Digital Commons Network^™

November 26, 2024 Ereporter, University Of Alabama At Birmingham

eReporter (campus newsletter)

No abstract provided.

Casey Gill Named Vice President For Student Development And Chief Student Experience Officer, University Of Dayton

News Releases

Casey Gill, vice president for student development and dean of students at Wittenberg University, will become vice president for student development and chief student experience officer at the University of Dayton Jan. 1.

Effect Of Patient Resilience On Functional Outcomes After Meniscectomy, Adeeb Hanna, Andres Perez, Alice He, John Sonnier, Henson Destine, Rahul Muchintala, Ralph Cook, Sean Bryan, Fotios Tjoumakaris, Kevin Freedman

Rothman Institute Papers

BACKGROUND: Recent literature has identified that patient resilience may affect outcomes after meniscectomy. Research into psychological risk factors for poor surgical outcomes has been a focus in orthopaedic surgery.

PURPOSE/HYPOTHESIS: The purpose of this study was to examine the relationship between preoperative patient resilience and 2-year postoperative outcomes after arthroscopic meniscectomy. It was hypothesized that there would be no relationship between resilience and patient-reported outcomes after meniscectomy.

STUDY DESIGN: Cohort study; Level of evidence, 2.

METHODS: Patients who underwent meniscectomy between January and June 2020 at a single multicenter institution were identified, and those aged ≥18 years without evidence of …

Manufacturing Organizations’ Effective Resilience Strategies For Mitigating The Effects Of Supply Chain Disruptions, Ernesto Barquet-Gonzalez

Walden Dissertations and Doctoral Studies

Supply chain disruptions have the potential to have a negative impact on organizations of all sizes and disciplines. Leaders in manufacturing organizations must learn how to adapt to mitigate the impact of supply chain disruptions on their firm’s performance. Grounded in the dynamic capabilities theory, the purpose of this qualitative multiple-case research project was to explore the strategies that leaders in manufacturing organizations use to mitigate the impact of supply chain disruptions on their organization’s profitability and market share. The participants were 15 leaders of manufacturing organizations from the United States with at least five years of experience in supply …

Acute Care Hospitalizations: Intentional Rounding And The Relationship To Patient Satisfaction, Ernestine Lucrecia Quick

Walden Dissertations and Doctoral Studies

Patients evaluate their experiences to determine if they will allow hospitals to provide their needed health services. Patient experience scores are used by hospitals to assess patients’ feelings about their interactions with the health care team and providers, the hospital facilities, and their likelihood to recommend the hospital to others. The purpose of this quantitative study was to determine whether a significant difference existed in patient satisfaction between those receiving care in a North Carolina inpatient health system before and after implementing intentional rounding (IR). The three research questions addressed the independent variable by comparing Press Ganey survey data for …

Effective Strategies Human Resource Business Leaders Use To Implement Diversity, Equity, And Inclusion Initiatives That Reduce Worker Turnover, Kerese Whyte-Phillips

Walden Dissertations and Doctoral Studies

Human resource (HR) business leaders who prioritize diversity, equity, and inclusion (DEI) champion a more dynamic and innovative workforce and alleviate labor turnover, a costly hindrance to growth. HR business leaders orchestrate these strategies, promoting an environment where diverse talents are valued and equitable opportunities abound, reducing labor turnover. Rooted in the social identity theory (SIT) and the Equity, Diversity, and Inclusion (EDI) framework, this qualitative pragmatic inquiry aimed to identify and explore effective strategies HR business leaders use to implement DEI initiatives that reduce employee turnover in the Southeast United States. The participants were seven HR business leaders in …

Identifying Redundant Audio Content Over Cloud Environment Using Deduplication Techniques, Venkatesh K

Theses and Dissertations

Cloud computing has become an integral part of modern internet-based services, with users relying heavily on cloud environments as primary storage solutions. However, the exponential growth in data volume presents a challenge (i.e) the proliferation of duplicated content within cloud repositories. Deduplication techniques provide a promising approach to mitigate this issue. This research focuses on detecting redundant audio content within a cloud environment, specifically targeting the sharing of extensive audio files, such as those in Waveform Audio File Format (WAV). The study proposes the Refined Super Subset Identification Algorithm (RSSIA) to efficiently identify redundant content and segments within existing audio …

Economic Foundations Of Contraceptive Transitions: Theories And A Review Of The Evidence, Mahesh Karra, Joshua Wilde

Urban Studies and Planning Faculty Publications and Presentations

We review the foundations of the economic development–contraception nexus, focusing on the pathways through which economic factors drive contraceptive adoption and change. We investigate the channels through which the relationship between economic development and contraceptive dynamics is mediated. Using global data, we document the correlations between economic development and contraception transitions over time and across geographies. We briefly examine the evidence of the role of fertility, both desired and realized, as a central pathway through which the relationship has been historically theorized and empirically verified. We also discuss a range of mechanisms through which economic development drives contraceptive use independently …

Rsk1 Dependency In Flt3-Itd Acute Myeloid Leukemia, Tim Kong, Angelo B A Laranjeira, Christopher T Letson, Layow Yu, Fan He, Aarthi Jayanthan, Gerrit Los, Sandra E Dunn, Grant A Challen, Stephen T Oh

2020-Current year OA Pubs

Internal tandem duplications (ITD) in fms-like tyrosine kinase 3 (FLT3) represent the most common genetic alteration in de novo acute myeloid leukemia (AML). Here, we identify ribosomal protein s6 kinase a1 (RSK1) as a core dependency in FLT3-ITD AML and unveil the existence of crucial bi-directional regulation. RSK1 perturbation resulted in marked apoptosis and abrogated phosphorylation of FLT3 and associated downstream signaling cascades in FLT3-ITD AML cell lines. Using cycloheximide, MG-132, and ubiquitination assays, we further demonstrate mechanistically that RSK1 regulates FLT3-ITD activity, and protein stability through deubiqutinase USP1, which we identify as a second dependency. Importantly, multivariate analysis revealed …

Magrolimab Plus Rituximab In Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 3-Year Follow-Up Of A Phase 1/2 Trial, Amitkumar Mehta, Leslie Popplewell, Graham P Collins, Sonali M Smith, Ian W Flinn, Nancy L Bartlett, Nilanjan Ghosh, Gal Hacohen-Kleiman, Yanan Huo, Linda Su-Feher, Camille Renard, Ranjana Advani, Mark Roschewski

2020-Current year OA Pubs

Relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) is generally considered incurable with current treatment options. Previous phase 1b/2 results showed combining magrolimab (anti-cluster-of-differentiation [CD] 47 antibody) with the anti-CD20 antibody rituximab (M+R) has antitumor activity against R/R iNHL. We report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R in R/R iNHL. After magrolimab priming, 4 patient groups in phase 1b M+R received 10 to 45-mg/kg magrolimab doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end …

Protective Effect And Molecular Mechanisms Of Human Non-Neutralizing Cross-Reactive Spike Antibodies Elicited By Sars-Cov-2 Mrna Vaccination, Jordan J Clark, Ali H Ellebedy, Et Al.

2020-Current year OA Pubs

Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 …

Comparing Neoantigen Cancer Vaccines And Immune Checkpoint Therapy Unveils An Effective Vaccine And Anti-Trem2 Macrophage-Targeting Dual Therapy, Sunita Keshari, Martina Molgora, Marco Colonna, Et Al.

2020-Current year OA Pubs

The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to promote T cells with anti-tumor capabilities. Here, we compared mutant neoantigen (neoAg) peptide-based vaccines with ICT in preclinical models. NeoAg vaccines induce the most robust expansion of proliferating and stem-like PD-1

Spatial, Transcriptomic, And Epigenomic Analyses Link Dorsal Horn Neurons To Chronic Pain Genetic Predisposition, Cynthia M Arokiaraj, Alexander Chamessian, Et Al.

