Medicine and Health Sciences Commons^™

The Undiagnosed Diseases Network: Characteristics Of Solvable Applicants And Diagnostic Suggestions For Nonaccepted Ones, John J Mulvihill, Laura Findley, Weihong Ni, Janet S Sinsheimer, F Session Cole, Cecilia Esteves, Jonathan A Bernstein, John H Newman, Matthew T Wheeler, Jill R Mokry, Undiagnosed Diseases Network

Faculty, Staff and Students Publications

Purpose: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)?

Methods: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either …

Stareg: Statistical Replicability Analysis Of High Throughput Experiments With Applications To Spatial Transcriptomic Studies, Yan Li, Xiang Zhou, Rui Chen, Xianyang Zhang, Hongyuan Cao

Faculty, Staff and Students Publications

Replicable signals from different yet conceptually related studies provide stronger scientific evidence and more powerful inference. We introduce STAREG, a statistical method for replicability analysis of high throughput experiments, and apply it to analyze spatial transcriptomic studies. STAREG uses summary statistics from multiple studies of high throughput experiments and models the the joint distribution of p-values accounting for the heterogeneity of different studies. It effectively controls the false discovery rate (FDR) and has higher power by information borrowing. Moreover, it provides different rankings of important genes. With the EM algorithm in combination with pool-adjacent-violator-algorithm (PAVA), STAREG is scalable to datasets …

Unraveling The Link: Seizure Characteristics And Ammonia Levels In Urea Cycle Disorder During Hyperammonemic Crises, Mongkol Chanvanichtrakool, John M Schreiber, Wei-Liang Chen, John Barber, Anqing Zhang, Nicholas Ah Mew, Andreas Schulze, Greta Wilkening, Sandesh C S Nagamani, Andrea Gropman, Urea Cycle Disease Consortium

Faculty, Staff and Students Publications

Background: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA.

Methods: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently.

Results: Eighty-five individuals with UCD …

Inhaled Corticosteroids Attenuate The Association Of Fine Particulate Matter And Acute Asthma Events, Kristen A Staggers, Paula Sierra, Drew A Helmer, Charles Minard, Meredith C Mccormack, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

Evaluating Progress And Accountability For Achieving Cop26 Health Programme International Ambitions For Sustainable, Low-Carbon, Resilient Health-Care Systems, Iris Martine Blom, Fawzia N Rasheed, Hardeep Singh, Matthew J Eckelman, Meghnath Dhimal, Martin Hensher, Renzo R Guinto, Alice Mcgushin, Xuejuan Ning, Poornima Prabhakaran, Marina Romanello, Dana Van Alphen, Nick Watts, Jessica C Yu, Carol Zavaleta-Cortijo, Andrea J Macneill, Jodi D Sherman

Faculty, Staff and Students Publications

A global initiative to develop low-carbon, resilient health systems-the COP26 Health Programme-launched at the UN Framework Convention on Climate Change 26th Conference of the Parties (COP26) in 2021. As of May, 2024, 83 nations have committed to participate in this initiative. This analysis evaluates the effectiveness of existing and proposed indicators towards public monitoring and accountability to these commitments. Our findings reveal substantial gaps in data availability and indicator relevance, with many countries reporting process indicators that do not reflect actual progress towards achieving sustainable health-care systems. We found a dearth of suitable indicators and an urgent need to develop …

Psychometric Evaluation Of Clinician- And Caregiver-Reported Clinical Severity Assessments For Individuals With Cdkl5 Deficiency Disorder, Jacinta M Saldaris, Peter Jacoby, Jenny Downs, Eric D Marsh, Helen Leonard, Elia Pestana-Knight, Rajsekar Rajaraman, Judith Weisenberg, Bernhard Suter, Heather E Olson, Dana Price, William Hong, Erin Prange, Tim A Benke, Scott Demarest

Faculty, Staff and Students Publications

Objective: The CDKL5 Clinical Severity Assessment (CCSA) is a comprehensive, content-validated measurement tool capturing the diverse challenges of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a genetically caused developmental epileptic encephalopathy (DEE). The CCSA is divided into clinician-reported (CCSA-Clinician) and caregiver-reported (CCSA-Caregiver) assessments. The aim of this study was to evaluate the factor structure of these measures through confirmatory factor analysis (CFA) and evaluate their validity and reliability.

Methods: Participants were recruited from the International CDKL5 Clinical Research Network to take part in an in-clinic CCSA-Clinician evaluation (n = 148) and/or complete the CCSA-Caregiver questionnaire (n = 198). CFA was …

Correspondence Re Essam El-Sayed Felaya Et Al, Kiyeun Nam, Dongho Lee, Seokjoon Hwang, Minsu Seo, Taeheon Lee, Yonghoon Lee, Michael Y Lee

Faculty, Staff and Students Publications

No abstract provided.

Intimate Partner Violence-Related Brain Injury: Unmasking And Addressing The Gaps, Carrie Esopenko, Divya Jain, Shambhu Prasad Adhikari, Kristen Dams-O'Connor, Michael Ellis, Halina Lin Haag, Elizabeth S Hovenden, Finian Keleher, Inga K Koerte, Hannah M Lindsey, Amy D Marshall, Karen Mason, J Scott Mcnally, Deleene S Menefee, Tricia L Merkley, Emma N Read, Philine Rojcyk, Sandy R Shultz, Mujun Sun, Danielle Toccalino, Eve M Valera, Paul Van Donkelaar, Cheryl Wellington, Elisabeth A Wilde

Faculty, Staff and Students Publications

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and …

Global Presence And Penetrance Of, Jaroslaw Dulski, Matthew Baker, Samantha A Banks, Michael Bayat, Rose Bruffaerts, Gabriela Ortiz Cruz, Caio C Disserol, Kristen S Fisher, Jainy N Jose, Bernadette Kalman, Orhun H Kantarci, Dmytro Maltsev, Catherine Middleton, Gabriela Novotni, Dijana Plaseska-Karanfilska, Salmo Raskin, Josiane Souza, Helio A Teive, Zbigniew K Wszolek

Faculty, Staff and Students Publications

Objectives: To highlight the worldwide presence of CSF1R-related disorder (CSF1R-RD), discuss its penetrance, and provide the first haplotype analysis.

Methods: Data on patients worldwide were collected, including demographics, genotype, family history, and clinical status. For haplotype analysis, polymorphisms of short tandem repeats in 3 distinct families with CSF1R p.Ile794Thr variant were examined.

Results: Nineteen new patients were included, at a mean age of 38.7 years (ranging from 11 to 74 years), from 14 families from the Americas, Asia, Australia, and Europe, including the first from Mexico, North Macedonia, and Ukraine. Fifteen CSF1R variants were found, including 8 …

Correspondence Re Essam El-Sayed Felaya Et Al, Kiyeun Nam, Dongho Lee, Seokjoon Hwang, Minsu Seo, Taeheon Lee, Yonghoon Lee, Michael Y Lee

Faculty, Staff and Students Publications

No abstract provided.

The Relationship Between Adverse Childhood Experiences, Symptom Severity, Negative Thinking, Comorbidity, And Treatment Response In Youth With Obsessive-Compulsive Disorder, Mariana Vazquez, Amanda Palo, Mckenzie Schuyler, Brent J Small, Joseph F Mcguire, Sabine Wilhelm, Wayne K Goodman, Daniel Geller, Eric A Storch

Faculty, Staff and Students Publications

Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE …

Polycaprolactone-Based Shape Memory Foams As Self-Fitting Vaginal Stents, Ashley J Hicks, Courteney Roberts, Andrew Robinson, Kailey Wilson, Varsha Kotamreddy, Trace Larue, Arian Veyssi, Felipe Beltran, Julie Hakim, Manuel K Rausch, Melissa Grunlan, Elizabeth Cosgriff-Hernandez

Faculty, Staff and Students Publications

There is an urgent critical need for a patient-forward vaginal stent that can prevent debilitating vaginal stenosis that occurs after pelvic radiation treatments and vaginal reconstruction. To this end, we developed a self-fitting vaginal stent based on a shape-memory polymer (SMP) foam that can assume a secondary, compressed shape for ease of deployment. Upon insertion, the change in temperature and hydration initiates foam expansion to shape fit to the individual patient and restore the lumen of the stent to allow egress of vaginal secretions. To achieve rapid actuation at physiological temperature, we investigated the effect of architecture of two photocurable, …

Detection Of Mosaic And Population-Level Structural Variants With Sniffles2, Moritz Smolka, Luis F Paulin, Christopher M Grochowski, Dominic W Horner, Medhat Mahmoud, Sairam Behera, Ester Kalef-Ezra, Mira Gandhi, Karl Hong, Davut Pehlivan, Sonja W Scholz, Claudia M B Carvalho, Christos Proukakis, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Calling structural variations (SVs) is technically challenging, but using long reads remains the most accurate way to identify complex genomic alterations. Here we present Sniffles2, which improves over current methods by implementing a repeat aware clustering coupled with a fast consensus sequence and coverage-adaptive filtering. Sniffles2 is 11.8 times faster and 29% more accurate than state-of-the-art SV callers across different coverages (5-50×), sequencing technologies (ONT and HiFi) and SV types. Furthermore, Sniffles2 solves the problem of family-level to population-level SV calling to produce fully genotyped VCF files. Across 11 probands, we accurately identified causative SVs around MECP2, including highly complex …

Publisher Correction: Detection Of Mosaic And Population-Level Structural Variants With Sniffles2, Moritz Smolka, Luis F Paulin, Christopher M Grochowski, Dominic W Horner, Medhat Mahmoud, Sairam Behera, Ester Kalef-Ezra, Mira Gandhi, Karl Hong, Davut Pehlivan, Sonja W Scholz, Claudia M B Carvalho, Christos Proukakis, Fritz J Sedlazeck

Faculty, Staff and Students Publications

This corrects the article "Detection of mosaic and population-level structural variants with Sniffles2" on page 1571.

Epidural Interlay Graft For Pituitary Surgery: A 4-Year Institutional Experience, Rita Snyder, Sungho Lee, Prazwal Athukuri, Emmeline Monique Tan Ngo, Meha Goyal Fox, Samer Fakhri, Masayoshi Takashima, Bahar Kapoor Force, Susan Leanne Samson, Kathleen Kelly Gallagher, Daniel Yoshor, Ali Jalali

Faculty, Staff and Students Publications

Objective  Sellar repair techniques with varying complexity and effectiveness have been employed to reduce the incidence of postoperative cerebrospinal fluid (CSF) leaks following endoscopic transsphenoidal pituitary surgery. This study describes our institutional experience with a minimalistic, highly effective approach to sellar repair.

Methods  The authors performed a retrospective review of consecutive cases of transsphenoidal pituitary surgery performed at our institution. All included subjects underwent sellar repair with an epidural interlay graft. Relationships between patient and tumor characteristics, incidence of CSF leak, adjunct repair techniques, and endocrine outcomes were examined.

Results  Three hundred and thirty-four (334) cases were included. Intraoperative CSF …

“The Truth Should Not Be Hidden”: Experiences And Recommendations Of Individuals Making Npe Discoveries Through Genetic Genealogy Databases, Olivia Schuman, Caroline Beit, Jill Oliver Robinson, Whitney Bash Brooks, Amy L Mcguire, Christi Guerrini

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Fueled by direct-to-consumer (DTC) genetic testing and genetic-relative finder services, some participants in genetic genealogy databases are making "not parent expected" (NPE) discoveries. To better understand experiences of this phenomenon, we surveyed a large cohort of users of genetic relative finder (GRF) services concerning their experiences after an NPE discovery.

Methods: Using thematic analysis, we analyzed responses from a cohort of GRF users (n = 646) to open-ended survey items to understand these experiences and their recommendations for DTC genetic testing companies and other GRF users.

Results: We found that individuals had both positive and negative emotional experiences related …

A Method For Rapid And Reliable Quantification Of Vegf-Cell Binding Activity, Prabuddha Waduge, Avinash Kaur, Wei Li

Faculty, Staff and Students Publications

Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that binds a broad spectrum of cell types and regulates diverse cellular processes, including angiogenesis, growth and survival. However, it is technically difficult to quantify VEGF-cell binding activity because of reversible nature of ligand-receptor interactions. Here we used T7 bacteriophage display to quantify and compare binding activity of three human VEGF-A (hVEGF) isoforms, including hVEGF111, 165 and 206. All three isoforms bound equally well to immobilized aflibercept, a decoy VEGF receptor. hVEGF111-Phage exhibited minimal binding to immobilized heparan sulfate, whereas hVEGF206-Phage and hVEGF165-Phage had the highest and intermediate binding to …

Distinct Landscape And Clinical Implications Of Therapy-Related Clonal Hematopoiesis, Koichi Takahashi, Daisuke Nakada, Margaret Goodell

Faculty, Staff and Student Publications

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly …

Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) regulate translation and plasticity which are required for memory. RBP dysfunction has been linked to a range of neurological disorders where cognitive impairments are a key symptom. However, of the 2,000 RBPs in the human genome, many are uncharacterized with regards to neurological phenotypes. To address this, we used the model organism C. elegans to assess the role of 20 conserved RBPs in memory. We identified eight previously uncharacterized memory regulators, three of which are in the C. elegans Y-Box (CEY) RBP family. Of these, we determined that cey-1 is the closest ortholog to the mammalian Y-Box …

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy In Patients With Atrial Fibrillation And Stable Coronary Artery Disease, Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Raheel Ahmed, Mahboob Alam, Pierre Sabouret, Jamal S Rana, Gregg C Fonarow

Faculty, Staff and Students Publications

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited.

METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with …

Multivalent Protein-Nucleic Acid Interactions Probed By Composition-Gradient Multiangle Light Scattering, Josephine C Ferreon, Natee Kongchan, Phoebe S Tsoi, Kyoung-Jae Choi, Sophia Kenrick, Joel Neilson, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Many RNA-binding proteins, such as TDP-43 or CELF1, interact multivalently with nucleic acid repetitive elements. The molecular stoichiometry of protein to nucleic acid is often difficult to assess, particularly by standard electrophoretic mobility shift assays (EMSAs). Here, we investigate the use of composition-gradient multiangle light scattering (CG-MALS) for quantifying binding affinity and stoichiometry for two RNA-binding proteins with their nucleic acid partners of varied sequence and length: TDP43's N-terminal RNA recognition motifs with both TG/GU-repeat ssDNA and ssRNA, respectively, and CELF1's two N-terminal RNA recognition motifs with (TG/UGUU/GU) repeats and an experimentally defined cognate GU-rich element (GRE). Our CG-MALS data …

Editorial Expression Of Concern: Role Of Brca1 In Heat Shock Response, Yong Xian Ma, Saijun Fan, Jingbo Xiong, Ren-Qi Yuan, Qinghui Meng, Min Gao, Itzhak D Goldberg, Suzanne A Fuqua, Richard G Pestell, Eliot M Rosen

Faculty, Staff and Students Publications

Background

Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods

We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …

Targeting Snai1-Mediated Colorectal Cancer Chemoresistance And Stemness By Sphingosine Kinase 2 Inhibition, Harinarayanan Janakiraman, Zachary Gao, Yun Zhu, Jiangling Dong, Scott A Becker, Alhaji Janneh, Besim Ogretmen, E Ramsay Camp

Faculty, Staff and Students Publications

BACKGROUND: Epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs), and colorectal cancer (CRC) therapy resistance are closely associated. Prior reports have demonstrated that sphingosine-1-phosphate (S1P) supports stem cells and maintains the CSC phenotype. We hypothesized that the EMT inducer SNAI1 drives S1P signaling to amplify CSC self-renewal capacity and chemoresistance.

METHODS: CRC cell lines with or without ectopic expression of SNAI1 were used to study the role of S1P signaling as mediators of cancer stemness and 5-fluorouracil (5FU) chemoresistance. The therapeutic ability of sphingosine kinase 2 (SPHK2) was assessed using siRNA and ABC294640, a SPHK2 inhibitor. CSCs were isolated from patient-derived …

Psychological Distress Among Ethnically Diverse Participants From Eastern And Southern Africa, Kester B B Tindi, Allan Kalungi, Eugene Kinyanda, Bizu Gelaye, Alicia R Martin, Ronald Galiwango, Wilber Ssembajjwe, Fred Kirumira, Adele Pretorius, Anne Stevenson, Charles R J C Newton, Dan J Stein, Elizabeth G Atkinson, Emanuel K Mwesiga, Joseph Kyebuzibwa, Lori B Chibnik, Lukoye Atwoli, Mark Baker, Melkam Alemayehu, Rehema M Mwende, Rocky E Stroud, Solomon Teferra, Stella Gichuru, Symon M Kariuki, Zukiswa Zingela, Moffat Nyirenda, Segun Fatumo, Dickens H Akena

Faculty, Staff and Students Publications

IMPORTANCE: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups.

OBJECTIVE: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern …

Decoding Complex Inherited Phenotypes In Rare Disorders: The Decipherd Initiative For Rare Undiagnosed Diseases In Chile, M Cecilia Poli, Boris Rebolledo-Jaramillo, Catalina Lagos, Joan Orellana, Gabriela Moreno, Luz M Martín, Gonzalo Encina, Daniela Böhme, Víctor Faundes, M Jesús Zavala, Trinidad Hasbún, Sara Fischer, Florencia Brito, Diego Araya, Manuel Lira, Javiera De La Cruz, Camila Astudillo, Guillermo Lay-Son, Carolina Cares, Mariana Aracena, Esteban San Martin, Zeynep Coban-Akdemir, Jennifer E Posey, James R Lupski, Gabriela M Repetto

Faculty, Staff and Students Publications

Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the "diagnostic odyssey" for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international …

Integrated Safety And Efficacy Analyses Of Phase 3 Trials Of A Microbiome Therapeutic For Recurrent Cdi, Colleen S Kraft, Matthew Sims, Michael Silverman, Thomas J Louie, Paul Feuerstadt, Edward S Huang, Sahil Khanna, Charles S Berenson, Elaine E L Wang, Stuart H Cohen, Louis Korman, Christine Lee, Colleen R Kelly, Alberto Odio, Paul P Cook, Bret Lashner, Mayur Ramesh, Princy Kumar, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke, Darrell S Pardi, Ecospor Iii And Ecospor Iv Investigators

Faculty, Staff and Students Publications

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest …

Circulating Blood Plasma Profiling Reveals Proteomic Signature And A Causal Role For Svep1 In Sudden Cardiac Death, Thuyvy Duong, Thomas R Austin, Jennifer A Brody, Ali Shojaie, Alexis Battle, Joel S Bader, Yun Soo Hong, Christie M Ballantyne, Josef Coresh, Robert E Gerszten, Russell P Tracy, Bruce M Psaty, Nona Sotoodehnia, Dan E Arking

Faculty, Staff and Students Publications

No abstract provided.

Horizontal Gene Transfer And Beyond: The Delivery Of Biological Matter By Bacterial Membrane Vesicles To Host And Bacterial Cells, Alice X Wen, Christophe Herman

Faculty, Staff and Students Publications

Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.

Mutant Npm1 Marginally Impacts Ribosome Footprint In Acute Myeloid Leukemia Cells, Lorenzo Brunetti, Giulia Pianigiani, Michael C Gundry, Margaret A Goodell, Brunangelo Falini

Faculty, Staff and Students Publications

BACKGROUND:NPM1‐mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild‐type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in NPM1‐mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint.

METHODS: Here, we performed ribosome footprint profiling (Ribo-seq) and bulk messenger RNA (mRNA) sequencing in two

RESULTS AND DISCUSSION: Incubation of degron cells with the small compound dTAG-13 …

Design And Cohort Characteristics Of Track, A Prospective Study Of Hyperkalaemia Management Decision-Making, Judith Hsia, Nitin Shivappa, Ameet Bakhai, Jordi Bover, Javed Butler, Pietro Manuel Ferraro, Linda Fried, Markus P Schneider, Navdeep Tangri, Wolfgang C Winkelmayer, Meredith Bishop, Hungta Chen, Anna-Karin Sundin, Marc P Bonaca

Faculty, Staff and Students Publications

BACKGROUND: Guideline-recommended hyperkalaemia management includes dietary potassium (K

METHODS: This study enrolled participants within 21 days of an episode of hyperkalaemia in four European countries (UK, Spain, Germany, Italy) and the USA. During the 12-month follow up, data collected will include participant and healthcare provider characteristics (specialty and practice setting), hyperkalaemia treatment objectives and strategies, rationale for management decisions and indicators of response and patient-reported perceptions of their hyperkalaemia treatment.

RESULTS: The enrolled cohort includes 1330 participants, mean age 68 years, of whom 31% were women. At baseline, 6% reported heart failure, 55% chronic kidney disease, 29% both and 9% …