Medical Specialties Commons^™

Crosstalk Between Breast Cancer-Derived Micrornas And Brain Microenvironmental Cells In Breast Cancer Brain Metastasis, Munazza S Khan, Grace L Wong, Chuling Zhuang, Mariana K Najjar, Hui-Wen Lo

Faculty, Staff and Student Publications

Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. …

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study Of Before-After Data, Rossella Cannarella, Rupin Shah, Taha Abo-Almagd Abdel-Meguid Hamoda, Florence Boitrelle, Ramadan Saleh, Murat Gul, Amarnath Rambhatla, Parviz Kavoussi, Tuncay Toprak, Ahmed M Harraz, Edmund Ko, Gökhan Çeker, Damayanthi Durairajanayagam, Noora Alkahidi, Shinnosuke Kuroda, Andrea Crafa, Ralf Henkel, Gianmaria Salvio, Berk Hazir, Mahsa Darbandi, Marion Bendayan, Sara Darbandi, Marco Falcone, Nicolas Garrido, Raghavender Kosgi, Raneen Sawaid Kaiyal, Keshab Karna, Nguyen Ho Vinh Phuoc, Ponco Birowo, Giovanni M Colpi, Jean De La Rosette, Germar-Michael Pinggera, Quang Nguyen, Armand Zini, Wael Zohdy, Rajender Singh, Pallavi Saini, Sidney Glina, Haocheng Lin, Taymour Mostafa, Cesar Rojas-Cruz, Mohamed Arafa, Aldo E Calogero, Fotios Dimitriadis, Priyank Kothari, Vilvapathy Senguttuvan Karthikeyan, Keisuke Okada, Koji Chiba, Ates Kadıoglu, Baris Altay, Tahsin Turunc, Birute Zilaitiene, Fatih Gokalp, Aram Adamyan, Darren Katz, Eric Chung, Tiago Cesar Mierzwa, Daniel Suslik Zylbersztejn, Gustavo Marquesine Paul, Nikolaos Sofikitis, Ioannis Sokolakis, Vineet Malhotra, Sakti Ronggowardhana Brodjonegoro, Ricky Adriansjah, Akira Tsujimura, Toshiyasu Amano, Giancarlo Balercia, Imad Ziouziou, Isaac Ardianson Deswanto, Marlon Martinez, Hyun Jun Park, Mustafa Emre Bakırcıoglu, Erman Ceyhan, Kaan Aydos, Jonathan Ramsay, Suks Minhas, Manaf Al Hashimi, Ramy Abou Ghayda, Nicholas Tadros, Puneet Sindhwani, Christopher C K Ho, Rinaldo Indra Rachman, Marcelo Rodriguez Pena, Ahmad Motawi, Arun Karthik Ponnusamy, Satish Dipankar, Azwar Amir, Saleh Binsaleh, Ege Can Serefoglu, Ravi Banthia, Kareim Khalafalla, Ari Basukarno, Nguyen Hoai Bac, Karun Singla, Rafael F Ambar, Konstantinos Makarounis, Shivam Priyadarshi, Gede Wirya Kusuma Duarsa, Widi Atmoko, Sunil Jindal, Eko Arianto, Hamed Akhavizadegan, Haitham El Bardisi, Ohad Shoshany, Gian Maria Busetto, Mohamad Moussa, Mounir Jamali, Mohamed S Al-Marhoon, Mikhail Ruzaev, Hasan M A Farsi, Shingai Mutambirwa, Dong Sup Lee, Deniz Kulaksiz, Yu-Sheng Cheng, Abderrazak Bouzouita, Selcuk Sarikaya, Hussein Kandil, Georgios Tsampoukas, Ala'a Farkouh, Kasonde Bowa, Missy Savira, Nasser Mogharabian, Tan V Le, Maruto Harjanggi, Dang Tuan Anh, Tran Quang Tien Long, Mohammad Ayodhia Soebadi, Lukman Hakim, Marko Tanic, Umut Cagin Ari, Firuza R Parikh, Gokhan Calik, Vinod Kv, Gyem Dorji, Andri Rezano, Osvaldo Rajmil, Dung Mai Ba Tien, Yiming Yuan, Juan Francisco Lizarraga-Salas, Balantine Eze, Kay Seong Ngoo, Joe Lee, Umut Arslan, Ashok Agarwal, Global Andrology Forum

Faculty, Staff and Student Publications

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.

Materials and methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: …

Technical Aspects And Clinical Limitations Of Sperm Dna Fragmentation Testing In Male Infertility: A Global Survey, Current Guidelines, And Expert Recommendations, Ashok Agarwal, Ala'a Farkouh, Ramadan Saleh, Taha Abo-Almagd Abdel-Meguid Hamoda, Gianmaria Salvio, Florence Boitrelle, Ahmed M Harraz, Ramy Abou Ghayda, Parviz Kavoussi, Murat Gül, Tuncay Toprak, Giorgio Ivan Russo, Damayanthi Durairajanayagam, Amarnath Rambhatla, Ponco Birowo, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Armand Zini, Mohamed Arafa, Christine Wyns, Kelton Tremellen, Selçuk Sarıkaya, Sheena Lewis, Donald P Evenson, Edmund Ko, Aldo E Calogero, Fahmi Bahar, Marlon Martínez, Rafael F Ambar, Giovanni M Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alfakhri, Akira Tsujimura, Alireza Kheradmand, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Nguyen Quang, Germar-Michael Pinggera, Priyank Kothari, Sava Micic, Sheryl Homa, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Wael Ibrahim, Marjan Sabbaghian, Saad Mohammed Abumelha, Eric Chung, Muhammet Rasit Ugur, Mehmet Serkan Ozkent, Osama Selim, Mahsa Darbandi, Shinichiro Fukuhara, Mounir Jamali, Jean De La Rosette, Shinnosuke Kuroda, Ryan P Smith, Aykut Baser, Arif Kalkanli, Nicholas N Tadros, Kaan Aydos, Tiago Cesar Mierzwa, Kareim Khalafalla, Vineet Malhotra, Mohamad Moussa, Federica Finocchi, Rinaldo Indra Rachman, Carlo Giulioni, Tomer Avidor-Reiss, Oguzhan Kahraman, Gökhan Çeker, Cătălina Zenoaga-Barbăroșie, Trenton L Barrett, Mehmet Yilmaz, Ates Kadioglu, Sunil Jindal, Huda Omran, Kadir Bocu, Vilvapathy Senguttuvan Karthikeyan, Giorgio Franco, Jesús Fernando Solorzano, Ranjit B Vishwakarma, Eko Arianto, Nicolas Garrido, Divyanu Jain, Nazim Gherabi, Ioannis Sokolakis, Ayad Palani, Gokhan Calik, Deniz Kulaksiz, Vaida Simanaviciene, Mara Simopoulou, Nur Dokuzeylül Güngör, Gideon Blecher, Marco Falcone, Davor Jezek, Mirko Preto, Edouard Amar, Tan V Le, Sun Tae Ahn, Andri Rezano, Keerti Singh, Lucia Rocco, Missy Savira, Osvaldo Rajmil, Sara Darbandi, Emrullah Sogutdelen, Luca Boeri, Guadalupe Hernández, Lukman Hakim, Yoshiharu Morimoto, Andrian Japari, Nikolaos Sofikitis, Baris Altay, Asli Metin Mahmutoglu, Manaf Al Hashimi, Imad Ziouziou, Christina Anagnostopoulou, Haocheng Lin, Rupin Shah

Faculty, Staff and Student Publications

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice.

Materials and methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses …

Configuring Thermal Ablation Volumes For Treatment Of Distinct Tumor Shapes: A Repeatability Study Using A Robotic Approach, Milica Bulatović, Jan Hermann, Pascale Tinguely, Iwan Paolucci, Stefan Weber

Faculty, Staff and Student Publications

Objectives: In the current clinical practice of thermal ablation treatment for liver tumors, achieving consistent and effective clinical outcomes across tumors of varying shapes, sizes and locations remains challenging. The aim of this study was to evaluate the repeatability of a novel robotic approach for configurable ablation of distinct tumor shapes and compare it to the standard ablation technique for creating ellipsoidal ablation volumes.