2020-Current year OA Pubs

Key mechanisms underlying chronic pain occur within the dorsal horn. Genome-wide association studies (GWASs) have identified genetic variants predisposed to chronic pain. However, most of these variants lie within regulatory non-coding regions that have not been linked to spinal cord biology. Here, we take a multi-species approach to determine whether chronic pain variants impact the regulatory genomics of dorsal horn neurons. First, we generate a large rhesus macaque single-nucleus RNA sequencing (snRNA-seq) atlas and integrate it with available human and mouse datasets to produce a single unified, species-conserved atlas of neuron subtypes. Cellular-resolution spatial transcriptomics in mouse shows the precise …

Metabolite Signatures Of Chronological Age, Aging, Survival, And Longevity, Paola Sebastiani, Mary F Feitosa, Mary K Wojczynski, Gary J Patti, Et Al.

2020-Current year OA Pubs

Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicate many associations in independent studies. By summarizing the results into 19 signatures, we differentiate between metabolites that may mark aging-associated compensatory mechanisms from metabolites that mark cumulative damage of aging and from metabolites that characterize extreme longevity. We generate and validate a metabolomic …

Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al

School of Medicine Faculty Publications

Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by …

Cardiac Amyloidosis Versus Other Restrictive Cardiomyopathies: A Retrospective Analysis Of Cardiovascular Outcomes And Arrhythmic Burden, Andrew Sagalov, Waqas Ullah, Yevgeniy Brailovsky, Michael Buhnerkempe, Steve Scaife, Abhishek Kulkarni, Mohamed Labedi, Shruti Hegde

Abington Jefferson Health Papers

BACKGROUND: The arrhythmic burden and cardiovascular risks of cardiac amyloidosis compared with other types of restrictive cardiomyopathies (RCM), such as hemochromatosis and cardiac sarcoid, have not been well characterized in the literature. An increase in emphasis on screening has resulted in more diagnoses of cardiac amyloidosis and a larger data pool to analyze the cardiovascular outcomes of this cardiomyopathy.

METHODS AND RESULTS: We queried the National Inpatient Sample (NIS) database to identify all adult patients diagnosed with cardiac amyloidosis or other RCM between the years 2016 and 2019. Discharge-weighted analysis using survey regressions accounts for discharge weights and characteristics found …

Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al

School of Graduate Studies Faculty Publications

Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by …

Reparations And Higher Education: How Public Universities May Offer Reparation Scholarships To Black Students In The Post-Affirmative Action Era After Students For Fair Admissions V. Harvard, William Y. Chin

Tennessee Journal of Race, Gender, & Social Justice

No abstract provided.

Friends With Social Benefits: Queerplatonic Relationships And The Future Of Marriage

Tennessee Journal of Race, Gender, & Social Justice

No abstract provided.

Effectiveness And Durability Of A Workplace Sedentary Behavior Intervention Based On The Total Worker Health® Approach, Brad Wipfli, Sara Wild, Ginger Hanson, Steven A. Shea, Kerri Winters-Stone, Wura Olawole, Renee Kozlowski, Saurabh S. Thosar

OHSU-PSU School of Public Health Faculty Publications and Presentations

We used the Total Worker Health^® approach to develop a multi-component workplace sedentary behavior intervention and tested intervention effectiveness in a cluster randomized trial. Participants (n = 198; 75% female) were recruited from three call-centers (two intervention and one usual practice control). All worksites received pedal stand active workstations. The usual practice site received no additional support, while the intervention group completed a six-month program of activities including computer-based training, behavioral self-monitoring, health and safety discussions, and pedaling competitions. Data collection included a survey, a physical health assessment, and accelerometer measures of sedentary behavior, physical activity, and sitting/standing …

Scale-Dependent Effects Of Urban Canopy Cover, Canopy Volume, And Impervious Surfaces On Near-Surface Air Temperature In A Mid-Sized City, Carson Ralls, Anne Y. Polyakov, Vivek Shandas

Geography Faculty Publications and Presentations

Cities are significantly warmer than their surrounding rural environments. Known as the ‘urban heat island effect’, it can affect the health of urban residents and lead to increased energy use, public health impacts, and damage to infrastructure. Although this effect is extensively researched, less is known about how landscape characteristics within cities affect local temperature variation. This study examined how tree canopy cover, canopy volume, and impervious surface cover affect daytime near-surface air temperature, and how these effects vary between different scales of analysis (10, 30, 60, 90 m radii), ranging from approximate street corridor to city block size. Temperature …

