Medical Specialties Commons^™

Even Heterozygous Loss Of Cdkn2a/B Greatly Accelerates Recurrence In Aggressive Meningioma, A Basit Khan, Collin W English, William C Chen, Prazwal Athukuri, James C Bayley, Vicky L Brandt, Arya Shetty, Caroline C Hadley, Abrar Choudhury, Hsiang-Chih Lu, Arif O Harmanci, Akdes S Harmanci, Stephen T Magill, David R Raleigh, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Students Publications

No abstract provided.

Lung Volume Reduction In Copd: Scope Or Surgery, Francesca Polverino, Frank Sciurba

Faculty, Staff and Students Publications

No abstract provided.

Genomic Analysis Of Two Phlebotomine Sand Fly Vectors Of Leishmania From The New And Old World, Frédéric Labbé, Maha Abdeladhim, Jenica Abrudan, Alejandra Saori Araki, Ricardo N Araujo, Peter Arensburger, Joshua B Benoit, Reginaldo Pecanha Brazil, Rafaela V Bruno, Gustavo Bueno Da Silva Rivas, Vinicius Carvalho De Abreu, Jason Charamis, Iliano V Coutinho-Abreu, Samara G Da Costa-Latgé, Alistair Darby, Viv M Dillon, Scott J Emrich, Daniela Fernandez-Medina, Nelder Figueiredo Gontijo, Catherine M Flanley, Derek Gatherer, Fernando A Genta, Sandra Gesing, Gloria I Giraldo-Calderón, Bruno Gomes, Eric Roberto Guimaraes Rocha Aguiar, James G C Hamilton, Omar Hamarsheh, Mallory Hawksworth, Jacob M Hendershot, Paul V Hickner, Jean-Luc Imler, Panagiotis Ioannidis, Emily C Jennings, Shaden Kamhawi, Charikleia Karageorgiou, Ryan C Kennedy, Andreas Krueger, José M Latorre-Estivalis, Petros Ligoxygakis, Antonio Carlos A Meireles-Filho, Patrick Minx, Jose Carlos Miranda, Michael J Montague, Ronald J Nowling, Fabiano Oliveira, João Ortigão-Farias, Marcio G Pavan, Marcos Horacio Pereira, Andre Nobrega Pitaluga, Roenick Proveti Olmo, Marcelo Ramalho-Ortigao, José M C Ribeiro, Andrew J Rosendale, Mauricio R V Sant'anna, Steven E Scherer, Nágila F C Secundino, Douglas A Shoue, Caroline Da Silva Moraes, João Silveira Moledo Gesto, Nataly Araujo Souza, Zainulabueddin Syed, Samuel Tadros, Rayane Teles-De-Freitas, Erich L Telleria, Chad Tomlinson, Yara M Traub-Csekö, João Trindade Marques, Zhijian Tu, Maria F Unger, Jesus Valenzuela, Flávia V Ferreira, Karla P V De Oliveira, Felipe M Vigoder, John Vontas, Lihui Wang, Gareth D Weedall, Elyes Zhioua, Stephen Richards, Wesley C Warren, Robert M Waterhouse, Rod J Dillon, Mary Ann Mcdowell

Faculty, Staff and Students Publications

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control …

Intranasal Fentanyl And Discharge From The Emergency Department Among Children With Sickle Cell Disease And Vaso-Occlusive Pain: A Multicenter Pediatric Emergency Medicine Perspective, Chris A Rees, David C Brousseau, Fahd A Ahmad, Jonathan Bennett, Seema Bhatt, Amanda Bogie, Kathleen M Brown, T Charles Casper, Laura L Chapman, Corrie E Chumpitazi, Daniel M Cohen, Carlton Dampier, Angela M Ellison, Hartmut Grasemann, Dunia Hatabah, Robert W Hickey, Lewis L Hsu, Nitya Bakshi, Sara Leibovich, Prabhumallikarjun Patil, Elizabeth C Powell, Rachel Richards, Syana Sarnaik, Debra L Weiner, Claudia R Morris, Scd Arginine Study Group And Pecarn

