Digital Commons Network^™

Transgenerational Obesity Modulation Of Gut Mucosal Immunity, Chen-Ting Hung, Justin Kern, Tihana Trsan, Santosh K Panda, Marie Laury, Umang Jain, Marco Colonna, Thaddeus S Stappenbeck, Ta-Chiang Liu

2020-Current year OA Pubs

The prevalence of obesity in the United States has continued to increase over the past several decades. A growing concern is that transgenerational effects of obesity negatively impact physiologic functions. We showed that consumption of a high fat, high sugar "Western" diet (WD) decreased the density of both gut innate (Paneth cells) and adaptive immune cells (intraepithelial lymphocytes; IEL). We asked whether consumption of WD impacts gut mucosal immunity in the offspring. WD-mediated Paneth cell loss was reversible, whereas IEL loss was not. However, the overall composition of the fecal microbiome and response to infection were defined by the diet …

Clinical Profile Of Patients With Monocular Elevation Deficiency Undergoing Strabismus Surgery, Mohamad Reza Akbari, Babak Masoomian, Elham Azizi, Mohammed Omer Mahmood, Arash Mirmohammadsadeghi, Ali Majdi, Masoud Khorrami-Nejad

Wills Eye Hospital Papers

PURPOSE: To provide a comprehensive evaluation of the visual, refractive, and strabismic characteristics of patients with monocular elevation deficiency (MED) undergoing strabismus surgery.

METHODS: The medical records of patients at a single institution who were diagnosed with and underwent surgery for MED were reviewed retrospectively. Visual acuity, refractive error, angle of deviation, abnormal head posture (AHP), presence of ptosis, prevalence of amblyopia and strabismic patterns were analyzed, with MED eyes compared with fellow eyes.

RESULTS: A total of 105 patients were included. Mean cylindrical refractive error was significantly higher in MED eyes compared with fellow eyes (-1.40 ± 1.70 D …

Integrated Metabolomics And Spatial Transcriptomics Of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism As A Biomarker Of Progression, Ricardo A León-Letelier, Yihui Chen, Rongzhang Dou, Ehsan Irajizad, Michele T Yip-Schneider, Ranran Wu, Rahmah Ejaz, Hamid K Rudsari, Yaxi Li, Rachelle Spencer, Riccardo Ballarò, Jody Vykoukal, Mark Hurd, Jennifer B Dennison, Kim-Anh Do, Anirban Maitra, Jianjun Zhang, Samir Hanash, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

Purpose: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMNs.

Experimental design: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade (LG) dysplasia or high-grade (HG) dysplasia with/without concurrent pancreatic ductal adenocarcinoma (PDAC; IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared with CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMNs.

Results: …

Azacitidine, Venetoclax, And Magrolimab In Newly Diagnosed And Relapsed Refractory Acute Myeloid Leukemia: Phase Ib/Ii Study And Correlative Analysis, Naval Daver, Jayastu Senapati, Hagop M Kantarjian, Bofei Wang, Patrick K Reville, Sanam Loghavi, Musa Yilmaz, Courtney D Dinardo, Tapan M Kadia, Mhd Yousuf Yassouf, Abhishek Maiti, Sankalp Arora, Guillermo Montalban Bravo, Guilin Tang, Gautam Borthakur, Koji Sasaki, Naveen Pemmaraju, Joie Alvarez, Graciela M Nogueras Gonzalez, Jing Ning, Ghayas C Issa, Marina Konopleva, Michael Andreeff, Farhad Ravandi, Guillermo Garcia-Manero, Hussein A Abbas

Faculty, Staff and Student Publications

Purpose: Magrolimab is a monoclonal antibody directed against the macrophage checkpoint CD47 on myeloid leukemia cells that was preclinically synergistic with azacitidine-venetoclax, warranting further clinical evaluation.