Perceptions Of Pre-Exposure Prophylaxis Among American Indians, William Joshua Johnson

Walden Dissertations and Doctoral Studies

American Indians have seen a rise in the transmission of HIV infections compared to other racial and ethnic groups. Pre-exposure prophylaxis (PrEP), which is the use of antiviral medications to prevent HIV, there is insufficient literature to describe the acceptability, attitudes, or willingness to utilize PrEP by American Indians. The purpose of this descriptive qualitative study, guided by the health belief model, was to explore perceptions of PrEP among American Indians. Open-ended semi structured questions were used to interview eight participants to ascertain perceptions of PrEP to prevent HIV infections. Using coding and thematic analysis, four themes were identified: (a) …

Religious Attitudes And Fear Toward Traditional Biomedical And Psychological Services Among People Of The Christian Faith, Brennan Cackett

Walden Dissertations and Doctoral Studies

Adults who identify as Christian often seek help within their religious communities for mental health issues. Research suggested that religious counseling services may discourage members from reporting mental health issues to traditional biomedical and psychological providers. The purpose of this quantitative study was to examine the extent to which people who identify as Christian in Southern California seek help outside of the Church and whether their help seeking is influenced by their religious attitudes and perceived fear of traditional psychological services. Southern California was chosen as it is where the Christian Counseling movement was started and has a large population …

Social Media As Health Educator: An Assessment Of The Understandability And Accuracy Of Tiktok Content About Contraception, Julianna Coleman, Maetal Haas-Kogan, Andrea Pelletier, Rachel Stoddard, Natasha Johnson, Julia Beatini, Nora Sun, Alex Keuroghlian, Deborah Bartz

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Contraception knowledge and attitudes are largely formed from conversations within one's social network. More recently, this network has expanded to include social media. As the fastest growing social media platform, we aimed to assess popular contraception videos on TikTok for content understandability, actionability and accuracy.

METHODS: This is a secondary analysis of the most viewed, contraception-specific TikTok videos that were previously coded as containing educational messaging in a content-analysis study. We assessed videos for understandability (ability to explain a key message) and actionability (identify what they can do to act on that message) using the Patient Education Materials Assessment …

The Effectiveness Of Ultrasound-Indicated Cerclage For The Reduction Of Extreme Preterm Birth In Twin Pregnancies With A Short Cervix: A Systematic Review And Meta-Analysis, Lissa Van Gils, Renske Dutilh, Nerissa Denswil, Amanda Roman, Marjon A De Boer, Eva Pajkrt, Martijn A Oudijk

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: This study aimed to evaluate the effectiveness of cervical cerclage in women with a twin pregnancy and a midpregnancy asymptomatic short cervix (≤25 mm), in preventing preterm birth and improving neonatal outcomes.

DATA SOURCES: Systematic searches were conducted in MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to April 17, 2023, updated in September and February 2024.

STUDY ELIGIBILITY CRITERIA: Included were randomized controlled trials, cohort studies, and case-control studies comparing cerclage with expectant management in twin pregnancies and an asymptomatic short cervix (≤25 mm).

METHODS: Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale …

Multiple Factors Regulate The Expression Of Sufcdsub In Streptococcus Mutans, Kassapa Ellepola, Lauren C. Guillot, Bradley Comeaux, Yiran Han, Jessica K. Kajfasz, Jacob P. Bitoun, Grace Spatafora, Jose A. Lemos, Zezhang T. Wen

School of Dentistry Faculty Publications

Introduction: The sufCDSUB gene cluster, encoding the sole iron-sulfur (Fe-S) cluster assembly system in S. mutans, was recently shown to be up-regulated in response to oxidative stressors and Fe limitation. Methods: In this study, luciferase reporter fusion assays, electrophoretic gel mobility shift assays (EMSA) and in vitro transcription assays (IVT) were used to dissect the cis- and trans-acting factors that regulate the expression of sufCDSUB. Results and discussion: Results showed deletion of perR, for the only Fur-family transcriptional regulator in S. mutans, resulted in > 5-fold increases in luciferase activity under the control of the sufCDSUB promoter (P < 0.01), as compared to the parent strain, UA159 when the reporter strains were grown in medium with no supplemental iron. Site-directed mutagenesis of a PerR-box in the promoter region led to elevation of the reporter activity by >1.6-fold (P < 0.01). In an EMSA, recombinant PerR (rPerR) was shown to bind to the cognate sufCDSUB promoter leading to mobility retardation. On the other hand, the reporter activity was increased by > 84-fold …

Evaluating An Evidence-Based Quality Improvement Initiative For Food Insecurity Screening And Referral In Adults With Diabetes Initiating Continuous Glucose Monitor Therapy, Coni Dennis

Graduate Theses, Dissertations, and Capstones

Diabetes affects 37 million people annually in the United States, with direct medical costs exceeding $237 billion per year (American Diabetes Association, 2018; Xu et al., 2018). Complications account for up to 64% of diabetes-related expenses, emphasizing the importance of glycemic stability in preventing costly and debilitating outcomes (Dieleman et al., 2016). Diet and nutrition, essential for glycemic control, are often undermined by food insecurity—defined as inconsistent access to adequate, nutritious food—affecting 16% of adults with diabetes (Casagrande et al., 2022; Kirby et al., 2021). Food insecurity is linked to higher HbA1c levels, increased complications, and hospitalizations (Thomas et al., …

Genetic Manipulation Of Caveolin-1 In A Transgenic Mouse Model Of Aortic Root Aneurysm: Sex-Dependent Effects On Endothelial And Smooth Muscle Function, Tala Curry-Koski, Brikena Gusek, Ross M. Potter, T. B. Jones, Raechel Dickman, Nathan Johnson, John N. Stallone, Roshanak Rahimian, Johana Vallejo-Elias, Mitra Esfandiarei

Pacific Faculty Work

Marfan syndrome (MFS) is a systemic connective tissue disorder stemming from mutations in the gene encoding Fibrillin-1 (Fbn1), a key extracellular matrix glycoprotein. This condition manifests with various clinical features, the most critical of which is the formation of aortic root aneurysms. Reduced nitric oxide (NO) production due to diminished endothelial nitric oxide synthase (eNOS) activity has been linked to MFS aortic aneurysm pathology. Caveolin-1 (Cav1), a structural protein of plasma membrane caveolae, is known to inhibit eNOS activity, suggesting its involvement in MFS aneurysm progression by modulating NO levels. In this study, we examined the role of Cav1 in …

Cd4+ T Cells Drive Corneal Nerve Damage But Not Epitheliopathy In An Acute Aqueous-Deficient Dry Eye Model, Alexia Vereertbrugghen, Manuela Pizzano, Agostina Cernutto, Florencia Sabbione, Irene A Keitelman, Douglas Vera Aguilar, Ariel Podhorzer, Federico Fuentes, Celia Corral-Vázquez, Mauricio Guzmán, Mirta N Giordano, Analía Trevani, Cintia S De Paiva, Jeremías G Galletti

Faculty, Staff and Students Publications

Dry eye disease (DED) is characterized by a dysfunctional tear film in which the corneal epithelium and its abundant nerves are affected by ocular desiccation and inflammation. Although adaptive immunity and specifically CD4+ T cells play a role in DED pathogenesis, the exact contribution of these cells to corneal epithelial and neural damage remains undetermined. To address this, we explored the progression of a surgical DED model in wild-type (WT) and T cell-deficient mice. We observed that adaptive immune-deficient mice developed all aspects of DED comparably to WT mice except for the absence of functional and morphological corneal nerve changes, …

Current Therapeutic Opportunities For Estrogen Receptor Mutant Breast Cancer, Murugesan Palaniappan

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) drives two out of three breast cancers and therefore ERα is a major therapeutic target for ER-positive breast cancer patients. Drugs that inhibit ERα activity or block estrogen synthesis in the body are currently being used in the clinic to treat ER-positive breast cancer and have been quite successful in controlling breast cancer progression for the majority of patients. However, ER-positive breast cancer often becomes resistant to these endocrine therapies, leading to endocrine-resistant metastatic breast cancer, a very aggressive cancer that leads to death. Recent large-scale genomic studies have revealed a series of activating somatic mutations …