Previously, IC has predominantly been caused by C. albicans which is often drug susceptible. There has been a global trend towards decreasing rates of infection secondary to C. albicans and a rise in non-albicans species with a corresponding increase in drug resistance creating treatment challenges. With advances in management of malignancies, there has also been an increase in the population at risk from IC along with a corresponding increase in incidence of breakthrough IC infections. Additionally, the emergence of …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Biologic Complications Associated With Cylindrical Lead Spinal Cord Stimulator Implants: A Narrative Review, Peter D Vu, Dorina Pinkhasova, Zohal B Sarwary, Anush Rita Markaryan, Bakir Mousa, Omar Viswanath, Christopher L Robinson, Giustino Varrassi, Vwaire Orhurhu, Ivan Urits, Jamal Hasoon

Faculty, Staff and Student Publications

Purpose of review: Spinal cord stimulation (SCS) is a minimally invasive and reversible therapy for the treatment of severe neuropathic pain. There are several biologic complications that can arise during the implantation of SCS systems. This review aims to consolidate recent research on complications associated with SCS, specifically focusing on biologic complications.

Recent findings: Biologic complications are less frequently encountered compared to device-related complications but may have more severe consequences. Biologic complications covered in this review include infection, seromas, hematomas, dural puncture, nerve/spinal cord injury, and therapy habituation.

Conclusion: The application of SCS remains a viable and effective choice for …

Absolute Concentration Estimation Of Covid-19 Convalescent And Post-Vaccination Igg Antibodies, Melvin E Klegerman, Tao Peng, Ira Seferovich, Mohammad H Rahbar, Manouchehr Hessabi, Amirali Tahanan, Audrey Wanger, Carolyn Z Grimes, Luis Z Ostrosky-Zeichner, Kent Koster, Jeffrey D Cirillo, Dinuka Abeydeera, Steve De Lira, David D Mcpherson

Faculty, Staff and Student Publications

Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 …

Saprochaete Capitata Infection In Teen With Acute Myeloid Leukemia Receiving Echinocandin Prophylaxis, Jordan Killingsworth, Rachel Boren, Rachna Sheth, Michael L Chang

Faculty, Staff and Student Publications

We report a case of a 15-year-old with refractory and relapsed AML and profound prolonged neutropenia who developed a Saprochaete capitata disseminated invasive infection while on echinocandin prophylaxis for invasive fungal disease. Azole antifungal therapies, which are often used as prophylaxis, were initially avoided due to concerns for CYP drug interactions. Treatment with a combination of liposomal amphotericin B, voriconazole, and adjuvant granulocyte transfusions was successful as he awaited neutrophil recovery.

A One-Year Hospital System Review Of Plasma Next-Generation Sequencing In A Mixed Population, Ty C Drake, Jessica Babic, Audrey Wanger, Violeta Chavez

Faculty, Staff and Student Publications

Objective: To describe the use of plasma next-generation sequencing (NGS) and determine if it provided additional information from routine tests or lead to change in antimicrobial management.

Design and setting: This retrospective cohort study evaluated patients with a NGS test performed who were admitted to a hospital health system in the greater Houston area between May 2022 and May 2023.

Patients: In total, 143 NGS tests were ordered in the span of one year for 135 unique patients. Most patients were ≥ 18 years (74.1%), White/Caucasian (43.7%), male (61.5%), and immunocompetent (54.1%). Eight patients had repeat tests during the study …

Increased Rate Of Multidrug-Resistant Gram-Negative Bacterial Infections In Hospitalized Immunocompromised Pediatric Patients, Sarah Khafaja, Yara Salameh, Celina F Boutros, Cherine Awad, Kawthar Faour, Nadim Tfaily, Sarah Merhi, Zeinab El Zein, Samer Bou Karroum, Dana Oweini, Danielle Fayad, George F Araj, Ramia Zakhour, Ghassan S Dbaibo

Faculty, Staff and Student Publications

Introduction: Multidrug resistant Gram-negative bacterial infections are considered a major public health threat. Immunocompromised pediatric patients are at a great risk of severe or overwhelming infections. The aim of this study was to describe the frequency of infections with multidrug resistant (MDR) Gram-negative bacteria (GNB) in immunocompromised pediatric patients and to determine the risk factors. In addition, we aimed to identify the antimicrobial resistance patterns of these isolates.

Materials and methods: This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included immunocompromised patients 18 years of age …

Multiple Unfolded Protein Response Pathways Cooperate To Link Cytosolic Dsdna Release To Stimulator Of Interferon Gene Activation, Tiancheng Hu, Yiping Liu, Jeremy Fleck, Cason King, Elaine Schalk, Zhenyu Zhang, Andrew Mehle, Judith A Smith

Faculty, Staff and Student Publications

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-β expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in …