Digital Commons Network^™

Oral Decitabine And Cedazuridine Plus Venetoclax For Older Or Unfit Patients With Acute Myeloid Leukaemia: A Phase 2 Study, Alexandre Bazinet, Guillermo Garcia-Manero, Nicholas Short, Yesid Alvarado, Alex Bataller, Tareq Abuasab, Rabiul Islam, Kathryn Montalbano, Ghayas Issa, Abhishek Maiti, Musa Yilmaz, Nitin Jain, Lucia Masarova, Steven Kornblau, Elias Jabbour, Guillermo Montalban-Bravo, Caitlin R Rausch, Sherry Pierce, Courtney D Dinardo, Tapan Kadia, Naval Daver, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

BACKGROUND: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax.

METHODS: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. …

Cochlear Implantation After Head And Neck Radiation: A Case Series, Systematic Review, And Meta-Analysis, Jumah G Ahmad, Benjamin D Lovin, Anna Lee, Marc-Elie Nader, Paul W Gidley

Faculty, Staff and Student Publications

Objective: To determine if cochlear implant (CI) is safe and effective in patients with radiation therapy (XRT)-induced sensorineural hearing loss and to discuss considerations in this population through a retrospective cohort review, systematic review, and meta-analysis.

Databases reviewed: PubMed, Cochrane Library, and Embase.

Methods: We retrospectively reviewed all CI cases after head and neck (HN) XRT at our institution, noting intraoperative findings, postoperative complications, and hearing outcomes. Change in speech discrimination scores (SDSs) was the primary outcome measure. Systematic review was performed to identify all cases of CI after HNXRT. A meta-analysis was performed to assess SDS change.

Results: The …

Incidence And Presenting Characteristics Of Angiosarcoma In The Us, 2001-2020, Michael J Wagner, Vinod Ravi, Stephanie K Schaub, Ed Y Kim, Jeremy Sharib, Harveshp Mogal, Min Park, Michaela Tsai, Daniela Duarte-Bateman, Anthony Tufaro, Elizabeth T Loggers, Lee D Cranmer, Bonny Chau, Michael J Hassett, Juneko Grilley-Olson, Kelly G Paulson

Faculty, Staff and Student Publications

Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed.

Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US.

Design, setting, and participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Bone Mimetic Environments Support Engineering, Propagation, And Analysis Of Therapeutic Response Of Patient-Derived Cells, Ex Vivo And In Vivo, Claudia Paindelli, Vanessa Parietti, Sergio Barrios, Peter Shepherd, Tianhong Pan, Wei-Lien Wang, Robert L Satcher, Christopher J Logothetis, Nora Navone, Matthew T Campbell, Antonios G Mikos, Eleonora Dondossola

Faculty, Staff and Student Publications

Bone metastases are the most common milestone in the lethal progression of prostate cancer and prominent in a substantial portion of renal malignancies. Interactions between cancer and bone host cells have emerged as drivers of both disease progression and therapeutic resistance. To best understand these central host-epithelial cell interactions, biologically relevant preclinical models are required. To achieve this goal, we here established and characterized tissue-engineered bone mimetic environments (BME) capable of supporting the growth of patient-derived xenograft (PDX) cells, ex vivo and in vivo. The BME consisted of a polycaprolactone (PCL) scaffold colonized by human mesenchymal stem cells (hMSCs) differentiated …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Effectiveness Of A Training Program For The Management Of Risky Alcohol Use In Primary Care Professionals Based On Motivational Interviewing, Celia Pérula-Jiménez, Esperanza Romero-Rodríguez, Juan Manuel Parras-Rejano, Ana González De La Rubia, Juan Baleato Gómez, Luis Angel Pérula De Torres

Faculty, Staff and Student Publications

OBJECTIVE: To assess the effectiveness of a training program for Primary Care (PC) professionals developed to increase knowledge, attitudes, and skills for managing patients with risky alcohol use and in the motivational interview.

DESIGN: Multicenter, two-arm parallel, randomized, open-label controlled clinical trial.

SETTING: PC of the Andalusian Health Service.

PARTICIPANTS: The study was completed by 80 healthcare professionals from 31 PC centers.

