Medical Specialties Commons^™

Prediction Of Adverse Events Risk In Patients With Comorbid Post-Traumatic Stress Disorder And Alcohol Use Disorder Using Electronic Medical Records By Deep Learning Models, Oshin Miranda, Peihao Fan, Xiguang Qi, Haohan Wang, M Daniel Brannock, Thomas Kosten, Neal David Ryan, Levent Kirisci, Lirong Wang

Faculty, Staff and Students Publications

Background: Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population.

Methods: We analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, …

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

In Vivo Cardiac Electrophysiology In Mice: Determination Of Atrial And Ventricular Arrhythmic Substrates, Jose Alberto Navarro-Garcia, Florian Bruns, Oliver M Moore, Marcel A Tekook, Dobromir Dobrev, Christina Y Miyake, Xander H T Wehrens

Faculty, Staff and Students Publications

Cardiac arrhythmias are a common cardiac condition that might lead to fatal outcomes. A better understanding of the molecular and cellular basis of arrhythmia mechanisms is necessary for the development of better treatment modalities. To aid these efforts, various mouse models have been developed for studying cardiac arrhythmias. Both genetic and surgical mouse models are commonly used to assess the incidence and mechanisms of arrhythmias. Since spontaneous arrhythmias are uncommon in healthy young mice, intracardiac programmed electrical stimulation (PES) can be performed to assess the susceptibility to pacing-induced arrhythmias and uncover the possible presence of a proarrhythmogenic substrate. This procedure …

Cardiac Magnetic Resonance Imaging In Detection Of Progressive Graft Dysfunction In Pediatric Heart Transplantation, Kae Watanabe, Nicoleta C Arva, Joshua D Robinson, Cynthia Rigsby, Michael Markl, Melanie Sojka, Paul Tannous, Jennifer Arzu, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method.

METHODS: Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression …

Rates, Patterns, And Predictors Of Specialty Palliative Care Consultation Among Patients With Acute-On-Chronic Liver Failure, Arpan Patel, Anne Walling, Fasiha Kanwal, Marina Serper, Ruben Hernaez, Vinay Sundaram, David Kaplan, Tamar Taddei, Nadim Mahmud

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described.

METHODS: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, …

Mapping Gray And White Matter Volume Abnormalities In Early-Onset Psychosis: An Enigma Multicenter Voxel-Based Morphometry Study, Shuqing Si, Anbreen Bi, Zhaoying Yu, Cheryl See, Sinead Kelly, Sonia Ambrogi, Celso Arango, Inmaculada Baeza, Nerisa Banaj, Michael Berk, Josefina Castro-Fornieles, Benedicto Crespo-Facorro, Jacob J Crouse, Covadonga M Díaz-Caneja, Anne-Kathrin Fett, Adriana Fortea, Sophia Frangou, Benjamin I Goldstein, Ian B Hickie, Joost Janssen, Kody G Kennedy, Lydia Krabbendam, Marinos Kyriakopoulos, Bradley J Macintosh, Pedro Morgado, Stener Nerland, Saül Pascual-Diaz, Maria Picó-Pérez, Fabrizio Piras, Bjørn Rishovd Rund, Elena De La Serna, Gianfranco Spalletta, Gisela Sugranyes, Chao Suo, Diana Tordesillas-Gutiérrez, Daniela Vecchio, Joaquim Radua, Philip Mcguire, Sophia I Thomopoulos, Neda Jahanshad, Paul M Thompson, Claudia Barth, Ingrid Agartz, Anthony James, Matthew J Kempton

Faculty, Staff and Students Publications

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.

METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Generation Of A Dcx-Creert2 Knock-In Mouse For Genetic Manipulation Of Newborn Neurons, Gabriella A Perez, Kyung-Won Park, Denise Lanza, Jenna Cicardo, M Danish Uddin, Joanna L Jankowsky

Faculty, Staff and Students Publications

A wide variety of CreERT2 driver lines are available for genetic manipulation of adult-born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult-born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreERT2 driver line targeted to the endogenous mouse …

The Importance Of Considering Competing Risks In Recurrence Analysis Of Intracranial Meningioma, Christian Mirian, Lasse Rehné Jensen, Tareq A Juratli, Andrea Daniela Maier, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Fuyou Guo, Pedro Góes, Manoel Antonio De Paiva Neto, Aria Jamshidi, Ricardo Komotar, Michael Ivan, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Anders Broechner, Mathias Jacobsen Bach, Ian Law, David Scheie, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.

METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage …

Abortion Patients’ Decision Making About Where To Obtain Out-Of-State Care Following Texas’ 2021 Abortion Ban, Kari White, Whitney Arey, Brooke Whitfield, Asha Dane'el, Laura Dixon, Joseph E Potter, Tony Ogburn, Anitra D Beasley

Faculty, Staff and Students Publications

OBJECTIVE: To assess pregnant Texans' decisions about where to obtain out-of-state abortion care following the September 2021 implementation of Senate Bill 8 (SB8), which prohibited abortions after detectable embryonic cardiac activity.

DATA SOURCE: In-depth telephone interviews with Texas residents ≥15 years of age who obtained out-of-state abortion care after SB8's implementation.

STUDY DESIGN: This qualitative study explored participants' experiences identifying and contacting abortion facilities and their concerns and considerations about traveling out of state. We used inductive and deductive codes in our thematic analysis describing people's decisions about where to obtain care and how they evaluated available options.

DATA COLLECTION: …

Antiretroviral Therapy In Pregnancy: A 2023 Review Of The Literature, Alison N Goulding, Kasey Meeks, Lena Shay, Sarah Casey, Colton Applegarth, Jennifer Mckinney

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA.

RECENT FINDINGS: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple …

Timely Delivery Of Port For Head And Neck Squamous Cell Carcinoma In A County Hospital, Ana Maria Rosas Herrera, Angela D Haskins, Alexander N Hanania, Pavan M Jhaveri, Christina H Chapman, Quillan Huang, David J Hernandez

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway.

METHODS: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days …

Respiratory Viral Detection In The Plasma And Cerebrospinal Fluid (Csf) Of Young Febrile Infants, Erin G Nicholson, Vasanthi Avadhanula, Leila C Sahni, Laura Ferlic-Stark, Lauren Maurer, Julie A Boom, Pedro A Piedra

Faculty, Staff and Students Publications

BACKGROUND: Respiratory viral infections are common in febrile infants ≤90 days. However, the detection of viruses other than enterovirus in the blood and cerebrospinal fluid (CSF) of young infants is not well defined. We sought to quantify the occurrence of respiratory viruses in the blood and CSF of febrile infants ≤90 days.

METHODS: We conducted a nested cohort study examining plasma and CSF samples from febrile infants 15-90 days via rtPCR. The samples were tested for respiratory viruses (respiratory syncytial virus, influenza, enterovirus, parechovirus, adenovirus, bocavirus). Clinical and laboratory data were also collected to determine the presence of serious bacterial …

A Zika Virus Protein Expression Screen In Drosophila To Investigate Targeted Host Pathways During Development, Nichole Link, J Michael Harnish, Brooke Hull, Shelley Gibson, Miranda Dietze, Uchechukwu E Mgbike, Silvia Medina-Balcazar, Priya S Shah, Shinya Yamamoto

Faculty, Staff and Students Publications

In the past decade, Zika virus (ZIKV) emerged as a global public health concern. Although adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of disease caused by this virus, which includes microcephaly. In this study, we generated a toolkit to ectopically express ZIKV proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We used this toolkit to identify phenotypes and potential host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins caused …

Deep Learning Prediction Boosts Phosphoproteomics-Based Discoveries Through Improved Phosphopeptide Identification, Xinpei Yi, Bo Wen, Shuyi Ji, Alexander B Saltzman, Eric J Jaehnig, Jonathan T Lei, Qiang Gao, Bing Zhang

Faculty, Staff and Students Publications

Shotgun phosphoproteomics enables high-throughput analysis of phosphopeptides in biological samples. One of the primary challenges associated with this technology is the relatively low rate of phosphopeptide identification during data analysis. This limitation hampers the full realization of the potential offered by shotgun phosphoproteomics. Here we present DeepRescore2, a computational workflow that leverages deep learning-based retention time and fragment ion intensity predictions to improve phosphopeptide identification and phosphosite localization. Using a state-of-the-art computational workflow as a benchmark, DeepRescore2 increases the number of correctly identified peptide-spectrum matches by 17% in a synthetic dataset and identifies 19% to 46% more phosphopeptides in biological …

Serum Exosomal Microrna Pathway Activation In Placenta Accreta Spectrum: Pathophysiology And Detection, Jessian L Munoz, Brett D Einerson, Robert M Silver, Sureshkumar Mulampurath, Lauren S Sherman, Pranela Rameshwar, Egle Bytautiene Prewit, Patrick S Ramsey

Faculty, Staff and Students Publications

BACKGROUND: Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues.

OBJECTIVE: We aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection.

STUDY DESIGN: This study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with …

The Role Of Family Accommodation In Child Posttraumatic Stress Symptoms And Functional Impairment In The Context Of Cognitive Behavioral Therapy, Ogechi Cynthia Onyeka, Samuel D Spencer, Alison Salloum, Katie Jiannetto, Eric A Storch

Faculty, Staff and Students Publications

BACKGROUND: Caregiver behaviors such as family accommodation (FA) are negatively reinforced by reduced distress in the short term, but ultimately maintain symptoms. It is important to explore the role of FA on symptoms and impairment. The current study examined the relationship among FA, posttraumatic stress symptoms (PTSS), and functional impairment in a sample of children and their caregivers who completed trauma treatment.

METHOD: Participants included 183 children and their caregivers (M age = 7.89; 55.19 % female; 73.22 % non-Hispanic; 51.37 % White). Data consisted of parent-reported measures collected at baseline, post-treatment, and 12-month follow-up from a randomized control trial …

Biallelic Creld1 Variants Cause A Multisystem Syndrome, Including Neurodevelopmental Phenotypes, Cardiac Dysrhythmias, And Frequent Infections, Lauren Jeffries, Emily K Mis, Kirsty Mcwalter, Sandra Donkervoort, Nina N Brodsky, Jean-Marie Carpier, Weizhen Ji, Cristian Ionita, Bhaskar Roy, Jon S Morrow, Armine Darbinyan, Krishna Iyer, Ritu B Aul, Siddharth Banka, Katherine R Chao, Laura Cobbold, Stacey Cohen, Helena M Custodio, Margaret Drummond-Borg, Frances Elmslie, Erika Finanger, Bryan E Hainline, Ingo Helbig, Stacy Hewson, Ying Hu, Adam Jackson, Dragana Josifova, Monica Konstantino, Meganne E Leach, Bryan Mak, David Mccormick, Elisabeth Mcgee, Stanley Nelson, Joanne Nguyen, Kimberly Nugent, Lucy Ortega, Howard P Goodkin, Elizabeth Roeder, Sani Roy, Katie Sapp, Dimah Saade, Sanjay M Sisodiya, Karen Stals, Shelley Towner, William Wilson, Deciphering Developmental Disorders, Genomics England Research Consortium, Undiagnosed Disease Network, Mustafa K Khokha, Carsten G Bönnemann, Carrie L Lucas, Saquib A Lakhani

Faculty, Staff and Students Publications

PURPOSE: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

METHODS: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

RESULTS: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense …

Delays Starting Postoperative Radiotherapy Among Head And Neck Cancer Patients: A Systematic Review And Meta-Analysis, Kelsey A Duckett, Mohamed Faisal Kassir, Shaun A Nguyen, Emily A Brennan, Bhishamjit S Chera, Katherine R Sterba, Chanita Hughes Halbert, Elizabeth G Hill, Jessica Mccay, Sidharth V Puram, Vlad C Sandulache, Russel Kahmke, Salma Ramadan, Brian Nussenbaum, Anthony J Alberg, Evan M Graboyes

Faculty, Staff and Students Publications

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT.

DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL.

REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures …

Cocaine Use And Head And Neck Cancer Risk: A Pooled Analysis In The International Head And Neck Cancer Epidemiology Consortium, Mingyan Zhang, Chu Chen, Guojun Li, Alzina Koric, Yuan-Chin Amy Lee, Hal Morgenstern, Stephen M Schwartz, Erich M Sturgis, Paolo Boffetta, Mia Hashibe, Zuo-Feng Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC).

METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models.

RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC …

The Differences In Code Status Conversation Approaches Reported By Emergency Medicine And Palliative Care Clinicians: A Mixed-Method Study, Kei Ouchi, Thidathit Prachanukool, Emily L Aaronson, Joshua R Lakin, Masaya Higuchi, Shan W Liu, Maura Kennedy, Anna C Revette, Anita N Chary, Jenson Kaithamattam, Brandon Lee, Thanh H Neville, Mohammad A Hasdianda, Rebecca Sudore, Mara A Schonberg, James A Tulsky, Susan D Block

Faculty, Staff and Students Publications

BACKGROUND: During acute health deterioration, emergency medicine and palliative care clinicians routinely discuss code status (e.g., shared decision making about mechanical ventilation) with seriously ill patients. Little is known about their approaches. We sought to elucidate how code status conversations are conducted by emergency medicine and palliative care clinicians and why their approaches are different.

METHODS: We conducted a sequential-explanatory, mixed-method study in three large academic medical centers in the Northeastern United States. Attending physicians and advanced practice providers working in emergency medicine and palliative care were eligible. Among the survey respondents, we purposefully sampled the participants for follow-up interviews. …

Expression Of Atoh1, Gfi1, And Pou4f3 In The Mature Cochlea Reprograms Nonsensory Cells Into Hair Cells, Melissa M Mcgovern, Ishwar V Hosamani, Yichi Niu, Ken Y Nguyen, Chenghang Zong, Andrew K Groves

Faculty, Staff and Students Publications

Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate; consequently, loss of hair cells leads to permanent hearing loss. Although nonmammalian vertebrates can regenerate hair cells from neighboring supporting cells, many humans with severe hearing loss lack both hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of nonsensory cells. To determine whether the mature cochlea can produce hair cells in vivo, we reprogrammed nonsensory cells adjacent to the organ of Corti with three hair cell transcription factors: Gfi1, Atoh1, and Pou4f3. We generated numerous hair cell–like …

Frozen Tissue Coring And Layered Histological Analysis Improves Cell Type-Specific Proteogenomic Characterization Of Pancreatic Adenocarcinoma, Sara R Savage, Yuefan Wang, Lijun Chen, Scott Jewell, Chelsea Newton, Yongchao Dou, Qing Kay Li, Oliver F Bathe, Ana I Robles, Gilbert S Omenn, Mathangi Thiagarajan, Hui Zhang, Galen Hostetter, Bing Zhang

Faculty, Staff and Students Publications

BACKGROUND: Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and potential benefit of using a coring method to enrich specific regions from bulk tissue and then perform proteogenomic analyses.

METHODS: We used the Biopsy Trifecta Extraction (BioTExt) technique to isolate cores of epithelial-enriched and stroma-enriched tissue from pancreatic tumor and adjacent tissue blocks. Histology was assessed at multiple depths throughout each core. DNA sequencing, RNA sequencing, and proteomics were performed on the cored and bulk tissue samples. Supervised and unsupervised analyses were performed based on integrated molecular …

Invasive Group A Streptococcus In Infants Less Than 1-Year Of Age From 2012 To 2022: A Single-Center Experience, Taylor Nack, Jesus G Vallejo, James Dunn, Anthony R Flores, J Chase Mcneil

Faculty, Staff and Students Publications

The incidence of invasive Group A Streptococcus (iGAS) has varied throughout the COVID-19 pandemic. We reviewed iGAS infections in infants ≤1 year from 2012 to 2022. Twenty-five percent of cases occurred in the last quarter of 2022. Pneumonia (21.8%) was the most common presentation. Twenty-one patients (65.6%) were successfully transitioned to oral antibiotics.

Adult Neuromuscular Choristoma, A Rare Peripheral Nerve Pathology: Illustrative Case, Ashley Ricciardelli, Alex Flores, Hsiang-Chih Lu, Ekin Guney, Arie Perry, Joey Grochmal

Faculty, Staff and Students Publications

Background: Neuromuscular choristomas (NMCs) are rare tumors involving aberrant intercalation of muscle fibers into peripheral nerves, most commonly the sciatic nerve. Although benign, these lesions risk developing into NMCs with desmoid-type fibrosis (NMC-DTFs), aggressive lesions potentially requiring amputation. Currently, information on NMCs and the link between NMCs and NMC-DTFs is limited in adults, with the majority of cases reported in children. We present the case of a 66-year-old male with a sciatic NMC alongside a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-based systematic review of similar cases to better characterize this lesion in the adult population.

Observations: A male …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Yi-Jie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …

Novel Advancements In Covid-19 And Neuroscience, Alessio Simonetti, Evelina Bernardi, Gabriele Sani

Faculty, Staff and Students Publications

From an initial cluster of cases reported in Wuhan, the SARS-Cov-2 infection has since spread globally, causing a pandemic that began on 11 March 2020 [...].

Systematic Review Of Mortality And Survival Rates For Apds, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma, and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants in PIK3CD and PIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function variants in the PIK3CD gene, while loss of function variants in PIK3R1 have been reported to cause APDS2. We conducted a review of the medical …