Patients and methods: In this phase Ib/II study, the triplet combination of azacitidine, venetoclax, and magrolimab was evaluated in adult patients with first-line (ineligible for intensive chemotherapy) and relapsed/refractory acute myeloid leukemia. Azacitidine was dosed at 75 mg/m2 for 7 days, venetoclax at 400 mg/day for 28 days, and magrolimab (recommended phase II dose) as follows: 1 mg/kg dose on days 1 and 4, 15 mg/kg on day 8, and 30 mg/kg on days …

Time Dependency For Human Papillomavirus Circulating Tumor Dna Detection After Chemoradiation As A Prognostic Biomarker For Localized Anal Cancer, Van K Morris, Weihong Xiao, Kangyu Lin, Chi Wut Wong, Michael T Wotman, Emma B Holliday, Ryan W Huey, Sonal S Noticewala, Ethan B Ludmir, Alisha H Bent, Kaysia Ludford, Craig Messick, Eugene J Koay, Grace Smith, Tsuyoshi Konishi, Brian Bednarski, George J Chang, Albert C Koong, Y Nancy You, Prajnan Das, Maura L Gillison

Faculty, Staff and Student Publications

Purpose: Although detection of ctDNA weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined.

Experimental design: Patients with stages I to III anal cancer treated with chemoradiation between December 2020 and March 2024 were evaluated for human papillomavirus (HPV) ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay, targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was …

Mapping Vascular Network Architecture In Primate Brain Using Ferumoxytol-Weighted Laminar Mri, Joonas A Autio, Ikko Kimura, Takayuki Ose, Yuki Matsumoto, Masahiro Ohno, Yuta Urushibata, Takuro Ikeda, Matthew F Glasser, David C Van Essen, Takuya Hayashi

2020-Current year OA Pubs

Mapping the vascular organization of the brain is of great importance across various domains of basic neuroimaging research, diagnostic radiology, and neurology. However, the intricate task of precisely mapping vasculature across brain regions and cortical layers presents formidable challenges, resulting in a limited understanding of neurometabolic factors influencing the brain's microvasculature. Addressing this gap, our study investigates whole-brain vascular volume using ferumoxytol-weighted laminar-resolution multi-echo gradient-echo imaging in macaque monkeys. We validate the results with published data for vascular densities and compare them with cytoarchitecture, neuron and synaptic densities. The ferumoxytol-induced change in transverse relaxation rate (ΔR

Role Of Glucuronoxylomannan And Steryl Glucosides In Protecting Against Cryptococcosis, Gabriel Soares Matos, Tamara L Doering, Et Al.

2020-Current year OA Pubs

The development of vaccines for fungal diseases, including cryptococcosis, is an emergent line of research and development. In previous studies, we showed that a

Hematopoietic Stem Cell Transplantation Outcomes For High-Risk Aml: A Report From The Children's Oncology Group., Benjamin J. Huang, Lauren K. Meyer, Todd A. Alonzo, Yi-Cheng Wang, Adam J. Lamble, Rhonda E. Ries, Weijie Wang, Betsy Hirsch, Gordana Raca, Xiaotu Ma, Alan S. Gamis, Richard Aplenc, E Anders Kolb, Todd M. Cooper, Katherine Tarlock, Michael R. Loken, Soheil Meshinchi, Joseph H. Chewning, William G. Woods, John T. Horan

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Hematopoietic stem cell transplantation (HSCT) is used as consolidation for pediatric patients with high-risk AML in first complete remission (CR1). The definition of high-risk AML has evolved considerably over the past two decades with the successive identification of new unfavorable risk factors. We conducted a cross-study analysis to determine whether HSCT improves the outcomes of patients with contemporarily defined high-risk AML.

METHODS: We combined data from AAML0531 and AAML1031, the last two phase III clinical trials completed by the Children's Oncology Group (COG). These two trials established the prognostic importance of measurable residual disease (MRD) and several high-risk cryptic …

Real-World Outcomes For Young Adult Patients Receiving Cd19 Car T-Cell Therapy., Hannah Lust, Liora M. Schultz, Soyang Kwon, Gregory W. Roloff, Ibrahim Aldoss, Christina Baggott, Samuel John, Jenna E. Rossoff, Kevin O. Mcnerney, Vanessa A. Fabrizio, Julie-An Talano, Amy Moskop, Kevin J. Curran, Christine L. Phillips, Nicole Karras, Susanne H C Baumeister, Stacy L. Cooper, Michelle Hermiston, Prakash Satwani, Muna Qayed, Sunil S. Raikar, Margaret Macmillan, Erin Hall, Khanh Nguyen, Ryan D. Cassaday, Noam E. Kopmar, Vamsi K. Kota, John Mathews, Paul Shaughnessy, Marc S. Schwartz, Abdullah Ladha, George Yaghmour, Muthu V. Kumaran, Veronika Bachanova, Sean Tracy, Tamer Othman, Marlise R. Luskin, Evan C. Chen, Anjani S. Advani, Nikeshan Jeyakumar, Katharine Miller, Amy Zhang, Katherine C. Sutherland, Bijal D. Shah, Lori Muffly, Rawan Faramand