Faculty, Staff and Students Publications

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included …

Altered Lateralization Of The Cingulum In Deployment-Related Traumatic Brain Injury: An Enigma Military-Relevant Brain Injury Study, Emily L Dennis, Mary R Newsome, Hannah M Lindsey, Maheen Adamson, Tara A Austin, Seth G Disner, Blessen C Eapen, Carrie Esopenko, Carol E Franz, Elbert Geuze, Courtney Haswell, Sidney R Hinds, Cooper B Hodges, Andrei Irimia, Kimbra Kenney, Inga K Koerte, William S Kremen, Harvey S Levin, Rajendra A Morey, John Ollinger, Jared A Rowland, Randall S Scheibel, Martha E Shenton, Danielle R Sullivan, Leah D Talbert, Sophia I Thomopoulos, Maya Troyanskaya, William C Walker, Xin Wang, Ashley L Ware, John Kent Werner, Wright Williams, Paul M Thompson, David F Tate, Elisabeth A Wilde

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with …

Commentary: There Is More Than One Way To Skin A Cat, Joseph S Coselli, Jonathan C Hong

Faculty, Staff and Students Publications

No abstract provided.

Commentary: Atrial Fibrillation: Surgeons Can Do More Than Operate, Lauren Barron, Marc R Moon

Faculty, Staff and Students Publications

No abstract provided.

Corrigendum To Diagnosis And Management Of Severe Congenital Protein C Deficiency (Scpcd): Communication From The Ssc Of The Isth [J Thromb Haemost 2022 Jul; 20(7):1735–1743], Adrian Minford, Leonardo R Brandão, Maha Othman, Christoph Male, Rezan Abdul-Kadir, Paul Monagle, Andrew D Mumford, Dorothy Adcock, Björn Dahlbäck, Predrag Miljic, Maria T Desancho, Jun Teruya

Faculty, Staff and Students Publications

No abstract provided.

Kinase Inhibitors And Atrial Fibrillation: Mechanisms Of Action And Clinical Implications, Adam S Potter, Mohit M Hulsurkar, Lingling Wu, Bharat Narasimhan, Kaveh Karimzad, Efstratios Koutroumpakis, Nicolas Palaskas, Anita Deswal, Bharat K Kantharia, Xander H T Wehrens

Faculty, Staff and Students Publications

Recent advances have significantly expanded the options of available therapeutics for cancer treatment, including novel targeted cancer therapies. Within this broad category of targeted therapies is the class of kinase inhibitors (KIs), which target kinases that have undergone aberrant activation in cancerous cells. Although KIs have shown a benefit in treating various forms of malignancy, they have also been shown to cause a wide array of cardiovascular toxicities, with cardiac arrhythmias, in particular atrial fibrillation (AF), being 1 of the predominant side effects. The occurrence of AF in patients undergoing cancer treatment can complicate the treatment approach and poses unique …

E-Cigarette Aerosols Of Propylene Glycol Impair Bk Channel Activity And Parameters Of Mucociliary Function, Michael D Kim, Samuel Chung, Nathalie Baumlin, Liang Sun, Neerupma Silswal, John S Dennis, Makoto Yoshida, Juan Sabater, Frank T Horrigan, Matthias Salathe

Faculty, Staff and Students Publications

Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro. Five-day exposure of sheep to e-cig aerosols of 100% PG increased mucus concentrations (% mucus solids) of tracheal secretions. PG e-cig aerosols further increased the activity …

Coevolutionary Signals In Metabotropic Glutamate Receptors Capture Residue Contacts And Long-Range Functional Interactions, Eunna Huh, Melina A Agosto, Theodore G Wensel, Olivier Lichtarge

Faculty, Staff and Students Publications

Upon ligand binding to a G protein-coupled receptor, extracellular signals are transmitted into a cell through sets of residue interactions that translate ligand binding into structural rearrangements. These interactions needed for functions impose evolutionary constraints so that, on occasion, mutations in one position may be compensated by other mutations at functionally coupled positions. To quantify the impact of amino acid substitutions in the context of major evolutionary divergence in the G protein-coupled receptor subfamily of metabotropic glutamate receptors (mGluRs), we combined two phylogenetic-based algorithms, Evolutionary Trace and covariation Evolutionary Trace, to infer potential structure-function couplings and roles in mGluRs. We …

Rational Design Of A Self-Assembling High Performance Organic Nanofluorophore For Intraoperative Nir-Ii Image-Guided Tumor Resection Of Oral Cancer, Xianwei Sun, Praveen Kumar Chintakunta, Andrew A Badachhape, Rohan Bhavane, Huan-Jui Lee, David S Yang, Zbigniew Starosolski, Ketan B Ghaghada, Peter G Vekilov, Ananth V Annapragada, Eric A Tanifum

Faculty, Staff and Students Publications

The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high …

Therapeutic Plasma Exchange Is Associated With Improved Major Adverse Kidney Events In Children And Young Adults With Thrombocytopenia At The Time Of Continuous Kidney Replacement Therapy Initiation, Dana Y Fuhrman, Sameer Thadani, Claire Hanson, Joseph A Carcillo, John A Kellum, Hyun Jung Park, Liling Lu, Nahmah Kim-Campbell, Christopher M Horvat, Ayse Akcan Arikan

Faculty, Staff and Students Publications

Therapeutic plasma exchange (TPE) has been shown to improve organ dysfunction and survival in patients with thrombotic microangiopathy and thrombocytopenia associated with multiple organ failure. There are no known therapies for the prevention of major adverse kidney events after continuous kidney replacement therapy (CKRT). The primary objective of this study was to evaluate the effect of TPE on the rate of adverse kidney events in children and young adults with thrombocytopenia at the time of CKRT initiation.

DESIGN: Retrospective cohort.

SETTING: Two large quaternary care pediatric hospitals.

PATIENTS: All patients less than or equal to 26 years old who received …

Nfkb2 Haploinsufficiency Identified Via Screening For Ifn-Α2 Autoantibodies In Children And Adolescents Hospitalized With Sars-Cov-2-Related Complications, Aaron Bodansky, Sara E Vazquez, Janet Chou, Tanya Novak, Amer Al-Musa, Cameron Young, Margaret Newhams, Suden Kucukak, Laura D Zambrano, Anthea Mitchell, Chung-Yu Wang, Kristin Moffitt, Natasha B Halasa, Laura L Loftis, Stephanie P Schwartz, Tracie C Walker, Elizabeth H Mack, Julie C Fitzgerald, Shira J Gertz, Courtney M Rowan, Katherine Irby, Ronald C Sanders, Michele Kong, Jennifer E Schuster, Mary A Staat, Matt S Zinter, Natalie Z Cvijanovich, Keiko M Tarquinio, Bria M Coates, Heidi R Flori, Mary K Dahmer, Hillary Crandall, Melissa L Cullimore, Emily R Levy, Brandon Chatani, Ryan Nofziger, Overcoming Covid-19 Network Study Group Investigators, Raif S Geha, Joseph Derisi, Angela P Campbell, Mark Anderson, Adrienne G Randolph

Faculty, Staff and Students Publications

BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown.

OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections.

METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding …

Temporal Single-Cell Atlas Of Non-Neuronal Retinal Cells Reveals Dynamic, Coordinated Multicellular Responses To Central Nervous System Injury, Inbal Benhar, Jiarui Ding, Wenjun Yan, Irene E Whitney, Anne Jacobi, Malika Sud, Grace Burgin, Karthik Shekhar, Nicholas M Tran, Chen Wang, Zhigang He, Joshua R Sanes, Aviv Regev

Faculty, Staff and Students Publications

Non-neuronal cells are key to the complex cellular interplay that follows central nervous system insult. To understand this interplay, we generated a single-cell atlas of immune, glial and retinal pigment epithelial cells from adult mouse retina before and at multiple time points after axonal transection. We identified rare subsets in naive retina, including interferon (IFN)-response glia and border-associated macrophages, and delineated injury-induced changes in cell composition, expression programs and interactions. Computational analysis charted a three-phase multicellular inflammatory cascade after injury. In the early phase, retinal macroglia and microglia were reactivated, providing chemotactic signals concurrent with infiltration of CCR2+ monocytes from …

Neurochemical Effects Of Sepsis On The Brain, Tatiana Barichello, Vijayasree V Giridharan, Carlos Henrique R Catalão, Cristiane Ritter, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB …

Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen

Faculty, Staff and Student Publications

A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide …

Genome-Wide Crispr Screens Reveal Zatt As A Synthetic Lethal Target Of Top2-Poison Etoposide That Can Act In A Tdp2-Independent Pathway, Jeong-Min Park, Huimin Zhang, Litong Nie, Chao Wang, Min Huang, Xu Feng, Mengfan Tang, Zhen Chen, Yun Xiong, Namsoo Lee, Siting Li, Ling Yin, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5'-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly …

Functional Effects Of Disease-Associated Variants Reveal That The S1-M1 Linker Of The Nmda Receptor Critically Controls Channel Opening, Lingling Xie, Miranda J Mcdaniel, Riley E Perszyk, Sukhan Kim, Gerarda Cappuccio, Kevin A Shapiro, Beatriz Muñoz-Cabello, Pedro A Sanchez-Lara, Katheryn Grand, Jing Zhang, Kelsey A Nocilla, Rehan Sheikh, Lluis Armengol, Roberta Romano, Tyler Mark Pierson, Hongjie Yuan, Scott J Myers, Stephen F Traynelis

Faculty, Staff and Students Publications

The short pre-M1 helix within the S1-M1 linker (also referred to as the pre-M1 linker) between the agonist-binding domain (ABD, S1) and the M1 transmembrane helix of the NMDA receptor (NMDAR) is devoid of missense variants within the healthy population but is a locus for de novo pathogenic variants associated with neurological disorders. Several de novo variants within this helix have been identified in patients presenting early in life with intellectual disability, developmental delay, and/or epilepsy. In this study, we evaluated functional properties for twenty variants within the pre-M1 linker in GRIN1, GRIN2A, and GRIN2B genes, including six novel missense …

The Prognostic Value Of Baseline Clinical And Radiologic Imaging Features In Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane asymmetry means that the two sides of membrane are structurally, physically and functionally different. Membrane asymmetry is largely related to the lipid sidedness and particularly to compositional (lipid head and acyl group) and physical (lipid packing order, charge, hydration and H-bonding interactions) differences in the inner and outer leaflets of lipid bilayer. Chemically, structurally and conformationally different non-covalent bound lipid molecules are physically fluid and deformable and enable to interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. Although biological membranes are almost universally asymmetric however the asymmetry is …

Renovating A Double Fence With Or Without Notifying The Next Door And Across The Street Neighbors: Why The Biogenic Cytoplasmic Membrane Of Gram-Negative Bacteria Display Asymmetry?, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex two-membrane organization of the envelope of Gram-negative bacteria imposes an unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on the cytoplasm facing leaflet of the cytoplasmic (inner) membrane (IM), across the IM and between the IM and outer membrane (OM). Balanced growth of two membranes and continuous loss of phospholipids in the periplasmic leaflet of the IM as metabolic precursors for envelope components and for translocation to the OM requires a constant supply of phospholipids in the IM cytosolic leaflet. At present we have no explanation as to why the biogenic E. …

Renovating A Double Fence With Or Without Notifying The Next Door And Across The Street Neighbors: Why The Biogenic Cytoplasmic Membrane Of Gram-Negative Bacteria Display Asymmetry?, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex two-membrane organization of the envelope of Gram-negative bacteria imposes an unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on the cytoplasm facing leaflet of the cytoplasmic (inner) membrane (IM), across the IM and between the IM and outer membrane (OM). Balanced growth of two membranes and continuous loss of phospholipids in the periplasmic leaflet of the IM as metabolic precursors for envelope components and for translocation to the OM requires a constant supply of phospholipids in the IM cytosolic leaflet. At present we have no explanation as to why the biogenic E. …

Targeting The Molecular And Immunologic Features Of Leiomyosarcoma, Brandon M Cope, Raymond S Traweek, Rossana Lazcano, Emily Z Keung, Alexander J Lazar, Christina L Roland, Elise F Nassif

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, …

Efficacy Of A Relaxation Scenario In Virtual Reality For The Comorbid Symptoms Of Anxiety And Asthenia In A General Hospital Setting: A Pilot Comparative Randomized Open-Label Study, Taisiya А Lepilkina, Allan G Beniashvili, Roman A Cheremin, Natalya G Malyukova, Margarita A Morozova, Mikhail A Bogdanov, Denis S Burminsky, Sergei S Potanin, Svetlana V Rodkina, George E Rupchev, Margarita N Eip

Faculty, Staff and Student Publications

BACKGROUND: Patients in general hospitals often display concomitant signs of mental maladjustment: low mood, anxiety, apathy, asthenia, all of which can have a negative impact on the course of the underlying disease and the recovery process. One of the non-pharmacological approaches that has gained wider acceptance in medical practice in recent years is the use of procedures based on virtual reality.

AIM: Assess the efficacy of the new domestic, virtual reality application Flow as relates to symptoms of anxiety and asthenia in patients undergoing inpatient treatment.

METHODS: The study was open-label and had a comparison group; the patients were assigned …

The En-Tex Resource Of Multi-Tissue Personal Epigenomes & Variant-Impact Models, Joel Rozowsky, Jiahao Gao, Beatrice Borsari, Yucheng T Yang, Timur Galeev, Gamze Gürsoy, Charles B Epstein, Kun Xiong, Jinrui Xu, Tianxiao Li, Jason Liu, Keyang Yu, Ana Berthel, Zhanlin Chen, Fabio Navarro, Maxwell S Sun, James Wright, Justin Chang, Christopher J F Cameron, Noam Shoresh, Elizabeth Gaskell, Jorg Drenkow, Jessika Adrian, Sergey Aganezov, François Aguet, Gabriela Balderrama-Gutierrez, Samridhi Banskota, Guillermo Barreto Corona, Sora Chee, Surya B Chhetri, Gabriel Conte Cortez Martins, Cassidy Danyko, Carrie A Davis, Daniel Farid, Nina P Farrell, Idan Gabdank, Yoel Gofin, David U Gorkin, Mengting Gu, Vivian Hecht, Benjamin C Hitz, Robbyn Issner, Yunzhe Jiang, Melanie Kirsche, Xiangmeng Kong, Bonita R Lam, Shantao Li, Bian Li, Xiqi Li, Khine Zin Lin, Ruibang Luo, Mark Mackiewicz, Ran Meng, Jill E Moore, Jonathan Mudge, Nicholas Nelson, Chad Nusbaum, Ioann Popov, Henry E Pratt, Yunjiang Qiu, Srividya Ramakrishnan, Joe Raymond, Leonidas Salichos, Alexandra Scavelli, Jacob M Schreiber, Fritz J Sedlazeck, Lei Hoon See, Rachel M Sherman, Xu Shi, Minyi Shi, Cricket Alicia Sloan, J Seth Strattan, Zhen Tan, Forrest Y Tanaka, Anna Vlasova, Jun Wang, Jonathan Werner, Brian Williams, Min Xu, Chengfei Yan, Lu Yu, Christopher Zaleski, Jing Zhang, Kristin Ardlie, J Michael Cherry, Eric M Mendenhall, William S Noble, Zhiping Weng, Morgan E Levine, Alexander Dobin, Barbara Wold, Ali Mortazavi, Bing Ren, Jesse Gillis, Richard M Myers, Michael P Snyder, Jyoti Choudhary, Aleksandar Milosavljevic, Michael C Schatz, Bradley E Bernstein, Roderic Guigó, Thomas R Gingeras, Mark Gerstein

Faculty, Staff and Students Publications

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding …

Covariate-Specific Evaluation Of Continuous Biomarker, Ziyi Li, Yijian Huang, Dattatraya Patil, Mark Rubin, Martin G Sanda

Faculty, Staff and Student Publications

Diagnostic tests usually need to operate at a high sensitivity or specificity level in practice. Accordingly, specificity at the controlled sensitivity, or vice versa, is a clinically sensible performance metric for evaluating continuous biomarkers. Meanwhile, the performance of a biomarker may vary across sub-populations as defined by covariates, and covariate-specific evaluation can be informative. In this article, we develop a novel modeling and estimation method for covariate-specific specificity at a controlled sensitivity level. Unlike existing methods which typically adopt elaborate models of covariate effects over the entire biomarker distribution, our approach models covariate effects locally at a specific sensitivity level …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Faculty, Staff and Student Publications

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H Elnaggar, Victoria O Huynh, Daniel Lin, R Tyler Hillman, Chike O Abana, Molly B El Alam, Katarina C Tomasic, Tatiana V Karpinets, Ramez Kouzy, Jae L Phan, Jennifer Wargo, Emma B Holliday, Prajnan Das, Melissa P Mezzari, Nadim J Ajami, Erica J Lynn, Bruce D Minsky, Van K Morris, Andrea Milbourne, Craig A Messick, Ann H Klopp, P Andrew Futreal, Cullen M Taniguchi, Kathleen M Schmeler, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.

METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

Ultralow-Dose Binary Oncolytic/Helper-Dependent Adenovirus Promotes Antitumor Activity In Preclinical And Clinical Studies, Daniel Wang, Caroline E Porter, Bora Lim, Amanda Rosewell Shaw, Catherine S Robertson, Mae L Woods, Ya Xu, Greyson G W Biegert, Daisuke Morita, Tao Wang, Bambi J Grilley, Helen Heslop, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

We show that a binary oncolytic/helper-dependent adenovirus (CAdVEC) that both lyses tumor cells and locally expresses the proinflammatory cytokine IL-12 and PD-L1 blocking antibody has potent antitumor activity in humanized mouse models. On the basis of these preclinical studies, we treated four patients with a single intratumoral injection of an ultralow dose of CAdVEC (NCT03740256), representing a dose of oncolytic adenovirus more than 100-fold lower than used in previous trials. While CAdVEC caused no significant toxicities, it repolarized the tumor microenvironment with increased infiltration of CD8 T cells. A single administration of CAdVEC was associated with both locoregional and abscopal …

Correction: Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

No abstract provided.