INTERVENTIONS: In both experimental and control groups, a workshop on managing patients with risky alcohol consumption and the resolution of two videotaped clinical cases with standardized patients were conducted. The experimental group attended a workshop on motivational interviewing. …

Machine Learning-Enabled Maternal Risk Assessment For Women With Pre-Eclampsia (The Piers-Ml Model): A Modelling Study, Tünde Montgomery-Csobán, Kimberley Kavanagh, Paul Murray, Chris Robertson, Sarah J E Barry, U Vivian Ukah, Beth A Payne, Kypros H Nicolaides, Argyro Syngelaki, Olivia Ionescu, Ranjit Akolekar, Jennifer A Hutcheon, Laura A Magee, Peter Von Dadelszen, Piers Consortium

Faculty, Staff and Student Publications

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia.

METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of …

Association Between Psychosocial Acuity And Glycemic Control In A Pediatric Type 1 Diabetes Clinic., Joseph Wardell, Dana K. Albright Phd, Claire Chang, Melissa A Plegue, Jung Eun Lee, Emily Hirschfeld, Ashley Garrity, Joyce M Lee, Melissa Dejonckheere

Health Services and Informatics Research

PURPOSE: The purpose of this study was to describe the frequency of psychosocial risk and its associations with glycemic levels in youth with type 1 diabetes (T1D) seen by social work staff during regular clinical care.

METHODS: A retrospective longitudinal analysis of observational clinical data was conducted. Individuals (1-26 years) with known T1D who were seen at a pediatric diabetes clinic in a US academic medical center between 2014 and 2021 were included. Variables included psychosocial acuity, A1C, and demographic characteristics. Chi-square tests, Wilcoxon rank sum tests, and mixed linear regressions were used to examine associations between demographic variables, psychosocial …

Reciprocal Relationships Between Stress And Depressive Symptoms: The Essential Role Of The Nucleus Accumbens, Yizhou Ma, Peter Kochunov, Mark D Kvarta, Tara Legates, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Eric L Goldwaser, Heather Bruce, Kathryn S Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E Nichols, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and …

Presentation Acuity And Surgical Outcomes For Patients With Health Insurance Living In Highly Deprived Neighborhoods, Susanne Schmidt, Michael A Jacobs, Jeongsoo Kim, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Importance: Insurance coverage expansion has been proposed as a solution to improving health disparities, but insurance expansion alone may be insufficient to alleviate care access barriers.

Objective: To assess the association of Area Deprivation Index (ADI) with postsurgical textbook outcomes (TO) and presentation acuity for individuals with private insurance or Medicare.

Design, setting, and participants: This cohort study used data from the National Surgical Quality Improvement Program (2013-2019) merged with electronic health record data from 3 academic health care systems. Data were analyzed from June 2022 to August 2023.

Exposure: Living in a neighborhood with an ADI greater than 85. …

Ems Treatment Guidelines In Major Traumatic Brain Injury With Positive Pressure Ventilation, Joshua B Gaither, Daniel W Spaite, Bentley J Bobrow, Bruce Barnhart, Vatsal Chikani, Kurt R Denninghoff, Gail H Bradley, Amber D Rice, Jeffrey T Howard, Samuel M Keim, Chengcheng Hu

Faculty, Staff and Student Publications

Importance: The Excellence in Prehospital Injury Care (EPIC) study demonstrated improved survival in patients with severe traumatic brain injury (TBI) following implementation of the prehospital treatment guidelines. The impact of implementing these guidelines in the subgroup of patients who received positive pressure ventilation (PPV) is unknown.

Objective: To evaluate the association of implementation of prehospital TBI evidence-based guidelines with survival among patients with prehospital PPV.

Design, setting, and participants: The EPIC study was a multisystem, intention-to-treat study using a before/after controlled design. Evidence-based guidelines were implemented by emergency medical service agencies across Arizona. This subanalysis was planned a priori and …

4r-Cembranoid Suppresses Glial Cells Inflammatory Phenotypes And Prevents Hippocampal Neuronal Loss In Lps-Treated Mice, Luis A Rojas-Colón, John B Redell, Pramod K Dash, Pedro E Vegas, Wanda Vélez-Torres

Faculty, Staff and Student Publications

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

Alk-Positive Histiocytosis Of External Auditory Canal In A 3-Year-Old Boy, Shu-Hsien Wang, Hsuan-Ying Huang, L Jeffrey Medeiros, Kung-Chao Chang

Faculty, Staff and Student Publications

No abstract provided.