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 chimeric antigen receptor T-cell therapy (CAR T) products for young adults (YA) with relapsed/refractory B-cell acute lymphoblastic leukemia. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Using retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe the efficacy and safety of tisa-cel and brexu-cel in 70 YAs (18-26 years; tisa-cel, n = 50; brexu-cel, n = 20). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed more frequently …

Olfaction And Plasma Biomarkers Of Alzheimer Disease And Neurodegeneration In The Atherosclerosis Risk In Communities Study, Srishti Shrestha, Xiaoqian Zhu, Michael E Griswold, Priya Palta, Kevin J Sullivan, Honglei Chen, Andrea Lauren Christman Schneider, Abhay Moghekar, Megan L Grove, Bharat Thyagarajan, James Russell Pike, Rebecca F Gottesman, B Gwen Windham, Thomas H Mosley, Jennifer A Deal, Vidyulata Kamath

Faculty, Staff and Student Publications

Background and objectives: Investigation of olfactory impairment, an early manifestation of Alzheimer disease (AD), in relation to plasma biomarkers of AD and neurodegeneration could provide insights into the disease's pathophysiology. Because few such studies based on large, diverse, community-based populations exist, we investigated associations of odor identification ability with plasma biomarkers of AD and other neurodegenerative pathologies in community-dwelling Black and White older adults.

Methods: This cross-sectional investigation included participants from the Atherosclerosis Risk in Communities study who attended visit 5 (2011-2013) and who completed olfactory testing and brain MRI examinations and had plasma biomarkers measured (namely, amyloid-beta [Aβ]42/Aβ40 ratio, …

Enhancing Dementia Classification For Diverse Demographic Groups: Using Vision Transformer-Based Continuous Scoring Of Clock Drawing Tests., Mengyao Hu, Yi Lu Murphey, Tian Qin, Edmundo R Melipillán, Laura B Zahodne, Richard Gonzalez, Vicki A Freedman

Faculty, Staff and Student Publications

Objectives: Alzheimer's disease and related dementias significantly affect older adults' quality of life. The clock-drawing test (CDT) is a widely used dementia screening tool due to its ease of administration and effectiveness. However, manual CDT-coding in large-scale studies can be time-intensive and prone to coding errors and is typically limited to ordinal responses. In this study, we developed a continuous CDT score using a deep learning neural network (DLNN) and evaluated its ability to classify participants as having dementia or not.

Methods: Using a nationally representative sample of older adults from the National Health and Aging Trends Study (NHATS), we …

Application Of Claims-Based Frailty Index To A Structured Electronic Health Record Data, Min Ji Kwak, Caroline Schaefer, Youngran Kim, Sunyang Fu, Chan Mi Park, Abhijeet Dhoble, Nahid Rianon, Holly M Holmes, Dae Hyun Kim

Faculty, Staff and Student Publications

Background: The Claims-based Frailty Index (CFI) has been developed and validated using Medicare claims data. However, whether CFI can be applied to structured electronic health record data has not been studied.

Methods: We applied the CFI to a structured electronic health record dataset (Explorys dataset) and a Medicare fee-for-service 5% sample data and compared the prevalence of frailty from each dataset, using the cohort of older adults. Then, we assessed the odds ratio and area under the curve of the frailty predicting adverse clinical outcomes, any hospital or emergency room visit, or any adverse drug events related encounter within 1 …

Structure-Function Coupling In The First Month Of Life: Associations With Age And Attention, Ursula A Tooley, Jeanette K Kenley, M Catalina Camacho, Aidan Latham, Dimitrios Alexopoulos, Ashley N Nielsen, Tara A Smyser, Barbara B Warner, Joshua S Shimony, Jeffrey J Neil, Joan L Luby, Deanna M Barch, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

How brain structure relates to function is a critical and open question in neuroscience. Here, we characterize regional variation in structure-function coupling, capturing the degree to which a cortical region's structural connections relate to patterns of coordinated neural activity in healthy, term-born neonates (

High Prevalence Of Co-Infections With Latent Tuberculosis, Syphilis And Hepatitis B And C Among People With Hiv In Ghana: A Call For Integrating Screening Into Routine Care, Helena Lamptey, James Odame Aboagye, Christopher Zaab-Yen Abana, Anthony Twumasi Boateng, Ephraim Mawufemor Kofi Kanda, Dzidzor Aku Attoh, Araba Abaidoo-Myles, Charlotte Borteley Bortey, Jonathan Klutse, Peter Puplampu, Gloria Ansa, Vincent Jessey Ganu, Joseph Oliver-Commey, Evelyn Yayra Bonney, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: People with HIV (PWH) are at risk of co-infections, such as latent tuberculosis (LTBI), hepatitis B (HBV), hepatitis C (HCV), and syphilis; hence, routine screening is critical. However, evaluation of routine screening is not being fully implemented in Ghana. This study assessed the prevalence of these co-infections among PWH in Accra, Ghana.

METHODS: The HIV Cure Research Infrastructure Study (H-CRIS) followed 390 PWH from three HIV treatment centres in Accra. A cross-sectional study was conducted within this cohort, and participants were screened for LTBI, hepatitis B, hepatitis C, and syphilis using standardized assays. LTBI was detected using the QuantiFERON-TB …

Lrrc8 Channel Complexes Counterbalance Katp Channels To Mediate Swell-Secretion Coupling In Mouse Pancreatic Β Cells, Tarek Mohamed Abd El-Aziz, Chen Kang, Litao Xie, John D. Tranter, Sumit Patel, Rahul Chadda, Maria S. Remedi, Rajan Sah

2020-Current year OA Pubs

Insulin secretion from pancreatic β cells is initiated by membrane potential depolarization, followed by activation of voltage-gated Ca2+ channels to trigger Ca2+-mediated insulin vesicle fusion with the β cell plasma membrane. Here, we show that β cell swelling associated with glucose metabolism was sensed by LRRC8 channel complexes and contributed to insulin secretion. Hypertonic perfusate (360-380 mOsm) dose dependently impaired glucose-stimulated insulin secretion by counteracting β cell swelling. Hypotonic perfusate alone, independent of glucose stimulation or KATP channel closure, was sufficient to increase β cell intracellular Ca2+ and trigger insulin secretion. Inhibition of sodium-potassium-chloride cotransporter-1 with bumetanide, which diminished the …

What Happens To Conservatively Managed Chronic Subdural Haematoma., J Read, E Edlmann

Peninsula Medical School

Background: Chronic subdural haematoma (CSDH) is a common neurosurgical problem, increasingly prevalent due to an ageing population. Conservative management is an option for asymptomatic or mild cases, though data on outcomes is limited. Aim/Objective: This study aims to address critical gaps in understanding around conservatively managedCSDH and whether there are features that can predict progression and the longer-term prognosis of these patients. Methods: A retrospective cohort study was performed at a major trauma centre in the UK. All patients with chronic subdural haematoma referred from March 2019 to March 2021 were included and grouped into surgical or conservative management. Demographic, …

Rewired M6a Of Promoter Antisense Rnas In Alzheimer’S Disease Regulates Neuronal Genes In 3d Nucleome, Benxia Hu, Yuqiang Shi, Feng Xiong, Yi-Ting Chen, Xiaoyu Zhu, Elisa Carrillo, Xingzhao Wen, Nathan Drolet, Chetan Singh Rajpurohit, Xiangmin Xu, Dung-Fang Lee, Claudio Soto, Sheng Zhong, Vasanthi Jayaraman, Hui Zheng, Wenbo Li

Faculty, Staff and Student Publications

N6-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both mRNAs and various noncoding RNAs. Notably, many promoter-antisense RNAs (paRNAs) displayed cell-type-specific expression and changes in AD, including one produced adjacent to MAPT that encodes the Tau protein. MAPT-paRNA is highly expressed …

The Effect Of Birthweight And Gestational Age On Cognitive Function In Midlife: The Bogalusa Heart Study, Eunsun Gill, David J Libon, Soo Jung Kang, Ileana De Anda-Duran, Lydia A Bazzano, Wei Chen, Camilo Fernandez-Alonso, Emily W Harville

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Although the relationships between birthweight, gestational age (GA), and cognitive function (CF) before midlife have been demonstrated, the relationships after midlife and potential racial disparities remain inconclusive. This study examined the association between birthweight, GA, and midlife CF stratified by race.

