Digital Commons Network^™

Risk Factors, Incidence, And Outcomes Associated With Clinically Significant Airway Ischemia, Gloria Li, Zejian Liu, Marcelo Salan-Gomez, Emma Keeney, Ethan D'Silva, Babith Mankidy, Andres Leon, Aladdein Mattar, Abdusallam Elsennousi, Jennalee Coster, Anupam Kumar, Bruno Rodrigues, Meng Li, Alexis Shafii, Puneet Garcha, Gabriel Loor

Faculty, Staff and Students Publications

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for …

Cardiac Tamponade Secondary To Esophagopericardial Fistula, Caitlin T Perez-Stable, Lauren T Callaghan, Christopher K Wong, Jorge M Escobar, Mahboob Alam

Faculty, Staff and Students Publications

Esophagopericardial fistulas are an extremely rare structural defect that may arise from malignant or iatrogenic etiologies. This article reports the case of a patient with cardiac tamponade secondary to hydropneumopericardium from esophagopericardial fistula. Given the high morbidity and mortality of this condition, this article describes challenges in diagnosis and clinical decision-making to improve early identification and interdisciplinary management.

Functional Genomics And Small Molecules In Mitochondrial Neurodevelopmental Disorders, Daniel G Calame, Lisa T Emrick

Faculty, Staff and Students Publications

Mitochondria are critical for brain development and homeostasis. Therefore, pathogenic variation in the mitochondrial or nuclear genome which disrupts mitochondrial function frequently results in developmental disorders and neurodegeneration at the organismal level. Large-scale application of genome-wide technologies to individuals with mitochondrial diseases has dramatically accelerated identification of mitochondrial disease-gene associations in humans. Multi-omic and high-throughput studies involving transcriptomics, proteomics, metabolomics, and saturation genome editing are providing deeper insights into the functional consequence of mitochondrial genomic variation. Integration of deep phenotypic and genomic data through allelic series continues to uncover novel mitochondrial functions and permit mitochondrial gene function dissection on an …

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

Faculty, Staff and Students Publications

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 …

Understanding The Role Of Ampa Receptors In Autism: Insights From Circuit And Synapse Dysfunction, Andres Jimenez-Gomez, Megan X Nguyen, Jason S Gill

Faculty, Staff and Students Publications

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the …

Branched-Chain Amino Acid Accumulation Fuels The Senescence-Associated Secretory Phenotype, Yaosi Liang, Christopher Pan, Tao Yin, Lu Wang, Xia Gao, Ergang Wang, Holly Quang, De Huang, Lianmei Tan, Kun Xiang, Yu Wang, Peter B Alexander, Qi-Jing Li, Tso-Pang Yao, Zhao Zhang, Xiao-Fan Wang

Faculty, Staff and Students Publications

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation …

Polygenic Scores And Mendelian Randomization Identify Plasma Proteins Causally Implicated In Alzheimer’S Disease, Davis B Cammann, Yimei Lu, Jerome I Rotter, Alexis C Wood, Jingchun Chen

Faculty, Staff and Students Publications

BACKGROUND: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

METHODS: We used a genome-wide association study (GWAS) of 90 different plasma proteins (

RESULTS: We identified …

International Society For Pediatric And Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery, Torben Biester, Cari Berget, Charlotte Boughton, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive …

Predictors Of Making A Referral To Child Protective Services Prior To Expert Consultation, Danielle Zamalin, Irene Hamlin, Justine Shults, M Katherine Henry, Kristine A Campbell, James D Anderst, Angela N Bachim, Rachel P Berger, Lori D Frasier, Nancy S Harper, Megan M Letson, John D Melville, Daniel M Lindberg, Joanne N Wood

Faculty, Staff and Students Publications

OBJECTIVE: Suspicion for child abuse is influenced by implicit biases. Evaluation by a Child Abuse Pediatrician (CAP) may reduce avoidable child protective services (CPS) referrals. Our objective was to investigate the association of patient demographic, social and clinical characteristics with CPS referral before consultation by a CAP (preconsultation referral).

METHODS: Children <5 years-old undergoing in-person CAP consultation for suspected physical abuse from February 2021 through April 2022 were identified in CAPNET, a multicenter child abuse research network. Marginal standardization implemented with logistic regression analysis examined hospital-level variation and identified demographic, social, and clinical factors associated with pre-consultation referral adjusting for CAP’s final assessment of abuse likelihood.

RESULTS: Among the 61% (1005/1657) of cases with preconsultation referral, the CAP consultant had low concern for abuse in 38% (384/1005). Preconsultation referrals ranged from 25% to 78% of cases across 10 hospitals (P < .001). In multivariable analyses, preconsultation referral was associated with public insurance, caregiver history of CPS involvement, history of intimate partner violence, higher CAP level of concern for abuse, hospital transfer, and near-fatality (all P < .05). The difference in preconsultation referral prevalence for children with public versus private insurance was significant for children with low CAP concern for abuse (52% vs 38%) but not those with higher concern for abuse (73% vs 73%), (P = .023 for interaction of insurance and abuse likelihood category). There were no differences in preconsultation referral based on race or ethnicity.

CONCLUSIONS: Biases based on socioeconomic status and social factors may impact decisions to refer to …

Changes In Patterns Of Referral For Inpatient Rehabilitation Cancer Patients Due To Covid-19: A Retrospective Study, Ekta Gupta, Amy H Ng, Aline Rozman De Moraes, Jack B Fu, Jegy M Tennison, Maaheen Ahmed, Bryan M Fellman, Eduardo Bruera

Faculty, Staff and Students Publications

There is a paucity of literature on the effect of COVID-19 on hospital processes. We hypothesized that COVID-19 was associated with decreased cancer physiatry referrals in 2020. This is a retrospective cohort study of consecutive patients from April to July 2019 and 2020 admitted at an academic quaternary cancer center. The main outcomes were number of hospital admissions, rate, and characteristics of inpatient rehabilitation admissions and change in percentage of physiatry referrals as the primary endpoint. Results showed that in 2019, there were 387 referrals from 10,274 inpatient admissions (3.8%; 95% confidence interval, 2.4-4.2), compared with 337 referrals from 7051 …

Crystal Structure Of Trichinella Spiralis Calreticulin And The Structural Basis Of Its Complement Evasion Mechanism Involving C1q, Zhihui Jia, Wen Yu, Jingmo Li, Mingming Zhang, Bin Zhan, Liming Yan, Zhenhua Ming, Yuli Cheng, Xiaolin Tian, Shuai Shao, Jingjing Huang, Xinping Zhu

Faculty, Staff and Students Publications

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT …

Associations Of Chronic Pain With Psychosocial Outcomes After Traumatic Brain Injury: A Nidilrr And Va Tbi Model Systems Collaborative Project, Robin Hanks, Jessica M Ketchum, Mackenzie Peckham, Mitch Sevigny, Angelle M Sander, Aaron M Martin, Stephanie Agtarap, Cynthia L Beaulieu, Librada Callender, Flora M Hammond, Jean Lengenfelder, Amanda R Rabinowitz, William C Walker, Jeanne M Hoffman, Cynthia Harrison-Felix, Risa Nakase-Richardson

Faculty, Staff and Students Publications

OBJECTIVE: To examine the differences in participation, life satisfaction, and psychosocial outcomes among individuals with traumatic brain injury (TBI) endorsing current, past, or no chronic pain.

SETTING: Community.

PARTICIPANTS: Three thousand eight hundred four TBI Model Systems participants 1 to 30 years of age postinjury classified into 1 of 3 groups based on their pain experience: current pain, past pain, no pain completed a Pain Survey at their usual follow-up appointment which on average was approximately 8 years postinjury.

DESIGN: Multisite, cross-sectional observational cohort study.

MAIN OUTCOME MEASURES: Sociodemographic and injury characteristics and psychosocial outcomes (ie, satisfaction with life, depression, …

Pre-Clinical Protective Potentials Of Carica Papaya Constituents In Experimentally Induced Anemia, Hassan Abdulsalam Adewuyi, Adamu Yusuf Kabiru, Hadiza Lami Muhammad, Halimat Yusuf Lukman, Mayowa Solomon Owolabi, Ibrahim Jonathan, Ahmed M El-Gazzar, Mohamed H Mahmoud, Gaber El-Saber Batiha, Bashir Lawal

Faculty, Staff and Students Publications

OBJECTIVE: Anemia is a pathological condition characterized by reduced oxygen bioavailability and/or changes in hematological parameters. This study investigated the anti-anemic activities of

METHOD: Twenty-seven rats were randomized into nine groups of three rats as follows; group 1 was the normal (non-induced) group, 2-9 were anemic rats administered 1 mL distilled water, standard drug (3 mg/kg body weight (bw) ferrous sulphate), 100, 300 and 500 mg/kg bw of crude methanolic extract of CP (CMECP) of the leaf and 100, 300 and 500 mg/kg bw of CMECP of the seed respectively in the first stage of the study. In the second …

Diagnostic Value Of Soluble Urokinase-Type Plasminogen Activator Receptor In Patients With Acute Coronary Syndrome: A Systematic Review And Meta-Analysis, Michal Pruc, Iwona Jannasz, Damian Swieczkowski, Grzegorz Procyk, Aleksandra Gasecka, Zubaid Rafique, Francesco Chirico, Nicola Luigi Bragazzi, Milosz J Jaguszewski, Jaroslaw Wysocki, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS.

METHODS: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used …

Recent Trends In The Incidence Of Gastric Cancer In The United States, Kyle S Liu, Syed Ahsan Raza, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population.

METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were …

Gene Content, Phage Cycle Regulation Model And Prophage Inactivation Disclosed By Prophage Genomics In The Helicobacter Pylori Genome Project, Filipa F Vale, Richard J Roberts, Ichizo Kobayashi, M Constanza Camargo, Charles S Rabkin, Hpgp Research Network

Faculty, Staff and Students Publications

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified …

The Tb27 Transcriptomic Model For Predicting Mycobacterium Tuberculosis Culture Conversion, Maja Reimann, Korkut Avsar, Andrew R Dinardo, Torsten Goldmann, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H E Kaufmann, Niklas Köhler, Anna M Mandalakas, Florian P Maurer, Marius Müller, Dörte Nitschkowski, Ioana D Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Helmut J F Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Elena Terhalle, Markus Unnewehr, Nika J Zielinski, Jan Heyckendorf, Christoph Lange

Faculty, Staff and Students Publications

RATIONALE: Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of Mycobacterium tuberculosis. Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.

OBJECTIVE: Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.

METHODS: Using a multi-step machine learning algorithm to identify an RNA-based algorithm to predict the remaining time to culture conversion at flexible time points during anti-tuberculosis therapy.

RESULTS: The identification cohort included 149 patients split into a training and a test cohort, to develop a multistep algorithm consisting of …

Contemporary Functional Coronary Angiography: An Update, Josiah Bennett, Sanjay Chandrasekhar, Edward Woods, Patrick Mclean, Noah Newman, Brett Montelaro, Hafeez Ul Hassan Virk, Mahboob Alam, Samin K Sharma, Hani Jned, Muzamil Khawaja, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Functional coronary angiography (FCA) is a novel modality for assessing the physiology of coronary lesions, going beyond anatomical visualization by traditional coronary angiography. FCA incorporates indices like fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR), which utilize pressure measurements across coronary stenoses to evaluate hemodynamic impacts and to guide revascularization strategies. In this review, we present traditional and evolving modalities and uses of FCA. We will also evaluate the existing evidence and discuss the applicability of FCA in various clinical scenarios. Finally, we provide insight into emerging evidence, current challenges, and future directions in FCA.

De Novo Missense Variants In Zbtb47 Are Associated With Developmental Delays, Hypotonia, Seizures, Gait Abnormalities, And Variable Movement Abnormalities, Scott K Ward, Alexandrea Wadley, Chun-Hui Anne Tsai, Paul J Benke, Lisa Emrick, Kristen Fisher, Kimberly M Houck, Hongzheng Dai, Undiagnosed Diseases Network, Maria J Guillen Sacoto, William Craigen, Kimberly Glaser, David R Murdock, Luis Rohena, Karin E M Diderich, Hennie T Bruggenwirth, Brendan Lee, Carlos Bacino, Lindsay C Burrage, Jill A Rosenfeld

Faculty, Staff and Students Publications

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in ZBTB47, with p.(Glu680Gly) (c.2039A>G) detected …

Blind To The Perils Of Pursuing Food: Behaviors Of Individuals With Smith-Magenis Syndrome, Citrine Elatrash, Jenna Shi, Theresa Wilson, Sarah H Elsea, Stephanie Sisley

Faculty, Staff and Students Publications

PURPOSE: Discrepancies exist between the need to lock food away and satiety scores in the Smith-Magenis syndrome (SMS) population. This study sought to uncover food-related behaviors within this unique group of individuals.

METHODS: Caregivers (

RESULTS: This study identified a global theme of "Blind to the perils while pursuing their goals," supported by 5 organizing themes: (1) Biology-impacting behaviors, (2) Need for personalized strategies, (3) Controlling food experiences, (4) Need for parents to orchestrate life, and (5) Surprising resourcefulness. Subthemes within these organizing themes highlighted that individuals with SMS have unique food-related behaviors and often fixate on certain types of …

Case Report: An Association Of Left Ventricular Outflow Tract Obstruction With 5p Deletions, Kira Mascho, Svetlana A Yatsenko, Cecilia W Lo, Xinxiu Xu, Jennifer Johnson, Lindsey R Helvaty, Stephanie Burns Wechsler, Chaya N Murali, Seema R Lalani, Vidu Garg, Jennelle C Hodge, Kim L Mcbride, Stephanie M Ware, Jiuann-Huey Ivy Lin

Faculty, Staff and Students Publications

INTRODUCTION: 5p deletion syndrome, also called Cri-du-chat syndrome 5p is a rare genetic syndrome with reports up to 36% of patients are associated with congenital heart defects. We investigated the association between left outflow tract obstruction and Cri-du-chat syndrome.

METHODS: A retrospective review of the abnormal microarray cases with congenital heart defects in Children's Hospital of Pittsburgh and the Cytogenomics of Cardiovascular Malformations Consortium.

RESULTS: A retrospective review at nine pediatric centers identified 4 patients with 5p deletions and left outflow tract obstruction (LVOTO). Three of these patients had additional copy number variants. We present data suggesting an association of …

International Society For Extracellular Vesicles Workshop Quantitatevs: Multiscale Analyses, From Bulk To Single Extracellular Vesicle, Manuela Basso, Alessandro Gori, Caterina Nardella, Mari Palviainen, Marija Holcar, Ioannis Sotiropoulos, Sylwia Bobis-Wozowicz, Vito G D'Agostino, Elena Casarotto, Yari Ciani, Shiro Suetsugu, Alice Gualerzi, Lorena Martin-Jaular, Daniela Boselli, Anna Kashkanova, Pietro Parisse, Lien Lippens, Martina Pagliuca, Martin Blessing, Roberto Frigerio, Thibaut Fourniols, Ana Meliciano, Anna Fietta, Paolo Vincenzo Fioretti, Karolina Soroczyńska, Silvia Picciolini, Amanda Salviano-Silva, Paolo Bergese, Davide Zocco, Marcella Chiari, Guido Jenster, Levi Waldron, Aleksandar Milosavljevic, John Nolan, Marco P Monopoli, Kenneth W Witwer, Benedetta Bussolati, Dolores Di Vizio, Juan Falcon Perez, Metka Lenassi, Marina Cretich, Francesca Demichelis

Faculty, Staff and Students Publications

The “QuantitatEVs: multiscale analyses, from bulk to single vesicle” workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV‐associated molecular components and EV biophysical features, which are considered the core of EV‐associated biomarker discovery and validation for their clinical translation. The in‐person‐only workshop was held in Trento, Italy, from January 31st to February 2nd, 2023, and continued in Milan on February 3rd with “Next …

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Cristin G Welle, Kevin B Wilkins, Helen M Bronte-Stewart, Valerie Voon, Takashi Morishita, Yuki Sakai, Amanda R Merner, Gabriel Lázaro-Muñoz, Theresa Williamson, Andreas Horn, Ro'ee Gilron, Jonathan O'Keeffe, Aryn H Gittis, Wolf-Julian Neumann, Simon Little, Nicole R Provenza, Sameer A Sheth, Alfonso Fasano, Abbey B Holt-Becker, Robert S Raike, Lisa Moore, Yagna J Pathak, David Greene, Sara Marceglia, Lothar Krinke, Huiling Tan, Hagai Bergman, Monika Pötter-Nerger, Bomin Sun, Laura Y Cabrera, Cameron C Mcintyre, Noam Harel, Helen S Mayberg, Andrew D Krystal, Nader Pouratian, Philip A Starr, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …

Multimodal Prediction Of Obsessive-Compulsive Disorder And Comorbid Depression Severity And Energy Delivered By Deep Brain Electrodes, Saurabh Hinduja, Ali Darzi, Itir Onal Ertugrul, Nicole Provenza, Ron Gadot, Eric A Storch, Sameer A Sheth, Wayne K Goodman, Jeffrey F Cohn

Faculty, Staff and Students Publications

To develop reliable, valid, and efficient measures of obsessive-compulsive disorder (OCD) severity, comorbid depression severity, and total electrical energy delivered (TEED) by deep brain stimulation (DBS), we trained and compared random forests regression models in a clinical trial of participants receiving DBS for refractory OCD. Six participants were recorded during open-ended interviews at pre- and post-surgery baselines and then at 3-month intervals following DBS activation. Ground-truth severity was assessed by clinical interview and self-report. Visual and auditory modalities included facial action units, head and facial landmarks, speech behavior and content, and voice acoustics. Mixed-effects random forest regression with Shapley feature …

Translational Symmetry In Convolutions With Localized Kernels Causes An Implicit Bias Toward High Frequency Adversarial Examples, Josue O Caro, Yilong Ju, Ryan Pyle, Sourav Dey, Wieland Brendel, Fabio Anselmi, Ankit B Patel

Faculty, Staff and Students Publications

Adversarial attacks are still a significant challenge for neural networks. Recent efforts have shown that adversarial perturbations typically contain high-frequency features, but the root cause of this phenomenon remains unknown. Inspired by theoretical work on linear convolutional models, we hypothesize that translational symmetry in convolutional operations together with localized kernels implicitly bias the learning of high-frequency features, and that this is one of the main causes of high frequency adversarial examples. To test this hypothesis, we analyzed the impact of different choices of linear and non-linear architectures on the implicit bias of the learned features and adversarial perturbations, …

Anesthetic Management Of A Patient With Renal Cell Carcinoma-Associated Venous Thrombosis And Massive Transfusion, Gary Zhang, Ryan Palacios, Jamal Hasoon, Christopher L Robinson, Anvinh Nguyen

Faculty, Staff and Students Publications

A 53-year-old male with a history of multiple deep venous thromboses (DVTs) underwent a right open radical nephrectomy with inferior vena cava (IVC) thrombectomy in the context of renal cell carcinoma (RCC)-associated venous thrombosis. Imaging and renal biopsy revealed a diagnosis of RCC with non-occlusive thrombosis of the left renal vein and occlusive thrombosis of the infrarenal IVC. The major risks of concern for the procedure included thrombus embolization from surgical manipulation and massive bleeding. Intraoperatively, the patient experienced significant hemorrhage requiring massive transfusion protocol. The purpose of this case report is to emphasize the importance of multidisciplinary involvement, intraoperative …

The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington

Faculty, Staff and Students Publications

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.

Moving From Conventional To Adaptive Risk Stratification For Oropharyngeal Cancer, Vlad C Sandulache, R Parker Kirby, Stephen Y Lai

Faculty, Staff and Students Publications

Oropharyngeal cancer (OPC) poses a complex therapeutic dilemma for patients and oncologists alike, made worse by the epidemic increase in new cases associated with the oncogenic human papillomavirus (HPV). In a counterintuitive manner, the very thing which gives patients hope, the high response rate of HPV-associated OPC to conventional chemo-radiation strategies, has become one of the biggest challenges for the field as a whole. It has now become clear that for ~30-40% of patients, treatment intensity could be reduced without losing therapeutic efficacy, yet substantially diminishing the acute and lifelong morbidity resulting from conventional chemotherapy and radiation. At the same …

Management Advice For Patients With Reflux-Like Symptoms: An Evidence-Based Consensus, A Pali Hungin, Rena Yadlapati, Foteini Anastasiou, Albert J Bredenoord, Hashem El Serag, Pierluigi Fracasso, Juan M Mendive, Edoardo V Savarino, Daniel Sifrim, Mihaela Udrescu, Peter J Kahrilas

Faculty, Staff and Students Publications

Patients with reflux-like symptoms (heartburn and regurgitation) are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes, lifestyle modifications, behavioural changes or fast-acting rescue therapies. One reason for this may be the lack of emphasis in management guidelines owing to 'low-quality' evidence and a paucity of interventional studies. Thus, a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus. A steering committee selected topics for literature searches using the PubMed database, and a modified Delphi process including two online meetings …

Anemia, Iron Deficiency, And Cause-Specific Mortality: The Atherosclerosis Risk In Communities Study, Ethan J Cannon, Jeffrey R Misialek, Leo F Buckley, Iman A F Aboelsaad, Christie M Ballantyne, John Leister, James S Pankow, Pamela L Lutsey

Faculty, Staff and Students Publications

Introduction: Anemia is a risk factor for all-cause mortality in older adults. Iron deficiency may also be associated with adverse outcomes, independent of its role in causing anemia. This study tested the hypotheses that anemia, and low ferritin among non-anemic participants, were associated with all-cause and cause-specific mortality in a community-based cohort of older adults.

Methods: Fasting blood was obtained from 5,070 ARIC participants (median age: 75 years) in 2011-2013. Anemia was defined by hemoglobin concentrations < 12 g/dL in women and < 13 g/dL in men. We classified 4,020 non-anemic participants by quartiles of plasma ferritin, measured by the SomaScan proteomics platform. Cox proportional hazards regression was used. Mortality was ascertained via phone calls with proxies as part of twice-yearly cohort follow-up, surveillance of local hospital discharge indexes, state death records, and linkage to the National Death Index.

Results: Of the total participants, 21% had anemia at baseline. Over a median of 7.5 years, there were 1,147 deaths, including 357 due to …