Medicine and Health Sciences Commons^™

Examining The Role Of Autonomy Support, Goal Setting, And Care Coordination Quality On Hiv Prep Adherence In Black Men Who Have Sex With Men: Hptn 073, Donte T Boyd, Laron E Nelson, Mandy J Hill, Darren Whitfield, S Raquel Ramos, Samuel Akyirem, Lynda Emel, Leo Wilton, Lisa Hightow-Weidman, Steve Shoptaw, Manya Magnus, Kenneth H Mayer, Estelle Piwowar-Manning, Stephaun E Wallace, Sheldon D Fields, Darrell P Wheeler

Faculty, Staff and Student Publications

Autonomy support is a concept that is derived from self-determination theory. Autonomy refers to the freedom to act as one chooses. The current study aimed to examine if autonomy support was associated with dried blood spot validated pre-exposure prophylaxis (PrEP) adherence, and whether the association was mediated by PrEP adherence goal setting and progress toward PrEP adherence goals. Our sample was drawn from Black men who have sex with men (MSM) from across three cities (Chapel Hill, NC; Los Angeles, CA; and Washington, DC) in the United States between February 2013 and September 2014. We used logistic regression to evaluate …

Analysis Of Immune Intratumor Heterogeneity Highlights Immunoregulatory And Coinhibitory Lymphocytes As Hallmarks Of Recurrence In Stage I Non-Small Cell Lung Cancer, Alejandro Francisco-Cruz, Pedro Rocha, Alexandre Reuben, Santhoshi N Krishnan, Priyam Das, Runzhe Chen, Kelly Quek, Jun Li, Edwin R Parra, Luisa M Solis, Souptik Barua, Mei Jiang, Rossana Lazcano, Chi-Wan Chow, Carmen Behrens, Curtis Gumb, Latasha Little, Junya Fukuoka, Neda Kalhor, Annikka Weissferdt, Humam Kadara, John V Heymach, Stephen Swisher, Boris Sepesi, Arvind Rao, Cesar Moran, Jianhua Zhang, J Jack Lee, Junya Fujimoto, P Andrew Futreal, Ignacio I Wistuba, Christine B Peterson, Jianjun Zhang

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Our understanding of the molecular mechanisms underlying postsurgical recurrence of non-small cell lung cancer (NSCLC) is rudimentary. Molecular and T cell repertoire intratumor heterogeneity (ITH) have been reported to be associated with postsurgical relapse; however, how ITH at the cellular level impacts survival is largely unknown. Here we report the analysis of 2880 multispectral images representing 14.2% to 27% of tumor areas from 33 patients with stage I NSCLC, including 17 cases (relapsed within 3 years after surgery) and 16 controls (without recurrence ≥5 years after surgery) using multiplex immunofluorescence. Spatial analysis was conducted to quantify the minimum distance between …

Accommodating Time-Varying Heterogeneity In Risk Estimation Under The Cox Model: A Transfer Learning Approach, Ziyi Li, Yu Shen, Jing Ning

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Transfer learning has attracted increasing attention in recent years for adaptively borrowing information across different data cohorts in various settings. Cancer registries have been widely used in clinical research because of their easy accessibility and large sample size. Our method is motivated by the question of how to utilize cancer registry data as a complement to improve the estimation precision of individual risks of death for inflammatory breast cancer (IBC) patients at The University of Texas MD Anderson Cancer Center. When transferring information for risk estimation based on the cancer registries (i.e., source cohort) to a single cancer center (i.e., …

Computed Tomography: State-Of-The-Art Advancements In Musculoskeletal Imaging, Hamza Ahmed Ibad, Cesar De Cesar Netto, Delaram Shakoor, Alejandro Sisniega, Stephen Z Liu, Jeffrey H Siewerdsen, John A Carrino, Wojciech Zbijewski, Shadpour Demehri

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Although musculoskeletal magnetic resonance imaging (MRI) plays a dominant role in characterizing abnormalities, novel computed tomography (CT) techniques have found an emerging niche in several scenarios such as trauma, gout, and the characterization of pathologic biomechanical states during motion and weight-bearing. Recent developments and advancements in the field of musculoskeletal CT include 4-dimensional, cone-beam (CB), and dual-energy (DE) CT. Four-dimensional CT has the potential to quantify biomechanical derangements of peripheral joints in different joint positions to diagnose and characterize patellofemoral instability, scapholunate ligamentous injuries, and syndesmotic injuries. Cone-beam CT provides an opportunity to image peripheral joints during weight-bearing, augmenting the …

Exaptation And Evolutionary Adaptation In Nociceptor Mechanisms Driving Persistent Pain, Edgar T Walters

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Background: Several evolutionary explanations have been proposed for why chronic pain is a major clinical problem. One is that some mechanisms important for driving chronic pain, while maladaptive for modern humans, were adaptive because they enhanced survival. Evidence is reviewed for persistent nociceptor hyperactivity (PNH), known to promote chronic pain in rodents and humans, being an evolutionarily adaptive response to significant bodily injury, and primitive molecular mechanisms related to cellular injury and stress being exapted (co-opted or repurposed) to drive PNH and consequent pain.

Summary: PNH in a snail (Aplysia californica), squid (Doryteuthis pealeii), fruit fly (Drosophila melanogaster), mice, rats, …

Oral Small Molecule Agents In Management Of Ulcerative Colitis: Fact Or Fancy?, Benan Kasapoğlu, Atilla Ertan

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Ulcerative colitis is a chronic, immune-mediated disease characterized by recurring episodes of mucosal inflammation in the colon and rectum. The primary pathogenic mechanism of ulcerative colitis is the dysregulation of the mucosal immune response. The disease follows a relapsing-remitting course, and the goal of management is to successfully induce and then maintain remission. Effectively managing this chronic disease requires addressing all aspects of it. Currently, we have various antitumor necrosis factor agents and novel biologics available for treating ulcerative colitis patients with moderate-to-severe disease. However, none of the existing treatments are considered entirely satisfactory or ideal in these cases. After …

The Involvement Of Kynurenine Pathway In Neurodegenerative Diseases, Lais B Martins, Ana L M Silveira, Antonio L Teixeira

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BACKGROUND: A growing body of evidence has shown the involvement of the kynurenine pathway (KP), the primary route of tryptophan (TRP) catabolism, in the pathophysiology of neuropsychiatric disorders.

OBJECTIVE: The study aims to provide a comprehensive and critical overview of the clinical evidence on the KP involvement in the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD), discussing therapeutic opportunities.

METHODS: We searched for studies investigating KP metabolites in human subjects with AD and/or PD.

RESULTS: Postmortem studies showed altered levels of KP metabolites in the brain of AD and PD patients compared with controls. Cross-sectional studies have reported …

Effect Of Concurrent Mitral Valve Surgery For Secondary Mitral Regurgitation Upon Mortality After Aortic Valve Replacement Or Coronary Artery Bypass Surgery, Shyamal R Asher, Chin Siang Ong, Raymond J Malapero, Mahyar Heydarpour, Gregory W Malzberg, Jasmine T Shahram, Thy B Nguyen, Douglas C Shook, Stanton K Shernan, Prem Shekar, Tsuyoshi Kaneko, Rodolfo Citro, Jochen D Muehlschlegel, Simon C Body

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OBJECTIVES: It is uncertain whether concurrent mitral valve repair or replacement for moderate or greater secondary mitral regurgitation at the time of coronary artery bypass graft or aortic valve replacement surgery improves long-term survival.

METHODS: Patients undergoing coronary artery bypass graft and/or aortic valve replacement surgery with moderate or greater secondary mitral regurgitation were reviewed. The effect of concurrent mitral valve repair or replacement upon long-term mortality was assessed while accounting for patient and operative characteristics and mitral regurgitation severity.

RESULTS: Of 1,515 patients, 938 underwent coronary artery bypass graft or aortic valve replacement surgery alone and 577 underwent concurrent …

G-Quadruplexes And Associated Proteins In Aging And Alzheimer’S Disease, M J Vijay Kumar, Rodrigo Morales, Andrey S Tsvetkov

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Aging is a prominent risk factor for many neurodegenerative disorders, such as Alzheimer's disease (AD). Alzheimer's disease is characterized by progressive cognitive decline, memory loss, and neuropsychiatric and behavioral symptoms, accounting for most of the reported dementia cases. This disease is now becoming a major challenge and burden on modern society, especially with the aging population. Over the last few decades, a significant understanding of the pathophysiology of AD has been gained by studying amyloid deposition, hyperphosphorylated tau, synaptic dysfunction, oxidative stress, calcium dysregulation, and neuroinflammation. This review focuses on the role of non-canonical secondary structures of DNA/RNA G-quadruplexes (G4s, …

Role Of Microrna-34a In Blood-Brain Barrier Permeability And Mitochondrial Function In Ischemic Stroke, Cole T Payne, Sidra Tabassum, Silin Wu, Heng Hu, Aaron M Gusdon, Huimahn A Choi, Xuefang S Ren

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Over the past decade, there has been an uptick in the number of studies conducting research on the role of microRNA (miRNA) molecules in stroke. Among these molecules, miR-34a has emerged as a significant player, as its levels have been observed to exhibit a substantial rise following ischemic events. Elevated levels of miR-34a have been found to have multiple effects, including the modulation of inflammatory molecules involved in the post-stroke recovery process, as well as negative effects on the blood-brain barrier (BBB) permeability. Interestingly, the increase of miR-34a appears to increase BBB permeability post stroke, through the negative effect on …

Antimicrobial Activity Of Plasma Rich In Platelets (Prp) On The Ocular Microbiota Of Healthy Horses From Minas Gerais, Luis E C Torres, Camilo O Florez, Jéssica G Oliveira, Giovanna D Vieira, Ilza S Ribeiro, Kelly M Keller, Fabíola O P Leme, Priscila Fantini, Renata P A Maranhão

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In equine ophthalmology, ulcerative keratitis is among the most common conditions and, in general, arises as a consequence of some trauma suffered. Secondarily, subsequent contamination by pathogenic or resident bacteria of the horse's ocular microbiota may have undesirable consequences. Under physiological conditions, the normal microbiota coexists with the immune status of the host, serving as a barrier, ensuring the health of the ocular surface, and inhibiting the proliferation of pathogens. However, in the imbalance of immune barriers, the normal microbiota can become pathogenic and lead to infection, acting as an opportunistic agent. The present study aims to demonstrate the antimicrobial …

Hepatocellular Carcinoma With Hepatic Vein And Inferior Vena Cava Invasion, Akash Shukla, Abhinav Jain

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Hepatocellular carcinoma (HCC) invades intrahepatic vessels causing tumor thrombosis. Infrequently, there is involvement of the hepatic vein (HV) and inferior vena cava (IVC). In this review, we summarize the epidemiology, classification, clinical features, and management of HCC with HV and IVC invasion. While the involvement of HV and IVC usually portends an overall poor survival, selected patients may be candidates for aggressive treatment and thus improving outcomes.

Editorial: Expert Opinions In Neurocognitive Aging And Behavior: Neural Rehabilitation For Elder People, Ping Zhou, Yingchun Zhang, Sheng Li

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No abstract provided.

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler

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Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

Clinical Outcomes: Endoscopic Resection Of Duodenal Ampullary Lesions, Stephanie M Woo, Mark J Real, Brett M Will, Eric J Kim, Jiling Chou, Ahmed A Alsaiari, Ahmad Nakshabandi, Walid M Chalhoub, Nadim G Haddad

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Background: Ampullary adenomas are lesions at the duodenum's major papilla commonly associated with familial adenomatous polyposis (FAP) but may also occur sporadically. Historically, ampullary adenomas were removed surgically, however endoscopic resection has become the preferred method of resection. Most of the literature on management of ampullary adenomas are small single-center retrospective reviews. The objective of this study is to describe endoscopic papillectomy outcomes to further refine management guidelines.

Methods: This is a retrospective study of patients who underwent endoscopic papillectomy. Demographic data were included. Details regarding lesions and procedures were also collected, including endoscopic impression, size, resection method and adjunctive …

Easy Nanostring Ncounter Data Analysis With The Nanotube, Caleb A Class, Caiden J Lukan, Christopher A Bristow, Kim-Anh Do

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Summary: The NanoTube is an open-source pipeline that simplifies the processing, quality control, normalization and analysis of NanoString nCounter gene expression data. It is implemented in an extensible R library, which performs a variety of gene expression analysis techniques and contains additional functions for integration with other R libraries performing advanced NanoString analysis techniques. Additionally, the NanoTube web application is available as a simple tool for researchers without programming expertise.

Availability and implementation: The NanoTube R package is available on Bioconductor under the GPL-3 license (https://www.bioconductor.org/packages/NanoTube/). The R-Shiny application can be downloaded at https://github.com/calebclass/Shiny-NanoTube, or a simplified …

Survival Outcomes Used To Validate Version 9 Of The American Joint Committee On Cancer Staging System For Appendiceal Cancer, Lauren M Janczewski, Amanda E Browner, Joseph H Cotler, Heidi Nelson, Sanjay Kakar, Norman J Carr, Nader N Hanna, Andreana N Holowatyj, Richard M Goldberg, M Kay Washington, Elliot A Asare, Michael J Overman, American Joint Committee On Cancer Expert Panel On Cancers For The Lower Gastrointestinal Appendix Disease Site

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The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 …

Treatment De-Escalation In Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia: The Emerging Role Of Chemotherapy-Free Regimens, Fadi G Haddad, Jacki Sawyers, Nicholas J Short

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The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many …

3,3′-Diindolylmethane Augments 5-Fluorouracil-Inducedgrowth Suppression In Gastric Cancer Cells Through Suppression Of The Akt/Gsk-3Β And Wnt/Beta-Catenin, Cong Shan Li, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Ju-Seog Lee, Soo Mi Kim

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Gastric cancer (GC) is one of the most lethal cancers in South Korea, and it is a cancer of concern worldwide. 5-fluorouracil (5-Fu) is commonly used as the first-line therapy for advanced GC; however, its side effects often limit the dosage range and impair patients' quality of life. Due to the limitations of current chemotherapy, new anticancer therapies are urgently needed. 3,3'-diindolylmethane (DIM) has been reported to have the ability to protect against various types of cancer. Our study aimed to elucidate the anticancer effect of DIM in GC when treated with the chemotherapeutic agent 5-Fu. In our results, combined …

Hras Mutations Define A Distinct Subgroup In Head And Neck Squamous Cell Carcinoma, Niamh Coleman, Kathrina L Marcelo, Julia F Hopkins, Nusrat Israr Khan, Robyn Du, Lingzhi Hong, Edward Park, Binaifer Balsara, Mollie Leoni, Curtis Pickering, Jeffrey Myers, John Heymach, Lee A Albacker, David Hong, Maura Gillison, Xiuning Le

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Purpose: In head and neck squamous cell carcinoma (HNSCC), HRAS mutation is a new actionable oncogene driver. We aimed to evaluate HRAS mutational variants, comutation profile, and survival outcomes of this molecularly defined population.

Methods: We leveraged four deidentified patient data sets with HRAS-mutant HNSCC, MD Anderson Cancer Center, Kura Oncology, Inc trial, Foundation Medicine, and American Association for Cancer Research GENIE v.12. Patient demographic information and clinical courses were extracted, when available, in addition to HRAS mutation type and co-occurring mutations. Survival outcomes were analyzed (Kaplan-Meier method).

Results: Two hundred forty-nine patients with HRAS-mutant HNSCC were identified …

Pilot Study Of A Spanish Language Measure Of Financial Toxicity In Underserved Hispanic Cancer Patients With Low English Proficiency, Julia J Shi, Gwendolyn J Mcginnis, Susan K Peterson, Nicolette Taku, Ying-Shiuan Chen, Robert K Yu, Chi-Fang Wu, Tito R Mendoza, Sanjay S Shete, Hilary Ma, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Diem-Khanh Nguyen, Kelsey W Kaiser, Grace L Smith

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BACKGROUND: Financial toxicity (FT) reflects multi-dimensional personal economic hardships borne by cancer patients. It is unknown whether measures of FT-to date derived largely from English-speakers-adequately capture economic experiences and financial hardships of medically underserved low English proficiency US Hispanic cancer patients. We piloted a Spanish language FT instrument in this population.

METHODS: We piloted a Spanish version of the Economic Strain and Resilience in Cancer (ENRICh) FT measure using qualitative cognitive interviews and surveys in un-/under-insured or medically underserved, low English proficiency, Spanish-speaking Hispanics (UN-Spanish,

RESULTS: UN-Spanish Hispanic participants reported high acceptability of the instrument (only 0% responded that the …

Genome-Wide Characterization Of Trichome Birefringence-Like Genes Provides Insights Into Fiber Yield Improvement, Ziyin Li, Yuzhen Shi, Xianghui Xiao, Jikun Song, Pengtao Li, Juwu Gong, Haibo Zhang, Wankui Gong, Aiying Liu, Renhai Peng, Haihong Shang, Qun Ge, Junwen Li, Jingtao Pan, Quanjia Chen, Quanwei Lu, Youlu Yuan

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Cotton is an important fiber crop. The cotton fiber is an extremely long trichome that develops from the epidermis of an ovule. The trichome is a general and multi-function plant organ, and trichome birefringence-like (TBL) genes are related to trichome development. At the genome-wide scale, we identified TBLs in four cotton species, comprising two cultivated tetraploids (Gossypium hirsutum and G. barbadense) and two ancestral diploids (G. arboreum and G. raimondii). Phylogenetic analysis showed that the TBL genes clustered into six groups. We focused on GH_D02G1759 in group IV because it was located in a …

Exosomal Lipid Biomarkers Of Oligodendrocyte Pathology To Predict Scoliosis In Children With Cerebral Palsy, Nune Darbinian, Emily C Sparks, Armine Darbinyan, Nana Merabova, Tamara Tatevosian-Geller, Katie Calaku, Sarah Bachman, Huaqing Zhao, Shohreh Amini, Laura Goetzl, Solomon P Samuel, Amer Samdani, Michael E Selzer

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INTRODUCTION: Cerebral Palsy (CP), the most common cause of disability in children, is phenotypically heterogeneous. Approximately 20% of cases develop severe scoliosis. A pathological hallmark of CP is periventricular leukomalacia (PVL), which is due to dysmyelination, suggesting the possibility of a lipidomic abnormality. Risk factors for CP include perinatal hypoxia, prematurity, multiple gestation, ischemia, infection, and maternal alcohol consumption. There is evidence for low serum levels of omega-3 (ω-3) fatty acids in CP patients, and separately in idiopathic scoliosis. Many effects of free fatty acids (FFAs) are mediated via specific G protein-coupled free fatty acid receptors (FFARs), which play essential …

Maternal Blood Lipid Biomarkers Of Oligodendrocyte Pathology To Predict Fetal Alcohol Spectrum Disorders, Nune Darbinian, Emily C Sparks, Armine Darbinyan, Nana Merabova, Gabriel Tatevosian, Ekaterina Vadachkoria, Huaqing Zhao, Shohreh Amini, Laura Goetzl, Michael E Selzer

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INTRODUCTION: Up to 9.9% of children have fetal alcohol spectrum disorders (FASD), the most frequent cause of intellectual disability in the US. FASD may involve abnormal brain development, including dysmyelination, suggesting abnormal development of oligodendrocytes (OLs), which make myelin and are rich in lipids. Indeed, low serum levels of omega-3 fatty acids (ω-3) have been reported in FASD. Free fatty acids bind to specific receptors (FFARs). We have isolated cell type-specific fetal brain-derived exosomes (FB-E) from maternal blood and sampled their contents to search for lipid-related biomarkers that predict FASD.

METHODS: Blood samples were collected from two groups of pregnant …

Bayesian Single-To-Double Arm Transition Design Using Both Short-Term And Long-Term Endpoints, Tianlin Xu, Haolun Shi, Ruitao Lin

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The choice between single-arm designs versus randomized double-arm designs has been contentiously debated in the literature of phase II oncology trials. Recently, as a compromise, the single-to-double arm transition design was proposed, combining the two designs into one trial over two stages. Successful implementation of the two-stage transition design requires a suspension period at the end of the first stage to collect the response data of the already enrolled patients. When the evaluation of the primary efficacy endpoint is overly long, the between-stage suspension period may unfavorably prolong the trial duration and cause a delay in treating future eligible patients. …

Evolutionary History Of Transformation From Chronic Lymphocytic Leukemia To Richter Syndrome, Erin M Parry, Ignaty Leshchiner, Romain Guièze, Connor Johnson, Eugen Tausch, Sameer A Parikh, Camilla Lemvigh, Julien Broséus, Sébastien Hergalant, Conor Messer, Filippo Utro, Chaya Levovitz, Kahn Rhrissorrakrai, Liang Li, Daniel Rosebrock, Shanye Yin, Stephanie Deng, Kara Slowik, Raquel Jacobs, Teddy Huang, Shuqiang Li, Geoff Fell, Robert Redd, Ziao Lin, Binyamin A Knisbacher, Dimitri Livitz, Christof Schneider, Neil Ruthen, Liudmila Elagina, Amaro Taylor-Weiner, Bria Persaud, Aina Martinez, Stacey M Fernandes, Noelia Purroy, Annabelle J Anandappa, Jialin Ma, Julian Hess, Laura Z Rassenti, Thomas J Kipps, Nitin Jain, William Wierda, Florence Cymbalista, Pierre Feugier, Neil E Kay, Kenneth J Livak, Brian P Danysh, Chip Stewart, Donna Neuberg, Matthew S Davids, Jennifer R Brown, Laxmi Parida, Stephan Stilgenbauer, Gad Getz, Catherine J Wu

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Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes. Through unsupervised clustering, clonally related RS was largely distinct from diffuse large B cell lymphoma. …

Risk Stratification Of Postoperative Cardiopulmonary Toxicity After Trimodality Therapy For Esophageal Cancer, Roman O Kowalchuk, Grant M Spears, Lindsay K Morris, Dawn Owen, Harry H Yoon, Krishan Jethwa, Michael D Chuong, Matthew J Ferris, Michael G Haddock, Christopher L Hallemeier, Dennis Wigle, Steven H Lin, Kenneth W Merrell

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Purpose/objective: Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes.

Materials/methods: Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used.

Results: From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and …

A Th2-Score In The Tumor Microenvironment As A Predictive Biomarker Of Response To Bacillus Calmette Guérin In Patients With Non-Muscle Invasive Bladder Carcinoma: A Retrospective Study, Gustavo Martín Villoldo, María Teresa Pombo, Mariana Aris, Joaquín Chemi, Pablo Mandó, Supriya Nagaraju, Juan Camean, Adrián Burioni, Deborah Egea, Mora Amat, José León Mellado, José Mordoh, Alberto Villaronga, María Marcela Barrio

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Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ …

Adolescent Loneliness During The Covid-19 Pandemic: The Role Of Pre-Pandemic Risk Factors, Hena Thakur, Morgan Stutts, Jae Wan Choi, Jeff R Temple, Joseph R Cohen

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The COVID-19 pandemic is a global mental health crisis that disproportionately impacts adolescents. Loneliness is a particularly salient pandemic psychosocial outcome to understand; however, research to date on this outcome is sparse and largely cross-sectional. In response, we examined pre-pandemic risk factors for pandemic loneliness. Further, we examined how risk may differ based on key demographics, and whether mediation or moderation models best explained potential disparities in experiencing loneliness. Self-reported, pre-pandemic mental health, trauma exposure, and family conflict survey data were collected at Wave 1 in a diverse sample of 369 adolescents (54.5% female, 45.5% male; 30.1% White; 30.9% Black; …

The Proteasome: A Key Modulator Of Nervous System Function, Brain Aging, And Neurodegenerative Disease, Kanisa Davidson, Andrew M Pickering

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The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of …