Genetic Phenomena Commons^™

Differences In Connected Speech Outcomes Across Elicitation Methods, Tatiana T Schnur, Sharon Wang

Faculty, Staff and Student Publications

Background: Connected speech is often used to assess many aspects of an individual's language abilities after stroke. However, it is unknown the degree to which elicitation methods differ in generating structural and syntactic aspects of connected speech, two critical components of successful communication. Quantifying the degree to which elicitation methods differ in eliciting structurally, syntactically, and lexically complex connected speech at the earliest stage of stroke before reorganization and rehabilitation of function independent of clinical diagnosis of aphasia has not been examined to date. Addressing this gap has implications for early clinical intervention as well as empirical studies of connected …

Monet: A Database For Prediction Of Neoantigens Derived From Microsatellite Loci, Nan Deng, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

BACKGROUND: Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).

METHOD: MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using …

Postmortem-Derived Ipsc Models In Substance Use Disorders Research, Emily Frances Mendez, Consuelo Walss-Bass

Faculty, Staff and Student Publications

No abstract provided.

Are Published Cancer Care Trial Protocols With Traditional Chinese Medicine Interventions Concordant With Spirit-Tcm Extension 2018? A Scoping Review On Published Trial Protocols Between 2019 And 2022, Hezheng Lai, Peiying Yang, Xin Shelley Wang, David Lim, Anderson Lam, Yucong Shi, Yishi Huang, Xiaoshu Zhu

Faculty, Staff and Student Publications

BACKGROUND: The SPIRIT-TCM Extension 2018 was created to guide the design and reporting of Traditional Chinese Medicine (TCM) clinical trial protocols. This study aims to investigate the extent of concordance with this guideline in the relevant field of cancer care research.

METHODS: A scoping review of TCM cancer trial protocols published in English and Chinese since January 2019 was conducted. Five major academic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, and China National Knowledge Infrastructure) were searched. Concordance with the SPIRIT-TCM Extension 2018 was assessed by descriptive analysis.

RESULTS: Fifty-three TCM cancer care trial protocols were identified, comprising 23 acupuncture, 26 Chinese …

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 …

Mt-Keyboard: A Bayesian Model-Assisted Interval Design To Account For Toxicity Grades And Types For Phase I Trials, Kai Chen, Li Wang, Ying Yuan

Faculty, Staff and Student Publications

Conventionally, dose finding trials are based on dose-limiting toxicity (DLT) that only captures the most severe toxicities, e.g., treatment related grade 3 or higher toxicity according to the NCI Common Terminology Criteria for Adverse Events. However, this approach is often problematic for certain novel targeted therapies and immunotherapies, which may not induce DLT within a clinically active dose range and are often characterized by low grade toxicities. This important issue has been highlighted and discussed in the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forums, and is also an important consideration of the Project Optimus initiated by FDA to …

Considerations On Design And Analysis Of External Control In Pediatric Oncology, Jingjing Ye, Haitao Pan, Gregory Reaman, Satrajit Roychoudhury, Chengxing Lu, Lindsay A Renfro, Yuan Ji, Rong Liu, Ying Yuan, Weidong Zhang

Faculty, Staff and Student Publications

Pediatric cancer consists of a diverse group of rare diseases. Due to limited patient populations, standard randomized and controlled trials are often infeasible. As a result, single-arm trials are common in pediatric oncology and the use of external controls is often desirable or necessary to help generate actionable evidence and contextualize trial results. In this paper, we illustrate unique features in pediatric oncology clinical trials and describe their impact on the use of external controls. Various types of relevant external control data sources are described in terms of their utility and drawbacks. Statistical methodologies and design implications with external control …

Development Of The “Laser Surgical Skills Evaluation For Residents” (Laser) Scale Through A Modified Delphi Method, E Sédillot-Daniel, A Melkane, C Chiesa, N Fakhry, V N Young, L J Smith, J R Lechien, L Guertin, M J Olivier, A Maniakas, R Jun Lin, E Bissada, A Christopoulos, T Ayad, Andrée-Anne Leclerc

Faculty, Staff and Student Publications

Background: The CO2 laser is frequently used during microlaryngeal surgery (MLS) for a variety of pathology including laryngeal malignancy and stenosis. Learning how to use the laser safely is part of the curriculum for every otolaryngology resident. However, assessment of laryngoscopy technical skills can be challenging for supervisors, making it difficult to adequately provide feedback to trainees.

