Digital Commons Network^™

Exploring The Impact Of Teacher Curiosity On Job Satisfaction And Self-Efficacy: A Quantitative Study In Stem Education, Christopher Jeffcoat

Theses and Dissertations

This dissertation presents a quantitative study involving 96 teachers of STEM subjects, aimed at investigating the relationship between teacher curiosity, job satisfaction, and teacher self-efficacy. The primary objective was to examine the significance of teacher curiosity in the context of educators' job satisfaction. The research findings indicate a moderate positive correlation between teacher curiosity and job satisfaction (r=0.57), suggesting that educators with higher curiosity tend to experience greater job satisfaction. Also, a moderate positive correlation (r=0.51) was identified between teacher curiosity and teacher self-efficacy, emphasizing the connection between curiosity and educators' belief in their ability to positively impact student learning. …

Providing A Social Emotional Learning Opportunity To Virtual Students Struggling With Social Anxiety: Group Counseling As An Intervention, Josie Kate White Ivey

Theses and Dissertations

The purpose of this mixed methods action research dissertation was to offer a social/emotional learning opportunity for virtual students struggling with social anxiety. A six-week group counseling experience was offered to on-campus high school students focused on social anxiety in order to determine is group counseling would be a beneficial intervention strategy for virtual students also dealing with social anxiety. An observer protocol was used to make note of participants responses and physical characteristics related to social anxiety and make reflective notes after each counseling session. Group participants also completed quick-check exit tickets to help the researcher determine the student’s …

In Search Of Cognitive Justice: One District’S Approach To Implementing Culturally Responsive Practices, Anne Marie Mancini

Theses and Dissertations

This action research study examined district leaders' approach to integrating culturally responsive practices into classrooms in a medium-sized urban Connecticut public school system. The framework for this study was supported by two theories: transformative learning and culturally responsive pedagogy. Following a case study model of design, the project focused on the work of the Supervisor of Professional Learning and the Department Supervisor for English Language Arts (ELA) as they provided training, support, and resources to the Grade 7 team. Two research questions guided this study: (1) What successes, if any, did district leaders experience in implementing culturally responsive teaching practices …

Development Of Avalanche Photo Detector For Uv-C Using Gallium Oxide Material System, Md Ghulam Ghulam Zakir

Theses and Dissertations

This work describes the metal-organic chemical vapor deposition (MOCVD) optimization process for epitaxially grown gallium oxide (Ga2O3) layers, electrical field distribution, and the design for Avalanche Photo Detector (APD). MOCVD is a well-accepted process in the semiconductor industry, as it is well-known for its precise deposition of ultra-thin, high-quality semiconductor layers with extraordinary control over composition and thickness. The choice of Ga2O3 is due to r its distinctive properties of ultra-wide bandgap and low turn-on resistance. Thus, Ga₂O₃-based materials can withstand high voltage and current with the least energy loss, making them an attractive choice for …

The Dengue Vaccine Initiative: A Bibliometric Analysis Of Research Publications, Festus Mulakoli, Abednego Ongeso, Horatius Musembi

School of Nursing & Midwifery, East Africa

Dengue fever has become a significant public health problem in tropical and subtropical regions and affects millions of people annually. Approximately 390 million people worldwide are estimated to be infected with dengue every year, of which 96 million develop dengue fever. Recently, there has been a noticeable increase in dengue cases, primarily in areas with tropical and subtropical climates. Vaccines have been developed to prevent or reduce the severity of the disease. This study reviews the number of publications on dengue vaccines and related topics worldwide. We aimed to evaluate the research output and create a narrative on global vaccine …

Immunohistochemical Expression Of Galectin-3 In Thyroid Neoplasms And Its Correlation With Cd56, Banan Mohammed, Wahda Al.Nuaimy

