Digital Commons Network^™

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Rebecca Bernal, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Tumor Expression Of Cd83 Reduces Glioma Progression And Is Associated With Reduced Immunosuppression, Alexis Cervantes, Zhung-Fu Lee, Anna Rosenbaum, Peihao He, Carrie Mohila, Arif O Harmanci, Akdes Serin Harmanci, Benjamin Deneen, Ganesh Rao

Faculty, Staff and Student Publications

Immunosuppression in malignant glioma remains a barrier to therapeutic development. CD83 overexpression in human and mouse glioma increases survival. CD83+ tumor cells promote signatures related to cytotoxic T cells, enhanced activation of CD8+ T cells, and increased proinflammatory cytokines. These findings suggest that tumor-expressed CD83 could mediate tumor-immune communications.

Metaverse-Powered Basic Sciences Medical Education: Bridging The Gaps For Lower Middle-Income Countries., Syeda Samnita Batool Zaidi, Umer Adnan, Kadriye O. Lewis, Syeda Sadia Fatima

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Traditional medical education often lacks contextual experience, hindering students' ability to effectively apply theoretical knowledge in real-world scenarios. The integration of the metaverse into medical education holds great enormous promise for addressing educational disparities, particularly in lower-middle-income countries (LMICs) accompanied by rapid technological advancements. This commentary paper aimed to address the potential of the metaverse in enhancing basic sciences education within the constraints faced by universities in LMICs. We also addressed learning design challenges by proposing fundamental design elements and a suggested conceptual framework for developing metaverse-based teaching methods.The goal is to assist educators and medical practitioners in comprehensivley …

Responding To The Workforce Crisis: Consensus Recommendations From The Second Workforce Summit Of The American Society Of Pediatric Nephrology., Danielle E. Soranno, Sandra Amaral, Isa Ashoor, Meredith A. Atkinson, Gina-Marie Barletta, Michael C. Braun, Joann Carlson, Caitlin Carter, Annabelle Chua, Vikas R. Dharnidharka, Keri Drake, Elif Erkan, Dan Feig, Stuart L. Goldstein, David Hains, Lyndsay A. Harshman, Elizabeth Ingulli, Alexander J. Kula, Mary Leonard, Sudha Mannemuddhu, Shina Menon, Zubin J. Modi, Marva Moxey-Mims, Arwa Nada, Victoria Norwood, Michelle C. Starr, Priya S. Verghese, Darcy K. Weidemann, Adam Weinstein, Jodi Smith

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.

OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.

EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN …

Decreasing Endomyocardial Biopsy Frequency In Pediatric Heart Transplantation Using A Rejection Risk Prediction Score-A Single Center Study., Drishti Tolani, Ryan J. Butts, David Sutcliffe, Alyssa Power

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Rejection remains an important cause of morbidity and mortality after pediatric heart transplantation (HT). Endomyocardial biopsy (EMB) is the gold standard for rejection diagnosis, but it comes with procedural risk. The frequency of EMB varies significantly across centers. Since April 2018, our center's surveillance EMB schedule is based on a rejection risk prediction score employing age, pre-HT diagnosis, and panel reactive antibodies (PRA). We aimed to evaluate outcomes in the 1st year post-HT before and after risk score implementation.

METHODS: Patients who underwent HT at our center at ≤ 18 years of age from January 2015 to December 2020 …

Azacitidine As Epigenetic Priming For Chemotherapy Is Safe And Well-Tolerated In Infants With Newly Diagnosed Kmt2a-Rearranged Acute Lymphoblastic Leukemia: Children's Oncology Group Trial Aall15p1, Erin M. Guest, John A Kairalla, Meenakshi Devidas, Emily Hibbitts, Andrew J. Carroll, Nyla A. Heerema, Holly R. Kubaney, Margaret A. August, Sidharth Ramesh, Byunggil Yoo, Midhat S. Farooqi, Melinda G. Pauly, Daniel S. Wechsler, Rodney R. Miles, Joel M. Reid, Cynthia D. Kihei, Lia Gore, Elizabeth A. Raetz, Stephen P. Hunger, Mignon L. Loh, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of failure to achieve remission, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children's Oncology Group trial AALL15P1 tested the safety and tolerability of 5 days of azacitidine treatment immediately prior to the start of chemotherapy on day 6, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was well-tolerated, with only …

Delivery Of Hand Care To Patients With High Anxiety Burden, Caellagh D Catley, Sarah C Romans, Abby L Cheng, Ryan P Calfee

2020-Current year OA Pubs

PURPOSE: To determine whether patients presenting with Patient-Reported Outcome Measurement Information System (PROMIS) anxiety scores at >95th percentile of the US population undergo elective hand surgery at rates different from patients with less anxiety. Secondarily, we aimed to assess surgeon notation of these patients' emotional states and incidences of postoperative complications.

METHODS: This single-center retrospective cohort study analyzed data from new adult patients presenting for hand care between January 2019 and December 2020. Patients with initial PROMIS anxiety scores ≥70 were identified as the high anxiety burden (HAB) group. For each patient with HAB presenting with carpal tunnel syndrome, trigger …

Pain Interference Prior To And 1 Year After Surgery For Adult Traumatic Brachial Plexus Injury, Christopher J Dy, David M Brogan, Bryan J Loeffler, Steve K Lee, Harvey Chim, Mihir J Desai, Sami H Tuffaha, Yusha Liu, Planet Study Group

2020-Current year OA Pubs

PURPOSE: Pain after brachial plexus injury (BPI) can be severely debilitating and is poorly understood. We hypothesized that pain interference (PI) ("the extent to which pain hinders engagement in life") would be predicted by depression, anxiety, severity of pain symptoms, and poorer preoperative muscle function.

METHODS: Among patients in a prospective multicenter BPI cohort study, 37 completed Patient-Reported Outcomes Measurement Information System (PROMIS) PI questionnaires before and 1 year after surgery. At both times, participants completed anxiety and depression questionnaires and BPI-specific measures of pain symptoms, physical limitations, and emotional recovery. Surgeon-graded muscle testing, injury severity, age at the time …

Effect Of Screw Length In Volar Plating For Intra-Articular Distal Radius Fractures: A Biomechanical Study, Thomas S Hong, Daniel J Lee, Babak Jahani, Kaitlyn S Broz, Donald A Aboytes, Simon Tang, Stephen Demartini, David M Brogan

2020-Current year OA Pubs

PURPOSE: The purpose of this study was to compare the effect of varying screw lengths on load to failure and retention of the dorsal ulnar corner fragment after fixation of comminuted intra-articular distal radius fractures in a cadaveric model.

METHODS: Twenty-four fresh frozen cadaveric forearms were subjected to a standardized distal radius osteotomy to mimic an intra-articular fracture pattern. Dual X-ray absorptiometry scans were performed to ensure minimal variability in bone density. All fractures were fixed with a volar locking plate and distal locking screws. Three different lengths of distal locking screws were used in each group of eight specimens …

Molecular Imaging In Experimental Pulmonary Fibrosis Reveals That Nintedanib Unexpectedly Modulates Ccr2 Immune Cell Infiltration, Hasan Farooq, Hannah P Luehmann, Jeffrey R Koenitzer, Gyu Seong Heo, Deborah H Sultan, Devesha H Kulkarni, Sean P Gunsten, Rekha M Sashti, Tao Huang, Amanda R Keller, Kory J Lavine, Jeffrey J Atkinson, Laura M Wingler, Yongjian Liu, Steven L Brody

2020-Current year OA Pubs

BACKGROUND: Pulmonary fibrosis is a challenging clinical problem with lung pathology featuring immune cell infiltrates, fibroblast expansion, and matrix deposition. Molecular analysis of diseased lungs and preclinical models have uncovered C-C chemokine receptor type 2 (CCR2)+ monocyte egress from the bone marrow into the lung, where they acquire profibrotic activities. Current drug treatment is focused on fibroblast activity. Alternatively, therapeutic targeting and monitoring CCR2+ cells may be an effective patient management strategy.

METHODS: Inhibition of CCR2+ cells and, as a benchmark, the clinical antifibrotic agent, nintedanib, were used in mouse lung fibrosis models. Lungs were evaluated directly for CCR2+ cell …

Complex Emotion Processing And Early Life Adversity In The Healthy Brain Network Sample, Emily J Furtado, M Catalina Camacho, Jenna H Chin, Deanna M Barch

2020-Current year OA Pubs

OBJECTIVE: Early life adversity (ELA) has shown to have negative impacts on mental health. One possible mechanism is through alterations in neural emotion processing. We sought to characterize how multiple indices of ELA were related to naturalistic neural socio-emotional processing.

METHOD: In 521 5-15-year-old participants from the Healthy Brain Network Biobank, we identified scenes that elicited activation of the Default Mode Network (DMN), Ventral Attention Network (VAN), Cingulo-Opercular Network (CON) and amygdala, all of which are networks shown to be associated with ELA. We used linear regression to examine associations between activation and ELA: negative parenting, social status, financial insecurity, …

Disentangling The Unique Contributions Of Age, Pubertal Stage, And Pubertal Hormones To Brain Structure In Childhood And Adolescence, Mark Curtis, John C Flournoy, Sridhar Kandala, Ashley F P Sanders, Michael P Harms, Adam Omary, Leah H Somerville, Deanna M Barch

2020-Current year OA Pubs

Puberty and associated changes in pubertal hormones influence structural brain development. Hormones such as dehydroepiandrosterone (DHEA) and progesterone remain understudied, and it remains unclear how these aspects of puberty contribute uniquely to structural brain development. We used the Human Connectome Project in Development cross-sectional sample of 1304 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone to cortical thickness, surface area, and subcortical volume development within functionally-relevant networks. Sex and age explain the most unique variance in all three aspects of structural development. Pubertal stage and pubertal hormones uniquely contribute more …

Quantifying Brain Development In The Healthy Brain And Child Development (Hbcd) Study: The Magnetic Resonance Imaging And Spectroscopy Protocol, Douglas C Dean 3rd, Chad M Sylvester, Michael P Harms, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition …

Minority Stress Mediates Associations Of Sexual Minority State Policies And Tobacco Use Among Us Sexual Minority Young Adults, Katelyn F Romm, Erin A Vogel, Christina Dyar, Laurie A Drabble, Patricia A Cavazos-Rehg, Carla J Berg

2020-Current year OA Pubs

INTRODUCTION: State policies surrounding sexual minority (SM) rights are associated with tobacco use among SM individuals. Research is scant regarding the role of distinct SM policy categories on SM young adults' (SMYAs) tobacco use and mechanisms explaining these associations.

METHODS: We analyzed 2023 survey data from 1100 SMYAs (ages 18-34; 14.2 % gender minority; 66.1 % bisexual+, 29.1 % monosexual; 53.2 % racial/ethnic minority) with representation across 45 US states and DC. Regression-based models examined: 1) direct associations of residing in states with negative and limited (vs. comprehensive) SM state policies with respect to 7 policy categories (relationship/parent recognition, nondiscrimination, …

Tyk2 Regulates Tau Levels, Phosphorylation And Aggregation In A Tauopathy Mouse Model, Jiyoen Kim, Bakhos Tadros, Yan Hong Liang, Youngdoo Kim, Cristian Lasagna-Reeves, Jun Young Sonn, Dah-Eun Chloe Chung, Bradley Hyman, David M Holtzman, Huda Yahya Zoghbi

2020-Current year OA Pubs

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau …

Inferring Allele-Specific Copy Number Aberrations And Tumor Phylogeography From Spatially Resolved Transcriptomics, Cong Ma, Metin Balaban, Jingxian Liu, Siqi Chen, Michael J Wilson, Christopher H Sun, Li Ding, Benjamin J Raphael

2020-Current year OA Pubs

Analyzing somatic evolution within a tumor over time and across space is a key challenge in cancer research. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of spatial locations in a tumor, but does not directly reveal genomic aberrations. We introduce CalicoST, an algorithm to simultaneously infer allele-specific copy number aberrations (CNAs) and reconstruct spatial tumor evolution, or phylogeography, from SRT data. CalicoST identifies important classes of CNAs-including copy-neutral loss of heterozygosity and mirrored subclonal CNAs-that are invisible to total copy number analysis. Using nine patients' data from the Human Tumor Atlas Network, CalicoST achieves an average accuracy of …

Sitravatinib In Patients With Solid Tumors Selected By Molecular Alterations: Results From A Phase Ib Study, Lyudmila Bazhenova, Douglas R Adkins, Et Al.

2020-Current year OA Pubs

No abstract provided.

Dysfunctional Alpha Modulation As A Mechanism Of Working Memory Impairment In Serious Mental Illness, Molly A Erickson, Megan A Boudewyn, Kurt Winsler, Charlotte Li, Deanna M Barch, Cameron S Carter, Michael J Frank, James M Gold, Angus W Macdonald 3rd, John D Ragland, Steven M Silverstein, Andrew Yonelinas, Steven J Luck

2020-Current year OA Pubs

BACKGROUND: People with psychosis and mood disorders experience disruptions in working memory; however, the underlying mechanism remains unknown. We focused on 2 potential mechanisms: poor attentional engagement should be associated with elevated levels of prestimulus alpha-band activity within the electroencephalogram (EEG), whereas impaired working memory encoding should be associated with reduced poststimulus alpha suppression.

METHODS: We collected EEG data from 68 people with schizophrenia, 43 people with bipolar disorder with a history of psychosis, 53 people with major depressive disorder, and 90 healthy comparison subjects while they completed a spatial working memory task. We quantified attention lapsing, memory precision, and …

Pedicle Screw Placement In The Cervical Vertebrae Using Augmented Reality-Head Mounted Displays: A Cadaveric Proof-Of-Concept Study, Miguel A Ruiz-Cardozo, Karma Barot, Samuel Brehm, Tim Bui, Karan Joseph, Michael Ryan Kann, Gabriel Trevino, Michael Olufawo, Som Singh, Alexander T Yahanda, Alexander Perdomo-Pantoja, Magalie Cadieux, Camilo A Molina, Et Al.

2020-Current year OA Pubs

BACKGROUND: The accurate and safe positioning of cervical pedicle screws is crucial. While augmented reality (AR) use in spine surgery has previously demonstrated clinical utility in the thoracolumbar spine, its technical feasibility in the cervical spine remains less explored.

PURPOSE: The objective of this study was to assess the precision and safety of AR-assisted pedicle screw placement in the cervical spine.

STUDY DESIGN: In this experimental study, 5 cadaveric cervical spine models were instrumented from C3 to C7 by 5 different spine surgeons. The navigation accuracy and clinical screw accuracy were evaluated.

METHODS: Postprocedural CT scans were evaluated for clinical …

Radiation Oncology Opinions And Practice On Cardiotoxicity In Lung Cancer: A Cross-Sectional Study By The International Cardio-Oncology Society, G M Walls, J D Mitchell, A R Lyon, M Harbinson, G G Hanna

2020-Current year OA Pubs

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guidelines on practice.

MATERIALS AND METHODS: A bespoke questionnaire was designed following an extensive review of the …

Machine Learning-Augmented Interventions In Perioperative Care: A Systematic Review And Meta-Analysis, Divya Mehta, Xiomara T Gonzalez, Grace Huang, Joanna Abraham

2020-Current year OA Pubs

BACKGROUND: We lack evidence on the cumulative effectiveness of machine learning (ML)-driven interventions in perioperative settings. Therefore, we conducted a systematic review to appraise the evidence on the impact of ML-driven interventions on perioperative outcomes.

METHODS: Ovid MEDLINE, CINAHL, Embase, Scopus, PubMed, and ClinicalTrials.gov were searched to identify randomised controlled trials (RCTs) evaluating the effectiveness of ML-driven interventions in surgical inpatient populations. The review was registered with PROSPERO (CRD42023433163) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was conducted for outcomes with two or more studies using a random-effects model, and vote …

Correlating Clinical Course With Baseline Subcortical Shape In Provisional Tic Disorder, Tiffanie Che, Soyoung Kim, Deanna J Greene, Ashley Heywood, Jimin Ding, Tamara Hershey, Bradley L Schlaggar, Kevin J Black, Lei Wang

2020-Current year OA Pubs

OBJECTIVE: This study examined children at the onset of tic disorder (tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the baseline shape and volume of subcortical nuclei, diagnosis, and tic symptom outcomes.

METHODS: 187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 with chronic tic disorder/Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic …

Pet Clinical Study Of Novel Antipsychotic Lb-102 Demonstrates Unexpectedly Prolonged Dopamine Receptor Target Engagement, Dean F Wong, Ganesh B Chand, Nicole Caito, Anna Eramo, Vincent T Grattan, Mark S Hixon, Ginger Nicol, Erin Lessie, Zachary Prensky, Hiroto Kuwabara, Lucy Tian, Ines Valenta, Thomas H Schindler, Gerhard Gründer, Andrew R Vaino

2020-Current year OA Pubs

Regulation of dopamine activity has important clinical consequences, most notably in schizophrenia. LB-102, N-methyl amisulpride, is a novel dopamine D

Volumetric Breast Density Estimation From Three-Dimensional Reconstructed Digital Breast Tomosynthesis Images Using Deep Learning, Vinayak S Ahluwalia, Nehal Doiphode, Walter C Mankowski, Eric A Cohen, Sarthak Pati, Lauren Pantalone, Spyridon Bakas, Ari Brooks, Celine M Vachon, Emily F Conant, Aimilia Gastounioti, Despina Kontos

2020-Current year OA Pubs

PURPOSE: Breast density is a widely established independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from two-dimensional (2D) images acquired using DBT and/or depend on the existence of raw DBT data, which is rarely archived by clinical centers because of storage constraints.

METHODS: We retrospectively analyzed 1,080 nonactionable three-dimensional (3D) reconstructed DBT screening examinations acquired between 2011 and 2016. Reference tissue segmentations were generated using previously validated software that uses 3D reconstructed slices …

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Cancer And Leukemia Group B-Southwest Oncology Group 80702 (Alliance), Justin C Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M Goldberg, Eileen M O'Reilly, Anthony F Shields, Jeffrey A Meyerhardt

2020-Current year OA Pubs

BACKGROUND: Inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown.

METHODS: This cohort study was nested within the Cancer and Leukemia Group B (now part of the Alliance for Clinical Trials in Oncology) and Southwest Oncology Group randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free …

Cxcr3-Cxcl11 Signaling Restricts Angiogenesis And Promotes Pericyte Recruitment, Jihui Lee, Megan E. Goeckel, Allison Levitas, Sarah Colijn, Jimann Shin, Anna Hindes, Geonyoung Mun, Zarek Burton, Bharadwaj Chintalapati, Ying Yin, Javier Abello, Lilianna Solnica-Krezel, Amber N. Stratman

2020-Current year OA Pubs

BACKGROUND: Endothelial cell (EC)-pericyte interactions are known to remodel in response to hemodynamic forces; yet there is a lack of mechanistic understanding of the signaling pathways that underlie these events. Here, we have identified a novel signaling network regulated by blood flow in ECs-the chemokine receptor CXCR3 (CXC motif chemokine receptor 3) and one of its ligands, CXCL11 (CXC motif chemokine ligand 11)-that delimits EC angiogenic potential and promotes pericyte recruitment to ECs during development.

METHODS: We investigated the role of CXCR3 on vascular development using both 2- and 3-dimensional in vitro assays, to study EC-pericyte interactions and EC behavioral …

A Genetically Inducible Endothelial Niche Enables Vascularization Of Human Kidney Organoids With Multilineage Maturation And Emergence Of Renin Expressing Cells, Joseph C Maggiore, Haojia Wu, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. …

Mucosal Single-Cell Profiling Of Crohn's-Like Disease Of The Pouch Reveals Unique Pathogenesis And Therapeutic Targets, Siyan Cao, Khai M Nguyen, Kaiming Ma, Xiaotang Du, Xiuli Liu, Alina Ulezko Antonova, Richard P Rood, Anas Gremida, Chien-Huan Chen, Alexandra Gutierrez, Deborah C Rubin, Martin H Gregory, Mate Gergely, Guadalupe Oliva Escudero, Katherine Huang, Natalia Jaeger, Marina Cella, Rodney D Newberry, Nicholas O Davidson, Matthew A Ciorba, Parakkal Deepak, Marco Colonna

2020-Current year OA Pubs

BACKGROUND & AIMS: The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses.

METHODS: Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently …

Kras Mutations In Endometrial Cancers: Possible Prognostic And Treatment Implications, Karolina A Kilowski, Martin F Dietrich, Joanne Xiu, Yasmine Baca, Andrew Hinton, Sarfraz Ahmad, Thomas J Herzog, Premal Thaker, Robert W Holloway

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options.

METHODS: A molecular database of 7870 ECs was queried for presence of oncogenic mutations and immunotherapy biomarkers. Comparisons were performed using Fisher-Exact/ChiSquare (p-values) and adjusted for multiple tests by Benjamini-Hochberg (q) and …

Acral Fibrochondromyxoid Tumor: A Clinicopathologic And Molecular Genetic Study Of 37 Cases, Carina A Dehner, Jonathan C Baker, John S A Chrisinger, Et Al.

2020-Current year OA Pubs

Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent THBS1::ADGRF5 fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that …