Objectives: "LAser Surgical skills Evaluation for Residents" (LASER) Scale aims to facilitate the evaluation of residents' performance and promote constructive feedback.

Methods: The initial evaluation grid was based on a literature review of CO2 laser laryngoscopy (with an emphasis on indications, technique, safety, …

Hybrid Open-Endovascular Onyx Embolization Of Spinal Type Ivb Perimedullary Spinal Arteriovenous Fistula Through Direct Posterior Spinal Vein Access: A Case Report, Romulo Augusto Andrade De Almeida, Francisco Call-Orellana, Christopher C Young, Franco Rubino, Sara L Thrower, Stephen R Chen, Robert Y North

Faculty, Staff and Student Publications

Background: Spinal arteriovenous fistulas (SAVFs) are direct communication between arteries and veins without intervening abnormal vessel nidus, which often results in venous congestion and spinal cord dysfunction. Ventrally located SAVF can be challenging to treat through traditional open or endovascular approaches.

Case description: We describe a hybrid (open/endovascular) procedure in a 72-year-old male with a Takai Type IVb SAVF presenting with paraparesis and sphincter dysfunction. Imaging revealed a conus medullaris SAVF in which the main fistulous connection was located ventrally. The conventional endovascular approach was deemed risky, and open surgery failed in the first attempt. The SAVF was resolved using …

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 …

Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang

Faculty, Staff and Student Publications

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune …

A Review Of The Clinical Introduction Of 4d Particle Therapy Research Concepts, Barbara Knäusl, Gabriele Belotti, Jenny Bertholet, Juliane Daartz, Stella Flampouri, Mischa Hoogeman, Antje C Knopf, Haibo Lin, Astrid Moerman, Chiara Paganelli, Antoni Rucinski, Reinhard Schulte, Shing Shimizu, Kristin Stützer, Xiaodong Zhang, Ye Zhang, Katarzyna Czerska

Faculty, Staff and Student Publications

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments.

Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic.

Results: Available technological capabilities …

From Mitochondria To Tumor Suppression: Acat1’S Crucial Role In Gastric Cancer, Wei He, Yanfang Li, Song-Bai Liu, Ying Chang, Shiyuan Han, Xingyu Han, Zixin Ma, Hesham M Amin, Yao-Hua Song, Jin Zhou

Faculty, Staff and Student Publications

Acetyl CoA acetyltransferase 1 (ACAT1), a mitochondrial enzyme, is mainly involved in the formation and decomposition of ketones, isoleucine, and fatty acids. Previous clinical studies showed that mutations in the ACAT1 gene lead to ketoacidosis, Notably the role of ACAT1 in human cancer' pathogenesis varies depending on cancer type, and its specific role in gastric cancer remains largely unknown. In the current study, we found that the expression of ACAT1 in primary late-stage gastric cancer tumor tissues was significantly lower than in early-stage tumors. This observation was further confirmed in high-grade gastric cancer cell line MKN45. The expression of CD44 …

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.

Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer

Faculty, Staff and Student Publications

A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of …

Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying

Faculty, Staff and Student Publications

Inborn errors of immunity (IEIs) are a group of typically monogenic disorders characterized by dysfunction in the immune system. Individuals with these disorders experience increased susceptibility to infections, autoimmunity and malignancies due to abnormal immune responses. Epigenetic modifications, including DNA methylation, histone modifications and chromatin remodeling, have been well explored in the regulation of immune cell development and effector function. Aberrant epigenetic modifications can disrupt gene expression profiles crucial for immune responses, resulting in impaired immune cell differentiation and function. Dysregulation of these processes caused by mutations in genes involving in epigenetic modifications has been associated with various IEIs. In …

Monitoring Variations In The Use Of Automated Contouring Software, Kelly A Nealon, Eun Young Han, Stephen F Kry, Callistus Nguyen, Mary Pham, Valerie K Reed, David Rosenthal, Samantha Simiele, Laurence E Court

Faculty, Staff and Student Publications

PURPOSE: Our purpose was to identify variations in the clinical use of automatically generated contours that could be attributed to software error, off-label use, or automation bias.

METHODS AND MATERIALS: For 500 head and neck patients who were contoured by an in-house automated contouring system, Dice similarity coefficient and added path length were calculated between the contours generated by the automated system and the final contours after editing for clinical use. Statistical process control was used and control charts were generated with control limits at 3 standard deviations. Contours that exceeded the thresholds were investigated to determine the cause. Moving …

Lights And Shadows On Local Recurrence After Renal Surgery: When, Why And How To Manage, Luca Di Gianfrancesco, Alessandro Crestani, Antonio Amodeo, Paolo Corsi, Davide De Marchi, Eugenio Miglioranza, Giuliana Lista, Ferdinando Daniele Vitelli, Francesca Simonetti, Gian Maria Busetto, Ugo Giovanni Falagario, Martina Maggi, Filippo Marino, Giannicola Genovese, Roberto Falabella, Angelo Porreca

Faculty, Staff and Student Publications

Introduction: This review aims to analyze the existing literature on local recurrence (LR) in patients undergoing partial nephrectomy (PN) for renal cell carcinoma, identifying relative risk factors, and exploring optimal clinical management strategies.

Methods: A comprehensive literature search was conducted across bibliographic databases, primarily focusing on LR rates. Secondary outcomes included evaluation of positive surgical margins (PSM), nephrometry scores, pathological stage (T and grading), perioperative outcomes, time-to-LR, overall survival, and cancer-specific survival.

Results: Due to the heterogeneity, a narrative synthesis was performed. LR rates after PN varied in the literature; with PSM emerging as a significant risk factor. Other LR …

Obesity Is Associated With Improved Progression-Free Survival In Microsatellite-Instability-High Endometrial Cancer Treated With Pembrolizumab, Laurence Bernard, Jeffrey A How, Shrina Patel, Melinda S Yates, Amir Jazaeri

Faculty, Staff and Student Publications

Objectives: To determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas.

Methods: A retrospective, single institution study was conducted among women with recurrent or advanced MMRd or MSI-H endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Logistic regression was used for univariable and multivariable analyses. PFS and OS were estimated using the methods of Kaplan and Meier and modeled via Cox proportional hazards regression. Log-rank test was used for intergroup comparisons based on body …

Mri-Guided High-Dose-Rate Gynecologic Brachytherapy Using An Mr-Linac As An Mr Simulator: A Single Institutional Experience, Whitney Massock, Yusung Kim, M Alex Dresner, Wenqing Sun, Joseph Caster, Quentin Adams, Jill Jespersen, Joel St-Aubin

Faculty, Staff and Student Publications

Purpose: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development.

Methods and materials: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New …

Stereotactic Body Radiation Therapy For Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review, Colton Ladbury, Mark H Sueyoshi, Nellie M Brovold, Ritesh Kumar, Therese Y Andraos, Emile Gogineni, Minsun Kim, Ann Klopp, Kevin Albuquerque, Charles Kunos, Eric Leung, Constantine Mantz, Tithi Biswas, Sushil Beriwal, William Small, Beth Erickson, David Gaffney, Simon S Lo, Akila N Viswanathan

Faculty, Staff and Student Publications

Purpose: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients.

Methods and materials: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a …

Outcomes For Patients With Head And Neck Sarcoma Treated Curatively With Radiation Therapy And Surgery, Alison K Yoder, Ahsan Farooqi, Devarati Mitra, J Andrew Livingston, Dejka M Araujo, Erich M Sturgis, Ryan Goepfert, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

PURPOSE: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.

METHODS AND MATERIALS: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model.

