Digital Commons Network^™

Association Between Mri Findings Of Facet Arthropathy And Synovitis With Health-Related Outcome And Pain Scores Following Therapeutic Lumbar Facet Injections, Michael Stuart Green, Michele Van Hal, Matthew Onimus, Christopher R. Hoffman, Dhruv K. C. Goyal, Valeria Potigailo, Khuram S. Kazmi

Department of Anesthesiology Faculty Papers

Low back pain is a common complaint among adults. The facet joint is a major source of lumbar pain, and therapeutic facet injections have gained popularity as a minimally invasive treatment option. In addition, magnetic resonance imaging (MRI) utilization for diagnosing low back pain has increased significantly over the past few decades. Facet synovitis is an entity characterized by edema and inflammatory changes affecting the facet joints, adjacent bone marrow, and surrounding soft tissues. Although its underlying etiology remains poorly understood, recent reports suggest a high incidence in patients with arthropathy and arthritis. It is essential to explore potential correlations …

Health Risks Associated With Adopting New-Generation Disposable Products Among Young Adults Who Use E-Cigarettes, Shuyao Ran, James J Yang, Megan E Piper, Hsien-Chang Lin, Anne Buu

Faculty, Staff and Student Publications

New-generation disposable e-cigarettes have become increasingly popular among young adults in the USA since the FDA's partial flavor ban. This study aims to examine longitudinal changes in health risks among young adults who adopted these novel products, as well as the health effects of device types beyond the effects of other important e-cigarette characteristics. This study recruited e-cigarette users via voluntary response sampling from three college campuses in the USA to respond to four-wave online surveys conducted in four consecutive semesters. Among the participants who adopted disposables during the study, their health risks (dependence symptoms, respiratory symptoms, combustible tobacco use) …

Evaluation Of Ki-67 Expression And Large Cell Content As Prognostic Markers In Mzl: A Multicenter Cohort Study, Natalie S. Grover, Kaitlin Annunzio, Marcus Watkins, Pallawi Torka, Reem Karmali, Andrea Anampa-Guzmán, Timothy S. Oh, Heather Reves, Montreh Tavakkoli, Emily Hansinger, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla

Department of Medicine Faculty Papers

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among …

Progress In Physical Activity Research, Policy, And Surveillance In Canada: The Global Observatory For Physical Activity – Gopa!, Ashley Cathro, John C Spence, Christine Cameron, Andrea Ramirez Varela, Diana Morales, Eduardo Ribes Kohn, Michael Pratt, Pedro C Hallal

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this paper is to examine the evolution of physical activity research and the comprehensiveness of national physical activity policies and surveillance systems in Canada.

METHODS: A systematic review was conducted by the Global Observatory for Physical Activity (GoPA! ) on physical activity and health publications between 1950 and 2019. Findings from Canada were extracted and included in the present analysis. The number of articles published, female researcher involvement in authorship, author institution affiliations, and publication themes were examined. Policies were evaluated by determining if there was a standalone physical activity plan and if national guidelines existed. …

Safety Of Kidney Transplantation From Donors With Hiv, Christine M Durand, Allan Massie, Sander Florman, Tao Liang, Meenakshi M Rana, Rachel Friedman-Moraco, Alexander Gilbert, Peter Stock, Sapna A Mehta, Shikha Mehta, Valentina Stosor, Marcus R Pereira, Michele I Morris, Jonathan Hand, Saima Aslam, Maricar Malinis, Ghady Haidar, Catherine B Small, Carlos A Q Santos, Joanna Schaenman, John Baddley, David Wojciechowski, Emily A Blumberg, Karthik Ranganna, Oluwafisayo Adebiyi, Nahel Elias, Jose A Castillo-Lugo, Emmanouil Giorgakis, Senu Apewokin, Diane Brown, Darin Ostrander, Yolanda Eby, Niraj Desai, Fizza Naqvi, Serena Bagnasco, Natasha Watson, Erica Brittain, Jonah Odim, Andrew D Redd, Aaron A R Tobian, Dorry L Segev

Faculty, Staff and Student Publications

Background: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls.

Methods: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. …

Influence Of Tp53 Gene Mutations And Their Allelic Status In Myelodysplastic Syndromes With Isolated 5q Deletion, Maria Julia Montoro, Laura Palomo, Claudia Haferlach, Pamela Acha, Onyee Chan, Víctor Navarro, Yasuo Kubota, Felicitas Isabel Schulz, Manja Meggendorfer, Robert Briski, Najla Al Ali, Blanca Xicoy, Félix López-Cadenas, Francesc Bosch, Teresa González, Lea Naomi Eder, Andrés Jerez, Yu-Hung Wang, Alessia Campagna, Valeria Santini, Teresa Bernal Del Castillo, Esperanza Such, Hwei-Fang Tien, Nicolás Diaz Varela, Uwe Platzbecker, Detlef Haase, María Díez-Campelo, Matteo Della Porta, Guillermo Garcia-Manero, Daniel H Wiseman, Ulrich Germing, Jaroslaw P Maciejewski, Rami S Komrokji, Francesc Sole, Torsten Haferlach, David Valcárcel

Faculty, Staff and Student Publications

Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, whereas the remaining patients displayed monoallelic …

Bridging Big Data In The Enigma Consortium To Combine Non-Equivalent Cognitive Measures, Eamonn Kennedy, Shashank Vadlamani, Hannah M Lindsey, Pui-Wa Lei, Mary Jo-Pugh, Paul M Thompson, David F Tate, Frank G Hillary, Emily L Dennis, Elisabeth A Wilde, Enigma Clinical Endpoints Working Group Collaborators

Faculty, Staff and Student Publications

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample size. These efforts unveil new questions about how to integrate data across distinct sources and instruments. The goal of this study was to link scores across common auditory verbal learning tasks (AVLTs). This international secondary analysis aggregated multisite raw data for AVLTs across 53 studies totaling 10,505 individuals. Using the ComBat-GAM algorithm, we isolated and removed the component of memory scores associated with site effects while preserving instrumental effects. After adjustment, a continuous item response theory model used multiple memory items of varying …

Genotype And Phenotype Of 21-Hydroxylase Deficiency: A Single Center Experience From Western India, Manjiri Karlekar, Rohit Barnabas, Vijaya Sarathi, Anurag Lila, Sneha Arya, Samiksha Hegishte, Vishwambhar V Bhandare, Saba Samad Memon, Virendra Patil, Tushar Bandgar, Ambarish Kunwar, Nalini Shah

Faculty, Staff and Student Publications

Objective: To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency.

Methods: Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA).

Results: Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed. 41 had SW, 34 had SV, and 5 had NC phenotype. Disease-causing mutations were identified in 158/160 alleles. The common mutations were Deletions/Large …

Trends In Gaps Of Care For Patients With Congenital Heart Disease: Implications For Social Determinants Of Health And Child Opportunity Index, Abbas H. Zaidi, Adam Alberts, Devyani Chowdhury, Claude Beaty, Benjamin Brewer, Ming Hui Chen, Sarah D. De Ferranti

Department of Surgery Faculty Papers

BACKGROUND: Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood.

METHODS AND RESULTS: This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such …

Institutional Experience Of Lymphoproliferative Disorders With Initial Diagnosis Made Via Fine Needle Aspiration At Otolaryngology Clinic, Alaa S. Hrizat, Jerald Gong, Stacey M. Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: This study characterizes lymphomas presenting as palpable head and neck masses and evaluates the role of fine needle aspiration (FNA) and flow cytometry (FC) in diagnosis.

DESIGN: A 5-year retrospective review of FNAs performed by pathologists in an ENT clinic identified cases with a predominant lymphoid population that lacked an epithelial component. Cytology, FC, and subsequent surgical pathology diagnoses were correlated.

RESULTS: Of 821 FNAs, 154 (19%) met selection criteria. Reactive lymph nodes accounted for 43% (67/154), with most diagnosed as 'negative for malignancy,' except one 'atypical' (ATY) case. Lymphoma was confirmed in 57% (87/154) of cases, categorized as …

Biochemical And Structural Insights Into A 5′ To 3′ Rna Ligase Reveal A Potential Role In Trna Ligation, Yingjie Hu, Victor A Lopez, Hengyi Xu, James P Pfister, Bing Song, Kelly A Servage, Masahiro Sakurai, Benjamin T Jones, Joshua T Mendell, Tao Wang, Jun Wu, Alan M Lambowitz, Diana R Tomchick, Krzysztof Pawłowski, Vincent S Tagliabracci

Faculty, Staff and Student Publications

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic …

Reproduction Has Immediate Effects On Female Mortality, But No Discernible Lasting Physiological Impacts: A Test Of The Disposable Soma Theory, Sharon E Mitchell, Megan Simpson, Lena Coulet, Solenn Gouedard, Catherine Hambly, Juliano Morimoto, David B Allison, John R Speakman

Children’s Nutrition Research Center Staff Publications

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and over lifetime. We found that reproduction had an immediate and negative effect on survival due to problems encountered during parturition for some females. However, there was no statistically significant residual effect on …

Npm1-Mutated Myeloid Neoplasms Are A Unique Entity Not Defined By Bone Marrow Blast Percentage, Georgina Gener-Ricos, Alex Bataller, Juan Jose Rodriguez-Sevilla, Kelly S Chien, Andres E Quesada, Emmanuel Almanza-Huante, Danielle Hammond, Koji Sasaki, Courtney Dinardo, Tapan Kadia, Naval Daver, Gautam Borthakur, Ghayas C Issa, Nicholas J Short, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Introduction: NPM1-mutated (NPM1mut) myeloid neoplasms (MNs) with < 20% bone marrow (BM) blasts (NPM1mut MNs< 20) are uncommon, and their classification remains inconsistent.

Methods: The clinicopathologic features of 54 patients with NPM1mut MNs < 20 were evaluated and compared with wild-type NPM1 MNs < 20 and NPM1mut MNs≥20, respectively.

Results: NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty-three (61%) patients with NPM1mut MNs < 20 received low-intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age < 60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for < 10%, 10%-19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty-three patients (43%) with NPM1mut MNs < 20 had marrow blast progression to ≥20%.

Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.

Exposure To Per- And Polyfluoroalkyl Substances And Alterations In Plasma Microrna Profiles In Children, Yijie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Haotian Wu, Shelley H Liu, Hongxu Wang, Emily Beglarian, Scott M Bartell, Sandrah Proctor Eckel, Douglas Walker, Damaskini Valvi, Michele Andrea La Merrill, Thomas H Inge, Todd Jenkins, Justin R Ryder, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Marina Vafeiadi, Aikaterini Margetaki, Theano Roumeliotaki, Max Aung, Rob Mcconnell, Andrea Baccarelli, David Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans.

OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children.

METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and …

Clean Intermittent Catheterisation Determinants And Caregiver Adherence In Paediatric Patients With Spinal Dysraphism And Spinal Cord Injury In A Paediatric Spinal Differences Clinic: A Mixed Methods Study Protocol., Azadeh Wickham, Cynthia L. Russell, John Gatti

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Clean intermittent catheterisation (CIC) is the standard of care for treating neurogenic lower urinary tract dysfunction (NLUTD), the most common bladder dysfunction in children diagnosed with spinal dysraphism (SD) and spinal cord injury (SCI). Failure to follow the prescribed CIC regimen results in urinary tract infections, incontinence and renal insufficiency. Adherence to CIC is suboptimal, with reported non-adherence rates of 18%-66%. Despite the efficacy of CIC, the research on CIC adherence is not well defined in the literature and even less for caregivers of children on CIC protocols.

METHODS: This proposed study aims to identify caregiver CIC adherence and …

Left Ventricular Diastolic Dysfunction With Elevated Filling Pressures Is Associated With Embolic Stroke Of Undetermined Source And Atrial Fibrillation, Zubair Bashir, Liqi Shu, Yuqian Guo, Edward W Chen, Shuyuan Wang, Eric D Goldstein, Maheen Rana, Narendra Kala, Xing Dai, Daniel Mandel, Shadi Yaghi, Phinnara Has, Mingxing Xie, Tao Wang, James Simmons, Christopher Song, Philip Haines

Faculty, Staff and Student Publications

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring.

Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by …

Memory Modulation: Dominance Of Negative Visual Context Over Neutral Verbal Memory, Stas Kozak, Noa Herz, Maya Tocker, Yair Bar-Haim, Nitzan Censor

Department of Neurology Faculty Papers

Neutral memories can be modulated via intentional memory control paradigms such as directed forgetting. In addition, previous studies have shown that neutral visual memories can be modulated indirectly, via remember and forget instructions towards competing verbal memories. Here we show that direct modulation of neutral verbal memory strength is impaired by negative visual context, and that negative visual context is resistant to indirect memory modulation. Participants were directly instructed to intentionally remember or forget newly encoded neutral verbal information. Importantly, this verbal information was interleaved with embedded negative visual context. Results showed that negative visual context eliminated the well-documented effect …

Multicenter Pivotal Study Of The Alterra Adaptive Prestent For The Treatment Of Pulmonary Regurgitation, V Vivian Dimas, Vasilis Babaliaros, Dennis Kim, D Scott Lim, Gareth Morgan, Thomas K Jones, Aimee K Armstrong, Darren Berman, Jamil Aboulhosn, Vaikom S Mahadevan, Matthew J Gillespie, David Balzer, Thomas Zellers, Xiao Yu, Girish Shirali, Anitha Parthiban, Jonathan Leipsic, Philipp Blanke, Evan Zahn, Shabana Shahanavaz

Faculty, Staff and Students Publications

Background: A dilated native right ventricular outflow tract (RVOT) presents unique challenges for transcatheter management using balloon-expandable valves. The Alterra Adaptive Prestent was designed to expand transcatheter therapy to treat patients with dilated RVOTs.

Objectives: The aim of this study was to report 2-year outcomes of the main cohort of the ALTERRA (Multicenter Study of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent) pivotal trial using the prestent with transcatheter pulmonary valve replacement.

Methods: The prestent device used with the 29 mm SAPIEN 3 transcatheter heart valve (THV) was evaluated for the management of …

Regular Nonsteroidal Anti-Inflammatory Drug Use Increases Stress Fracture Risk In The General Population: A Retrospective Case-Control Study, Alexandra Ciuciu, Chris Mulholland, Michael A. Bozzi, Chris C. Frymoyer, Leonardo Cavinatto, David Yaron, Marc I. Harwood, Jeremy D. Close, Christopher J. Mehallo, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Previous studies have shown that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased stress fracture risk. This phenomenon has been studied predominantly in high-activity individuals, so data regarding the general population are limited despite the substantial economic and resource burden of stress fracture injuries within the general US population. Furthermore, our preclinical studies demonstrate that regular use of NSAIDs also diminishes the intrinsic ability of bone to resist fracture. To determine the association of regular NSAID use with stress fractures in the general population, we surveyed subjects presenting with either stress fracture or uncomplicated ankle sprain to …

Pain After Licorice Or Sugar-Water Gargling In Patients Recovering From Oropharyngeal Surgery-A Randomized, Double-Blind Trial, Marita Windpassinger, Michal Prusak, Jana Gemeiner, Olga Plattner, Stefan Janik, Gerold Besser, Wolfgang Gstoettner, Pu Xuan, Daniel I Sessler, Kurt Ruetzler

Faculty, Staff and Student Publications

Background: Glycyrrhiza glabrata (licorice) is used in traditional medicine and herbal remedies and reduces sore throats consequent to intubation, but whether it is protective for more intense pain after oropharyngeal surgery remains unclear. We thus tested the joint hypothesis that gargling with licorice, which has anti-inflammatory and antioxidant properties, reduces postoperative pain and morphine consumption.

Methods: We enrolled patients having elective oropharyngeal surgery. Participants were randomly allocated to gargle with either 1 g licorice or a sugar placebo before and for up to three days after surgery. A numerical rating scale (NRS) for pain along with morphine consumption was evaluated …

Sex Hormones And Risk Of Lung And Colorectal Cancers In Women: A Mendelian Randomization Study, Marion Denos, Yi-Qian Sun, Ben Michael Brumpton, Yafang Li, Demetrius Albanes, Andrea Burnett-Hartman, Peter T Campbell, Sébastien Küry, Christopher I Li, Emily White, Jewel N Samadder, Mark A Jenkins, Xiao-Mei Mai

Faculty, Staff and Students Publications

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval …

Long Covid Among Undocumented Latino Immigrant Populations In The Emergency Department., Karen P. Reyes, Zubaid Rafique, Brian Chinnock, Vijaya Arun Kumar, Michael Gottlieb, Kristin L. Rising, Robert M. Rodriguez

Department of Emergency Medicine Faculty Papers

Although many investigators have examined post–COVID-19 condition (long COVID) and its effects in the general population, to our knowledge, no studies have investigated its effect on one of the largest underserved US populations: undocumented Latino immigrants.¹ This group comprises 7% of the US population and has high rates of uninsurance, limited access to primary care, and language barriers when seeking health care.^2-4 Anti-immigrant political rhetoric and immigrants’ fear of discovery of their undocumented status when accessing health care make evaluation of this population more challenging.⁵ We leveraged emergency departments (EDs) as the primary health care …

A Complex Eprescribing Antimicrobial Stewardship-Based (Epams+) Intervention For Hospitals: Mixed-Methods Feasibility Trial Results, Christopher J Weir, Susan Hinder, Imad Adamestam, Rona Sharp, Holly Ennis, Andrew Heed, Robin Williams, Kathrin Cresswell, Omara Dogar, Sarah Pontefract, Jamie Coleman, Richard Lilford, Neil Watson, Ann Slee, Antony Chuter, Jillian Beggs, Sarah Slight, James Mason, David W Bates, Aziz Sheikh

Faculty, Staff and Students Publications

Background: Antibiotic resistant infections cause over 700,000 deaths worldwide annually. As antimicrobial stewardship (AMS) helps minimise the emergence of antibiotic resistance resulting from inappropriate use of antibiotics in healthcare, we developed ePAMS+ (ePrescribing-based Anti-Microbial Stewardship), an ePrescribing and Medicines Administration (EPMA) system decision-support tool complemented by educational, behavioural and organisational elements.

Methods: We conducted a non-randomised before-and-after feasibility trial, implementing ePAMS+ in two English hospitals using the Cerner Millennium EPMA system. Wards of several specialties were included. Patient participants were blinded to whether ePAMS+ was in use; prescribers were not. A mixed-methods evaluation aimed to establish: acceptability and usability of …

Impact Of Age On Pharmacogenomics And Treatment Outcomes Of B-Cell Acute Lymphoblastic Leukemia, Satoshi Yoshimura, Zhenhua Li, Yoshihiro Gocho, Wenjian Yang, Kristine R Crews, Shawn H R Lee, Kathryn G Roberts, Charles G Mullighan, Mary V Relling, Jiyang Yu, Allen E J Yeoh, Mignon L Loh, Caner Saygin, Mark R Litzow, Sima Jeha, Seth E Karol, Hiroto Inaba, Ching-Hon Pui, Marina Konopleva, Nitin Jain, Wendy Stock, Elisabeth Paietta, Elias Jabbour, Steven M Kornblau, William E Evans, Jun J Yang

Faculty, Staff and Student Publications

Purpose: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.

Methods: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations …

Larp1 Haploinsufficiency Is Associated With An Autosomal Dominant Neurodevelopmental Disorder, James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R Dupont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden

Faculty, Staff and Students Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and …

Rare Variant Contribution To The Heritability Of Coronary Artery Disease, Ghislain Rocheleau, Shoa L Clarke, Gaëlle Auguste, Natalie R Hasbani, Alanna C Morrison, Adam S Heath, Lawrence F Bielak, Kruthika R Iyer, Erica P Young, Nathan O Stitziel, Goo Jun, Cecelia Laurie, Jai G Broome, Alyna T Khan, Donna K Arnett, Lewis C Becker, Joshua C Bis, Eric Boerwinkle, Donald W Bowden, April P Carson, Patrick T Ellinor, Myriam Fornage, Nora Franceschini, Barry I Freedman, Nancy L Heard-Costa, Lifang Hou, Yii-Der Ida Chen, Eimear E Kenny, Charles Kooperberg, Brian G Kral, Ruth J F Loos, Sharon M Lutz, Joann E Manson, Lisa W Martin, Braxton D Mitchell, Rami Nassir, Nicholette D Palmer, Wendy S Post, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Elizabeth A Regan, Stephen S Rich, Jennifer A Smith, Kent D Taylor, Lisa R Yanek, Kendra A Young, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Austin T Hilliard, Catherine Tcheandjieu, Patricia A Peyser, Ramachandran S Vasan, Jerome I Rotter, Clint L Miller, Themistocles L Assimes, Paul S De Vries, Ron Do

Faculty, Staff and Student Publications

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin …

Pandemic Perspectives From Detained Youth During Covid-19: Bridging The Knowledge Gap For Future Safeguards., April Mcneill-Johnson, Zuri Hudson, Brittany Moore, Dumebi Okocha, Megha Ramaswamy, Kimberly Randell

Manuscripts, Articles, Book Chapters and Other Papers

Despite the worsening health disparities among youth in detention during the COVID-19 pandemic, there has been minimal exploration into the pandemic experiences of detained youth and opportunities for pandemic mitigation. This paper analyzes the perspectives of youth in detention on the pandemic, including the effect of the pandemic on their detention experience and their perceptions about COVID-19 vaccination. The study used purposive sampling to recruit 16 participants (aged 14-17 years) from two juvenile detention centers in the urban Midwest. We conducted semi-structured interviews and analyzed verbatim transcripts using a hybrid deductive-inductive approach and thematic analysis. Four themes emerged: 1) personal …

Forecasting The Effects Of Smoking Prevalence Scenarios On Years Of Life Lost And Life Expectancy From 2022 To 2050: A Systematic Analysis For The Global Burden Of Disease Study 2021, Gbd 2021 Tobacco Forecasting Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies.

METHODS: In this analysis, we use …

Promoting Healthful And Diverse Eating Behaviours Through An Extracurricular Culinary Skills Intervention In Philadelphia, Matthew D. Kearney, Arlene R. Maheu, Madalyn Booth, Andrew B. Newberg, Peter F. Cronholm, Soussan Ayubcha

SKMC Student Presentations and Publications

In the current study we evaluated an afterschool nutrition education programme, called Vetri Cooking Lab (VCL), for promoting healthy and diverse eating habits among at-risk children in the Greater Philadelphia area. To understand potential programme impacts, we conducted a longitudinal analysis of survey data collected before and after participation in VCL. Main study included cooking confidence, cooking knowledge, changes in dietary consumption behaviours, and changes in vegetable preferences. Participants included students in grades 3-11 enrolled in VCL during the 2018-19 school year at VCL sites (n = 60) throughout Philadelphia, PA, and Camden, NJ. Eligible participants completed surveys both before …

Rapid Hyperspectral Photothermal Mid-Infrared Spectroscopic Imaging From Sparse Data For Gynecologic Cancer Tissue Subtyping, Reza Reihanisaransari, Chalapathi Charan Gajjela, Xinyu Wu, Ragib Ishrak, Sara Corvigno, Yanping Zhong, Jinsong Liu, Anil K Sood, David Mayerich, Sebastian Berisha, Rohith Reddy

Faculty, Staff and Student Publications

Ovarian cancer detection has traditionally relied on a multistep process that includes biopsy, tissue staining, and morphological analysis by experienced pathologists. While widely practiced, this conventional approach suffers from several drawbacks: it is qualitative, time-intensive, and heavily dependent on the quality of staining. Mid-infrared (MIR) hyperspectral photothermal imaging is a label-free, biochemically quantitative technology that, when combined with machine learning algorithms, can eliminate the need for staining and provide quantitative results comparable to traditional histology. However, this technology is slow. This work presents a novel approach to MIR photothermal imaging that enhances its speed by an order of magnitude. This …