Iraqi Postgraduate Medical Journal

AbstractBackground: The incidence of thyroid cancer has been increasing significantly since the mid-1990s.Some studies have revealed that in thyroid gland, the galectin-3 plays a role in the pathogenesis of well-differentiated carcinoma. For that, it is may be one of the markers that may help to assist in distinguishing thyroid neoplasms. Objective : To detect the frequency of immunohistochemical expression and diagnostic value of Galectin-3 in different types of thyroid neoplasms.To correlate the expression of galectin-3 findings with immunoprofile data of CD56. To correlate the result of immunohistochemical expression of Galectin-3 with the age and gender of the sampled cases.Patients and …

Neoadjuvant And Adjuvant Treatments For Early Stage Resectable Nsclc: Consensus Recommendations From The International Association For The Study Of Lung Cancer, Jonathan D Spicer, Tina Cascone, Murry W Wynes, Myung-Ju Ahn, Sanja Dacic, Enriqueta Felip, Patrick M Forde, Kristin A Higgins, Mark G Kris, Tetsuya Mitsudomi, Mariano Provencio, Suresh Senan, Benjamin J Solomon, Ming Sound Tsao, Masahiro Tsuboi, Heather A Wakelee, Yi-Long Wu, James Chih-Hsin Yang, Caicun Zhou, David H Harpole, Karen L Kelly

Faculty, Staff and Student Publications

Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer …

Multifocal, Multiphenotypic Tumours Arising From An Mtor Mutation Acquired In Early Embryogenesis, Clarissa N Pacyna, Madhanagopal Anandapadamanaban, Kevin W Loudon, Iain M Hay, Olga Perisic, Ruoyan Li, Matthew Byrne, Laura Allen, Kirsty Roberts, Yvette Hooks, Anne Y Warren, Grant D Stewart, Menna R Clatworthy, Sarah A Teichmann, Sam Behjati, Peter J Campbell, Roger L Williams, Thomas J Mitchell

Faculty, Staff and Student Publications

Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the wide dissemination of cells predisposed to disease within mature organs. We characterised the evolutionary history of four synchronous renal tumours from a 14-year-old girl using whole genome sequencing alongside single cell and bulk transcriptomic sequencing. Phylogenetic reconstruction timed the origin of all tumours to a multipotent embryonic cell committed to the right kidney, around 4 weeks post-conception. Biochemical and structural analysis of their shared MTOR mutation, absent from normal tissues, demonstrates enhanced protein flexibility, enabling a FAT domain hinge to dramatically increase activity of mTORC1 and mTORC2. …

Dual Targeting Macrophages And Microglia Is A Therapeutic Vulnerability In Models Of Pten-Deficient Glioblastoma, Yang Liu, Junyan Wu, Hinda Najem, Yiyun Lin, Lizhi Pang, Fatima Khan, Fei Zhou, Heba Ali, Amy B Heimberger, Peiwen Chen

Faculty, Staff and Student Publications

Tumor-associated macrophages and microglia (TAMs) are critical for tumor progression and therapy resistance in glioblastoma (GBM), a type of incurable brain cancer. We previously identified lysyl oxidase (LOX) and olfactomedin like-3 (OLFML3) as essential macrophage and microglia chemokines, respectively, in GBM. Here, single-cell transcriptomics and multiplex sequential immunofluorescence followed by functional studies demonstrate that macrophages negatively correlate with microglia in the GBM tumor microenvironment. LOX inhibition in PTEN-deficient GBM cells upregulates OLFML3 expression via the NF-κB-PATZ1 signaling pathway, inducing a compensatory increase of microglia infiltration. Dual targeting macrophages and microglia via inhibition of LOX and the CLOCK-OLFML3 axis generates potent …

Challenges And Opportunities For Early Phase Clinical Trials Of Novel Drug-Radiotherapy Combinations: Recommendations From Nrg Oncology, The American Society For Radiation Oncology (Astro), The American College Of Radiology (Acr), The Sarah Cannon Research Institute, And The American College Of Radiation Oncology (Acro), Zachary S Zumsteg, Siddharth Sheth, Salma K Jabbour, Krishnan R Patel, Randall J Kimple, Terence M Williams, Meng Xu-Welliver, Pedro A Torres-Saavedra, Arta M Monjazeb, Jyoti Mayadev, Steven E Finkelstein, John M Buatti, Sandip P Patel, Steven H Lin

Faculty, Staff and Student Publications

NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug-drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug-radiotherapy combinations.

