Digital Commons Network^™

The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino

Center on Aging Staff Publications

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues …

Defining Lipedema’S Molecular Hallmarks By Multi-Omics Approach For Disease Prediction In Women, Leon G Straub, Jan-Bernd Funcke, Nolwenn Joffin, Chanmin Joung, Sara Al-Ghadban, Shangang Zhao, Qingzhang Zhu, Ilja L Kruglikov, Yi Zhu, Paul R Langlais, Ruth Gordillo, Karen L Herbst, Philipp E Scherer

Children’s Nutrition Research Center Staff Publications

Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Clonal Evolution Of Hematopoietic Stem Cells After Autologous Stem Cell Transplantation, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Linda Zhang, Jennifer Padilla, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi

Faculty, Staff and Student Publications

The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other chemotherapeutic agents had minimal effects. Consequently, the clonal diversity and architecture of post-treatment HSPCs resemble those observed in normal elderly individuals, particularly through the progression of oligoclonal hematopoiesis, thereby suggesting that chemotherapy accelerates clonal aging. Integrated …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …

C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol

Duncan NRI Faculty and Staff Publications

Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …

Reduced Risk Of Cesarean Delivery With Oxytocin Discontinuation In Active Labor: A Systematic Review And Meta-Analysis, Julia Whitley, Julia Burd, Michelle Doering, Jeannie Kelly, Antonina Frolova, Nandini Raghuraman

2020-Current year OA Pubs

OBJECTIVE: Our objective was to determine if oxytocin discontinuation in the active phase of labor impacts the rate of cesarean delivery compared to continuation of oxytocin.

DATA SOURCES: This study was a systematic review and meta-analysis of randomized controlled trials. A research librarian performed a database search using a combination of standardized terms and keywords related to oxytocin discontinuation and stages of labor from database inception until February 2024. This protocol was registered in The International Prospective Register of Systematic Reviews (PROSPERO).

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of pregnant patients who received oxytocin for induction or augmentation of labor, …

Fetal Body Composition And Organ Volume Trajectories In Association With Maternal Perceived Stress Or Depressive Symptoms In The Fetal 3d Study, Alexandra Jean-Louis, Jessica L Gleason, Zhen Chen, Kathryn A Wagner, William A Grobman, Roger B Newman, Wesley Lee, Robert Gore-Langton, Seth Sherman, John Owen, Deborah A Wing, Daniel W Skupski, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Objectives: Evaluate associations between maternal perceived stress and depressive symptoms, and fetal body composition and organ volumes.

Methods: In the NICHD Fetal 3D Study (2015-2019; n = 2457), stress and depressive symptoms were assessed at enrollment (10-13 weeks). High stress was defined as a Perceived Stress Scale (PSS) score ≥15 and high depressive symptoms, defined as an Edinburgh Postnatal Depression Scale (EPDS) score ≥10. Fetal body composition and organ volumes (cerebellar, lung, liver, and kidney) were measured up to five times between 15 and 40 weeks using three-dimensional (3D) ultrasound technology. Trajectories of body composition and organ volumes across pregnancy …

Distinct Patterns Of Weight Gain, Age, And Subcortical Microstructure In Early Adolescence, Shana Adise, Zhaolong Adrian Li, Jonatan Ottino-González, Filip Morys, Peter A Chiarelli, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Associations between childhood obesity and brain microstructural differences have been observed. It remains unknown whether these associations are driven by sex-specific excessive weight gain. Restriction spectrum imaging characterizes brain tissue microstructural health via water diffusion, where the restricted normalized isotropic (RNI) compartment assesses neuronal and glial cellularity, which may reflect neuroinflammation, synaptic pruning, or both.

OBJECTIVE: To identify associations among RNI scaling factor values, normal neurodevelopment, and weight gain during early adolescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study, a 10-year, ongoing, multisite longitudinal cohort study conducted among youths …

Genetic Structuring And Estimation Of Reproductive Adults In Onchocerca Volvulus: A Genome-Wide Analysis Across Hosts And Regions, Pawan Kumar, Young-Jun Choi, Kerstin Fischer, Shannon M. Hedtke, Anusha Kode, Nicholas Opoku, Lincoln Gankpala, Tony O. Ukety, Jöel Lonema Mande, Timothy J. C. Anderson, Warwick N. Grant, Peter U. Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Genomic analysis of parasites can deepen our understanding of their transmission, population structure, and important biological characteristics. Onchocerciasis (river blindness), caused by the parasitic nematode Onchocerca volvulus, involves adult worms residing in subcutaneous nodules that produce larval-stage microfilariae (mf), which are routinely detected in the skin for diagnosis. Whole-genome studies of mf are limited; most analyses have focused on the mitochondrial genome. We conducted a genome-wide analysis with 94% median nuclear genome coverage, analyzing 171, 37, and 98 mf from 16, 3, and 5 individuals from Ghana, Liberia, and the Democratic Republic of Congo, respectively. These data were used to …

Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker

Faculty, Staff and Students Publications

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …

Diagnostic Accuracy Of Screening Tools For Depression And Anxiety In Cervical Dystonia, Davide Martino, Mehrafarin Ramezani, Steven Bellows, Brian D Berman, Florence Ching-Fen Chang, Jeanne Feuerstein, Victor Fung, Gamze Kilic Berkmen, Irene A Malaty, Claire Maciver, Scott A Norris, Kathryn J Peall, Joel S Perlmutter, Sarah Pirio Richardson, Laura J Wright, Zahra Goodarzi, Hyder A Jinnah

Faculty, Staff and Students Publications

Introduction: Despite their high prevalence and impact, depression and anxiety are not routinely screened for, and accuracy of screening procedures is unknown in adult-onset dystonia. We evaluated accuracy parameters of selected self-rated scales for depression and anxiety in patients with idiopathic cervical dystonia (CD).

Methods: Two-hundred-and-ten patients with idiopathic CD were recruited from 10 movement disorders centers from the US, Canada, Australia, and UK. At the end of each botulinum toxin cycle, participants were administered the Adult Standard Mini-International Neuropsychiatric Interview (MINI) as reference standard for depression and anxiety. Participants completed 8 self-administered index instruments (2 for depression, 2 for …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

Mass Spectrometry Imaging Reveals Alterations In Protein And N-Glycan Molecular Signatures In Endometriosis Tissues, Monica Lin, Erin H Seeley, Suzanne Ledet, Christina Salazar, Michael T Breen, Livia S Eberlin

Faculty, Staff and Students Publications

Endometriosis is a gynecological condition characterized by the uncontrolled growth of endometrial-like tissue outside the uterine cavity. Although highly prevalent, the biological mechanisms of endometriosis are poorly understood, and the disease is often misdiagnosed due to the unavailability of pre-operative diagnostic methods. Thus, better characterization of molecular markers of endometriosis are critical to improve our understanding of the disease and management of patients. Here, we used matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) imaging to investigate protein and N-glycan molecular signatures in eutopic endometrium and endometriosis lesions from tissues prospectively collected from patients. MALDI MS imaging of intact proteins …

Mayo Normative Studies: Regression-Based Normative Data For Remote Self-Administration Of The Stricker Learning Span, Symbols Test, And Mayo Test Drive Screening Battery Composite And Validation In Individuals With Mild Cognitive Impairment And Dementia, Nikki H Stricker, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

No abstract provided.

Projection-Tags Enable Multiplex Projection Tracing And Multi-Modal Profiling Of Projection Neurons, Lite Yang, Fang Liu, Hannah Hahm, Takao Okuda, Xiaoyue Li, Yufen Zhang, Vani Kalyanaraman, Monique R Heitmeier, Vijay K Samineni

2020-Current year OA Pubs

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain-wide projections. However, investigating the complex wiring diagram, spatial organization, transcriptional, and epigenetic landscapes of brain-wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons in female mice. Projection-TAGs can be leveraged …

Gut Virome Profile In New Onset Treatment Naïve Saudi Children With Ulcerative Colitis, Mohammad El Mouzan, Tor C Savidge, Ahmed Al Sarkhy, Shyam Badu, Badr Alsaleem, Mohammad Al Mofarreh, Abdullah Almasood, Asaad Assiri

Faculty, Staff and Students Publications

Background: Gut microbiome imbalance is well established in ulcerative colitis (UC) in Western populations. Significantly less is known about the gut virome and whether geography impacts the UC-associated microbiome. The aim of this study was to characterize gut bacteriophage changes, as well as to identify phage-bacterial associations that can serve as potential biomarkers of UC.

Methods: Twenty children with UC and 20 healthy controls were enrolled in the study. Inclusion criteria included newly diagnosed treatment-naïve children with UC with no antibiotic exposure for at least six months prior to sample collection. Deoxyribonucleic acid (DNA) was extracted from stool and rectal …

Identification Of Distinct Biological Groups Of Patients With Cryptogenic Norse Via Inflammatory Profiling, Martin Guillemaud, Mario Chavez, Firas Kobeissy, Annamaria Vezzani, Anthony D Jimenez, Maysaa Merhi Basha, Ayush Batra, Sophie Demeret, Onome Eka, Krista Eschbach, Brandon Foreman, Nicolas Gaspard, Elizabeth E Gerard, Teneille Emma Gofton, Hiba A Haider, Stephen T Hantus, Charles L Howe, Amy Jongeling, Mariel Kalkach-Aparicio, Padmaja Kandula, Karnig Kazazian, Minjee Kim, Yi-Chen Lai, Clémence Marois, Andrew Mellor, Wazim Mohamed, Mikaela Morales, Cederic M Pimentel, Alexandra M Ramirez, Claude Steriade, Aaron F Struck, Olga Taraschenko, Nathan Torcida Sedano, Mark S Wainwright, Ji Yeoun Yoo, Kevin K W Wang, Vincent Navarro, Lawrence J Hirsch, Aurélie Hanin

Faculty, Staff and Students Publications

Background and objectives: Emerging evidence suggests that immune dysregulation plays a pivotal role in triggering cryptogenic new-onset refractory status epilepticus (c-NORSE), prompting a consensus on early initiation of immunotherapy. However, despite similar timing of administration, responses to immunotherapies have been varied and unpredictable, suggesting the presence of heterogeneous underlying mechanisms. The aim of this study was to identify distinct inflammatory response subtypes in patients with c-NORSE by analyzing their cytokine profiles. Insights into underlying mechanisms were sought to understand the pathophysiology and guide personalized therapies to improve patient outcomes.

Methods: Sixty-two patients with c-NORSE were included. A comprehensive panel …

Inhibition Of Srebp-1c Rescues Hepatic Cyp7b1 Expression And Bile Acid Synthesis In Malnourished Mice, Xiaoyang Wan, Krishnakant G Soni, Jong Min Choi, Sun Yun Jung, Margaret E Conner, Geoffrey A Preidis

Faculty, Staff and Students Publications

Malnutrition decreases intestinal bile acids, resulting in inefficient nutrient absorption and impaired catch-up growth. Mechanisms by which bile acid depletion occurs in malnutrition are unknown. Using a mouse model of early-life malnutrition, we explored bile acid homeostasis, focusing on transcriptional repression of CYP7B1, a rate-limiting enzyme in the alternative pathway of bile acid biosynthesis, by SREBP-1c, a master regulator of lipid metabolism. Mice were maintained on a low-protein low-fat or isocaloric control chow until eight weeks of age when livers were harvested for proteome profiling, western blot, RT-qPCR, and chromatin immunoprecipitation. Cultured hepatocytes and mice were treated with the SREBP-1c …

Medications To Reduce Breast Cancer Risk: A Network Meta-Analysis Of Randomized Controlled Trials, Ghazaleh Pourali, Minglu Liu, Supriya S Sherpa, Angela Hardi, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Given the rising incidence of breast cancer, especially in premenopausal women, there is an urgent need to identify additional risk-reducing medications to accelerate prevention, as only a few are currently approved. We, therefore, performed network meta-analysis (NMA) to identify and compare the efficacy of medications for primary breast cancer prevention.

METHODS: We performed a literature search completed on November 16, 2023, in Embase, Ovid-Medline, Scopus, and Cochrane Library for randomized controlled trials (RCTs) evaluating risk-reducing medications in women without a history of invasive breast cancer. Two reviewers independently screened and extracted data based on predefined criteria, following the Preferred …

Effect Of A Pay-It-Forward Strategy On Reducing Hpv Vaccine Delay And Increasing Uptake Among 15- To 18-Year-Old Girls In China: A Randomized Controlled Trial, Jing Li, Elvin H. Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Catch-up human papillomavirus (HPV) vaccination is challenging in many low- and middle-income countries (LMICs). Pay-it-forward offers an individual a subsidized vaccine, then an opportunity to donate to help others access vaccinations. Our randomized control trial assessed the effectiveness of pay-it-forward in improving HPV vaccination among girls aged 15-18 years in China.

METHODS AND FINDINGS: This study was conducted from July 6, 2022, to June 9, 2023, in four community health centers (CHCs) in Chengdu, western China. Eligible participants were unvaccinated girls living in the service areas of CHCs. Participants were initially recruited via telephone and, after providing verbal consent, …

Eculizumab Treatment Of Tacrolimus-Associated Autoimmune Haemolytic Anaemia And Thrombotic Microangiopathy In A Child With Orthotopic Heart Transplant, Daniel Pike, Monica Hulbert, Alicia Kamsheh

2020-Current year OA Pubs

BACKGROUND: Tacrolimus is the standard immunosuppressant used in paediatric orthotopic heart transplantation, but it can be associated with rare and life-threatening haemolysis.

METHODS: Retrospective chart review was used for this case report.

RESULTS/CONCLUSION: We present the case of a 6-year-old heart transplant recipient who developed life-threatening haemolysis in the setting of mycoplasma infection while on tacrolimus immunosuppression that was treated successfully with eculizumab.

Where Should The Cancer Control Interventions Target: A Geospatial Hotspot Analysis For Major Cancer Mortality 2018 To 2022 In The United States, Chongliang Luo, Saira Khan, Liyan Jin, Aimee S James, Graham A Colditz, Bettina F Drake

2020-Current year OA Pubs

BACKGROUND: Identifying changes in geographic disparities of cancer mortality reveals locations where cancer prevention and control efforts should be focused/targeted. We use recent cancer surveillance data to demonstrate the geographic disparity of major cancer mortality rates in the United States and its shift compared with previous data.

METHODS: This cross-sectional study used the 2018 to 2022 county-level mortality rates of colorectal, lung, breast, and prostate cancers from the Centers for Disease Control mortality data. Counties with suppressed death counts were imputed by spatial regression models. Getis-Ord Gi* statistics were used to evaluate the spatial clustering of county mortality. Identified hotspot …

Dna Methylation Epitypes Of Burkitt Lymphoma With Distinct Molecular And Clinical Features, Nicole Thomas, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

UNLABELLED: The genetic subtypes of Burkitt lymphoma have been defined, but the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by the Epstein-Barr virus status or mutation status, leading to two epitypes described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression, and mutational differences between the epitypes …

Integrating Nonindividual Patient Features In Machine Learning Models Of Hospital-Onset Bacteremia, M Cristina Vazquez-Guillamet, Jingwen Zhang, Alice Bewley, Andrew Atkinson, Heidi Holtz, Ziqian Wang, Nicole Brougham, Chenyang Lu, Marin H Kollef, Philip Payne, David Warren, Victoria J Fraser

2020-Current year OA Pubs

IMPORTANCE: Hospital-onset bacteremia and fungemia (HOB) are common and potentially preventable complications of hospital care.

OBJECTIVE: To assess whether nonindividual patient features, which summarize interactions with other patients and health care workers (HCWs), can contribute to predictive and causal machine learning models for HOB.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study included adult patients admitted to Barnes-Jewish Hospital, an academic hospital in St Louis, Missouri, in 2021. Analyses were developed between October 2023 and August 2024 and in April 2025.

EXPOSURE: Individual patient features were extracted from electronic health records and used to engineer nonpatient features, including interactions with HCWs …

Postoperative Delirium In Older Adults Undergoing Noncardiac Surgery, Heather L Lander, Andrew W Dick, Karen E Joynt Maddox, Mark A Oldham, Lee A Fleisher, Michael Mazzeffi, Stewart J Lustik, Jingjing Shang, Patricia W Stone, Marjorie S Gloff, Jacob Nadler, Isaac Wu, Raymond Zollo, Laurent G Glance

2020-Current year OA Pubs

IMPORTANCE: Understanding the association of postoperative delirium with adverse outcomes and the hospital-level variation of postoperative delirium is important for efforts to improve perioperative brain health.

OBJECTIVE: To examine (1) the association of postoperative delirium with 30-day mortality and complications and (2) hospital-level variation in postoperative delirium.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study examined hospitalizations among patients aged 65 years and older who underwent noncardiac surgery in US hospitals between January 1, 2017, and December 31, 2020. Data were analyzed between August 28, 2024, and April 10, 2025.

EXPOSURE: Postoperative delirium.

MAIN OUTCOMES AND MEASURES: The association of …

First-Trimester Antibiotic Use For Urinary Tract Infection And Risk Of Congenital Malformations, Sarah S Osmundson, Katelin B Nickel, Susan M. Shortreed, Sascha Dublin, Dustin Stwalley, Michael J Durkin, Paige D Wartko, John M Sahrmann, Ryan Colvin, Anne M Butler

2020-Current year OA Pubs

IMPORTANCE: Clinical guidelines recommend screening and treating bacteriuria in early pregnancy given that urinary tract infections (UTIs) can cause serious maternal and neonatal consequences. Evidence regarding antibiotic exposure during early pregnancy and risk of congenital malformations is limited and inconsistent.

OBJECTIVE: To compare the risk of congenital malformations following first-trimester exposure to different antibiotic agents used to treat UTI.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included commercially insured pregnant individuals aged 15 to 49 years who were treated for UTI and linked liveborn infants in the Merative MarketScan Commercial Database (2006-2022).

EXPOSURE: First-trimester antibiotic prescription fill of nitrofurantoin, …

History Of Hypoxia Exposure Aids Future Cell Invasion According To Cell Type And Collagen Density, José A Almeida, Diego B Avila, Gregory D Longmore, Amit Pathak

2020-Current year OA Pubs

In cancer progression, tumor microenvironments (TME) progressively become denser and hypoxic, and cell migrate toward higher oxygen levels as they invade across the tumor-stromal boundary. Although cell invasion dependence on optimal collagen density is well appreciated, it remains unclear whether past oxygen conditions alter future invasion phenotype of cells. Here, we show that normal human mammary epithelial cells (MCF10A) and leader-like human breast tumor cells (BT549) undergo higher rates of invasion and collagen deformation after past exposure to hypoxia, compared with normoxia controls. Upon increasing collagen density by ∼50%, cell invasion under normoxia reduced, as expected due to the increased …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Antonina I Frolova, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

OBJECTIVE: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Molecular Profile Of Adult Primary Leptomeningeal Gliomatosis Aligns With Glioblastoma, Idh-Wildtype, Yi Zhu, Darin D Carabenciov, Derek R Johnson, Jorge A Trejo-Lopez, Aivi T Nguyen, Aditya Raghunathan, Giuseppe Lanzino, Cristiane M Ida, Cinthya J Zepeda-Mendoza, Surendra Dasari, Emilie Russler-Germain, Sonika Dahiya, Martha Quezado, Kenneth Aldape, Caterina Giannini

2020-Current year OA Pubs

Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH-wildtype, …