Medical Specialties Commons^™

Attempts To Understand Oral Mucositis In Head And Neck Cancer Patients Through Omics Studies: A Narrative Review, Erin Marie D San Valentin, Kim-Anh Do, Sai-Ching J Yeung, Cielito C Reyes-Gibby

Faculty, Staff and Student Publications

Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host …

What Matters To You? Engaging With Children In The James Lind Alliance Children’S Cancer Priority Setting Partnership, Susie Aldiss, Penelope Hart-Spencer, Loveday Langton, Sonia Malik, Keeley Mcevoy, Jessica E Morgan, Rosa Reed-Berendt, Rachel Hollis, Bob Phillips, Faith Gibson, James Lind Alliance Children’S Cancer Priority Setting Partnership Steering Group

Faculty, Staff and Student Publications

BACKGROUND: Previous priority setting exercises have sought to involve children, but in the final reporting, it is evident that few children had been engaged through the process. A primary aim in the Children's Cancer Priority Setting Partnership was to find out from children what they want research to focus on. We report on our experience to inform methods of engagement with children in future James Lind Alliance Priority Setting Partnerships and similar exercises.

METHODS: We followed the James Lind Alliance process, collecting and shortlisting questions via online surveys with adult survivors of childhood cancer, carers, and professionals, and holding a …

Cannabinoids In Periodontology: Where Are We Now?, Yésica Carmona Rendón, Hernán Santiago Garzón, Bruno Bueno-Silva, Roger M Arce, Lina Janeth Suárez

Faculty, Staff and Student Publications

Introduction: Cannabinoids are a well-documented treatment modality for various immune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease, Crohn's disease, arthritis, multiple sclerosis, and a range of neurodegenerative conditions. However, limited information is available regarding the therapeutic potential of cannabinoids in treating periodontal disease.

Objective: The objective of this study is to analyze the current evidence on the antibacterial and immunomodulatory effects of cannabis and its role in the healing and regeneration processes within periodontal tissues.

Results: This review discusses the potential role of cannabinoids in restoring periodontal tissue homeostasis.

Conclusions: The examination of the endocannabinoid system and the …

Loss Of The Methylarginine Reader Function Of Snd1 Confers Resistance To Hepatocellular Carcinoma, Tanner Wright, Yalong Wang, Sabrina A Stratton, Manu Sebastian, Bin Liu, David G Johnson, Mark T Bedford

Faculty, Staff and Student Publications

Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that 'reads' methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two genetically engineered SND1 mouse models, an Snd1 knockout (Snd1 KO) and an Snd1 Tudor domain-mutated (Snd1 KI) mouse, whose mutant SND1 can …

Correction: Precision Dosimetry In Yttrium-90 Radioembolization Through Ct Imaging Of Radiopaque Microspheres In A Rabbit Liver Model, E Courtney Henry, Matthew Strugari, George Mawko, Kimberly Brewer, David Liu, Andrew C Gordon, Jeffrey N Bryan, Charles Maitz, James J Karnia, Robert Abraham, S Cheenu Kappadath, Alasdair Syme

Faculty, Staff and Student Publications

No abstract provided.

Data-Driven Multiscale Model Of Macaque Auditory Thalamocortical Circuits Reproduces In Vivo Dynamics, Salvador Dura-Bernal, Erica Y Griffith, Annamaria Barczak, Monica N O'Connell, Tammy Mcginnis, Joao V S Moreira, Charles E Schroeder, William W Lytton, Peter Lakatos, Samuel A Neymotin

Faculty, Staff and Student Publications

We developed a detailed model of macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator and NetPyNE tool. The A1 model simulates a cortical column with over 12,000 neurons and 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, and connectivity across six cortical layers. It is reciprocally connected to the MGB thalamus, which includes interneurons and core and matrix-layer-specific projections to A1. The model simulates multiscale measures, including physiological firing rates, local field potentials (LFPs), current source densities (CSDs), and electroencephalography (EEG) signals. Laminar CSD patterns, …

A Heritable Iron Memory Enables Decision-Making In Escherichia Coli, Souvik Bhattacharyya, Nabin Bhattarai, Dylan M Pfannenstiel, Brady Wilkins, Abhyudai Singh, Rasika M Harshey

Faculty, Staff and Student Publications

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when Escherichia coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This “iron” memory preexists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, which tracks with …

Reducing Stress After Trauma (Reset): Study Protocol For A Randomized, Controlled Trial Of An Online Psychoeducational Program And Video Therapy Sessions For Children Hospitalized After Trauma, Heather T Keenan, Shari L Wade, Devi Miron, Angela P Presson, Amy E Clark, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

BACKGROUND: Post-traumatic stress symptoms develop in a quarter to half of injured children affecting their longer-term psychologic and physical health. Evidence-based care exists for post-traumatic stress; however, it is not readily available in some communities. We have developed an eHealth program consisting of online, interactive educational modules and telehealth therapist support based in trauma-focused cognitive behavioral therapy, the Reducing Stress after Trauma (ReSeT) program. We hypothesize that children with post-traumatic stress who participate in ReSeT will have fewer symptoms compared to the usual care control group.

METHODS: This is a randomized controlled trial to test the effectiveness of the ReSeT …

Multidisciplinary Care For Women With Aortic Disease: The Way To Improve Disparities, Rana O Afifi

Faculty, Staff and Student Publications

No abstract provided.

Precision Recruitment And Engagement Of Individuals At Risk For Diabetes And Hypertension In Clinical Trials (Predhict): A Randomized Trial For An E-Persuasive Mobile Application To Inform Decision Making About Clinical Trials, Azizi Seixas, Shannique Richards, Jesse Q Moore, Chigozirim Izeogu, Laronda A Hollimon, Peng Jin, Girardin Jean-Louis

Faculty, Staff and Student Publications

The primary objective of this randomized trial was to test the effectiveness of the PREDHiCT digital application, which provides educational and supportive navigation to increase willingness to participate in a future clinical trial. The second objective was to test whether PREDHiCT increased clinical trial literacy or enhanced psychological facilitators of clinical trial participation, such as altruism. To test these two objectives, we conducted a 1-month remote decentralized trial with 100 participants who either have a personal or family history of cardiometabolic health conditions, such as hypertension, diabetes, and obesity. Results indicated significant changes in altruism (mean: -2.94 vs. 0.83;

Outcomes Of Cardiothoracic Surgery In Women With Turner Syndrome, Lucas Ribé, Ferial D Shihadeh, Rana O Afifi, Anthony L Estrera, Siddharth K Prakash

Faculty, Staff and Student Publications

BACKGROUND: To describe short- and mid-term surgical outcomes of patients with Turner syndrome (TS) after cardiovascular interventions.

METHODS: All individuals >12 years of age at the time of surgical repair for cardiovascular disease (valve or coarctation repairs, aortic disease, aortic dissection) from 2002 to 2022 were eligible. The primary endpoint was complications or death within 30 days of intervention. Secondary outcomes included late complications and reinterventions within six months. Combined data from the University of Texas Health Science Center at Houston and the Turner Syndrome Society of the United States were included in the analysis.

RESULTS: We identified 22 patients …

Hybrid Repair Of A Thoracoabdominal Aortic Aneurysm In Female Patient With Loeys-Dietz Syndrome, Sabine Helena Wipper, Tilo Kölbel, Bernhard Dorweiler, Julia Dumfarth, Alexandra Gratl, Olaf Gorny, Anthony L Estrera, Harleen K Sandhu, E Sebastian Debus

Faculty, Staff and Student Publications

No abstract provided.

Rcc2 Promotes Prostate Cancer Cell Proliferation And Migration Through Hh/Gli1 Signaling Pathway And Cancer Stem-Like Cells, Shenghan Wang, Zhentao Lei, Wei Liu, Jie Xiong, Yuqiang Shi, Lin Yang, Qiang Gao, Kai Le, Bao Zhang

Faculty, Staff and Student Publications

BACKGROUND: Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.

METHODS: The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were …

Case Of New-Onset Scleromyxoedema-Scleroedema Spectrum Disorder In A Patient With Cll, Yuanteng Jeff Li, Victor G Prieto, Jean Tayar

Faculty, Staff and Student Publications

No abstract provided.

Varlock: Sequencing-Independent, Rapid Detection Of Sars-Cov-2 Variants Of Concern For Point-Of-Care Testing, Qpcr Pipelines And National Wastewater Surveillance, Xinsheng Nan, Patrick Hardinge, Sven Hoehn, Shrinivas Nivrutti Dighe, John Ukeri, Darius F Pease, Joshua Griffin, Jessica I Warrington, Zack Saud, Emma Hottinger, Gordon Webster, Davey Jones, Peter Kille, Andrew Weightman, Richard Stanton, Oliver K Castell, James A H Murray, Tomasz P Jurkowski

Faculty, Staff and Student Publications

The COVID-19 pandemic demonstrated the need for rapid molecular diagnostics. Vaccination programs can provide protection and facilitate the opening of society, but newly emergent and existing viral variants capable of evading the immune system endanger their efficacy. Effective surveillance for Variants of Concern (VOC) is therefore important. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. Here we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to provide rapid and sensitive discrimination of SARS-CoV-2 VOCs that can be used at point of care, …

Chimeric Antigen Receptor T Cells To Target Cd79b In B-Ceall Lymphomas, Fuliang Chu, Jingjing Cao, Jingwei Liu, Haopeng Yang, Timothy J Davis, Shao-Qing Kuang, Xiaoyun Cheng, Zheng Zhang, Swathi Karri, Long T Vien, Laura Bover, Ryan Sun, Francisco Vega, Michael Green, Richard Eric Davis, Sattva S Neelapu

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas.

METHODS: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR …

Growth Rates And Histopathological Outcomes Of Small (6-9 Mm) Colorectal Polyps Based On Ct Colonography Surveillance And Endoscopic Removal, B Dustin Pooler, David H Kim, Kristina A Matkowskyj, Michael A Newton, Richard B Halberg, William M Grady, Cesare Hassan, Perry J Pickhardt

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: The natural history of small polyps is not well established and rests on limited evidence from barium enema studies decades ago. Patients with one or two small polyps (6-9 mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy. This practice allows direct observation of the growth of subcentimetre polyps, with histopathological correlation in patients undergoing subsequent polypectomy.

DESIGN: Of 11 165 asymptomatic patients screened by CTC over a period of 16.4 years, 1067 had one or two 6-9 mm polyps detected (with no polyps ≥10 mm). Of these, …

Sustained Remissions In Cll After Frontline Fcr Treatment With Very-Long-Term Follow-Up, Philip A Thompson, Alexandre Bazinet, William G Wierda, Constantine S Tam, Susan M O'Brien, Satabdi Saha, Christine B Peterson, William Plunkett, Michael J Keating

Faculty, Staff and Student Publications

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up …

N6-Methyladenosine-Mediated Overexpression Of Long Noncoding Rna Adamts9-As2 Triggers Neuroblastoma Differentiation Via Regulating Lin28b/Let-7/Mycn Signaling, Yun Liu, Jun Zhang, Fang Cao, Xiaobao Dong, Jie Li, Yanna Cao, Zhanglin Li, Yan Guo, Jie Yan, Yuanyuan Liu, Qiang Zhao

Faculty, Staff and Student Publications

Neuroblastomas have shed light on the differentiation disorder that is associated with spontaneous regression or differentiation in the same tumor at the same time. Long noncoding RNAs (lncRNAs) actively participate in a broad spectrum of biological processes. However, the detailed molecular mechanisms underlying lncRNA regulation of differentiation in neuroblastomas remain largely unknown. Here, we sequenced clinical samples of ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. We compared transcription profiles of neuroblastoma cells, ganglion cells, and intermediate state cells; verified the profiles in a retinoic acid-induced cell differentiation model and clinical samples; and screened out the lncRNA ADAMTS9 antisense RNA 2 (ADAMTS9-AS2), which contributed …

Glial Cell Adhesion Molecule (Glialcam) Determines Proliferative Versus Invasive Cell States In Glioblastoma, Arpan De, John M Lattier, John E Morales, Jack R Kelly, Xiaofeng Zheng, Zhihua Chen, Sumod Sebastian, Zahra Nassiri Toosi, Jason T Huse, Frederick F Lang, Joseph H Mccarty

Faculty, Staff and Student Publications

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in subpopulations of GBM cells. High levels of GlialCAM promote …

Antibody-Directed Evolution Reveals A Mechanism For Enhanced Neutralization At The Hiv-1 Fusion Peptide Site, Bailey B Banach, Sergei Pletnev, Adam S Olia, Kai Xu, Baoshan Zhang, Reda Rawi, Tatsiana Bylund, Nicole A Doria-Rose, Thuy Duong Nguyen, Ahmed S Fahad, Myungjin Lee, Bob C Lin, Tracy Liu, Mark K Louder, Bharat Madan, Krisha Mckee, Sijy O'Dell, Mallika Sastry, Arne Schön, Natalie Bui, Chen-Hsiang Shen, Jacy R Wolfe, Gwo-Yu Chuang, John R Mascola, Peter D Kwong, Brandon J Dekosky

Faculty, Staff and Student Publications

The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to …

Safety And Efficacy Of Direct Oral Anticoagulants In Stroke Prevention In Patients With Atrial Fibrillation Complicated With Anemia And/Or Thrombocytopenia: A Retrospective Cohort Study, Wenlin Xu, Jiana Chen, Shuyi Wu, Nianxu Huang, Xia Chen, Wang Zhang, Wei Hu, Jun Su, Hengfen Dai, Ping Gu, Xiaohong Huang, Xiaoming Du, Ruijuan Li, Qiaowei Zheng, Xiangsheng Lin, Yanxia Zhang, Lang Zou, Yuxin Liu, Min Zhang, Xiumei Liu, Zhu Zhu, Jinhua Zhang

Faculty, Staff and Student Publications

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.

METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 10

RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any …

Early And Empirical High-Dose Cryoprecipitate For Hemorrhage After Traumatic Injury: The Cryostat-2 Randomized Clinical Trial, Ross Davenport, Nicola Curry, Erin E Fox, Helen Thomas, Joanne Lucas, Amy Evans, Shaminie Shanmugaranjan, Rupa Sharma, Alison Deary, Antoinette Edwards, Laura Green, Charles E Wade, Jonathan R Benger, Bryan A Cotton, Simon J Stanworth, Karim Brohi, Cryostat-2 Principal Investigators

Faculty, Staff and Student Publications

IMPORTANCE: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.

OBJECTIVE: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.

DESIGN, SETTING, AND PARTICIPANTS: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US …

Silencing Of Genes By Promoter Hypermethylation Shapes Tumor Microenvironment And Resistance To Immunotherapy In Clear-Cell Renal Cell Carcinomas, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Alexandra Helleux, Véronique Lindner, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, Virginie Verkarre, Cheng-Ming Sun, Mostefa Bennamoun, Hervé Lang, Philippe Barthelemy, Wenxuan Cheng, Li Xu, Irwin Davidson, Fangrong Yan, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

The efficacy of immune checkpoint inhibitors varies in clear-cell renal cell carcinoma (ccRCC), with notable primary resistance among patients. Here, we integrate epigenetic (DNA methylation) and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We develop and validate an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition (ICI) in the BIONIKK trial. High iMES is associated with VEGF pathway silencing, endothelial cell depletion, immune activation/suppression, EZH2 activation, BAP1/SETD2 deficiency, and resistance to ICI. Combination therapy with hypomethylating agents or tyrosine kinase inhibitors may benefit …

A Conceptual Framework For Nomenclatural Stability And Validity Of Medically Important Fungi: A Proposed Global Consensus Guideline For Fungal Name Changes Supported By Abp, Asm, Clsi, Ecmm, Escmid-Efisg, Eucast-Afst, Fdlc, Idsa, Isham, Mmsa, And Msgerc, Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Barbara D Alexander, Maiken Cavling Arendrup, Esther Babady, Feng-Yan Bai, Joan-Miquel Balada-Llasat, Andrew Borman, Anuradha Chowdhary, Andrew Clark, Robert C Colgrove, Oliver A Cornely, Tanis C Dingle, Philippe J Dufresne, Jeff Fuller, Jean-Pierre Gangneux, Connie Gibas, Heather Glasgow, Yvonne Gräser, Jacques Guillot, Andreas H Groll, Gerhard Haase, Kimberly Hanson, Amanda Harrington, David L Hawksworth, Randall T Hayden, Martin Hoenigl, Vit Hubka, Kristie Johnson, Julianne V Kus, Ruoyu Li, Jacques F Meis, Michaela Lackner, Fanny Lanternier, Sixto M Leal, Francesca Lee, Shawn R Lockhart, Paul Luethy, Isabella Martin, Kyung J Kwon-Chung, Wieland Meyer, M Hong Nguyen, Luis Ostrosky-Zeichner, Elizabeth Palavecino, Preeti Pancholi, Peter G Pappas, Gary W Procop, Scott A Redhead, Daniel D Rhoads, Stefan Riedel, Bryan Stevens, Kaede Ota Sullivan, Paschalis Vergidis, Emmanuel Roilides, Amir Seyedmousavi, Lili Tao, Vania A Vicente, Roxana G Vitale, Qi-Ming Wang, Nancy L Wengenack, Lars Westblade, Nathan Wiederhold, Lewis White, Christina M Wojewoda, Sean X Zhang

Faculty, Staff and Student Publications

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the …

New Insights Into Yap/Taz-Tead-Mediated Gene Regulation And Biological Processes In Cancer, Yang Zhao, Marisela Sheldon, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

The Hippo pathway is conserved across species. Key mammalian Hippo pathway kinases, including MST1/2 and LATS1/2, inhibit cellular growth by inactivating the TEAD coactivators, YAP, and TAZ. Extensive research has illuminated the roles of Hippo signaling in cancer, development, and regeneration. Notably, dysregulation of Hippo pathway components not only contributes to tumor growth and metastasis, but also renders tumors resistant to therapies. This review delves into recent research on YAP/TAZ-TEAD-mediated gene regulation and biological processes in cancer. We focus on several key areas: newly identified molecular patterns of YAP/TAZ activation, emerging mechanisms that contribute to metastasis and cancer therapy resistance, …

Widespread Brca1/2-Independent Homologous Recombination Defects Are Caused By Alterations In Rna-Binding Proteins, Daniel J Mcgrail, Yang Li, Roger S Smith, Bin Feng, Hui Dai, Limei Hu, Briana Dennehey, Sharad Awasthi, Marc L Mendillo, Anil K Sood, Gordon B Mills, Shiaw-Yih Lin, S Stephen Yi, Nidhi Sahni

Faculty, Staff and Student Publications

Defects in homologous recombination DNA repair (HRD) both predispose to cancer development and produce therapeutic vulnerabilities, making it critical to define the spectrum of genetic events that cause HRD. However, we found that mutations in BRCA1/2 and other canonical HR genes only identified 10%-20% of tumors that display genomic evidence of HRD. Using a networks-based approach, we discovered that over half of putative genes causing HRD originated outside of canonical DNA damage response genes, with a particular enrichment for RNA-binding protein (RBP)-encoding genes. These putative drivers of HRD were experimentally validated, cross-validated in an independent cohort, and enriched in cancer-associated …

A Network Pharmacology And Molecular-Docking-Based Approach To Identify The Probable Targets Of Short-Chain Fatty-Acid-Producing Microbial Metabolites Against Kidney Cancer And Inflammation, Md Rezaul Karim, Md Niaj Morshed, Safia Iqbal, Shahnawaz Mohammad, Ramya Mathiyalagan, Deok Chun Yang, Yeon Ju Kim, Joon Hyun Song, Dong Uk Yang

Faculty, Staff and Student Publications

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species …

Trend Of Outcome Metrics In Recent Out-Of-Hospital-Cardiac-Arrest Research: A Narrative Review Of Clinical Trials, Natalie N Htet, Daniel Jafari, Jennifer A Walker, Ali Pourmand, Anna Shaw, Khai Dinh, Quincy K Tran

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Cardiopulmonary resuscitation (CPR) research traditionally focuses on survival. In 2018, the International Liaison Committee on Resuscitation (ILCOR) proposed more patient-centered outcomes. Our narrative review assessed clinical trials after 2018 to identify the trends of outcome metrics in the field OHCA research. We performed a search of the PubMed database from 1 January 2019 to 22 September 2023. Prospective clinical trials involving adult humans were eligible. Studies that did not report any patient-related outcomes or were not available in full-text or English language were excluded. The articles were assessed for demographic information and primary and secondary outcomes. We included 89 studies …

Eicosanoid And Eicosanoid-Related Inflammatory Mediators And Exercise Intolerance In Heart Failure With Preserved Ejection Fraction, Emily S Lau, Athar Roshandelpoor, Shahrooz Zarbafian, Dongyu Wang, James S Guseh, Norrina Allen, Vinithra Varadarajan, Matthew Nayor, Ravi V Shah, Joao A C Lima, Sanjiv J Shah, Bing Yu, Mona Alotaibi, Susan Cheng, Mohit Jain, Gregory D Lewis, Jennifer E Ho

Faculty, Staff and Student Publications

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.