A Randomized, Non-Comparative Phase 2 Study Of Neoadjuvant Immune-Checkpoint Blockade In Retroperitoneal Dedifferentiated Liposarcoma And Extremity/Truncal Undifferentiated Pleomorphic Sarcoma, Christina L Roland, Elise F Nassif Haddad, Emily Z Keung, Wei-Lien Wang, Alexander J Lazar, Heather Lin, Manoj Chelvanambi, Edwin R Parra, Khalida Wani, B Ashleigh Guadagnolo, Andrew J Bishop, Elizabeth M Burton, Kelly K Hunt, Keila E Torres, Barry W Feig, Christopher P Scally, Valerae O Lewis, Justin E Bird, Ravin Ratan, Dejka Araujo, M Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P Conley, J Andrew Livingston, Vinod Ravi, Hussein A Tawbi, Patrick P Lin, Bryan S Moon, Robert L Satcher, Bilal Mujtaba, Russell G Witt, Raymond S Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M Mohammad, Randy A Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A Wargo, Neeta Somaiah

Faculty, Staff and Student Publications

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

Automatic End-To-End Vmat Treatment Planning For Rectal Cancers, Kai Huang, Christine Chung, Ethan B Ludmir, Lifei Zhang, Constance A Owens, Jean Gumma-De La Vega, Jack Duryea, Yao Zhao, Xinru Chen, David Fuentes, Carlos E Cardenas, Tina Marie Briere, Sam Beddar, Laurence E Court, Prajnan Das

Faculty, Staff and Student Publications

BACKGROUND: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear.

PURPOSE: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs.

METHODS: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the …

Accuracy Of Influenza Icd-10 Diagnosis Codes In Identifying Influenza Illness In Children., James W. Antoon, Tess Stopczynski, Justin Z. Amarin, Laura S. Stewart, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Janet A. Englund, Eileen J. Klein, Mary A. Staat, Elizabeth P. Schlaudecker, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Ariana Perez, Heidi L. Moline, Andrew J. Spieker, Carlos G. Grijalva, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown.

OBJECTIVE: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings.

DESIGN, SETTING, AND PARTICIPANTS: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 …

Cranio-Cervical Abnormalities In Moderate-To-Severe Osteogenesis Imperfecta – Genotypic And Phenotypic Determinants, Juliana Marulanda, Jean-Marc Retrouvey, Brendan Lee, V Reid Sutton, Frank Rauch, Michelle Briner

Faculty, Staff and Students Publications

INTRODUCTION: Cranio-cervical anomalies are significant complications of osteogenesis imperfecta (OI), a rare bone fragility disorder that is usually caused by mutations in collagen type I encoding genes.

OBJECTIVE: To assess cranio-cervical anomalies and associated clinical findings in patients with moderate-to-severe OI using 3D cone beam computed tomography (CBCT) scans.

METHODS: Cross-sectional analysis of CBCT scans in 52 individuals with OI (age 10-37 years; 32 females) and 40 healthy controls (age 10-32 years; 26 females). Individuals with a diagnosis of OI type III (severe, n = 11), type IV (moderate, n = 33) and non-collagen OI (n = 8) were recruited …

Load703, An Oncolytic Virus-Based Immunostimulatory Gene Therapy, Combined With Chemotherapy For Unresectable Or Metastatic Pancreatic Cancer (Lokon001): Results From Arm 1 Of A Non-Randomised, Single-Centre, Phase 1/2 Study, Benjamin L Musher, Eric K Rowinsky, Brandon G Smaglo, Wasif Abidi, Mohamed Othman, Kalpesh Patel, Salmaan Jawaid, James Jing, Amanda Brisco, Ann M Leen, Mengfen Wu, Linda C Sandin, Jessica Wenthe, Emma Eriksson, Gustav J Ullenhag, Bambi Grilley, Justyna Leja-Jarblad, Susan G Hilsenbeck, Malcolm K Brenner, Angelica S I Loskog

Faculty, Staff and Students Publications

Background: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma.

Methods: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. …

Hepatocellular Carcinoma Screening In A Contemporary Cohort Of At-Risk Patients, Darine Daher, Karim Seif El Dahan, Nicole E Rich, Nabihah Tayob, Vincent Merrill, Daniel Q Huang, Ju Dong Yang, Anand V Kulkarni, Fasiha Kanwal, Jorge Marrero, Neehar Parikh, Amit G Singal

Faculty, Staff and Students Publications

IMPORTANCE: Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases.

OBJECTIVE: To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 …

Bringing Proteomics To Bear On Male Fertility: Key Lessons, Rachel Parkes, Thomas X Garcia

Faculty, Staff and Students Publications

Introduction: Male infertility is a major public health concern globally. Proteomics has revolutionized our comprehension of male fertility by identifying potential infertility biomarkers and reproductive defects. Studies comparing sperm proteome with other male reproductive tissues have the potential to refine fertility diagnostics and guide infertility treatment development.

Areas covered: This review encapsulates literature using proteomic approaches to progress male reproductive biology. Our search methodology included systematic searches of databases such as PubMed, Scopus, and Web of Science for articles up to 2023. Keywords used included 'male fertility proteomics,' 'spermatozoa proteome,' 'testis proteomics,' 'epididymal proteomics,' and 'non-hormonal male contraception.' Inclusion criteria …

Cognitive Outcomes Of Children With Sagittal Craniosynostosis Treated With Either Endoscopic Or Open Calvarial Vault Surgery, Suresh N Magge, Annahita R Fotouhi, Virginia Allhusen, Brent R Collett, Gary B Skolnick, Sybill D Naidoo, Matthew D Smyth, Robert F Keating, Raj Vyas, Gary F Rogers, Kamlesh B Patel

2020-Current year OA Pubs

IMPORTANCE: Several studies have reported a higher incidence of neurodevelopmental delays and cognitive deficits in patients with single-suture craniosynostosis; however, there are few studies examining the associations of repair type with cognitive outcomes.

OBJECTIVE: To measure differences in neuropsychological outcomes between school-age children who were treated for sagittal craniosynostosis and unaffected controls and explore differences in cognitive function among children with sagittal craniosynostosis who were previously treated with either endoscopic strip craniectomy or open calvarial vault surgery.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed between 2018 and 2022. Eligible participants included patients aged 5 to 17 years who …

Sensory Experiences Questionnaire Unravels Differences In Sensory Profiles Between Mecp2-Related Disorders, Bernhard Suter, Davut Pehlivan, Muharrem Ak, Holly K Harris, Ariel M Lyons-Warren

Faculty, Staff and Students Publications

The methyl CpG-binding protein-2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 …

Epigenetic Underpinnings Of Tumor-Immune Dynamics In Prostate Cancer Immune Suppression, Duminduni Hewa Angappulige, Nupam P Mahajan, Kiran Mahajan

2020-Current year OA Pubs

Prostate cancer (PC) is immunosuppressive and refractory to immunotherapy. Infiltration of myeloid-derived suppressor cells (MDSCs) and senescent-like neutrophils and T cell exhaustion are observed in the tumor microenvironment (TME) following androgen receptor (AR) antagonism with antiandrogens or androgen ablation. De novo post-translational acetylation of the AR, HOXB13, and H2A at K609, K13, and K130, respectively, and phosphorylation of H4 at Y88 have emerged as key epigenetic modifications associated with castration-resistant PC (CRPC). The resulting chromatin changes are integrated into cellular processes via phosphorylation of the AR, ACK1, ATPF1A, and SREBP1 at Y267, Y284, Y243/Y246, and Y673/Y951, respectively. In this review, …

An Oocyte-Specific Cas9-Expressing Mouse For Germline Crispr/Cas9-Mediated Genome Editing, Denise G Lanza, Jianqiang Mao, Isabel Lorenzo, Lan Liao, John R Seavitt, M Cecilia Ljungberg, Elizabeth M Simpson, Francesco J Demayo, Jason D Heaney

Faculty, Staff and Students Publications

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo …

Neural And Behavioural State Switching During Hippocampal Dentate Spikes, Jordan S Farrell, Ernie Hwaun, Barna Dudok, Ivan Soltesz

Faculty, Staff and Students Publications

Distinct brain and behavioural states are associated with organized neural population dynamics that are thought to serve specific cognitive functions^1–3. Memory replay events, for example, occur during synchronous population events called sharp-wave ripples in the hippocampus while mice are in an ‘offline’ behavioural state, enabling cognitive mechanisms such as memory consolidation and planning^4–11. But how does the brain re-engage with the external world during this behavioural state and permit access to current sensory information or promote new memory formation? Here we found that the hippocampal dentate spike, an understudied population event that …

Prescription And Dispensation Of Qt-Prolonging Medications In Individuals Receiving Hemodialysis, Virginia Wang, Chin-Hua Lily Wang, Magdalene M Assimon, Patrick H Pun, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

IMPORTANCE: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population.

OBJECTIVE: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis.

DESIGN, …