Digital Commons Network^™

Large-Scale Mutational Analysis Identifies Unc93b1 Variants That Drive Tlr-Mediated Autoimmunity In Mice And Humans., Victoria E. Rael, Julian A. Yano, John P. Huizar, Leianna C. Slayden, Madeleine A. Weiss, Elizabeth A. Turcotte, Jacob M. Terry, Wenqi Zuo, Isabelle Thiffault, Tomi Pastinen, Emily G. Farrow, Janda L. Jenkins, Mara L. Becker, Stephen C. Wong, Anne M. Stevens, Catherine Otten, Eric J. Allenspach, Devon E. Bonner, Jonathan A. Bernstein, Matthew T. Wheeler, Robert A. Saxton, Undiagnosed Diseases Network, Bo Liu, Olivia Majer, Gregory M. Barton

Manuscripts, Articles, Book Chapters and Other Papers

Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus …

Characteristics And Treatment Of Acute Myeloid Neoplasms With Cutaneous Involvement In Infants Up To 6 Months Of Age: A Retrospective Study., Juliette Renaud, Bianca F. Goemans, Franco Locatelli, Martina Pigazzi, Shelagh Redmond, Claudia E. Kuehni, Alice Destaillats, Todd A. Alonzo, Robert B. Gerbing, Alan S. Gamis, Richard Aplenc, Raffaele Renella, Todd Cooper, Francesco Ceppi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Myeloid neoplasms account for 50% of cases of pediatric leukemias in infants. Approximately 25%-50% of patients with newborn leukemia have cutaneous extramedullary disease (EMD). In less than 10% of patients, aleukemic leukemia cutis or isolated extramedullary disease with cutaneous involvement (cEMD) occurs when skin lesions appear prior to bone marrow involvement and systemic symptoms. Interestingly, in acute myeloid leukemia with cutaneous EMD (AML-cEMD) and cEMD, spontaneous remissions have been reported.

METHOD: This is a multicentric retrospective cohort study aiming to describe characteristics, treatment, and outcome of infants with either cEMD or presence of cutaneous disease with involvement of the …

Efficacy And Safety Of Tepotinib In Asian Patients With Advanced Nsclc With Met Exon 14 Skipping Enrolled In Vision, Terufumi Kato, James Chih-Hsin Yang, Myung-Ju Ahn, Hiroshi Sakai, Masahiro Morise, Yuh-Min Chen, Ji-Youn Han, Jin-Ji Yang, Jun Zhao, Te-Chun Hsia, Karin Berghoff, Rolf Bruns, Helene Vioix, Simone Lang, Andreas Johne, Xiuning Le, Paul K Paik

Journal Articles

BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022).

METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily.

PRIMARY ENDPOINT: objective response (RECIST 1.1) by independent review. Secondary endpoints included: …

Event-Free Survival Of Maralixibat-Treated Patients With Alagille Syndrome Compared To A Real-World Cohort From Gala., Bettina E. Hansen, Shannon M. Vandriel, Pamela Vig, Will Garner, Douglas B. Mogul, Kathleen M. Loomes, David A. Piccoli, Elizabeth B. Rand, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzińska, Emmanuel M. Gonzales, Emmanuel Jacquemin, Jérôme Bouligand, Lorenzo D'Antiga, Emanuele Nicastro, Henrik Arnell, Björn Fischler, Étienne Sokal, Tanguy Demaret, Susan Siew, Michael Stormon, Saul J. Karpen, Rene Romero, Noelle H. Ebel, Jeffrey A. Feinstein, Amin J. Roberts, Helen M. Evans, Shikha S. Sundaram, Alexander Chaidez, Winita Hardikar, Sahana Shankar, Ryan T. Fischer, Florence Lacaille, Dominique Debray, Henry C. Lin, M Kyle Jensen, Catalina Jaramillo, Palaniswamy Karthikeyan, Giuseppe Indolfi, Henkjan J. Verkade, Catherine Larson-Nath, Ruben E. Quiros-Tejeira, Pamela L. Valentino, Maria Rogalidou, Antal Dezsőfi, James E. Squires, Kathleen Schwarz, Pier Luigi Calvo, Jesus Quintero Bernabeu, Andréanne N Zizzo, Gabriella Nebbia, Pinar Bulut, Ermelinda Santos-Silva, Rima Fawaz, Silvia Nastasio, Wikrom Karnsakul, María Legarda Tamara, Cristina Molera Busoms, Deirdre A. Kelly, Thomas Damgaard Sandahl, Carolina Jimenez-Rivera, Jesus M. Banales, Quais Mujawar, Li-Ting Li, Huiyu She, Jian-She Wang, Kyung Mo Kim, Seak Hee Oh, Maria Camila Sanchez, Maria Lorena Cavalieri, Way Seah Lee, Christina Hajinicolaou, Chatmanee Lertudomphonwanit, Orith Waisbourd-Zinman, Cigdem Arikan, Seema Alam, Elisa Carvalho, Melina Melere, John Eshun, Zerrin Önal, Dev M. Desai, Sabina Wiecek, Raquel Borges Pinto, Victorien M. Wolters, Jennifer Garcia, Marisa Beretta, Nanda Kerkar, Jernej Brecelj, Nathalie Rock, Eberhard Lurz, Niviann Blondet, Uzma Shah, Richard J. Thompson, Binita M. Kamath, Global Alagille Alliance (Gala) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.

APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 …

Barriers To Pregnancy Prevention For Adolescents In Rural Haiti: Perceptions Of Healthcare Providers., Shelbie Wooten, Emily A. Hurley, Nikolaus Schuetz, Melissa K. Miller, Jonathan Rodean, Emily Rupe, Kemi Lewis, Marie Daphnée Boncoeur, Abbey R. Masonbrink

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Little is known about healthcare providers' (HCPs) contraceptive views for adolescents in Haiti, who experience high rates of unintended pregnancy. We sought to describe HCPs' perspectives on barriers and facilitators to contraceptive care delivery in rural Haiti.

METHODS: We conducted a cross-sectional survey and qualitative interviews with HCPs in two rural communities in Haiti from 08/2021-03/2022. We assessed demographics, clinical practice behaviors and explored contraception perspectives according to Theory of Planned Behavior constructs: attitudes, subjective norms, and perceived behavioral control (e.g., people's perceptions of their ability to perform a given behavior, barriers and facilitators of a behavior).

RESULTS: Among …

Common Single-Base Insertions In The Vntr Of The Carboxyl Ester Lipase (Cel) Gene Are Benign And Also Likely To Arise Somatically In The Exocrine Pancreas, Ranveig S Brekke, Anny Gravdal, Khadija El Jellas, Grace E Curry, Jianguo Lin, Steven J Wilhelm, Solrun J Steine, Eric Mas, Stefan Johansson, Mark E Lowe, Bente B Johansson, Xunjun Xiao, Karianne Fjeld, Anders Molven

2020-Current year OA Pubs

The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), which always associated with a VNTR length of 13 repeats. The combined INS allele frequency (0.078) was similar to that observed in …

Seasonality, Clinical Characteristics, And Outcomes Of Respiratory Syncytial Virus Disease By Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020., Ariana P. Toepfer, Justin Z. Amarin, Andrew J. Spieker, Laura S. Stewart, Mary Allen Staat, Elizabeth P. Schlaudecker, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Marian G. Michaels, John V. Williams, Rangaraj Selvarangan, Christopher J. Harrison, Joana Y. Lively, Pedro A. Piedra, Vasanthi Avadhanula, Brian Rha, James Chappell, Meredith Mcmorrow, Heidi Moline, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established.

METHODS: During 2016-2020, children aged/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction.

RESULTS: Among 6398 RSV-positive …

Acute Pulmonary Injury In Hematology Patients Supported With Pathogen-Reduced And Conventional Platelet Components, Allison P Wheeler, Ronald Jackups, Et Al.

2020-Current year OA Pubs

Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded …

Prognostic Impact Of Cooccurring Mutations In Flt3-Itd Pediatric Acute Myeloid Leukemia., Katherine Tarlock, Robert B. Gerbing, Rhonda E. Ries, Jenny L. Smith, Amanda Leonti, Benjamin J. Huang, Danielle Kirkey, Leila Robinson, Jack H. Peplinksi, Beverly Lange, Todd M. Cooper, Alan S. Gamis, E Anders Kolb, Richard Aplenc, Jessica A. Pollard, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

We sought to define the cooccurring mutational profile of FLT3-ITD-positive (ITDpos) acute myeloid leukemia (AML) in pediatric and young adult patients and to define the prognostic impact of cooperating mutations. We identified 464 patients with FLT3-ITD mutations treated on Children's Oncology Group trials with available sequencing and outcome data. Overall survival, event-free survival (EFS), and relapse risk were determined according to the presence of cooccurring risk stratifying mutations. Among the cohort, 79% of patients had cooccurring alterations across 239 different genes that were altered through mutations or fusions. Evaluation of the prognostic impact of the cooccurring mutations demonstrated that patients …

Identifying Strategies To Support Implementation Of Interprofessional Primary Care Teams In Nova Scotia: Results Of A Survey And Knowledge Sharing Event., Amy Grant, Rachel Giacomantonio, Kelly Lackie, Adrian Mackenzie, Elizabeth Jeffers, Julia Kontak, Emily Gard Marshall, Susan Philpott, Debbie Sheppard-Lemoine, Elizabeth Lappin, Alice Bruce, Amy Mireault, Deanna Beck, Lindsay Cormier, Ruth Martin-Misener

Nursing Publications

BACKGROUND: Interprofessional primary care teams (IPCTs) work together to enhance care. Despite evidence on the benefits of IPCTs, implementation remains challenging. This research aims to 1) identify and prioritize barriers and enablers, and 2) co-develop team-level strategies to support IPCT implementation in Nova Scotia, Canada.

METHODS: Healthcare providers and staff of IPCTs were invited to complete an online survey to identify barriers and enablers, and the degree to which each item impacted the functioning of their team. Top ranked items were identified using the sum of frequency x impact for each response. A virtual knowledge sharing event was held to …

Gut Microbiota, Blood Metabolites, And Left Ventricular Diastolic Dysfunction In Us Hispanics/Latinos, Kai Luo, Alkis Taryn, Eun-Hye Moon, Brandilyn A Peters, Scott D Solomon, Martha L Daviglus, Mayank M Kansal, Bharat Thyagarajan, Marc D Gellman, Jianwen Cai, Robert D Burk, Rob Knight, Robert C Kaplan, Susan Cheng, Carlos J Rodriguez, Qibin Qi, Bing Yu

Journal Articles

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD.

RESULTS: We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion …

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki

Department of Medical Oncology Faculty Papers

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens …

Factitious Disorder Presenting As Sickle Cell Disease: A Case Report, Jeremy Jacobs, Juliana Guarente, Julie Karp, Brenda Grossman, Alyssa Ziman, Andrea Mcgonigle, Thomas Binns, Tappy Gish, James Gorham, Yara Park, Ingrid Perez-Alvarez, James Burner, Zhen Mei, Dawn Ward, Jennifer Woo, Garrett Booth, Brian Adkins, Christopher Webb, Chisa Yamada, Grace Lee, Elizabeth Abels, Marisa Marques, Elizabeth Allen, Ross Fasano, Elizabeth Crowe, Aaron Tobian, Christopher Tormey, Evan Bloch

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Determinants Of Mosaic Chromosomal Alteration Fitness, Yash Pershad, Taralynn Mack, Hannah Poisner, Yasminka A Jakubek, Adrienne M Stilp, Braxton D Mitchell, Joshua P Lewis, Eric Boerwinkle, Ruth J F Loos, Nathalie Chami, Zhe Wang, Kathleen Barnes, Nathan Pankratz, Myriam Fornage, Susan Redline, Bruce M Psaty, Joshua C Bis, Ali Shojaie, Edwin K Silverman, Michael H Cho, Jeong H Yun, Dawn Demeo, Daniel Levy, Andrew D Johnson, Rasika A Mathias, Margaret A Taub, Donna Arnett, Kari E North, Laura M Raffield, April P Carson, Margaret F Doyle, Stephen S Rich, Jerome I Rotter, Xiuqing Guo, Nancy J Cox, Dan M Roden, Nora Franceschini, Pinkal Desai, Alex P Reiner, Paul L Auer, Paul A Scheet, Siddhartha Jaiswal, Joshua S Weinstock, Alexander G Bick

Journal Articles

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI toPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design., Rachel S. Gross, Tanayott Thaweethai, Erika B. Rosenzweig, James Chan, Lori B. Chibnik, Mine S. Cicek, Amy J. Elliott, Valerie J. Flaherman, Andrea S. Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L. Jernigan, Elizabeth W. Karlson, Stuart D. Katz, Patricia A. Kinser, Lawrence C. Kleinman, Michelle F. Lamendola-Essel, Joshua D. Milner, Sindhu Mohandas, Praveen C. Mudumbi, Jane W. Newburger, Kyung E. Rhee, Amy L. Salisbury, Jessica N. Snowden, Cheryl R. Stein, Melissa S. Stockwell, Kelan G. Tantisira, Moriah E. Thomason, Dongngan T. Truong, David Warburton, John C. Wood, Shifa Ahmed, Almary Akerlundh, Akram N. Alshawabkeh, Brett R. Anderson, Judy L. Aschner, Andrew M. Atz, Robin L. Aupperle, Fiona C. Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M. Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C. Bind, Amanda L. Bogie, Tamara Bradford, Natalie C. Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B. Clark, Rebecca G. Clifton, Katharine N. Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B. Dummer, Matthew D. Elias, Shari Esquenazi-Karonika, Danielle N. Evans, E Vincent S. Faustino, Alexander G. Fiks, Daniel Forsha, John J. Foxe, Naomi P. Friedman, Greta Fry, Sunanda Gaur, Dylan G. Gee, Kevin M. Gray, Stephanie Handler, Ashraf S. Harahsheh, Keren Hasbani, Andrew C. Heath, Camden Hebson, Mary M. Heitzeg, Christina M. Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R. Horowitz, Daniel S. Hsia, Matthew Huentelman, Kathy D. Hummel, Katherine Irby, Joanna Jacobus, Vanessa L. Jacoby, Pei-Ni Jone, David C. Kaelber, Tyler J. Kasmarcak, Matthew J. Kluko, Jessica S. Kosut, Angela R. Laird, Jeremy Landeo-Gutierrez, Sean M. Lang, Christine L. Larson, Peter Paul C. Lim, Krista M. Lisdahl, Brian W. Mccrindle, Russell J. Mcculloh, Kimberly Mchugh, Alan L. Mendelsohn, Torri D. Metz, Julie Miller, Elizabeth C. Mitchell, Lerraughn M. Morgan, Eva M. Müller-Oehring, Erica R. Nahin, Michael C. Neale, Manette Ness-Cochinwala, Sheila M. Nolan, Carlos R. Oliveira, Onyekachukwu Osakwe, Matthew E. Oster, R Mark Payne, Michael A. Portman, Hengameh Raissy, Isabelle G. Randall, Suchitra Rao, Harrison T. Reeder, Johana M. Rosas, Mark W. Russell, Arash A. Sabati, Yamuna Sanil, Alice I. Sato, Michael S. Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M. Squeglia, Shubika Srivastava, Michelle D. Stevenson, Jacqueline Szmuszkovicz, Maria M. Talavera-Barber, Ronald J. Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M. Udosen, Megan R. Warner, Sara E. Watson, Alan Werzberger, Jordan C. Weyer, Marion J. Wood, H Shonna Yin, William T. Zempsky, Emily Zimmerman, Benard P. Dreyer, Recover-Pediatric Consortium

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Teacher, Model, Father: An Autoethnography Of Long-Term Mentoring Between A Male Teacher And A Male Student, Si Chen

The Qualitative Report

This autoethnography offered an opportunity to have an open conversation to explore the nature of the long-term relationship with my mentor, Mr. Jiang, who has guided me to grow since I was a high school student. With confidence being a significant theme, our interaction has changed along with my growth from a boy to an independent adult man, a teacher, and now, a doctoral student. Feelings between us have been complicated and featured as puzzled, doubtful, hurt, happy, guilty, and moved. The nature of the relationship is challenging to define accurately, but it is similar to a father/son-like mutually beneficial …

Novel Loss-Of-Function Variants Expand Abcc9-Related Intellectual Disability And Myopathy Syndrome, Stephanie Efthymiou, Robert C Tryon, Colin G Nichols, Et Al.

2020-Current year OA Pubs

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle …

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Biallelic Borcs8 Variants Cause An Infantile-Onset Neurodegenerative Disorder With Altered Lysosome Dynamics., Raffaella De Pace, Reza Maroofian, Adeline Paimboeuf, Mina Zamani, Maha S. Zaki, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Jawaher Zeighami, Chad D. Williamson, Emily Fleming, Dihong Zhou, Jennifer L. Gannon, Isabelle Thiffault, Emmanuel Roze, Mohnish Suri, Giovanni Zifarelli, Peter Bauer, Henry Houlden, Mariasavina Severino, Shunmoogum A. Patten, Emily G. Farrow, Juan S. Bonifacino

Manuscripts, Articles, Book Chapters and Other Papers

BLOC-one-related complex (BORC) is a multiprotein complex composed of eight subunits named BORCS1-8. BORC associates with the cytosolic face of lysosomes, where it sequentially recruits the small GTPase ARL8 and kinesin-1 and -3 microtubule motors to promote anterograde transport of lysosomes toward the peripheral cytoplasm in non-neuronal cells and the distal axon in neurons. The physiological and pathological importance of BORC in humans, however, remains to be determined. Here, we report the identification of compound heterozygous variants [missense c.85T>C (p.Ser29Pro) and frameshift c.71-75dupTGGCC (p.Asn26Trpfs*51)] and homozygous variants [missense c.196A>C (p.Thr66Pro) and c.124T>C (p.Ser42Pro)] in BORCS8 in five …

Cut The Pressure: Blood Pressure Screening In A Community Based Setting, Harold Kareem Knight Jr., Katharine Milani

Rowan-Virtua Research Day

This study addresses the pressing issue of cardiovascular health disparities in African American males through community-based interventions, specifically blood pressure screenings and surveys conducted in a local barbershop setting. Despite a preference among participants for clinical settings, an overwhelming 97.7% expressed high comfort levels in the community-based environment, highlighting the importance of culturally sensitive approaches in healthcare delivery. With 92.5% indicating willingness to return for future screenings, the study underscores the efficacy of non-traditional settings in fostering healthcare engagement. Findings suggest the potential for broader impact through scalable, community-centric initiatives, offering promising avenues for improving health outcomes in underserved populations.

Interactions Between Repetitive Mild Traumatic Brain Injury And Methylphenidate Administration On Catecholamine Transporter Protein Levels Within The Rodent Prefrontal Cortex, Anna Abrimian, Eleni Papadopoulos, Christopher P. Knapp, J. Loweth, Barry Waterhouse, Rachel Navarra

Rowan-Virtua Research Day

It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following …

Variables Contributing To The Psychosocial Strain On Caregivers Of Patients With Autism Spectrum Disorder, Maduka Gunasinghe, Krisha S. Patel, Usmaan Al-Shehab, Brian Joseph Mathew, Maithri Goud, Andrea Iannuzzelli

Rowan-Virtua Research Day

This research, conducted at the Rowan-Virtua Integrated Special Needs (RISN) Center, Sewell, New Jersey, explores the psychosocial strain on caregivers of patients with Autism Spectrum Disorder (ASD). Utilizing the Caregiver Burden Inventory (CBI), we assessed multiple psychosocial dimensions, including time dependency, emotional health, development, social relationships, and physical health. Data was extracted from a total of 295 patient charts; this poster analyzes the initial sample of 99 patients by incorporating demographic variables and caregiver burden scores into a tailored database for comprehensive analysis. Our findings reveal a statistically significant correlation between the age of patients and increased developmental scores in …

A Stroke Or Not A Stroke? A Case Of Chronic Hemiplegic Migraines, Bum J. Kim, Matthew Orap, Bret Farrow-Cypel, Naseer Ahmed

Rowan-Virtua Research Day

Hemiplegic migraine (HM) is a rare subtype of migraine with both familial and sporadic patterns. These migraines present episodically with reversible attacks of unilateral motor weakness. Patients may experience visual changes, sensory loss, impaired level of consciousness, ataxia, and speech changes. Symptoms can last from hours to days and can mimic acute stroke.

The patient is a 45-year-old male with a past medical history of hypertension and possible cerebral vascular accident use who presents to the emergency department complaining of left extremity numbness and weakness. Neuroimaging showed no acute findings and CT angiogram showed no large vessel occlusion. Tenecteplase was …

Integrated Transcriptomics And Histopathology Approach Identifies A Subset Of Rejected Donor Livers With Potential Suitability For Transplantation, Ankita Srivastava, Alexandra Manchel, John Waters, Manju Ambelil, Benjamin K. Barnhart, Jan B. Hoek, Ashesh P. Shah, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation).

RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, …

Low Absolute Risk Of Thrombotic And Cardiovascular Events In Outpatient Pregnant Women With Covid-19, Behnood Bikdeli, Darsiya Krishnathasan, Candrika Khairani, Antoine Bejjani, Julia Davies, Nicole Porio, Anthony Tristani, Andre Armero, Ali Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Marcos Ortiz-Rios, Valeria Zuluaga-Sánchez, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno Merli, Orly Leiva, John Fanikos, Elvira Grandone, Aditya Sharma, Samantha Rizzo, Mariana Pfeferman, Ruth Morrison, Alec Vishnevsky, Judith Hsia, Mark Nehler, James Welker, Marc Bonaca, Brett Carroll, Samuel Goldhaber, Zhou Lan, Gregory Piazza

Division of Cardiology Faculty Papers

INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.

MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and …

Healthcare Social Network Research And The Echo Model™: Exploring A Community Of Practice To Support Cultural Brokers And Transfer Cultural Knowledge, Phil Nixon, Chiara Broccatelli, Perrin Moss, Sarah Baggio, Angela Young, Dana Newcomb

Project ECHO Bibliography

BACKGROUND: Project ECHO

METHODS: Social network theories and methods informed the collection of network data and analysis of advice-seeking relationships among ECHO network members and their nominees. Registered members from two ECHO networks were invited to complete the Qualtrics survey. Networks analysed comprised 398 professionals from mainstream health, Aboriginal and Torres Strait Islander Community Controlled Health Organisation, education, disability and child safety service settings.

RESULTS: Brokers were well represented, both those who hold knowledge brokerage positions as well as cultural brokers who incorporate clinical and cultural knowledge enabling holistic care for Aboriginal and Torres Strait Islander patients (38 individuals, 17% …

Key Variants Via The Alzheimer's Disease Sequencing Project Whole Genome Sequence Data, Yanbing Wang, Chloé Sarnowski, Honghuang Lin, Achilleas N Pitsillides, Nancy L Heard-Costa, Seung Hoan Choi, Dongyu Wang, Joshua C Bis, Elizabeth E Blue, Eric Boerwinkle, Philip L De Jager, Myriam Fornage, Ellen M Wijsman, Sudha Seshadri, Josée Dupuis, Gina M Peloso, Anita L Destefano

Journal Articles

INTRODUCTION: Genome-wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire genome and captures rare variations, may identify causal variants within GWAS loci.

METHODS: We performed single common variant association analysis and rare variant aggregate analyses in the pooled population (N cases = 2184, N controls = 2383) and targeted analyses in subpopulations using WGS data from the Alzheimer's Disease Sequencing Project (ADSP). The analyses were restricted to variants within 100 kb of 83 previously …

Patient Priorities Care Increases Long-Term Service And Support Use: Propensity Match Cohort Study, Rafael Samper-Ternent, Javad Razjouyan, Lilian Dindo, Jaime Halaszynski, Jennifer Silva, Terri Fried, Aanand D Naik

Journal Articles

OBJECTIVES: Patient priorities care (PPC) is an evidence-based approach designed to help patients achieve what matters most to them by identifying their health priorities and working with clinicians to align the care they provide to the patient's priorities. This study examined the impact of the PPC approach on long-term service and support (LTSS) use among veterans.

DESIGN: Quasi-experimental study examining differences in LTSS use between veterans exposed to PPC and propensity-matched controls not exposed to PPC adjusting for covariates.

SETTING AND PARTICIPANTS: Fifty-six social workers in 5 Veterans Health Administration (VHA) sites trained in PPC in 2018, 143 veterans who …

Availability And Utilization Of Endoscopic Retrograde Cholangiopancreatography At Children's Hospitals., Sagar J. Pathak, Thomas M. Attard, Matthew Hall, Mustafa Arain, Melvin B. Heyman, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors.

METHODS: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service.

RESULTS: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses …

Enhanced Resolution Profiling In Twins Reveals Differential Methylation Signatures Of Type 2 Diabetes With Links To Its Complications., Colette Christiansen, Louis Potier, Tiphaine C. Martin, Sergio Villicaña, Juan E. Castillo-Fernandez, Massimo Mangino, Cristina Menni, Pei-Chien Tsai, Purdey J. Campbell, Shelby Mullin, Juan R. Ordoñana, Olga Monteagudo, Perminder S. Sachdev, Karen A. Mather, Julian N. Trollor, Kirsi H. Pietilainen, Miina Ollikainen, Christine Dalgård, Kirsten Kyvik, Kaare Christensen, Jenny Van Dongen, Gonneke Willemsen, Dorret I. Boomsma, Patrik K E Magnusson, Nancy L. Pedersen, Scott G. Wilson, Elin Grundberg, Tim D. Spector, Jordana T. Bell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.

METHODS: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.

FINDINGS: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify …