Medical Specialties Commons^™

The Microrna Processor Drosha Is A Candidate Gene For A Severe Progressive Neurological Disorder, Scott Barish, Mumine Senturk, Kelly Schoch, Amanda L Minogue, Diego Lopergolo, Chiara Fallerini, Jake Harland, Jacob H Seemann, Nicholas Stong, Peter G Kranz, Sujay Kansagra, Mohamad A Mikati, Joan Jasien, Mays El-Dairi, Paolo Galluzzi, Francesca Ariani, Alessandra Renieri, Francesca Mari, Michael F Wangler, Swathi Arur, Yong-Hui Jiang, Shinya Yamamoto, Vandana Shashi, Hugo J Bellen

Faculty, Staff and Students Publications

DROSHA encodes a ribonuclease that is a subunit of the Microprocessor complex and is involved in the first step of microRNA (miRNA) biogenesis. To date, DROSHA has not yet been associated with a Mendelian disease. Here, we describe two individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. DROSHA is constrained for missense variants and moderately intolerant to loss-of-function (o/e = 0.24). The loss of the fruit fly ortholog drosha causes developmental arrest and death in third instar larvae, a severe reduction in brain size and loss …

The Roles Of Gut Microbiome And Plasma Metabolites In The Associations Between Abo Blood Groups And Insulin Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Ruifang Li-Gao, Kirk Grubbs, Alain G Bertoni, Kristi L Hoffman, Joseph F Petrosino, Gautam Ramesh, Martin Wu, Jerome I Rotter, Yii-Der Ida Chen, Anne M Evans, Richard J Robinson, Laura Sommerville, Dennis Mook-Kanamori, Mark O Goodarzi, Gregory A Michelotti, Patricia A Sheridan

Faculty, Staff and Students Publications

Non-O blood groups are associated with decreased insulin sensitivity and risk of type 2 diabetes. A recent study pinpointed the associations between ABO blood groups and gut microbiome, which may serve as potential mediators for the observed increased disease risks. We aimed to characterize associations between ABO haplotypes and insulin-related traits as well as potential mediating pathways. We assessed insulin homeostasis in African Americans (AAs; n = 109) and non-Hispanic whites (n = 210) from the Microbiome and Insulin Longitudinal Evaluation Study. The ABO haplotype was determined by six SNPs located in the ABO gene. Based on prior knowledge, …

Cardiovascular Outcomes Of Transradial Versus Transfemoral Percutaneous Coronary Intervention In End-Stage Renal Disease: A Regression-Based Comparison, Yasar Sattar, Mohammed Faisaluddin, Talal Almas, Noora Alhajri, Rajendra Shah, Mohamed Zghouzi, Fnu Zafrullah, Prasana M Sengodon, Muhammad Zia Khan, Waqas Ullah, Mahboob Alam, Sudharshan Balla, Nasser Lakkis, Akram Kawsara, Ramesh Daggubati, M Chadi Alraies

Faculty, Staff and Students Publications

Background: Limited data is available on the comparison of outcomes of transradial (TR) and transfemoral (TF) access for percutaneous coronary intervention (PCI) in patients with end-stage stage renal disease (ESRD).

Methods: Online databases were queried to compare cardiovascular outcomes among TR. and TF in ESRD patients. The outcomes assessed included differences in mortality, cerebrovascular accidents (CVA), periprocedural myocardial infarction (MI), bleeding, transfusion, and periprocedural cardiogenic shock (CS). Unadjusted odds ratios (OR) were calculated using a random-effect effect model.

Results: A total of 6 studies including 7,607 patients (TR-PCI = 1,288; TF-PCI = 6,319) were included. The overall mean age was …

Genome-Wide Interaction Analysis Identified Low-Frequency Variants With Sex Disparity In Lung Cancer Risk, Yafang Li, Xiangjun Xiao, Jianrong Li, Jinyoung Byun, Chao Cheng, Yohan Bossé, James Mckay, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne Arnold, Gary Goodman, John K Field, Michael P A Davies, Sanjay S Shete, Loic Le Marchand, Olle Melander, Hans Brunnström, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Hongbing Shen, Ryan Sun, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Dawn M Teare, Yun-Chul Hong, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Ann G Schwartz, Ivan Gorlov, Kristen Purrington, Ping Yang, Yanhong Liu, Younghun Han, Joan E Bailey-Wilson, Susan M Pinney, Diptasri Mandal, James C Willey, Colette Gaba, Paul Brennan, Christopher I Amos, Integral-Ilcco Lung Cancer Consortium

Faculty, Staff and Students Publications

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 [odds ratio (OR) = 0.71, P = 4.29×10-8); rs79942605 (OR = 2.17, P = 2.81×10-8) and rs208908 (OR = 0.70, P = 4.54×10-8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.

Adiposity, Insulin Resistance, Cardiorespiratory Fitness, And Bone Health In Hispanic Children, Reem S Shawar, Maurice Puyau, Roman Shypailo, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

CONTEXT: Childhood obesity disproportionately affects Hispanic youth. The skeletal system appears to be a target organ of the adverse effects of obesity. Yet, the relationship between adiposity and bone health in youth and the modulating factors are not well understood.

OBJECTIVE: This work aims to examine the relationship between adiposity, insulin resistance (IR), cardiorespiratory fitness (CRF), and bone mass in Hispanic youth.

METHODS: A total of 951 Hispanic youth (50% male), aged 4 to 19 years, participated in this cross-sectional design study from the Viva La Familia Study at Children's Nutrition Research Center. Bone mineral content (BMC) and density (BMD), …

A Case Series Of Children With Acute Hepatitis And Human Adenovirus Infection, L Helena Gutierrez Sanchez, Henry Shiau, Julia M Baker, Stephanie Saaybi, Markus Buchfellner, William Britt, Veronica Sanchez, Jennifer L Potter, L Amanda Ingram, David Kelly, Xiaoyan Lu, Stephanie Ayers-Millsap, Wesley G Willeford, Negar Rassaei, Julu Bhatnagar, Hannah Bullock, Sarah Reagan-Steiner, Ali Martin, Michael E Rogers, Anna M Banc-Husu, Sanjiv Harpavat, Daniel H Leung, Elizabeth A Moulton, Daryl M Lamson, Kirsten St George, Aron J Hall, Umesh Parashar, Adam Macneil, Jacqueline E Tate, Hannah L Kirking

Faculty, Staff and Students Publications

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.

METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children’s of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.

RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 …

A Nanoengineered Topical Transmucosal Cisplatin Delivery System Induces Anti-Tumor Response In Animal Models And Patients With Oral Cancer, Manijeh Goldberg, Aaron Manzi, Amritpreet Birdi, Brandon Laporte, Peter Conway, Stefanie Cantin, Vasudha Mishra, Alka Singh, Alexander T Pearson, Eric R Goldberg, Sam Goldberger, Benjamin Flaum, Rifat Hasina, Nyall R London, Gary L Gallia, Chetan Bettegowda, Simon Young, Vlad Sandulache, James Melville, Jonathan Shum, Sonya E O'Neill, Erkin Aydin, Alex Zhavoronkov, Anxo Vidal, Atenea Soto, Maria Jose Alonso, Ari J Rosenberg, Mark W Lingen, Anil D'Cruz, Nishant Agrawal, Evgeny Izumchenko

Faculty, Staff and Students Publications

Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor …

The Prostate Cancer Androgen Receptor Cistrome In African American Men Associates With Upregulation Of Lipid Metabolism And Immune Response, Jacob E Berchuck, Elio Adib, Sarah Abou Alaiwi, Amit K Dash, Jin Na Shin, Dallin Lowder, Collin Mccoll, Patricia Castro, Ryan Carelli, Elisa Benedetti, Jenny Deng, Matthew Robertson, Sylvan C Baca, Connor Bell, Heather M Mcclure, Talal El Zarif, Matthew P Davidsohn, Gitanjali Lakshminarayanan, Kinza Rizwan, Darlene G Skapura, Sandra L Grimm, Christel M Davis, Erik A Ehli, Kaitlin M Kelleher, Ji-Heui Seo, Nicholas Mitsiades, Cristian Coarfa, Mark M Pomerantz, Massimo Loda, Michael Ittmann, Matthew L Freedman, Salma Kaochar

Faculty, Staff and Students Publications

African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and …

Genetic Variants In Cyp2b6 And Hsd17b12 Associated With Risk Of Squamous Cell Carcinoma Of The Head And Neck, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Kristina R Dahlstrom, Mulong Du, Christopher I Amos, David C Christiani, Philip Lazarus, Qingyi Wei

Faculty, Staff and Students Publications

Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10

Insights Into Microbiome And Metabolic Signatures Of Children Undergoing Peanut Oral Immunotherapy, Andrea C Blackman, Santosh Thapa, Alamelu Venkatachalam, Thomas D Horvath, Jessica K Runge, Sigmund J Haidacher, Kathleen M Hoch, Anthony M Haag, Ruth Ann Luna, Aikaterini Anagnostou

Faculty, Staff and Students Publications

BACKGROUND: Peanut oral immunotherapy has emerged as a novel, active management approach for peanut-allergic sufferers, but limited data exist currently on the role of the microbiome in successful desensitization.

OBJECTIVE: We examined the oral and gut microbiome in a cohort of 17 children undergoing peanut oral immunotherapy with the aim to identify the microbiome signatures associated with successful desensitization. We also set out to characterize their fecal metabolic profiles after successful therapy.

METHODS: Participants gradually built up their daily dose from 2 mg (starting dose) to 300 mg (maintenance dose) within approximately 40 weeks. We collected a buccal and stool …

A Mouse Holder For Awake Functional Imaging In Unanesthetized Mice: Applications In 31p Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, And Resting-State Functional Magnetic Resonance Imaging, Lindsay C Fadel, Ivany V Patel, Jonathan Romero, I-Chih Tan, Shelli R Kesler, Vikram Rao, S A Amali S Subasinghe, Russell S Ray, Jason T Yustein, Matthew J Allen, Brian W Gibson, Justin J Verlinden, Stanley Fayn, Nicole Ruggiero, Caitlyn Ortiz, Elizabeth Hipskind, Aaron Feng, Chijindu Iheanacho, Alex Wang, Robia G Pautler

Faculty, Staff and Students Publications

Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in …

Qualitative Interviews To Understand Health Care Providers’ Experiences Of Prescribing Licensed Peanut Oral Immunotherapy, Aikaterini Anagnostou, Claire Lawrence, Stephen A Tilles, Susan Laubach, Sarah M Donelson, Mohamed Yassine, Anna Nowak-Wegrzyn

Faculty, Staff and Students Publications

OBJECTIVE: This research sought to explore health care providers' (HCPs) experiences of delivering the first US Food and Drug Administration (FDA) and European Commission (EC) approved peanut oral immunotherapy (peanut OIT; Palforzia). Semi-structured qualitative interviews with HCPs who had initiated treatment with ≥ 3 patients in the first nine months following FDA approval sought to identify challenges faced and successful implementation strategies.

RESULTS: Eight allergists and three nurse practitioners from eight sites based in the United States participated. The HCPs included in this research were motivated to implement this novel treatment, however, entered the process with some reservations. HCPs described …

Spectral Library-Based Single-Cell Proteomics Resolves Cellular Heterogeneity, Lakmini Senavirathna, Cheng Ma, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

Dissecting the proteome of cell types and states at single-cell resolution, while being highly challenging, has significant implications in basic science and biomedicine. Mass spectrometry (MS)-based single-cell proteomics represents an emerging technology for system-wide, unbiased profiling of proteins in single cells. However, significant challenges remain in analyzing an extremely small amount of proteins collected from a single cell, as a proteome-wide amplification of proteins is not currently feasible. Here, we report an integrated spectral library-based single-cell proteomics (SLB-SCP) platform that is ultrasensitive and well suited for a large-scale analysis. To overcome the low MS/MS signal intensity intrinsically associated with a …

An Auto-Inhibited State Of Protein Kinase G And Implications For Selective Activation, Rajesh Sharma, Jeong Joo Kim, Liying Qin, Philipp Henning, Madoka Akimoto, Bryan Vanschouwen, Gundeep Kaur, Banumathi Sankaran, Kevin R Mackenzie, Giuseppe Melacini, Darren E Casteel, Friedrich W Herberg, Choel Kim

Faculty, Staff and Students Publications

Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory (AI) pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation …

Association Between Social Vulnerability Index And Cardiovascular Disease: A Behavioral Risk Factor Surveillance System Study, Vardhmaan Jain, Mahmoud Al Rifai, Safi U Khan, Ankur Kalra, Fatima Rodriguez, Zainab Samad, Yashashwi Pokharel, Arunima Misra, Laurence S Sperling, Jamal S Rana, Waqas Ullah, Ankit Medhekar, Salim S Virani

Faculty, Staff and Students Publications

Background Social and environmental factors play an important role in the rising health care burden of cardiovascular disease. The Centers for Disease Control and Prevention developed the Social Vulnerability Index (SVI) from US census data as a tool for public health officials to identify communities in need of support in the setting of a hazardous event. SVI (ranging from a least vulnerable score of 0 to a most vulnerable score of 1) ranks communities on 15 social factors including unemployment, minoritized groups status, and disability, and groups them under 4 broad themes: socioeconomic status, housing and transportation, minoritized groups, and …

Chronic Granulomatous Disease-Like Presentation Of A Child With Autosomal Recessive Pkcδ Deficiency, Anna-Lena Neehus, Karen Tuano, Tom Le Voyer, Sarada L Nandiwada, Kruthi Murthy, Anne Puel, Jean-Laurent Casanova, Javier Chinen, Jacinta Bustamante

Faculty, Staff and Students Publications

BACKGROUND: Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and viral infections. PKCδ is involved in the intracellular production of reactive oxidative species (ROS).

MATERIAL AND METHODS: We studied a 5-year old girl presenting with a history of Burkholderia cepacia infection. She had no history of autoimmunity, lymphocyte counts were normal, and no auto-antibodies were detected in her plasma. We performed a targeted panel analysis of 407 immunity-related genes and immunological investigations of the underlying genetic condition in this patient.

RESULTS: Consistent with a history suggestive of …

Factors Associated With Parental Acceptance Of Covid-19 Vaccination: A Multicenter Pediatric Emergency Department Cross-Sectional Analysis, Brigitte M Baumann, Robert M Rodriguez, Amy M Delaroche, David Rayburn, Stephanie A Eucker, Nicole L Nadeau, Lisa A Drago, Danielle Cullen, Sarah Dennis Meskill, Suzanne Bialeck, Michael Gillman

Faculty, Staff and Students Publications

STUDY OBJECTIVE: During the delta surge of the COVID-19 pandemic in 2021, we sought to identify characteristics and beliefs associated with COVID-19 vaccination acceptance in parents of pediatric emergency department (ED) patients.

METHODS: We conducted a cross-sectional survey-based study of the parents of children aged 3 to 16 years presenting to 1 of 9 pediatric EDs from June to August 2021 to assess the parental acceptance of COVID-19 vaccines. Using multiple variable regression, we ascertained which factors were associated with parental and pediatric COVID-19 vaccination acceptance.

RESULTS: Of 1,491 parents approached, 1,298 (87%) participated, of whom 50% of the parents …

Exome Sequencing Identifies Genetic Variants In Anophthalmia And Microphthalmia, Jingjing Li, Wei Yang, Yuejun Jessie Wang, Chen Ma, Cynthia J Curry, Daniel Mcgoldrick, Deborah A Nickerson, Jessica X Chong, Elizabeth E Blue, James C Mullikin, Jennita Reefhuis, Wendy N Nembhard, Paul A Romitti, Martha M Werler, Marilyn L Browne, Andrew F Olshan, Richard H Finnell, Marcia L Feldkamp, Faith Pangilinan, Lynn M Almli, Mike J Bamshad, Lawrence C Brody, Mary M Jenkins, Gary M Shaw, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 …

Early Growth Response 1 Transcription Factor Is Essential For The Pathogenic Properties Of Human Endometriotic Epithelial Cells, Vineet K Maurya, Maria M Szwarc, Rodrigo Fernandez-Valdivia, David M Lonard, Song Yong, Niraj Joshi, Asgerally T Fazleabas, John P Lydon

Faculty, Staff and Students Publications

Although a non-malignant gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the …

Combined Laryngeal Cleft Injection Laryngoplasty And Salivary Botulinum Toxin For Saliva Aspiration, Justin Nguyen, Julina Ongkasuwan, Grace Anand, Elton M Lambert

Faculty, Staff and Students Publications

OBJECTIVES: Children with type I laryngeal clefts and sialorrhea can have posterior drooling, aspiration of oral secretions, and respiratory complications. Laryngeal cleft injection laryngoplasty (LCIL) and salivary botulinum injections (Sal-Bot) have been used separately for short-term treatment of type I laryngeal clefts and sialorrhea. Our goal was to evaluate combined LCIL and Sal-Bot and create recommendations for further treatment based on response to initial treatment.

METHODS: Retrospective chart review of nine patients who underwent direct laryngoscopy and bronchoscopy with combined LCIL and Sal-Bot from 2012 to 2019. Charts were reviewed for patient characteristics, response to treatment, and pre and post-op …

Conventional And Advanced Mr Imaging Findings In A Cohort Of Pathology-Proven Dermoid Cysts Of The Pediatric Scalp And Skull, Bettina L Serrallach, Gunes Orman, M John Hicks, Nilesh Desai, Stephen Kralik, Thierry Agm Huisman

Faculty, Staff and Students Publications

BACKGROUND: In the pediatric population, dermoid cysts are among the most frequent lesions of the scalp and skull. Imaging plays a key role in characterizing scalp and skull lesions in order to narrow the differential diagnoses. In general, dermoids are described as heterogeneous T1-/T2-hypo- to hyperintense lesions on magnetic resonance imaging.

METHODS: The goal of this retrospective study is to evaluate the diffusion weighted imaging findings while reviewing the conventional T1-/T2-/T1+C-weighted MR characteristics in a pathology-proven series of 14 dermoids of the pediatric scalp and skull.

RESULTS: In our pediatric cohort (eight boys, six girls, age range 3-95 months), half …

Gestational Age And Quintero Staging As Predictors Of Single Fetal Demise In Twin-Twin Transfusion Syndrome After Fetoscopic Laser Photocoagulation: A Systematic Review And Meta-Analysis, Ahmed A Nassr, Kamran Hessami, Jimmy Espinoza, Roopali Donepudi, Magdalena Sanz Cortes, Michael A Belfort, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

BACKGROUND: Single fetal demise after intervention for twin-twin transfusion syndrome is a relatively common complication and is often devastating for the patients.

OBJECTIVE: This meta-analysis aimed to evaluate the risk of single fetal demise based on gestational age and Quintero staging at the time of interventions in twin-to-twin transfusion syndrome after fetoscopic laser photocoagulation.

STUDY DESIGN: Systematic search was performed in PubMed, Web of Science, and Scopus from inception to August 2021. The primary outcome was to compare the incidence of fetal demise between low (I and II) and high (III and IV) twin-to-twin transfusion syndrome Quintero stages. The rate …

Proteomes Of Extracellular Vesicles From Pancreatic Cancer Cells And Cancer-Associated Fibroblasts, Sharon Pan, Lisa A Lai, Diane M Simeone, David W Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A Brentnall

Faculty, Staff and Students Publications

OBJECTIVES: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis.

METHODS: Proteomic and functional analyses were applied to characterize the proteomes of EVs released from 5 pancreatic cancer lines, 2 CAF cell lines, and a normal pancreatic epithelial cell line (HPDE).

RESULTS: More than 1400 nonredundant proteins were identified …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

A Large-Scale Genome-Wide Gene-Gene Interaction Study Of Lung Cancer Susceptibility In Europeans With A Trans-Ethnic Validation In Asians, Ruyang Zhang, Sipeng Shen, Yongyue Wei, Ying Zhu, Yi Li, Jiajin Chen, Jinxing Guan, Zoucheng Pan, Yuzhuo Wang, Meng Zhu, Junxing Xie, Xiangjun Xiao, Dakai Zhu, Yafang Li, Demetrios Albanes, Maria Teresa Landi, Neil E Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angela Cox, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Juncheng Dai, Hongxia Ma, Yang Zhao, Zhibin Hu, Rayjean J Hung, Christopher I Amos, Hongbing Shen, Feng Chen, David C Christiani

Faculty, Staff and Students Publications

INTRODUCTION: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).

METHODS: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms …

A Novel Approach To The Removal Of A Silastic Band Via The Peroral Endoscopic Tunneling-Silastic Bandectomy Technique, Wasif M Abidi, Salmaan Jawaid

Faculty, Staff and Students Publications

The peroral endoscopic tunneling-silastic bandectomy technique to remove a silastic band causing a vertical banded gastroplasty stenosis. This method is a viable alternative to surgical removal of foreign bodies outside the gastrointestinal lumen.

Becoming A Doctor During A Pandemic: Impact On Medical Student Social Identity Formation, Sanghamitra M Misra, Nital P Appelbaum, Maria A Jaramillo, Ruifei Wang, Connor T Hoch, Nadia Ismail, Jennifer Christner

Faculty, Staff and Students Publications

The COVID-19 pandemic required modifications to undergraduate medical education that likely affected medical students' social identity formation (SIF). SIF is shaped by experiences throughout the medical education continuum. This commentary explores factors potentially affecting medical student SIF during the COVID-19 pandemic focusing on students' perceptions of being part of the healthcare team, their role in medicine, and their engagement during the pandemic. Based on such considerations, we propose that educators should aim to design effective learning environments to support a full educational experience that encompasses acquiring medical knowledge and building strong social identities even during a pandemic.

Roles And Responsibilities Of Medicine Subinternship Directors : Medicine Subinternship Director Roles, Nicholas S Duca, Cindy J Lai, Temple A Ratcliffe, Irene Alexandraki, Nadia Ismail, Michael Kisielewski, Jackcy Jacob, Katherine Walsh, Diane L Levine, Karen Szauter, Harish Jasti, Amber T Pincavage, Jeffrey Larochelle, Susan A Glod

Faculty, Staff and Students Publications

BACKGROUND: The internal medicine (IM) subinternship (also referred to as acting internship) plays a crucial part in preparing medical students for residency. The roles, responsibilities, and support provided to subinternship directors have not been described.

OBJECTIVE: We sought to describe the current role of IM subinternship directors with respect to their responsibilities, salary support, and reporting structure.

DESIGN: Nationally representative, annually recurring thematic survey of IM core clerkship directors with membership in an academic professional association as of September 2017.

PARTICIPANTS: A total of 129 core clinical medicine clerkship directors at Liaison Committee on Medical Education fully accredited U.S./U.S.-territory-based medical …

Integrated Multi-Omic Characterization Of Congenital Heart Disease, Matthew C Hill, Zachary A Kadow, Hali Long, Yuka Morikawa, Thomas J Martin, Emma J Birks, Kenneth S Campbell, Jeanne Nerbonne, Kory Lavine, Lalita Wadhwa, Jun Wang, Diwakar Turaga, Iki Adachi, James F Martin

Faculty, Staff and Students Publications

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We …

Surgical Extraction Of Traumatic Lodgment Of A Pen Nib Between The Eye And Nasal Bridge Of An Infant: A Case Report, Krishna Shah, Vaishali Prajapati, Smeet Desai, Karishma Dhaval Desai, Mayur B Wanjari, Deepika Singhal

Faculty, Staff and Students Publications

Unintentional eye injuries are common in small children. If left unobserved by parents or caretakers, it is challenging to assess as the kids are in distress and pain. Penetrating trauma in or near the eye requires urgent treatment as it can lead to infection and other complications. Early diagnosis and management help avoid further complications. An 11-month-old female was presented by her parents at a tertiary care clinic with inconsolable crying and swelling over the right eye's upper lid for one day. There was a history of possible trauma with a pen while the child was playing. During the examination, …