METHOD: 1,032 subjects from the Bogalusa Heart Study (67% Whites, 33% Blacks, mean age 48.1 ± 5.3 years) were studied. Cognition was assessed with tests measuring verbal episodic memory, working memory, attention, graphomotor information processing speed, and global CF. Each test was standardized by sex and age, then averaged. The global CF was computed by averaging all cognitive …

Senescence Caused By Telomerase Inactivation In Myeloid, Mesenchymal, And Endothelial Cells Has Distinct Effects On Cancer Progression, Joseph Rupert, Zhanguo Gao, Yongmei Yu, Mikhail G Kolonin

Faculty, Staff and Student Publications

The effects of cell senescence in individual cell populations of the tumor microenvironment (TME) on cancer progression remain unclear. Here, we investigated the effects of cell senescence caused by inactivation of the catalytic subunit of telomerase (Tert) in distinct TME components. We generated genetic Tert knockout (KO) mice driven by the LysM promoter in myeloid cells, by the Pdgfra or Pdgfrb promoter in mesenchymal cells, and by the Tie2e promoter in endothelial cells. We compared the effect of the Tert KOs in syngeneic models of orthotopically grafted E0771 breast adenocarcinoma, RM1 prostate adenocarcinoma, and KPC pancreatic adenocarcinoma. Tumors in LysM-Tert …

Variants In Bsn, Encoding The Presynaptic Protein Bassoon, Result In A Distinct Neurodevelopmental Disorder With A Broad Phenotypic Range, Stacy G Guzman, Sarah M Ruggiero, Shiva Ganesan, Colin A Ellis, Alicia G Harrison, Katie R Sullivan, Zornitza Stark, Natasha J Brown, Sajel L Kana, Anabelle Tuttle, Jair Tenorio, Pablo Lapunzina, Julián Nevado, Marie T Mcdonald, Courtney Jensen, Patricia G Wheeler, Lila Stange, Jennifer Morrison, Boris Keren, Solveig Heide, Meg W Keating, Kameryn M Butler, Mike A Lyons, Shailly Jain, Mehdi Yeganeh, Michelle L Thompson, Molly Schroeder, Hoanh Nguyen, Jorge Granadillo, Kari M Johnston, Chaya N Murali, Katie Bosanko, T Andrew Burrow, Chop Birth Defects Biorepository, Penn Medicine Biobank, Syreeta Morgan, Deborah J Watson, Hakon Hakonarson, Ingo Helbig

Faculty, Staff and Students Publications

Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders (NDDs) and epilepsy. Here, we describe 14 individuals with de novo disruptive variants in BSN, which encodes the presynaptic protein Bassoon. To expand the phenotypic spectrum, we identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks. Clinical features were standardized using the Human Phenotype Ontology (HPO) across all 29 individuals, which revealed common clinical characteristics including epilepsy (13/29, 45%), febrile seizures (7/29, 25%), generalized tonic-clonic seizures (5/29, 17%), and focal-onset seizures (3/29, 10%). Behavioral phenotypes were present in almost half of all individuals (14/29, 48%), …

Loss Of Function Of The Zinc Finger Homeobox 4 Gene, Zfhx4, Underlies A Neurodevelopmental Disorder, María Del Rocío Pérez Baca, María Palomares-Bralo, Michiel Vanhooydonck, Lisa Hamerlinck, Eva D'Haene, Sebastian Leimbacher, Eva Z Jacobs, Laurenz De Cock, Erika D'Haenens, Annelies Dheedene, Zoë Malfait, Lies Vantomme, Ananilia Silva, Kathleen Rooney, Xiaonan Zhao, Amir Hossein Saeidian, Nichole Marie Owen, Fernando Santos-Simarro, Roser Lleuger-Pujol, Sixto García-Miñaúr, Itsaso Losantos-García, Björn Menten, Gaia Gestri, Nicola Ragge, Bekim Sadikovic, Elke Bogaert, Kris Vleminckx, Thomas Naert, Delfien Syx, Bert Callewaert, Sarah Vergult

Faculty, Staff and Students Publications

8q21.11 microdeletions involving ZFHX4 have previously been associated with a syndromic form of intellectual disability, hypotonia, unstable gait, and hearing loss. We report on 63 individuals-57 probands and 6 affected family members-with protein-truncating variants (n = 41), (micro)deletions (n = 21), or an inversion (n = 1) affecting ZFHX4. Probands display variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis. The phenotypes associated with 8q21.11 microdeletions and ZFHX4 intragenic loss-of-function (LoF) variants largely overlap, although leukocyte-derived DNA shows a mild …

Psilocybin's Acute And Persistent Brain Effects: A Precision Imaging Drug Trial, Subha Subramanian, Travis Rick Reneau, Demetrius Perry, Ravi Chacko, Timothy O Laumann, Karin Flavin, Christine Horan, Julie Schweiger, Nicholas Metcalf, Eric J Lenze, Abraham Z Snyder, Nico U F Dosenbach, Ginger Nicol, Joshua S Siegel

2020-Current year OA Pubs

Psilocybin (PSIL) is a psychedelic drug and a promising experimental therapeutic for many psychiatric conditions. Precision functional mapping (PFM) combines densely repeated resting state fMRI sampling and individual-specific network mapping to improve signal-to-noise ratio (SNR) and effect size in brain imaging research. We present a randomized cross-over study in which PFM was used to characterize acute and persistent effects of psilocybin or methylphenidate (MTP) on brain networks. Seven healthy volunteers (mean age 34.1 years, SD = 9.8; n = 3 females, n = 6 Caucasians) underwent (1) extensive baseline imaging, (2) imaging beginning 60-90 minutes after drug exposure, and (3) …

Career Impact Of The National Interprofessional Fellowship In Patient Safety: An Alumni Evaluation, Bradley V Watts, Kathleen Carluzzo, Blake F Webb, Kelley Arredondo

Faculty, Staff and Students Publications

Background: There has been a proliferation of health professions training programmes focused on quality and patient safety, but little information regarding the outcomes of these programmes. The purpose of this study was to examine the impact of an interprofessional quality and patient safety curriculum on career outcomes of interprofessional healthcare learners for the Veterans Affairs Patient Safety Fellowship.

Method: We conducted a survey-based assessment of 117 alumni of the Interprofessional Fellowship in Patient Safety assessing their satisfaction with the training program and career impacts.

Results: 84 of 117 alumni were located and participated in the assessment. Fellows entered the training …

Linking Dna Methylation In Brain Regions To Alzheimer’S Disease Risk: A Mendelian Randomization Study, Hua Zhong, Jingjing Zhu, Shuai Liu, Dan Zhou, Quan Long, Chong Wu, Bingxin Zhao, Chao Cheng, Yaohua Yang, Qing Wu, Yong Wu, Changwei Li, Zhaoming Wang, Jianyong Wu, Xingyi Guo, Degui Zhi, Youping Deng, Lang Wu

Faculty, Staff and Students Publications

Aim: DNA methylation in brain regions represents a potential mechanism linking genetic variation to Alzheimer's disease (ad) risk, yet most studies have focused on blood-derived methylation markers. In this study, we conducted a systematic Mendelian randomization (MR) study to evaluate associations between predicted brain region-specific DNA methylation levels and ad risk, using methylation quantitative trait loci (mQTL) as genetic instruments.

Methods: We analyzed mQTLs from five human brain regions: cerebellum (CRBLM), frontal cortex (FCTX), causal pons (PONS), and temporal cortex (TCTX) from 600 individuals in Gibbs et al's study, as well as mQTLs from dorsolateral prefrontal cortex (DLPFC) of 543 …

Mesenchymal Stem Cells And Fibroblasts Contribute To Microvascular Proliferation In Glioblastoma And Are Correlated With Immunosuppression And Poor Outcome, Candice C Poon, Shelley M Herbrich, Yulong Chen, Anwar Hossain, Gregory N Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynnette M Phillips, Joy Gumin, Zhong He, Brittany C Parker Kerrigan, Sanjay K Singh, Pratishtha Singh, Mohammed Fayyad Zaman, Derek Ng Tang, Sangeeta Goswami, Frederick F Lang, Padmanee Sharma

Faculty, Staff and Student Publications

Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma and other World Health Organization grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP are controversial and remain unclear. In this study, we performed single-cell RNA sequencing on paired CD45-CD105+ vascular/perivascular stromal cells (PVSC) and CD45+CD105± immune cells from 16 primary glioma patient samples, both with and without MVP. This analysis revealed the presence of developmentally related mesenchymal stem cells alongside cancer-associated fibroblasts, pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA …

Cross-Sectional Analysis Of Wound-Associated Soluble Factors In Early, Established, And Chronic Wounds Of Recessive Dystrophic Epidermolysis Bullosa Patients, Vitali Alexeev, Leonie Huitema, Taylor Phillips, Paras Patel, Mauricio Garza, Franziska Ringpfeil, Julio Salas-Alanis, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Poorly healing wounds represent the primary health-related burden for hereditary recessive dystrophic epidermolysis bullosa (RDEB) patients. Contribution of wound-associated soluble constituents to wound progression remains not well defined.