Mechanisms By Which The Intratumoral Microbiome May Potentiate Immunotherapy Response, Dalissa Negrón-Figueroa, Lauren E Colbert

Faculty, Staff and Student Publications

No abstract provided.

Lower Intensity Therapy With Cladribine/Low Dose Cytarabine/Venetoclax In Older Patients With Acute Myeloid Leukemia Compares Favorably With Intensive Chemotherapy Among Patients Undergoing Allogeneic Stem Cell Transplantation, Jayastu Senapati, Hagop M Kantarjian, Alexandre Bazinet, Patrick Reville, Nicholas J Short, Naval Daver, Gautam Borthakur, Alex Bataller, Elias Jabbour, Courtney Dinardo, Fadi Haddad, Koji Sasaki, Uday Popat, Betul Oran, Amin M Alousi, Sanam Loghavi, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age …

Asxl1/Tet2 Genotype-Based Risk Stratification Outperforms Asxl1 Mutational Impact And Is Independent Of Mutant Variant Allele Fractions In Chronic Myelomonocytic Leukemia, Clifford M Csizmar, Mark Gurney, Rashmi Kanagal-Shamanna, Kelly Chien, Danielle Hammond, Terra L Lasho, Christy M Finke, Christopher Dean, Anuya Natu, Abhishek A Mangaonkar, Aref Al-Kali, Naseema Gangat, Ayalew Tefferi, Hassan Alkhateeb, Guillermo Garcia-Manero, Rami S Komrokji, Najla A Ali, Eric Padron, Guillermo Montalban-Bravo, Mrinal M Patnaik

Faculty, Staff and Student Publications

No abstract provided.

Fast Model Calibration For Predicting The Response Of Breast Cancer To Chemotherapy Using Proper Orthogonal Decomposition, Chase Christenson, Chengyue Wu, David A Hormuth, Casey E Stowers, Megan Lamonica, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Constructing digital twins for predictive tumor treatment response models can have a high computational demand that presents a practical barrier for their clinical adoption. In this work, we demonstrate that proper orthogonal decomposition, by which a low-dimensional representation of the full model is constructed, can be used to dramatically reduce the computational time required to calibrate a partial differential equation model to magnetic resonance imaging (MRI) data for rapid predictions of tumor growth and response to chemotherapy. In the proposed formulation, the reduction basis is based on each patient's own MRI data and controls the overall size of the "reduced …

Artificial Intelligence Applications In Oral Cancer And Oral Dysplasia, Chi T Viet, Michael Zhang, Neeraja Dharmaraj, Grace Y Li, Alexander T Pearson, Victoria A Manon, Anupama Grandhi, Ke Xu, Bradley E Aouizerat, Simon Young

Faculty, Staff and Student Publications

Oral squamous cell carcinoma (OSCC) is a highly unpredictable disease with devastating mortality rates that have not changed over the past decades, in the face of advancements in treatments and biomarkers, which have improved survival for other cancers. Delays in diagnosis are frequent, leading to more disfiguring treatments and poor outcomes for patients. The clinical challenge lies in identifying those patients at the highest risk of developing OSCC. Oral epithelial dysplasia (OED) is a precursor of OSCC with highly variable behavior across patients. There is no reliable clinical, pathological, histological, or molecular biomarker to determine individual risk in OED patients. …

Subsyndromes And Symptom Clusters: Multilevel Factor Analysis Of Behavioral And Psychological Symptoms Of Dementia With Intensive Longitudinal Data, Carolyn E Z Pickering, Vicki Winstead, Mustafa Yildiz, Danny Wang, Maria Yefimova, Andrew M Pickering

Faculty, Staff and Student Publications

Introduction: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between-person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within-person factors) that represent contextually driven daily symptom experiences.

Methods: This study used an intensive longitudinal design in which 68 co-residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient's daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries). A multilevel exploratory/confirmatory factor analysis was used to account …

Structures And Compositional Dynamics Of Mediator In Transcription Regulation, Tao Li, Ti-Chun Chao, Kuang-Lei Tsai

Faculty, Staff and Student Publications

The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), functions as a critical coregulator during RNA polymerase II (RNAPII) transcription. cMED recruits RNAPII and facilitates the assembly of the pre-initiation complex (PIC) at promoters. In contrast, CKM prevents RNAPII binding to cMED while simultaneously exerting positive or negative influence on gene transcription through its kinase function. Recent structural studies on cMED and CKM have revealed their intricate architectures and subunit interactions. Here, we explore these structures, providing a comprehensive insight into Mediator (cMED-CKM) architecture and its potential mechanism in regulating RNAPII transcription. Additionally, we …

Impact Of Race And Ethnicity On Outcomes After Umbilical Cord Blood Transplantation, Karen Ballen, Tao Wang, Naya He, Jennifer M Knight, Sanghee Hong, Haydar Frangoul, Leo F Verdonck, Amir Steinberg, Miguel A Diaz, C Fred Lemaistre, Sherif M Badawy, Jeffrey J Pu, Hasan Hashem, Bipin Savani, Akshay Sharma, Hillard M Lazarus, Muhammad Bilal Abid, Jason Tay, Hemalatha G Rangarajan, Tamila Kindwall-Keller, Cesar O Freytes, Amer Beitinjaneh, Lena E Winestone, Usama Gergis, Nosha Farhadfar, Neel S Bhatt, Raquel M Schears, David Gómez-Almaguer, Mahmoud Aljurf, Vaibhav Agrawal, Yachiyo Kuwatsuka, Sachiko Seo, David I Marks, Leslie Lehmann, William A Wood, Shahrukh Hashmi, Wael Saber

Faculty, Staff and Student Publications

Background: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients.

Objective: To compare outcomes by social determinants of health.

Study design: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, …

A Brave New Framework For Glioma Drug Development, Kelly M Hotchkiss, Philipp Karschnia, Karisa C Schreck, Marjolein Geurts, Timothy F Cloughesy, Jason Huse, Elizabeth S Duke, Justin Lathia, David M Ashley, Edjah K Nduom, Georgina Long, Kirit Singh, Anthony Chalmers, Manmeet S Ahluwalia, Amy Heimberger, Stephen Bagley, Tomoki Todo, Roel Verhaak, Patrick D Kelly, Shawn Hervey-Jumper, John De Groot, Anoop Patel, Peter Fecci, Ian Parney, Victoria Wykes, Colin Watts, Terry C Burns, Nader Sanai, Matthias Preusser, Joerg Christian Tonn, Katharine J Drummond, Michael Platten, Sunit Das, Kirk Tanner, Michael A Vogelbaum, Michael Weller, James R Whittle, Mitchel S Berger, Mustafa Khasraw

Faculty, Staff and Student Publications

Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential postoperative deficits. …

Inulin-Gel-Based Oral Immunotherapy Remodels The Small Intestinal Microbiome And Suppresses Food Allergy, Kai Han, Fang Xie, Olamide Animasahun, Minal Nenwani, Sho Kitamoto, Yeji Kim, May Thazin Phoo, Jin Xu, Fulei Wuchu, Kehinde Omoloja, Abhinav Achreja, Srinadh Choppara, Zhaoheng Li, Wang Gong, Young Seok Cho, Hannah Dobson, Jinsung Ahn, Xingwu Zhou, Xuehui Huang, Xinran An, Alexander Kim, Yao Xu, Qi Wu, Soo-Hong Lee, Jessica J O'Konek, Yuying Xie, Yu Leo Lei, Nobuhiko Kamada, Deepak Nagrath, James J Moon

Faculty, Staff and Student Publications

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells …

Tailoring Neoadjuvant Systemic Therapy In Breast Cancer: “The Advent Of A Personalized Approach”-The Breast-Gynecological And Immuno-Oncology International Cancer Conference (Bgicc) Consensus And Recommendations, Hesham Elghazaly, Hamdy A Azim, Hope S Rugo, David Cameron, Sandra M Swain, Giuseppe Curigliano, Nadia Harbeck, Debu Tripathy, Banu Arun, Matti Aapro, Martine Piccart, Fatima Cardoso, Joseph Gligorov, Hagar Elghazawy, Nagi S El Saghir, Frederique Penault-Llorca, Edith A Perez, Philip Poortmans, Hany Abdelaziz, Heba M El-Zawahry, Loay Kassem, Mohamed Sabry, Giuseppe Viale, Sana Al-Sukhun, Neven Gado, Jessica W T Leung, Lobna Ezz Elarab, Maria João Cardoso, Khaled Abdel Karim, Meteb Foheidi, Merit M Elmaadawy, Pierfranco Conte, Ashraf S M Selim, Alaa Kandil, Rasha M Kamal, Ruslan M Paltuev, Valentina Guarneri, Omalkhair Abulkhair, Omar Zakaria, Mehra Golshan, Roberto Orecchia, Manal Elmahdy, Ahmed M Abdel-Aziz, Nermean Bahie Eldin

Faculty, Staff and Student Publications

Background: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus.

Methods: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this …

Exploring The Influence Of Molecular Chaperones On The Aggregation Of Transthyretin, Adam S. Knier

Dissertations (1934 -)

Molecular chaperones assist in maintaining protein homeostasis by limiting protein aggregation, including populations of protein aggregates that may be associated with the onset of debilitating and/or often fatal diseases. Chaperones are known to limit protein aggregate populations through disaggregase activity, in which chaperone complexes work together to disassemble multi-subunit aggregate species into smaller populations, or holdase activity, in which chaperones bind to proteins or smaller aggregates to prevent further aggregation. In this dissertation we assess if molecular chaperones can limit the aggregation of human transthyretin (TTR) expressed within a yeast system and explore the relationship between chaperone concentration and activity. …

The Tragedy Of Our Trajectory, Marisola Xhelili Ciaccio

Dissertations (1934 -)

In this project, I argue that the trajectory of Western European civilization has resulted in increasingly tragic predicaments that are not to be taken as given features of being human. Though both Ancient Western and Eastern wisdom traditions concur that suffering is a part of life, the point of living is not to suffer but to learn to overcome it and flourish. But because the purported successes of Western “progress” necessarily depend on structural oppression, and oppression produces superfluous sufferings that interfere with our capacities to actualize our freedom and flourish, they ultimately make us all worse-off. Reflecting on such …

The Role Of Aldh1a1 In Glioblastoma Proliferation And Invasion, Yu-Kai Huang, Tzu-Ming Wang, Chi-Yu Chen, Chia-Yang Li, Shu-Chi Wang, Khushboo Irshad, Yuan Pan, Kun-Che Chang

Faculty, Staff and Student Publications

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Methods For Pragmatic Randomized Clinical Trials Of Pain Therapies: Immpact Statement, David Hohenschurz-Schmidt, Dan Cherkin, Andrew S C Rice, Robert H Dworkin, Dennis C Turk, Michael P Mcdermott, Matthew J Bair, Lynn L Debar, Robert R Edwards, Scott R Evans, John T Farrar, Robert D Kerns, Michael C Rowbotham, Ajay D Wasan, Penney Cowan, Mckenzie Ferguson, Roy Freeman, Jennifer S Gewandter, Ian Gilron, Hanna Grol-Prokopczyk, Smriti Iyengar, Cornelia Kamp, Barbara I Karp, Bethea A Kleykamp, John D Loeser, Sean Mackey, Richard Malamut, Ewan Mcnicol, Kushang V Patel, Kenneth Schmader, Lee Simon, Deborah J Steiner, Christin Veasley, Jan Vollert

Faculty, Staff and Student Publications

Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the …

Astrocyte-Induced Cdk5 Expedites Breast Cancer Brain Metastasis By Suppressing Mhc-I Expression To Evade Immune Recognition, Arseniy E Yuzhalin, Frank J Lowery, Yohei Saito, Xiangliang Yuan, Jun Yao, Yimin Duan, Jingzhen Ding, Sunil Acharya, Chenyu Zhang, Abigail Fajardo, Hao-Nien Chen, Yongkun Wei, Yutong Sun, Lin Zhang, Yi Xiao, Ping Li, Philip L Lorenzi, Jason T Huse, Huihui Fan, Zhongming Zhao, Mien-Chie Hung, Dihua Yu

Faculty, Staff and Student Publications

Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1-Stat1-importin α-Nlrc5 pathway, enabling BrMs to …

The Qiba Profile For Diffusion-Weighted Mri: Apparent Diffusion Coefficient As A Quantitative Imaging Biomarker, Michael A Boss, Dariya Malyarenko, Savannah Partridge, Nancy Obuchowski, Amita Shukla-Dave, Jessica M Winfield, Clifton D Fuller, Kevin Miller, Virendra Mishra, Michael Ohliger, Lisa J Wilmes, Raj Attariwala, Trevor Andrews, Nandita M Desouza, Daniel J Margolis, Thomas L Chenevert

Faculty, Staff and Student Publications

The apparent diffusion coefficient (ADC) provides a quantitative measure of water mobility that can be used to probe alterations in tissue microstructure due to disease or treatment. Establishment of the accepted level of variance in ADC measurements for each clinical application is critical for its successful implementation. The Diffusion-Weighted Imaging Biomarker Committee of the Quantitative Imaging Biomarkers Alliance (QIBA) has recently advanced the ADC Profile from the consensus to clinically feasible stage for the brain, liver, prostate, and breast. This profile distills multiple studies on ADC repeatability and describes detailed procedures to achieve stated performance claims on an observed ADC …

Targeting The Peripheral Neural-Tumour Microenvironment For Cancer Therapy, Dan Yaniv, Brandi Mattson, Sebastien Talbot, Frederico O Gleber-Netto, Moran Amit

Faculty, Staff and Student Publications

As the field of cancer neuroscience expands, the strategic targeting of interactions between neurons, cancer cells and other elements in the tumour microenvironment represents a potential paradigm shift in cancer treatment, comparable to the advent of our current understanding of tumour immunology. Cancer cells actively release growth factors that stimulate tumour neo-neurogenesis, and accumulating evidence indicates that tumour neo-innervation propels tumour progression, inhibits tumour-related pro-inflammatory cytokines, promotes neovascularization, facilitates metastasis and regulates immune exhaustion and evasion. In this Review, we give an up-to-date overview of the dynamics of the tumour microenvironment with an emphasis on tumour innervation by the peripheral …

Extent Of Resection Thresholds In Molecular Subgroups Of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma, Antonio Dono, Ping Zhu, Takeshi Takayasu, Octavio Arevalo, Roy Riascos, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Background and objectives: Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, previous GBM studies have not addressed the EOR impact in molecular subgroups beyond IDH1/IDH2 status. In the current article, we evaluate whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups.

Methods: A retrospective cohort of newly diagnosed GBM isocitrate dehydrogenase (IDH)-wildtype undergoing resection were prospectively included in a database (n = 138). EOR and residual tumor volume (RTV) were quantified with semiautomated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations …