Medicine and Health Sciences Commons^™

Synergistic Inhibition Of Hiv-1 Regulatory Function Using A Dual Expression Shrna Plasmid, Christine Sanderson, William H. Jackson

Journal of the South Carolina Academy of Science

HIV infection of CD4⁺ T Helper lymphocytes results in a gradual loss of immune competence, which ultimately leads to development of the acquired immune deficiency syndrome (AIDS). HIV-1 expresses two regulatory proteins, Tat and Rev, which act to upregulate viral transcription and facilitate mRNA transport enhancing the rate of translation. Inhibition of Tat and Rev have been shown to block virus replication. Therefore, Tat and Rev represent critical key points in the virus replication cycle. This study investigated the potential of RNA interference (RNAi) to inhibit these proteins using short hairpin RNAs (shRNAs). For this, plasmids expressing shRNAs targeting …

Beyond Chronic Fatigue: Studying The Role Of Neuroinflammation, Glutamate, And Glutamine, Indonesia Alohn Jordan

All ETDs from UAB

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multifaceted disease characterized by persistent, severe fatigue lasting six months or longer that is not relieved by rest. An estimated 20 million people worldwide suffer from ME/CFS. ME/CFS has long been suspected to be a post-viral illness, as viral infections can stimulate inflammatory cytokine production. Millions of coronavirus disease 2019 (COVID-19) patients are also predicted to develop persistent symptoms that mimic ME/CFS symptomology after the resolution of the acute infection, referred to as Post-Acute Sequelae of COVID-19 (PASC). Inflammatory mediators produced by sustained microglia activation have been shown to lead to illness …

09.09.2024 Orsp Connect, Liz Williamson

ORED Newsletter

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OpenScholar Overview

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NSF Sessions on Phase 1 ISBIR/STTR Proposals

Project Give: Using A Virtual Genetics Service Platform To Reduce Health Inequities And Improve Access To Genomic Care In An Underserved Region Of Texas, Blake Vuocolo, Roberta Sierra, Keila Rodriguez, Ana Hernandez, Alberto Allegre, Humberto Hidalgo, Sarah Rodriguez, Jeremy Gibson, Robert Nelson, Lizbeth Mellin-Sanchez, Lori Berry, Kent Carter

School of Medicine Publications

Background

The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of …

An Analysis Of Flavor Descriptors On Tobacco Products In The Philippines: Regulatory Implications And Lessons For Low- And Middle-Income Countries, Samantha J. Ackary, Patrick James Cabrera, Alen Josef A. Santiago, Gianna Gayle H. Amul

Ateneo School of Government Publications

Background

Historically, tobacco companies have used flavored tobacco products to enhance the appeal of tobacco consumption, encourage initiation and experimentation of tobacco use, and contribute to sustained tobacco use. While flavored tobacco products are regulated in several countries, there is no existing regulation on flavored tobacco products in the Philippines, specifically for cigarettes and cigars. This study aims to update evidence on the flavored tobacco product landscape in the Philippines by assessing both the flavor descriptors and flavor imagery featured on cigarette and cigar packaging.

Results

We collected 106 cigarette and cigar products from four major cities in the National …

Proteomic Characterization Of Antibody Drug Conjugate Target Expression Profiles In Small Cell Lung Cancer (Sclc), Edwin Lin, Atulya A. Khosla, Nina K. Smrecek, Abdul Rafeh Naqash, Kaushal Parikh, Yanis Boumber, Muhammad Khalil, Aakash Desai

Conference Presentation Abstracts

No abstract provided.

The Aphasia Recovery Cohort, An Open-Source Chronic Stroke Repository, Makayla Gibson, Roger Newman-Norlund, Leonardo Bonilha, Julius Fridriksson, Gregory Hickok, Argye E. Hillis, Dirk B. Den Ouden, Chris Rorden

Communication Sciences and Disorders Faculty Articles and Research

Sharing neuroimaging datasets enables reproducibility, education, tool development, and new discoveries. Neuroimaging from many studies are publicly available, providing a glimpse into progressive disorders and human development. In contrast, few stroke studies are shared, and these datasets lack longitudinal sampling of functional imaging, diffusion imaging, as well as the behavioral and demographic data that encourage novel applications. This is surprising, as stroke is a leading cause of disability, and acquiring brain imaging is considered standard of care. The first release of the Aphasia Recovery Cohort includes imaging data, demographics and behavioral measures from 230 chronic stroke survivors who experienced aphasia. …

Lessons Learned From Developing Dashboards To Support Decision-Making For Community Opioid Response By Community Stakeholders: Mixed Methods And Multisite Study., Naleef Fareed, Ramona G. Olvera, Yiting Wang, Michael Hayes, Elizabeth Liz Larimore, Peter Balvanz, Ronald Langley, Corinna A. Noel, Peter J. Rock, Daniel Redmond, Jessica Neufeld, Sarah Kosakowski, Daniel R. Harris, Marc Larochelle, Timothy R. Huerta, Lashawn Glasgow, Emmanuel Oga, Jennifer Villani, Elwin Wu

Center on Drug and Alcohol Research Faculty Publications

BACKGROUND: Data dashboards are published tools that present visualizations; they are increasingly used to display data about behavioral health, social determinants of health, and chronic and infectious disease risks to inform or support public health endeavors. Dashboards can be an evidence-based approach used by communities to influence decision-making in health care for specific populations. Despite widespread use, evidence on how to best design and use dashboards in the public health realm is limited. There is also a notable dearth of studies that examine and document the complexity and heterogeneity of dashboards in community settings.

OBJECTIVE: Community stakeholders engaged in the …

A Case Demonstration Of The Open Health Natural Language Processing Toolkit From The National Covid-19 Cohort Collaborative And The Researching Covid To Enhance Recovery Programs For A Natural Language Processing System For Covid-19 Or Postacute Sequelae Of Sars Cov-2 Infection: Algorithm Development And Validation, Andrew Wen, Liwei Wang, Huan He, Sunyang Fu, Sijia Liu, David A Hanauer, Daniel R Harris, Ramakanth Kavuluru, Rui Zhang, Karthik Natarajan, Nishanth P Pavinkurve, Janos Hajagos, Sritha Rajupet, Veena Lingam, Mary Saltz, Corey Elowsky, Richard A Moffitt, Farrukh M Koraishy, Matvey B Palchuk, Jordan Donovan, Lora Lingrey, Garo Stone-Derhagopian, Robert T Miller, Andrew E Williams, Peter J Leese, Paul I Kovach, Emily R Pfaff, Mikhail Zemmel, Robert D Pates, Nick Guthe, Melissa A Haendel, Christopher G Chute, Hongfang Liu, National Covid Cohort Collaborative, Recover Initiative

Faculty, Staff and Student Publications

BACKGROUND: A wealth of clinically relevant information is only obtainable within unstructured clinical narratives, leading to great interest in clinical natural language processing (NLP). While a multitude of approaches to NLP exist, current algorithm development approaches have limitations that can slow the development process. These limitations are exacerbated when the task is emergent, as is the case currently for NLP extraction of signs and symptoms of COVID-19 and postacute sequelae of SARS-CoV-2 infection (PASC).

OBJECTIVE: This study aims to highlight the current limitations of existing NLP algorithm development approaches that are exacerbated by NLP tasks surrounding emergent clinical concepts and …

Preventing Patient Deterioration And Increasing Family Satisfaction By Creating A Reassessment And Escalation Process For The Emergency Department Waiting Room, Virginia Elizondo

EBP Fellowship

No abstract provided.