Materials and methods: The repeatability was evaluated in terms of width variability in created ablation volumes. Using a robotic navigation platform, custom ablation profiles configured with power, time, and distance parameters were designed to create four …

Pet Image Denoising Based On Denoising Diffusion Probabilistic Model, Kuang Gong, Keith Johnson, Georges El Fakhri, Quanzheng Li, Tinsu Pan

Faculty, Staff and Student Publications

Purpose: Due to various physical degradation factors and limited counts received, PET image quality needs further improvements. The denoising diffusion probabilistic model (DDPM) was a distribution learning-based model, which tried to transform a normal distribution into a specific data distribution based on iterative refinements. In this work, we proposed and evaluated different DDPM-based methods for PET image denoising.

Methods: Under the DDPM framework, one way to perform PET image denoising was to provide the PET image and/or the prior image as the input. Another way was to supply the prior image as the network input with the PET image included …

Transcriptomics Analysis Reveals Potential Mechanisms Underlying Mitochondrial Dysfunction And T Cell Exhaustion In Astronauts’ Blood Cells In Space, Maria Moreno-Villanueva, Luis E Jimenez-Chavez, Stephanie Krieger, Liang-Hao Ding, Ye Zhang, Adriana Babiak-Vazquez, Mark Berres, Sandra Splinter, Kristen E Pauken, Brian C Schaefer, Brian E Crucian, Honglu Wu

Faculty, Staff and Student Publications

Introduction: The impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.

Methods: In this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.

Results: In comparison to pre-flight, a total of 2030 …

Faslpr Gene Dosage Tunes The Extent Of Lymphoproliferation And T Cell Differentiation In Lupus, Ritu Bohat, Xiaofang Liang, Yanping Chen, Chunyu Xu, Ningbo Zheng, Ashley Guerrero, Jiakai Hou, Roshni Jaffery, Nicholas A Egan, Yaxi Li, Yitao Tang, Esra Unsal, Adolfo Robles, Si Chen, Angela M Major, Hadil Elldakli, Sang-Hyuk Chung, Han Liang, M John Hicks, Yong Du, Jamie S Lin, Xiqun Chen, Chandra Mohan, Weiyi Peng

Faculty, Staff and Student Publications

Sle1 and Fas^lpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Fas^lpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Fas^lpr/+ (Sle1homo.lprhet) and compared it with B6.Fas^lpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Fas^lpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly …

Steroid Receptor Coactivators In Treg And Th17 Cell Biology And Function, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Inhibition Of Src-3 As A Potential Therapeutic Strategy For Aggressive Mantle Cell Lymphoma, Imani Bijou, Yang Liu, Dong Lu, Jianwei Chen, Shelby Sloan, Lapo Alinari, David M Lonard, Bert W O'Malley, Michael Wang, Jin Wang

Faculty, Staff and Students Publications

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams

Faculty, Staff and Students Publications

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT;

Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader

Faculty, Staff and Students Publications

No abstract provided.

Cutting Edge Of Genetically Modified Pigs Targeting Complement Activation For Xenotransplantation, Qin Sun, Si-Yuan Song, Jiabao Ma, Danni Li, Yiping Wang, Zhengteng Yang, Yi Wang

Faculty, Staff and Students Publications

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of …

Fam20a: A Potential Diagnostic Biomarker For Lung Squamous Cell Carcinoma, Yalin Zhang, Qin Sun, Yangbo Liang, Xian Yang, Hailian Wang, Siyuan Song, Yi Wang, Yong Feng

Faculty, Staff and Students Publications

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC.

Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, …

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

Faculty, Staff and Student Publications

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 …

Differences In Set-Based Tests For Sparse Alternatives When Testing Sets Of Outcomes Compared To Sets Of Explanatory Factors In Genetic Association Studies, Ryan Sun, Andy Shi, Xihong Lin

Faculty, Staff and Student Publications

Set-based association tests are widely popular in genetic association settings for their ability to aggregate weak signals and reduce multiple testing burdens. In particular, a class of set-based tests including the Higher Criticism, Berk-Jones, and other statistics have recently been popularized for reaching a so-called detection boundary when signals are rare and weak. Such tests have been applied in two subtly different settings: (a) associating a genetic variant set with a single phenotype and (b) associating a single genetic variant with a phenotype set. A significant issue in practice is the choice of test, especially when deciding between innovated and …

Gap Junctions Or Hemichannel-Dependent And Independent Roles Of Connexins In Fibrosis, Epithelial-Mesenchymal Transitions, And Wound Healing, Yuting Li, Francisca M Acosta, Jean X Jiang

Faculty, Staff and Student Publications

Fibrosis initially appears as a normal response to damage, where activated fibroblasts produce large amounts of the extracellular matrix (ECM) during the wound healing process to assist in the repair of injured tissue. However, the excessive accumulation of the ECM, unresolved by remodeling mechanisms, leads to organ dysfunction. Connexins, a family of transmembrane channel proteins, are widely recognized for their major roles in fibrosis, the epithelial-mesenchymal transition (EMT), and wound healing. Efforts have been made in recent years to identify novel mediators and targets for this regulation. Connexins form gap junctions and hemichannels, mediating communications between neighboring cells and inside …

Recombination-Mediated Dissemination Of Methicillin-Resistant S Aureus Clonal Complex 1 In The Egyptian Health Care Settings, Salma W Elsayed, Reem A Elghaish, Eman Badr, Shaimaa F Mouftah, Nehal A Saif, Iman S Naga, Ahmed H Shata, Ben Pascoe, Samuel K Sheppard, Mohamed Elhadidy

Faculty, Staff and Student Publications

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly evolving pathogen that is frequently associated with outbreaks and sustained epidemics. This study investigated the population structure, resistome, virulome, and the correlation between antimicrobial resistance determinants with phenotypic resistance profiles of 36 representative hospital-acquired MRSA isolates recovered from hospital settings in Egypt.

Results: The community-acquired MRSA lineage, clonal complex 1 (CC1) was the most frequently detected clone, followed by three other globally disseminated clones, CC121, CC8, and CC22. Most isolates carried SCCmec type V and more than half of isolates demonstrated multi-drug resistant phenotypes. Resistance to linezolid, a last resort antibiotic for …

Cannabis Use Among Cancer Survivors: Use Pattern, Product Type, And Timing Of Use, Ikponmwosa Osaghae, Onyema Greg Chido-Amajuoyi, Banda A A Khalifa, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Despite growing interest in the use of cannabis for the treatment of cancer-related symptoms, there are limited studies that have assessed the use pattern, type, and mode of delivery of cannabis products used by cancer survivors. This study describes the current state of the use pattern, product type, and mode of delivery of cannabis used by cancer survivors. This was a cross-sectional study of cancer survivors from 41 U.S. states who received treatment at the largest NCI-designated comprehensive cancer center. The weighted prevalence of the use patterns, product types, and modes of delivery of cannabis used by cancer survivors was …

Identification Of Candidate Dna Methylation Biomarkers Related To Alzheimer’S Disease Risk By Integrating Genome And Blood Methylome Data, Yanfa Sun, Jingjing Zhu, Yaohua Yang, Zichen Zhang, Hua Zhong, Guanghua Zeng, Dan Zhou, Richard S Nowakowski, Jirong Long, Chong Wu, Lang Wu

Faculty, Staff and Student Publications

Alzheimer disease (AD) is a common neurodegenerative disease with a late onset. It is critical to identify novel blood-based DNA methylation biomarkers to better understand the extent of the molecular pathways affected in AD. Two sets of blood DNA methylation genetic prediction models developed using different reference panels and modelling strategies were leveraged to evaluate associations of genetically predicted DNA methylation levels with AD risk in 111,326 (46,828 proxy) cases and 677,663 controls. A total of 1,168 cytosine-phosphate-guanine (CpG) sites showed a significant association with AD risk at a false discovery rate (FDR) < 0.05. Methylation levels of 196 CpG sites were correlated with expression levels of 130 adjacent genes in blood. Overall, 52 CpG sites of 32 genes showed consistent association directions for the methylation-gene expression-AD risk, including nine genes (CNIH4, THUMPD3, SERPINB9, MTUS1, CISD1, FRAT2, CCDC88B, FES, and SSH2) firstly reported as AD risk genes. Nine of 32 genes were enriched in dementia and AD disease categories (P values ranged from 1.85 × 10-4 to 7.46 × 10-6), and 19 genes in a neurological disease network (score = 54) were also observed. Our findings improve the understanding of genetics and etiology for AD.

Genetic Determinants Underlying The Progressive Phenotype Of Β-Lactam/Β-Lactamase Inhibitor Resistance In Escherichia Coli, William C Shropshire, Hatim Amiji, Jordan Bremer, Selvalakshmi Selvaraj Anand, Benjamin Strope, Pranoti Sahasrabhojane, Marc Gohel, Samuel Aitken, Sarah Spitznogle, Xiaowei Zhan, Jiwoong Kim, David E Greenberg, Samuel A Shelburne

Faculty, Staff and Student Publications

Currently, whole-genome sequencing (WGS) data have not shown strong concordance with Escherichia coli susceptibility profiles to the commonly used β-lactam/β-lactamase inhibitor (BL/BLI) combinations: ampicillin-sulbactam (SAM), amoxicillin-clavulanate (AMC), and piperacillin-tazobactam (TZP). Progressive resistance to these BL/BLIs in the absence of cephalosporin resistance, also known as extended-spectrum resistance to BL/BLI (ESRI), has been suggested to primarily result from increased copy numbers of bla TEM variants, which is not routinely assessed in WGS data. We sought to determine whether addition of gene amplification could improve genotype-phenotype associations through WGS analysis of 147 E. coli bacteremia isolates with increasing categories of BL/BLI non-susceptibility ranging …

Nitric Oxide Is Required For Lung Alveolarization Revealed By Deficiency Of Argininosuccinate Lyase, Zixue Jin, Ming-Ming Jiang, Brendan Lee

Faculty, Staff and Students Publications

Inhaled nitric oxide (NO) therapy has been reported to improve lung growth in premature newborns. However, the underlying mechanisms by which NO regulates lung development remain largely unclear. NO is enzymatically produced by three isoforms of nitric oxide synthase (NOS) enzymes. NOS knockout mice are useful tools to investigate NO function in the lung. Each single NOS knockout mouse does not show obvious lung alveolar phenotype, likely due to compensatory mechanisms. While mice lacking all three NOS isoforms display impaired lung alveolarization, implicating NO plays a pivotal role in lung alveolarization. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable …

Optical Genome Mapping Helps To Identify Bcr::Jak2 Rearrangement Arising From Cryptic Complex Chromosomal Aberrations: A Case Report And Literature Review, Neelam Vanjari, Guilin Tang, Gokce A Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J Dave, Joseph D Khoury, L Jeffrey Medeiros, Zhenya Tang

Faculty, Staff and Student Publications

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical …

Rad54l2-Mediated Dna Damage Avoidance Pathway Specifically Preserves Genome Integrity In Response To Topoisomerase 2 Poisons, Huimin Zhang, Yun Xiong, Yilun Sun, Jeong-Min Park, Dan Su, Xu Feng, Sarah Keast, Mengfan Tang, Min Huang, Chao Wang, Mrinal Srivastava, Chang Yang, Dandan Zhu, Zhen Chen, Siting Li, Ling Yin, Yves Pommier, Junjie Chen

Faculty, Staff and Student Publications

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted …