Genetic Phenomena Commons^™

The Contribution Of Dna Ligase 4 Polymorphisms To Colorectal Cancer, Yang Deng, Tao-Wei Ke, Te-Cheng Yueh, Yu-Ting Chin, Yun-Chi Wang, Yi-Chih Hung, Mei-Chin Mong, Ya-Chen Yang, Wen-Tzu Wu, Wen-Shin Chang, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: While numerous biomarkers associated with genetic susceptibility to colorectal cancer (CRC) have been identified and validated through epidemiological studies, the specific influence of DNA ligase 4 (Lig4) genotypes remains unexplored. This study aimed to elucidate the hitherto unexamined relationship between Lig4 genotypes and CRC risk.

Materials and methods: The genotypes of Lig4 rs1805388 were determined applying the polymerase chain reaction-restriction fragment length polymorphism methodology. The potential association between these genotypes and CRC risk was assessed in a Taiwanese population comprising 362 CRC cases and an equal number of age- and sex-matched controls.

Results: In the genotypic analysis, the distribution …

Non-Homologous End-Joining Genotype, Mrna Expression, And Dna Repair Capacity In Childhood Acute Lymphocytic Leukemia, Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Yun-Chi Wang, Pei-Chen Hsu, Jie-Long He, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.

Materials and methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation …

Association Of Preoperative Lung Function With Complications After Lobectomy Using Race-Neutral And Race-Specific Normative Equations, Ajay Sheshadri, Ravi Rajaram, Aaron Baugh, Mario Castro, Arlene M Correa, Felipe Soto, Carrie R Daniel, Liang Li, Scott E Evans, Burton F Dickey, Ara A Vaporciyan, David E Ost

Faculty, Staff and Student Publications

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC.

Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative …

Chronic Lymphocytic Leukemia: Novel Perspectives - How To Teach An Old Dog New Tricks, Tamar Tadmor, Jan Burger

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No abstract provided.

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

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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 …

Voluntary Wheel Running Prevents Formation Of Membrane Attack Complexes And Myelin Degradation After Peripheral Nerve Injury, Suzanne M Green-Fulgham, Michael J Lacagnina, Kendal F Willcox, Jiahe Li, Michael E Harland, Adriano Polican Ciena, Igor R Correia Rocha, Jayson B Ball, Renee A Dreher, Younus A Zuberi, Joseph M Dragavon, Marucia Chacur, Steven F Maier, Linda R Watkins, Peter M Grace

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Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor …

Analysis Of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance, Juliana Mota Siqueira, Yoshitsugu Mitani, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mario L Marques-Piubelli, Anurag Purushothaman, Mutsumi Mitani, Hui Dai, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

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B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (< 5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high ( …

Best Practice Recommendations For The Management Of Anxiety During The Pegvaliase Journey, Kendra J Bjoraker, Caroline Eggerding, Elisheva Ellenberg, Suzanne Hollander, Brittany M Holmes, Kristin Lindstrom, Markey Mcnutt, Suzanne Miller, Hope Northrup, Meaghan Rogers, Sarah Rose, Mia Scott, Soo Shim, Bridget Wardley, Leah Wessenberg, Deborah A Bilder

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Background: Pegvaliase, an enzyme substitution therapy, is a treatment option for phenylketonuria (PKU). Due to the neuropathophysiology and disease burden of PKU, individuals can experience baseline anxiety unrelated to pegvaliase therapy. In addition, there are aspects of pegvaliase therapy that may be anxiety-inducing for those considering or receiving treatment. The aim of this manuscript is to present best practice recommendations for the identification and management of anxiety symptoms that can occur along the pegvaliase journey.

Methods: A modified Delphi approach was used to seek consensus among a multidisciplinary panel of experts. To this end, an in-person meeting was held that …

Multiplex Spatial Analysis Reveals Increased Cd137 Expression And M-Mdsc Neighboring Tumor Cells In Refractory Classical Hodgkin Lymphoma, José L Solórzano, Victoria Menéndez, Edwin Parra, Luisa Solis, Ruth Salazar, Mónica García-Cosío, Fina Climent, Sara Fernández, Eva Díaz, Alejandro Francisco-Cruz, Joseph Khoury, Mei Jiang, Auriole Tamegnon, Carlos Montalbán, Ignacio Melero, Ignacio Wistuba, Carlos De Andrea, Juan F García

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The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is …

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

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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 …

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

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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, …

Systemic Treatment Of Patients With Metastatic Breast Cancer: Asco Resource-Stratified Guideline, Sana Al Sukhun, Sarah Temin, Carlos H Barrios, Nicoleta Zenovia Antone, Yanin Chavarri Guerra, Mariana Chavez-Macgregor, Rakesh Chopra, Michael A Danso, Henry Leonidas Gomez, N'Da Marcelin Homian, Alaa Kandil, Benda Kithaka, Bogda Koczwara, Beverly Moy, Gertrude Nakigudde, Fernando Enrique Petracci, Hope S Rugo, Nagi S El Saghir, Banu K Arun

Faculty, Staff and Student Publications

Purpose: To guide clinicians and policymakers in three global resource-constrained settings on treating patients with metastatic breast cancer (MBC) when Maximal setting-guideline recommended treatment is unavailable.

Methods: A multidisciplinary, multinational panel reviewed existing ASCO guidelines and conducted modified ADAPTE and formal consensus processes.

Results: Four published resource-agnostic guidelines were adapted for resource-constrained settings; informing two rounds of formal consensus; recommendations received ≥75% agreement.

Recommendations: Clinicians should recommend treatment according to menopausal status, pathological and biomarker features when quality results are available. In first-line, for hormone receptor (HR)-positive MBC, when a non-steroidal aromatase inhibitor and CDK 4/6 inhibitor combination is unavailable, …

Practice Patterns Of Cardiovascular Magnetic Resonance Use In The Diagnosis Of Pediatric Myocarditis: A Survey-Based Study, Hannah M Jacobs, Jonathan H Soslow, Matthew D Cornicelli, Shae A Merves, Ruchira Garg, Mehul D Patel, Arpit Agarwal, Nilanjana Misra, Michael P Dilorenzo, M Jay Campbell, Jeremy Steele, Jennifer Co-Vu, Joshua D Robinson, Simon Lee, Jason N Johnson

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Background: Cardiovascular magnetic resonance (CMR) is used to diagnose myocarditis in adults and children based on the original Lake Louise criteria (LLC) and more recently the revised LLC. The major change included in the revised LLC was the incorporation of parametric mapping, which significantly increases the sensitivity and specificity of diagnosis. Subsequently, scientific statements have recommended the use of parametric mapping in the diagnosis of myocarditis in children. However, there are some challenges to parametric mapping that are unique to the pediatric population. Our goal is to characterize clinical CMR and parametric mapping practice patterns for the diagnosis of myocarditis …

Linking Trauma To Mental Health In The Statewide Texas Youth Depression And Suicide Research Network (Tx-Ydsrn), Lynnel C Goodman, Joshua S Elmore, Taryn L Mayes, Abu Minhajuddin, Holli Slater, Joseph C Blader, Israel Liberzon, Regina B Baronia, Emily J Bivins, Jacquelyn M Lagrone, Sierra Jackson, Sarah L Martin, Ryan Brown, Jair C Soares, Sarah M Wakefield, Madhukar H Trivedi

Faculty, Staff and Student Publications

Rates of youth depression and suicide are rising worldwide and represent public health crises. The present study examined the relationship between trauma history and symptoms of depression, suicidal ideation, and anxiety among suicidal and depressed youth. A diverse group of 1000 8-20-year-olds enrolled in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN) reported their trauma history (Traumatic Events Screening Inventory for Children) and symptoms of depression (Patient Health Questionnaire for adolescents; PHQ-A), anxiety (Generalized Anxiety Disorder scale; GAD-7), and suicidality (Concise Health Risk Tracking scale; CHRT-SR). Nearly half of the sample reported exposure to multiple categories of traumatic …

Exploratory Pilot Study To Characterize The Immune Landscapes Of Malignant Pleural Effusions And Their Corresponding Primary Tumors From Patients With Breast Carcinoma And Lung Adenocarcinoma, Caddie Laberiano-Fernandez, Qiong Gan, Sophia Mei Wang, Auriole Tamegnon, Ignacio Wistuba, Esther Yoon, Sinchita Roy-Chowdhuri, Edwin Roger Parra

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Introduction: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples.

Materials and methods: We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion-free survival.

Results: No MPE samples had positive programmed death-ligand 1 expression in malignant cells, although 3 of …

Association Of Perceived Neighborhood Air Quality Problems With Attempt To Quit Cigarette Smoking: A Cross-Sectional Study In Texas, Monalisa Chandra, Joel Fokom Domgue, Robert Yu, Sanjay Shete

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Background: Cigarette smoking is the major preventable cause of premature deaths in the United States. Attempting to quit smoking is an important step toward smoking cessation. Although it has been studied extensively, limited information on the association between attempts to quit smoking and neighborhood air quality problems is available. Therefore, we examined the association between attempts to quit smoking in the past year and perceived neighborhood air quality problems among adult Texans who smoke.

Methods: In 2018, a cross-sectional multistage area probability design-based survey was administered to collect sociodemographic, behavioral, and health-related information from a representative sample of 2050 Texas …

Prevalence And Disparities In Receiving Medical Advice To Quit Tobacco Use In The Us Adult Population, Monalisa Chandra, Rajesh Talluri, Joel Fokom Domgue, Sanjay Shete

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Introduction: Evidence suggests that advice from health care professionals (HCP) increases the likelihood of quit attempts and successful quitting of tobacco use. However, previous studies primarily focussed on cigarette smoking and did not include all forms of tobacco products. This study aimed to investigate the prevalence and disparities in receiving HCP's advice to quit tobacco use (combustible or noncombustible) in the US adult population.

Methods: Using the 2022 National Health Information Survey (NHIS) data, we examined 4,424 adults who reported (i) any tobacco product use within the past 12 months and (ii) having seen an HCP within the past 12 …

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

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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 …

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

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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

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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

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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;

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

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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

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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, …

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

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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

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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 …

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 …

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

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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 …