OBJECTIVE: To conduct cross-sectional analysis of cytokine, chemokine, and growth factor in exudates from RDEB wounds and define changes associated with wound progression.

METHODS: Concentrations of selected cytokines, chemokines, and growth factors were evaluated by multiplex ELISA in eight blister fluids and 66 exudates from early, established, and chronic RDEB and five chronic venous ulcers (VU). A cross-sectional analysis was performed.

RESULTS: Our data demonstrated that proinflammatory CXCL8 and IL-1β tend …

Impact Of Sociodemographic Determinants On Enrollment Into Contemporary Lymphoma Clinical Trials: A Systematic Review, Jun Yang Jiang, Ang Li, Alexis Romero, Christopher R Flowers, Chijioke Nze

Faculty, Staff and Students Publications

While the incidence and survival associated with lymphoma have improved in recent years, outcome disparities related to sociodemographic factors such as age, sex, race, ethnicity, socioeconomic status (SES), and other social determinants of health (SDOH) remain prevalent in the modern era. Clinical trials are crucial for further improving outcomes, yet not all sociodemographic groups are equally represented in contemporary lymphoma trials. We conducted a systematic review of the literature evaluating the impact of SDOH on enrollment into clinical trials in the United States and identified 21 relevant studies. We confirmed that Black and Hispanic individuals are underrepresented in lymphoma clinical …

Prediction Of Methotrexate Neurotoxicity Using Clinical, Sociodemographic, And Area-Based Information In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, Maria Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown

Center for Medical Ethics and Health Policy Staff Publications

Background: Methotrexate is a critical component of pediatric acute lymphoblastic leukemia (ALL) therapy that can result in neurotoxicity which has been associated with an increased risk of relapse. We leveraged machine learning to develop a neurotoxicity risk prediction model in a diverse cohort of children with ALL.

Methods: We included children (age 2-20 years) diagnosed with ALL (2005-2019) and treated in Texas without pre-existing neurologic disease. Clinical information was obtained by medical record review. Neurotoxicity occurring post-induction and prior to maintenance therapy was defined as neurologic episodes occurring within 21 days of methotrexate. Suspected cases were independently confirmed by 2 …

Lipoprotein(A) And Heart Failure Among Black And White Participants In Atherosclerosis Risk In Communities Study, Framingham Offspring Study, And Multi-Ethnic Study Of Atherosclerosis: The Pooling Project, Sarah Nomura, Weihua Guan, Yixin Zhang, Geoffrey H Tison, Hiroaki Ikezaki, Margaret R Diffenderfer, Ching-Ti Liu, Ron C Hoogeveen, Christie M Ballantyne, Ernst J Schaefer, Michael Y Tsai

Faculty, Staff and Students Publications

Background: This study investigated Lp(a) (lipoprotein(a)) levels with heart failure (HF) incidence overall and ejection fraction (EF) subtypes among Black and White participants in a pooled analysis of MESA (Multi-Ethnic Study of Atherosclerosis), FOS (Framingham Offspring Study), and ARIC (Atherosclerosis Risk in Communities Study).

Methods: This study was conducted among 16 771 White and Black participants in ARIC (N=10 347), MESA (N=4150), and FOS (N=2274). Baseline was time of Lp(a) measurement (ARIC Visit 4: 1996-1998; MESA Visit 1: 2000-2002; FOS Cycle 6: 1995-1998). HF with reduced EF (HFrEF) was defined as EF < 50% and ≥50% as HF with preserved EF (HFpEF). Cox proportional hazards regression was used to evaluate associations between Lp(a) (log-transformed continuous, dichotomized at ≥30 mg/dL and ≥50 mg/dL, and quartiles) and HF (overall, HFpEF, HFrEF) in the overall population and stratified by race. Analyses were replicated excluding prior history of myocardial infarction.

Results: There were 2759 HF cases (HFpEF N=859; …

Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn

Department of Surgery Faculty Papers

INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …