Medical Specialties Commons^™

Genetic Studies Of Paired Metabolomes Reveal Enzymatic And Transport Processes At The Interface Of Plasma And Urine, Pascal Schlosser, Nora Scherer, Franziska Grundner-Culemann, Sara Monteiro-Martins, Stefan Haug, Inga Steinbrenner, Burulça Uluvar, Matthias Wuttke, Yurong Cheng, Arif B Ekici, Gergely Gyimesi, Edward D Karoly, Fruzsina Kotsis, Johanna Mielke, Maria F Gomez, Bing Yu, Morgan E Grams, Josef Coresh, Eric Boerwinkle, Michael Köttgen, Florian Kronenberg, Heike Meiselbach, Robert P Mohney, Shreeram Akilesh, Gckd Investigators, Miriam Schmidts, Matthias A Hediger, Ulla T Schultheiss, Kai-Uwe Eckardt, Peter J Oefner, Peggy Sekula, Yong Li, Anna Köttgen

Faculty, Staff and Students Publications

The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the …

Physiological Age By Artificial Intelligence-Enhanced Electrocardiograms As A Novel Risk Factor Of Mortality In Kidney Transplant Candidates, Elizabeth C Lorenz, Isabella Zaniletti, Bradley K Johnson, Tanya M Petterson, Walter K Kremers, Carrie A Schinstock, Hatem Amer, Andrea L Cheville, Nathan K Lebrasseur, Wolfgang C Winkelmayer, Sankar D Navaneethan, Abraham Baez-Suarez, Zachi I Attia, Francisco Lopez-Jimenez, Paul A Friedman, Cassie C Kennedy, Andrew D Rule

Faculty, Staff and Students Publications

BACKGROUND: Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality.

METHODS: We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality.

RESULTS: Of the 2183 patients evaluated, 59.1% were male, …

A Short-Term Method To Evaluate Anti-Leishmania Drugs By Inhibition Of Stage Differentiation In Leishmania Mexicana Using Flow Cytometry, Christian Florian Teh-Poot, Victor Manuel Dzul-Huchim, Jonathan M Mercado, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Kathryn M Jones, Francis T F Tsai, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Leishmaniasis is a vector-borne neglected tropical disease caused by the Leishmania spp. Parasite. The disease is transmitted to humans and animals by the bite of infected female sandflies during the ingestion of bloodmeal. Because current drug treatments induce toxicity and parasite resistance, there is an urgent need to evaluate new drugs. Most therapeutics target the differentiation of promastigotes to amastigotes, which is necessary to maintain Leishmania infection. However, in vitro assays are laborious, time-consuming, and depend on the experience of the technician. In this study, we aimed to establish a short-term method to assess the differentiation status of Leishmania mexicana …

Long Non-Coding Rnas: Definitions, Functions, Challenges And Recommendations, John S Mattick, Paulo P Amaral, Piero Carninci, Susan Carpenter, Howard Y Chang, Ling-Ling Chen, Runsheng Chen, Caroline Dean, Marcel E Dinger, Katherine A Fitzgerald, Thomas R Gingeras, Mitchell Guttman, Tetsuro Hirose, Maite Huarte, Rory Johnson, Chandrasekhar Kanduri, Philipp Kapranov, Jeanne B Lawrence, Jeannie T Lee, Joshua T Mendell, Timothy R Mercer, Kathryn J Moore, Shinichi Nakagawa, John L Rinn, David L Spector, Igor Ulitsky, Yue Wan, Jeremy E Wilusz, Mian Wu

Faculty, Staff and Students Publications

Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates …

A Multisite Retrospective Review Of Direct Oral Anticoagulants Compared To Warfarin In Adult Fontan Patients, Amir Kazerouninia, Justin Georgekutty, Payton Kendsersky, Ryan D Byrne, Brendan Seto, Patricia Y Chu, Yunfei Wang, Fred H Rodriguez, Clayton Smith, Anita Saraf, Michael S Lloyd, Benjamin P Frischhertz, Dhaval R Parekh, Peter R Ermis, Wayne J Franklin, Wilson W Lam

Faculty, Staff and Students Publications

PURPOSE: Direct oral anticoagulants (DOACs) are not recommended in adult Fontan patients (Level of Evidence C). We hypothesized that DOACs are comparable to warfarin and do not increase thrombotic and embolic complications (TEs) or clinically significant bleeds.

METHODS: We reviewed the medical records of adult Fontan patients on DOACs or warfarin at three major medical centers. We identified 130 patients: 48 on DOACs and 107 on warfarin. In total, they were treated for 810 months on DOACs and 5637 months on warfarin.

RESULTS: The incidence of TEs in patients on DOACs compared to those on warfarin was not increased in …

The Impact Of Covid-19 On A Large Pragmatic Clinical Trial Embedded In Primary Care, Sarah M Leatherman, Cynthia Hau, Alison Klint, Peter A Glassman, Addison A Taylor, Ryan E Ferguson, William C Cushman, Areef Ishani

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic had significant impact on clinical care and clinical trial operations, but the impact on decentralized pragmatic trials is unclear. The Diuretic Comparison Project (DCP) is a Point-of Care (POC) pragmatic trial testing whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular (CV) events and non-cancer death. DCP utilized telephone consent, data collection from the electronic health record and Medicare, forwent study visits, and limited provider commitment beyond usual care. We assessed the impact of COVID-19 on recruitment, follow-up, data collection, and outcome ascertainment in DCP.

METHODS: We compared data from two 8-month periods: Pre-Pandemic (July …

Pediatric Swine Model Of Methicillin-Resistant Staphylococcus Aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, And Organ Injuries, Trung C Nguyen, Juan C Marini, Bobby Guillory, Christian Valladolid-Brown, Marina Martinez-Vargas, Deepika Subramanyam, Daniel Cohen, Sonya C Cirlos, Fong Lam, Barbara Stoll, Inka C Didelija, Caitlin Vonderohe, Renan Orellana, Arun Saini, Subhashree Pradhan, Dalia Bashir, Moreshwar S Desai, Saul Flores, Manpreet Virk, Hossein Tcharmtchi, Amir Navaei, Sheldon Kaplan, Linda Lamberth, Kristina G Hulten, Brooks P Scull, Carl E Allen, Ayse Akcan-Arikan, K Vinod Vijayan, Miguel A Cruz

Faculty, Staff and Students Publications

Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant

HYPOTHESIS: Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours.

METHODS AND MODELS: Ten 3 weeks old piglets, implanted with telemetry devices for continuous hemodynamic monitoring, were IV injected with MRSA (

RESULTS: Compared with the saline treated piglets (control), the septic piglets within 24 hours had significantly lower neurologic and respiratory scores. Over time, PT, d-dimer, and fibrinogen increased, while platelet counts and activities of factors …

Endovascular Exclusion Of Ascending Aortic Pseudoaneurysm With An Experimental Ascending Aortic Stent-Graft, Chibueze Onyemkpa, Joseph S Coselli

Faculty, Staff and Students Publications

No abstract provided.

Robotic Ivor-Lewis Esophagectomy In 15 Steps, Bryan M Burt, Mark Onaitis

Faculty, Staff and Students Publications

The technique of robotic Ivor-Lewis esophagectomy with intracorporeal anastomosis is demonstrated in 15 steps. Each step is outlined by short text and narrated video segments. The case demonstrated is a gentleman with a clinical stage T3 N1 M0 distal esophageal adenocarcinoma who underwent neoadjuvant chemotherapy and radiotherapy.

Commentary On "Mini-Open Intercostal Retroperitoneal Approach For Upper Lumbar Spine Lateral Interbody Fusion", Alexander E Ropper

Faculty, Staff and Students Publications

No abstract provided.

Cost-Effective Microscopic Draping: Covid-19 Umbrella, Yusif Hajiyev, Ronald J Vilela

Faculty, Staff and Students Publications

We describe a cost-effective solution to limit aerosol transmission to the surgeon and other personnel in the operating room during otologic surgery.

Splendid Isolation, Dimitrios Laurin Wagner, Maksim Mamonkin

Faculty, Staff and Students Publications

No abstract provided.

Synapse-Specific Changes In Arc And Bdnf In Rat Hippocampus Following Chronic Temporal Lobe Epilepsy, Daniel L Egbenya, Suleman Hussain, Yi-Chen Lai, Anne E Anderson, Svend Davanger

Faculty, Staff and Students Publications

Expression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brai Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE). Western blotting showed reduced concentrations of Arc and increased concentrations of BDNF in hippocampal synaptosomes in chronic TLE rats. Then, using quantitative electron microscopy, we …

A Primer For The Student Joining The Adult Cardiac Surgery Service Tomorrow: Primer 1 Of 7, Rohun Bhagat, Mary A Siki, Nicholas Anderson, Lena Trager, Edgar Aranda-Michel, Daniel Ziazadeh, Ashley Choi, John A Treffalls, Valentino Bianco, Clauden Louis, David Blitzer, Marc R Moon

Faculty, Staff and Students Publications

No abstract provided.

A Scalable Platform For Fabricating Biodegradable Microparticles With Pulsatile Drug Release, Tyler P Graf, Sherry Yue Qiu, Dhruv Varshney, Mei-Li Laracuente, Erin M Euliano, Pujita Munnangi, Brett H Pogostin, Tsvetelina Baryakova, Arnav Garyali, Kevin J Mchugh

Faculty, Staff and Students Publications

Pulsatile drug delivery systems have the potential to improve patient adherence and therapeutic efficacy by providing a sequence of doses in a single injection. Herein, a novel platform, termed Particles Uniformly Liquified and Sealed to Encapsulate Drugs (PULSED) is developed, which enables the high-throughput fabrication of microparticles exhibiting pulsatile release. In PULSED, biodegradable polymeric microstructures with an open cavity are formed using high-resolution 3D printing and soft lithography, filled with drug, and sealed using a contactless heating step in which the polymer flows over the orifice to form a complete shell around a drug-loaded core. Poly(lactic-co-glycolic acid) particles with this …

Imaging Of Pediatric Calvarial And Skull Base Tumors: A Cog Diagnostic Imaging Committee/Spr Oncology Committee/Asnpr White Paper, Jarunee Intrapiromkul, Pattana Wangaryattawanich, Zoltan Patay, Thierry A G M Huisman, Jason N Wright, Jeremy Y Jones, Raghu Ramakrishnaiah, Rajan Patel, Adam E Goldman-Yassen, Stephen Kralik, Mark Mamlouk, Nilesh K Desai

Faculty, Staff and Students Publications

A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology.

When Patient Rudeness Impacts Care: A Review Of Incivility In Healthcare, Alexandra Townsley, Jennifer Li-Wang, Rajani Katta

Faculty, Staff and Students Publications

Healthcare workers increasingly face incivility and rude behaviors from patients, families, and visitors. Although these are less severe than other types of mistreatment, studies have documented that they may still impact healthcare worker well-being and patient care. Defining and measuring incivility can be challenging because current research relies on the perceptions of the targets. Furthermore, there is often overlap among different types of mistreatment, and much of it goes unreported by those who experience it. Nevertheless, multiple studies have documented that incivility is common in healthcare and has been associated with burnout and intent to leave. In clinical settings, multiple …

Functional Response To A Microbial Synbiotic In The Gastrointestinal System Of Children: A Randomized Clinical Trial, Braden T Tierney, James Versalovic, Alessio Fasano, Joseph F Petrosino, Bruno P Chumpitazi, Emeran A Mayer, Jared Boetes, Gerard Smits, Shanthi G Parkar, Noah Voreades, Ece Kartal, Gabriel A Al-Ghalith, Marco Pane, Peter A Bron, Gregor Reid, Raja Dhir, Christopher E Mason

Faculty, Staff and Students Publications

BACKGROUND: Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.

METHODS: Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or …

Pediatric Ercp In The Setting Of Acute Pancreatitis: A Secondary Analysis Of An International Multicenter Cohort Study, Carolena Trocchia, Racha Khalaf, Ernest Amankwah, Wenly Ruan, Douglas S Fishman, Bradley A Barth, Quin Y Liu, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Filippo Torroni, Paola De Angelis, Simona Faraci, Sam Bitton, Steven L Werlin, Kulwinder Dua, Roberto Gugig, Clifton Huang, Petar Mamula, J Antonio Quiros, Yuhua Zheng, Travis Piester, Amit Grover, Victor L Fox, Michael Wilsey, David M Troendle

Faculty, Staff and Students Publications

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Rolling Out New Anti-Tuberculosis Drugs Without Diagnostic Capacity, Tara Ness, Le Hong Van, Ilze Petermane, Raquel Duarte, Christoph Lange, Dick Menzies, Daniela Maria Cirillo

Faculty, Staff and Students Publications

Deaths from tuberculosis (TB) reached over 1.6 million in 2021 with 10.6 million people becoming ill. Multidrug-resistant TB, defined as the Mycobacterium tuberculosis organism having resistance to at least isoniazid and rifampicin, represented 3.9% of new TB cases and 18% of previously treated cases. While new drug regimens continue to be developed and introduced to improve treatment of drug-resistant forms of TB, diagnostic capability to identify drug resistance lags woefully behind. While significant mortality benefits exist for these newer drug regimens, implementing them without proper drug resistance diagnostic capacity could lead to development of more drug resistances and exhaust these …

Pulse Oximetry And Arterial Saturation Difference In Pediatric Covid-19 Patients: Retrospective Analysis By Race, Fabio Savorgnan, Adel Hassan, Nirica Borges, Sebastian Acosta

Faculty, Staff and Students Publications

OBJECTIVES: Pulse oximetry (Sp o2 ) may overestimate arterial oxygen saturation (Sa o2 ) in blood laboratory testing. This study aimed to assess Sp o2 -Sa o2 difference in relation to race (i.e., patient self-reporting as Black or White), occult hypoxemia, and length of stay (LOS) in pediatric patients with COVID-19.

DESIGN: Single-center retrospective study in pediatric COVID-19 patients. We used multivariable linear regressions to examine the association between race and oximetry measurements and between occult hypoxemia and LOS. Oximetry bias was defined using Sp o2 and Sa o2 data according to approved comparisons. Occult hypoxemia was defined as Sp …

Fluid Overload Precedes And Masks Cryptic Kidney Injury In Pediatric Acute Respiratory Distress Syndrome, Celeste G Dixon, Sameer Thadani, Julie C Fitzgerald, Ayse Akcan-Arikan, Nadir Yehya

Faculty, Staff and Students Publications

OBJECTIVES: Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS).

DESIGN: Retrospective cohort study.

SETTING: Quaternary care PICU.

PATIENTS: Seven hundred twenty intubated children with ARDS between 2011 and 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Daily fluid balance, urine output (UOP), and creatinine for days 1-7 of ARDS were retrospectively abstracted. A subset of patients …

Conjugated Bile Acids Are Nutritionally Re-Programmable Antihypertensive Metabolites, Saroj Chakraborty, Anju Lulla, Xi Cheng, Ji-Youn Yeo, Juthika Mandal, Tao Yang, Xue Mei, Piu Saha, Rachel M Golonka, Beng San Yeoh, Blair Mell, Wei Jia, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Arun Sreekumar, Katie Meyer, Matam Vijay-Kumar, Bina Joe

Faculty, Staff and Students Publications

BACKGROUND: Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown.

METHOD: To address this, we analyzed bile acid profiles of human, hypertensive and germ-free rat models and report that conjugated bile acids are inversely …

Bi-Allelic Variants In Hmgcr Cause An Autosomal-Recessive Progressive Limb-Girdle Muscular Dystrophy, Joel A Morales-Rosado, Tanya L Schwab, Sarah K Macklin-Mantia, A Reghan Foley, Filippo Pinto E Vairo, Davut Pehlivan, Sandra Donkervoort, Jill A Rosenfeld, Grace E Boyum, Ying Hu, Anh T Q Cong, Timothy E Lotze, Carrie A Mohila, Dimah Saade, Diana Bharucha-Goebel, Katherine R Chao, Christopher Grunseich, Christine C Bruels, Hannah R Littel, Elicia A Estrella, Lynn Pais, Peter B Kang, Michael T Zimmermann, James R Lupski, Brendan Lee, Matthew J Schellenberg, Karl J Clark, Klaas J Wierenga, Carsten G Bönnemann, Eric W Klee

Faculty, Staff and Students Publications

Statins are a mainstay intervention for cardiovascular disease prevention, yet their use can cause rare severe myopathy. HMG-CoA reductase, an essential enzyme in the mevalonate pathway, is the target of statins. We identified nine individuals from five unrelated families with unexplained limb-girdle like muscular dystrophy and bi-allelic variants in HMGCR via clinical and research exome sequencing. The clinical features resembled other genetic causes of muscular dystrophy with incidental high CPK levels (>1,000 U/L), proximal muscle weakness, variable age of onset, and progression leading to impaired ambulation. Muscle biopsies in most affected individuals showed non-specific dystrophic changes with non-diagnostic immunohistochemistry. …

Discordant Calls Across Genotype Discovery Approaches Elucidate Variants With Systematic Errors, Elizabeth G Atkinson, Mykyta Artomov, Alexander A Loboda, Heidi L Rehm, Daniel G Macarthur, Konrad J Karczewski, Benjamin M Neale, Mark J Daly

Faculty, Staff and Students Publications

Large-scale high-throughput sequencing data sets have been transformative for informing clinical variant interpretation and for use as reference panels for statistical and population genetic efforts. Although such resources are often treated as ground truth, we find that in widely used reference data sets such as the Genome Aggregation Database (gnomAD), some variants pass gold-standard filters, yet are systematically different in their genotype calls across genotype discovery approaches. The inclusion of such discordant sites in study designs involving multiple genotype discovery strategies could bias results and lead to false-positive hits in association studies owing to technological artifacts rather than a true …

The Voltage-Gated Sodium Channel In Drosophila, Para, Localizes To Dendrites As Well As Axons In Mechanosensitive Chordotonal Neurons, Thomas A Ravenscroft, Ashleigh Jacobs, Mingxue Gu, Daniel F Eberl, Hugo J Bellen

Faculty, Staff and Students Publications

The fruit fly Drosophila melanogaster has provided important insights into how sensory information is transduced by transient receptor potential (TRP) channels in the peripheral nervous system (PNS). However, TRP channels alone have not been able to completely model mechanosensitive transduction in mechanoreceptive chordotonal neurons (CNs). Here, we show that, in addition to TRP channels, the sole voltage-gated sodium channel (NaV) in Drosophila, Para, is localized to the dendrites of CNs. Para is localized to the distal tip of the dendrites in all CNs, from embryos to adults, and is colocalized with the mechanosensitive TRP channels No mechanoreceptor potential C …

Snv/Indel Hypermutator Phenotype In Biallelic Rad51c Variant: Fanconi Anemia, Roni Zemet, Haowei Du, Tomasz Gambin, James R Lupski, Pengfei Liu, Paweł Stankiewicz

Faculty, Staff and Students Publications

We previously reported a fetus with Fanconi anemia (FA), complementation group O due to compound heterozygous variants involving RAD51C. Interestingly, the trio exome sequencing analysis also detected eight apparent de novo mosaic variants with variant allele fraction (VAF) ranging between 11.5 and 37%. Here, using whole genome sequencing and a 'home-brew' variant filtering pipeline and DeepMosaic module, we investigated the number and signature of de novo heterozygous and mosaic variants and the hypothesis of a rare phenomenon of hypermutation. Eight-hundred-thirty apparent de novo SNVs and 21 de novo indels had VAFs below 37.41% and were considered postzygotic somatic mosaic variants. …

The Nanoflow Repository, Jessie E Arce, Joshua A Welsh, Sean Cook, John Tigges, Ionita Ghiran, Jennifer C Jones, Andrew Jackson, Matthew Roth, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Motivation

Extracellular particles (EPs) are the focus of a rapidly growing area of exploration due to the widespread interest in understanding their roles in health and disease. However, despite the general need for EP data sharing and established community standards for data reporting, no standard repository for EP flow cytometry data captures rigor and minimum reporting standards such as those defined by MIFlowCyt-EV (https://doi.org/10.1080/20013078.2020.1713526). We sought to address this unmet need by developing the NanoFlow Repository.

Results

We have developed The NanoFlow Repository to provide the first implementation of the MIFlowCyt-EV framework.

Availability and implementation

The NanoFlow Repository …

Impact Of Race And Ethnicity On Presentation And Outcomes Of Patients Treated On Rhabdomyosarcoma Clinical Trials: A Report From The Children’S Oncology Group, Senna R Munnikhuysen, Princess A Ekpo, Wei Xue, Zhengya Gao, Philip J Lupo, Rajkumar Venkatramani, Christine M Heske

Faculty, Staff and Students Publications

BACKGROUND: Racial and ethnic disparities have been demonstrated in pediatric and adult cancers. However, there is no consensus on whether such disparities exist in the presentation, treatment, and outcome of patients with rhabdomyosarcoma (RMS).

METHODS: Patient information from the seven most recent RMS clinical trials was obtained from the Children's Oncology Group (COG). Chi-squared analyses were used to compare patient, tumor, and treatment characteristics across racial and ethnic groups. Pairwise analyses comparing Non-Hispanic Black (NHB) versus Non-Hispanic White (NHW) racial groups and Hispanic versus NHW ethnic groups were conducted for significant characteristics. Kaplan-Meier method and Wilcoxon signed-rank tests were performed …