Characterizing The Monomer-Dimer Equilibrium Of Ubch8/Ube2l6: A Combined Saxs And Nmr Study, Kerem Kahraman, Scott A. Robson, Oktay Göcenler, Cansu M. Yenici, Cansu D. Tozkoparan Ceylan, Jennifer M. Klein, Volker Dötsch, Emine Sonay Elgin, Arthur L. Haas, Joshua J. Ziarek, Çağdaş Dağ

School of Medicine Faculty Publications

Interferon-stimulated gene-15 (ISG15) is an interferon-induced protein with two ubiquitin-like (Ubl) domains linked by a short peptide chain and is a conjugated protein of the ISGylation system. Similar to ubiquitin and other Ubls, ISG15 is ligated to its target proteins through a series of E1, E2, and E3 enzymes known as Uba7, Ube2L6/UbcH8, and HERC5, respectively. Ube2L6/UbcH8 plays a central role in ISGylation, underscoring it as an important drug target for boosting innate antiviral immunity. Depending on the type of conjugated protein and the ultimate target protein, E2 enzymes have been shown to function as monomers, dimers, or both. UbcH8 …

Cardiomyocyte-Derived Small Extracellular Vesicle: A New Mechanism Driving Diabetic Cardiac Fibrosis And Cardiomyopathy, Yu Li, Yunhui Du, Yang Liu, Xiuhuan Chen, Xinxin Li, Yanru Duan, Yanwen Qin, Huirong Liu, Xinliang Ma, Shaoping Nie, Huina Zhang

Department of Emergency Medicine Faculty Papers

Rationale: Diabetic cardiomyopathy is one of the major diabetic cardiovascular complications in which fibrosis plays a critical pathogenetic role. However, the precise mechanisms by which diabetes triggers cardiac fibrosis in the heart remain elusive. Small extracellular vesicles (sEVs) play an important role in the cellular communication. Nevertheless, whether and how diabetes may adversely alter sEVs-mediated cardiomyocyte-fibroblast communication, promoting diabetic cardiac fibrosis and contributing to diabetic cardiomyopathy, has not been previously investigated. Methods and results: High-fat diet (HFD)-induced and genetic (db/db) type 2 diabetic models were utilized. Cardiomyocyte sEVs (Myo-sEVs) were isolated by ultracentrifugation. Normal cardiomyocyte-derived Myo-sEVs attenuated diabetic cardiac fibrosis …

Oral Administration Of Alpha-Cyclodextrin Corrects Diabetes Induced Retinopathy And Bone Marrow Pathology By Modulation Of The Gut-Retina Axis., Yvonne Adu-Agyeiwaah

All ETDs from UAB

Diabetic retinopathy represents a common complication of diabetes, exerting a significant financial burden globally across nations, particularly impacting the working-age population and thereby affecting productivity. Extensive investigations have unveiled its multifaceted etiology, implicating a convergence of diverse causative factors. Notably, seminal studies such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study have underscored the pivotal role of cholesterol dysregulation and dyslipidemia in the pathogenesis of diabetic retinopathy. This dysregulation stems from an imbalance characterized by heightened cholesterol production coupled with deficient cholesterol efflux or removal mechanisms. Liver X receptors (LXRs), ligand-activated nuclear receptors function in transcriptional …

Effects Of Probiotic Lactobacilli On Candida Albicans: Implications For Early Childhood Caries, Leena Unnikrishnan Menon

All ETDs from UAB

Purpose: Probiotic Lactobacillus species are shown to have beneficial effects against early childhood caries (ECC). On the other hand, the wide use of probiotic Lactobacillus spp. in dairy foods is believed to underline the global increase in ECC prevalence. Candida albicans has been frequently detected in children with ECC and has shown cariogenic potential in animal models of dental caries. The objective of this study was to determine the interactions between lactobacilli and C. albicans in growth competition, biofilm formation and acid production. Methods: Growth competition between C. albicans SC5314 and probiotic L. rhamnosus GG or caries-associated L. rhamnosus M72-26 …

Factors Associated With Early Onset Anal Cancer And Facilitators And Barriers To Screening Among Men Living With Hiv And Their Providers In The Deep South: A Mixed Methods Investigation, Anna Junkins

All ETDs from UAB

For my dissertation work, I aimed to 1) determine the occurrence of early onset (diagnosis at <50 years) anal cancer and the impact of HIV infection and other risk factors, and 2) utilize a mixed methods research approach to identify and explain factors associated with screening among men living with HIV (MLHIV) and their providers. In Aim 1, I used logistic regression to estimate the odds of early onset cancer by sociodemographic and clinical characteristics among anal cancer patients in the Alabama cancer registry from 2012-2018. Among 519 patients, 17.7% were diagnosed at <50 years. Male sex, Black race, and HIV infection were associated with younger age at diagnosis. Black patients had a 4-fold increased odds of early onset anal cancer compared to White patients and disproportionately lived in areas with higher social vulnerability. In Aim 2, I used logistic regression to estimate the odds of anal cancer screening by sociodemographic and sexual risk characteristics among MLHIV using retrospective survey data from 1917 Clinic in 2018. Among 1,114 men, 52% had received an anal pap within one year of completing the survey. Men who were screened were more likely to have multiple sexual partners. Heterosexual men had lower odds and men who reported unprotected anal sex had higher odds of screening. Older Black men were less likely to be screened. In Aim 3, I used thematic analyses to identify themes related to health beliefs, barriers and facilitators, and perceived and evaluated need of screening using in-depth interviews among MLHIV and their providers. Benefits of screening among MLHIV were early detection and awareness about one’s body. Suggestions for overcoming barriers to screening among providers included screening guidelines, patient education, inclusion of screening into routine care, and self-collection. Among men that were aware of HPV-associated cancers, there was perceived risk and desire to receive HPV vaccination. Individuals who are male, Black, or living with HIV may be at increased risk of developing anal cancer younger. Among MLHIV, improving education about HPV-associated cancer, and offering self-collected screening as part of routine care could facilitate screening in the South.

Cross-Sectional Retrospective Study To Determine The Prevalence Of Periodontal Bone Loss As A Function Of Age In The Predoctoral Clinic Patient Population, Lincoln Nguyen

All ETDs from UAB

Age has a significant effect on the body’s ability fight off disease, recover, and maintain collagen structures, and it has been observed that older adults have a higher prevalence of periodontal diseases. Studies have shown that age is a risk factor for alveolar bone loss. However, there is a lack of research done looking at if this is a linear progression or if there is a specific age that susceptibility increases. The aim of this study is to investigate (1) changes in radiographic bone loss in varying age groups in the University of Alabama patient population and (2) to evaluate …

Improving Direct Oncolytic Effect Of Oncolytic Hsv To Overcome Therapeutic Resistance Of Brain Tumors, Sam Edward Gary

All ETDs from UAB

Central nervous system tumors, especially malignant brain tumors, account for the most years of potential life lost in adults and children with cancer. Malignant brain tumors are typically fatal cancers due to their highly aggressive nature, inability to obtain gross total resection, location in sensitive brain areas, and intra- and intertumoral heterogeneity, making therapeutic targeting difficult. High-grade glioma (HGG), malignant brain tumors of glial cell origin invariably recur due to intrinsic and adaptive resistance mechanisms against standard therapies. Therefore, novel treatments that overcome therapeutic resistance are desperately needed. One promising approach is oncolytic viruses (OVs), which achieve tumor regression by …

Investigating Molecular Mechanisms Behind Neuronotypic Gba1 Mutations In Lewy Body Dementias, Casey Mahoney-Crane

All ETDs from UAB

Nonmotor deficits are present in nearly all Parkinson’s disease (PD) patients, with ~80% of these patients developing dementia. Importantly, expression of the severe GBA1 L444P heterozygous mutation increases the risk for Parkinson’s disease devel-opment by 5.43 times compared to mild mutation carriers. Currently, many PD treat-ments predominately focus motor symptoms, while treatments for nonmotor symptoms, such as visual-spatial difficulties and dementia, focus on symptom management and continue to remain elusive. Therefore, understanding the molecular mechanisms behind these nonmotor symptoms is essential for the development of effective therapeutics leading to slower disease progression. The work presented in this dissertation sought to …

O-Glcnacylation And Modulation Of Gabaergic Transmission, Shekinah Phillips

All ETDs from UAB

Changes in the strength of GABAergic transmission is heavily influenced by posttranslational modifications and allosteric modulators like benzodiazepines and neurosteroids. O-GlcNAcylation (O-GlcNAc) is a post-translational modification that is tightly regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add or remove the O-GlcNAc moiety of β–N-acetylglucosamine to serine and threonine residues on proteins, respectively. Published reports from our lab have demonstrated that an acute increase in O-GlcNAcylation induces a long-term depression (LTD) of evoked GABAAR mediated IPSCs (eIPSCs) and reduces the amplitude and frequency of spontaneous IPSC (sIPSC) in hippocampal principal cells, however the mechanism in which this occurs is …

Elementary Cone Photoreceptor Signals In V1 Neurons, Cyril Nyankerh

All ETDs from UAB

Daylight vision is initiated by the activation of cone photoreceptors in the retina in response to light, thereby generating spatial and temporal patterns of photoreceptor signals. Subsequent to this, the signals are combined and processed in downstream neural circuits, ultimately contributing to the formation of receptive fields of neurons in primary visual cortex (V1). Recent advances in adaptive optics (AO) have enabled imaging of the retina with near diffraction limited resolution, allowing for the probing of the visual system's processing at the resolution of individual cones. The central theme of this dissertation characterizes quantitively and qualitatively the physiological responses of …

Blood Transfusion Factors That Affect The Outcomes Of Patients Who Experienced Trauma-Related Hemorrhage, Justin Lee Miller

All ETDs from UAB

Trauma is a leading cause of death in the United States and in the world. It is the leading cause of death of Americans between the ages of one to 45 years old and is expected to increase due to increase over the next ten years. Most trauma deaths are attributed to hemorrhage and are considered preventable. The current standard of care for trauma-related hemorrhage (TRH) is damage control resuscitation using either whole blood (WB) or blood components (BC) in a ratio of 1 unit of red blood cells to 1 unit of plasma to 1 unit of platelets. The …

The T Cell Response In A Mouse Model Of Multiple System Atrophy, Nicole Jane Corbin-Stein

All ETDs from UAB

Multiple System Atrophy (MSA) is a fatal and rare demyelinating synucleinopathy, characterized by the accumulation of alpha-synuclein (α-syn) in glial cytoplasmic inclusions (GCIs) within oligodendrocytes. This condition is marked by neuroinflammation, demyelination, and neurodegeneration in areas showing GCI pathology, involving antigen presentation by myeloid cells and infiltration of CD4+ and CD8+ T cells. Despite strong evidence of neuroinflammation in post-mortem MSA tissue, the specific mechanisms driving the disease pathogenesis remain elusive. In prior research using the Olig001-SYN mouse model, which involves the modified AAV vector, it was shown that depleting CD4+ T cells can reduce neuroinflammation and demyelination. Notably, this …

Investigation On The Epigenetic Mechanisms Modified By Dietary Phytochemicals In Inhibiting Mammary Cancer, Mohammad Mijanur Rahman

All ETDs from UAB

Breast cancer (BC) is global burden for the health of women. It is the most commonly diagnosed cancer in women and the second leading cause of cancer mortality among women in the United States. One in every eight women in the USA has a chance of developing invasive BC in her lifetime. The limitations of the available therapeutics for BC treatment have brought the dietary prevention of BC to the attention of the scientific community as a safe, natural, and easy to implement therapeutic strategy. In this regard, our laboratory with many other laboratories have demonstrated the anti-BC effect of …

The Effect Of Lower Limb Neuromuscular Electrical Stimulation On The Muscle And Metabolic Health After Acute Spinal Cord Injury, Amal Alharbi

All ETDs from UAB

Spinal cord injury (SCI) is a devastating event with long-term consequences for individuals and their families. It causes immediate disruption to neuronal pathways, leading to paralysis and loss of muscle function below the injury level. A few weeks after the injury, there is a rapid decline in contractile activity, muscle mass, and cross-sectional area. This leads to muscle fiber degeneration and a shift towards a higher proportion of fast glycolytic fibers, which are more prone to fatigue and less efficient in energy utilization. Severe muscle atrophy in SCI is closely linked to metabolic dysfunction, affecting overall health and rehabilitation recovery. …

Hydrogen Peroxide Regulates Protein N-Glycosylation, Alexandria Hernandez-Nichols

All ETDs from UAB

N-glycosylation is a co- and post-translational modification wherein a variety of sugars are added to proteins in a linear pathway progressing from high mannose (HM) to hybrid, to complex type N-glycans. This modification is important to the understanding of protein maturation, stability, and function. Studies have shown that changes in cell N-glycomes, in particular, the HM N-glycan category, could be hallmarks of various pathologies. The biosynthetic pathway for N-glycosylation is well studied and the key enzymes involved in the progression of HM to hybrid N-glycans are the a-mannosidases. Little is understood about the regulation of this highly complex post-translational modification …

The Association Between Social Connectedness And Opioid Reuse Among Vulnerable Groups Receiving Medication For Opioid Use Disorder, Jolanda Lynn Hudson

All ETDs from UAB

THE ASSOCIATION BETWEEN SOCIAL CONNECTEDNESS AND OPIOID REUSE AMONG VULNERABLE GROUPS RECEIVING MEDICATION FOR OPIOID USE DISORDER JOLANDA L. HUDSON PUBLIC HEALTH ABSTRACT Introduction: Opioid Use Disorder (OUD) is a serious illness that continues to persist despite the many efforts of researchers, physicians, government agencies, state, and local programs, to eliminate the mortality rate associated with this disease. Although manageable, OUD is still taking the lives of citizens due to illegal opioid misuse. Understanding the dynamics of the disease and the contributing factors in various populations may inform researchers in successful intervention outcomes. Methods: A retrospective secondary data analysis utilizing …

Changes In Drug And Alcohol Behaviors Before And After An Educational Intervention Among At-Risk Adults And Youth, Isabel Cuellar Acker

All ETDs from UAB

Introduction: Substance abuse is defined as the excessive use of a drug in a way that is detrimental to oneself, society, or both. Gender is important to examine because it is becoming more common for females to develop substance use disorders and for their substance use to be more severe. This study will address the role of an education-based intervention on substance abuse in an area that is at the intersection of rural and urban geography with a unique pool of participants. Methods: This is a longitudinal cohort study that has a pre-post intervention design. A linear model was used …

Prevention Of Spina Bifida Through Fortification Of Iodized Salt With Folic Acid, Anastasia Arynchyna Smith

All ETDs from UAB

The overarching goal of the three-paper dissertation is to address the gaps in the literature on the clinical care burden of preventable spina bifida on the global neurosurgical community and the need for a universal food vehicle for fortification with folic acid as a novel prevention strategy. It is known that sufficient intake of folic acid is imperative to prevent neural tube defects (spina bifida) in the developing fetus in the first month post-conception. It is also known that fortifying staple foods is the most cost-saving and effective prevention method. However, very few countries have mandatory fortification policies. Therefore, the …

It's A Man's World: The Association Between Safe Sex Practices, Relationship Power, & Resilience Among African American Emerging Adults Between 18-24 In The Deep South, Jessica Morgan

All ETDs from UAB

The purpose of this dissertation was to examine the impact that power imbalance has on safe sex practices among African American emerging adults. The objectives included: provide a thorough review of preexisting literature that explores the impact of power imbalance on safe sex practices among African American women; understand the impact that power imbalance has on safe sex practices among African American emerging adults comparing data from men and women; and understand if resilience is associated with power imbalance among African American emerging adult women in the United States. Utilizing a retrospective, cross-sectional, quantitative study design, three methods were used …

Long-Term Longitudinal Analysis Of 4,187 Participants Reveals Insights Into Determinants Of Clonal Hematopoiesis, Md Mesbah Uddin, Seyedmohammad Saadatagah, Abhishek Niroula, Bing Yu, Whitney E Hornsby, Shriienidhie Ganesh, Kim Lannery, Art Schuermans, Michael C Honigberg, Alexander G Bick, Peter Libby, Benjamin L Ebert, Christie M Ballantyne, Pradeep Natarajan

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CHIP is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CHIP. Splicing factor genes (SF3B1, SRSF2, U2AF1, and ZRSR2) and TET2 CHIP grow significantly faster than DNMT3A non-R882 clones. We find that age at baseline and sex significantly …