RESULTS: One hundred ninety-two patients had a median follow-up of 82 …

Understanding Primary Care Physician Perspectives On The Diagnosis And Management Of Non-Alcoholic Fatty Liver Disease: A Qualitative Study, Natalia I Heredia, Jemima C John, Sonia Singh, Jessica P Hwang, Larkin L Strong, Maya Balakrishnan, Lorna H Mcneill

Faculty, Staff and Student Publications

Primary care physicians (PCPs) are well suited to manage patients with non-alcoholic fatty liver disease (NAFLD), but the limited, existing research suggests inadequate knowledge about the natural history, diagnostic methods, and management of NAFLD. The purpose of this qualitative study is to further understand the knowledge and practices for the diagnosis and management of NAFLD among PCPs. We conducted in-depth interviews with PCPs in the Greater Houston area, addressing current clinical practices used for diagnosing and managing NAFLD, as well as the perceptions of the PCPs regarding the burden of NAFLD on patients. We recorded interviews, transcribed them, coded transcripts, …

Genetic Inactivation Of Β-Catenin Is Salubrious, Whereas Its Activation Is Deleterious In Desmoplakin Cardiomyopathy, Melis Olcum, Siyang Fan, Leila Rouhi, Sirisha Cheedipudi, Benjamin Cathcart, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

AIMS: Mutations in the DSP gene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy. It is typically characterized by biventricular enlargement and dysfunction, myocardial fibrosis, cell death, and arrhythmias. The canonical wingless-related integration (cWNT)/β-catenin pathway is implicated in the pathogenesis of ACM. The β-catenin is an indispensable co-transcriptional regulator of the cWNT pathway and a member of the IDs. We genetically inactivated or activated β-catenin to determine its role in the pathogenesis of desmoplakin cardiomyopathy.

METHODS AND RESULTS: The Dsp gene was conditionally deleted in …

P53r245w Mutation Fuels Cancer Initiation And Metastases In Nash-Driven Liver Tumorigenesis, Denada Dibra, Mihai Gagea, Yuan Qi, Gilda P Chau, Xiaoping Su, Guillermina Lozano

Faculty, Staff and Student Publications

Obesity is a significant global health concern. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are common risk factors for hepatocellular carcinoma (HCC) and are closely associated with metabolic comorbidities, including obesity and diabetes. The TP53 tumor suppressor is the most frequently mutated gene in liver cancers, with half of these alterations being missense mutations. These mutations produce highly abundant proteins in cancer cells which have both inhibitory effects on wildtype (WT) p53, and gain-of-function (GOF) activities that contribute to tumor progression. A Western diet increases p53 activity in the liver. To elucidate the functional consequences of Trp53 mutations in …

Lidocaine Induces Apoptosis In Head And Neck Squamous Cell Carcinoma Through Activation Of Bitter Taste Receptor T2r14, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, Sahil Muthuswami, April Park, Derek B Mcmahon, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

Impact Of Cumulative Dose Of Brentuximab Vedotin On Outcomes Of Frontline Therapy For Advanced-Stage Hodgkin Lymphoma, Raphael E Steiner, Steven R Hwang, Arushi Khurana, Thomas M Habermann, Narendranath Epperla, Kaitlin Annunzio, Pamela Blair Allen, Katelin Baird, Darina Paulino, Juan Pablo Alderuccio, Izidore S Lossos, Kevin David, Andrew M Evens, Karan Pandya, Steven M Bair, Manali Kamdar, Sheeba Ba Aqeel, Pallawi Torka, Ryan Lynch, Stephen Smith, Lei Feng, Mansoor Noorani, Sairah Ahmed, Ranjit Nair, Francisco Vega, Susan Wu, Penny Fang, Chelsea C Pinnix, Jillian R Gunther, Bouthaina S Dabaja, Hun J Lee

Faculty, Staff and Student Publications

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Interleukin-17-Mediated Protective Cytokine Signaling Against Degeneration Of The Retinal Pigment Epithelium, Yan Chen, Sarah E Bounds, Xiang Ma, James Regun Karmoker, Yin Liu, Jian-Xing Ma, Jiyang Cai

Faculty, Staff and Student Publications

Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor …

Pathway Centric Analysis For Single-Cell Rna-Seq And Spatial Transcriptomics Data With Gsdensity, Qingnan Liang, Yuefan Huang, Shan He, Ken Chen

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Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are …