Digital Commons Network^™

Ilc2s Are The Predominant Source Of Intestinal Ilc-Derived Il-10, Jennifer K Bando, Susan Gilfillan, Blanda Di Luccia, José L Fachi, Cristiane Sécca, Marina Cella, Marco Colonna

Open Access Publications

Although innate lymphoid cells (ILCs) functionally analogous to T helper type 1 (Th1), Th2, and Th17 cells are well characterized, an ILC subset strictly equivalent to IL-10-secreting regulatory T cells has only recently been proposed. Here, we report the absence of an intestinal regulatory ILC population distinct from group 1 ILCs (ILC1s), ILC2s, and ILC3s in (1) mice bred in our animal facility; (2) mice from The Jackson Laboratory, Taconic Biosciences, and Charles River Laboratories; and (3) mice subjected to intestinal inflammation. Instead, a low percentage of intestinal ILC2s produced IL-10 at steady state. A screen for putative IL-10 elicitors …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Virus-Specific Memory T Cells Populate Tumors And Can Be Repurposed For Tumor Immunotherapy, Pamela C. Rosato, Sathi Wijeyesinghe, J Michael Stolley, Christine E. Nelson, Rachel Davis, Luke S. Manlove, Christopher A. Pennell, Bruce R. Blazar, Clark C. Chen, Melissa A. Geller, Vaiva Vezys, David Masopust

Faculty Publications

The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural …

Assessing The Effect Of Patient To Provider Language Discordance On Depression Screening Utilizing The Patient Health Questionnaire: An Epidemiology Study., Luis A. Murillo, Georgi Alex Grekoff, John C. Sheffield

Reading Hospital Family Medicine Residency

Background: As depression screening becomes a standard in primary care, the question remains of how effective and equitable screening can be implemented to avoid cultural and language-related disparities.

Methods: In this retrospective cohort study, rates of depression screening were compared for 3626 adult patients at a family medicine residency-based health centre in Pennsylvania, USA. The PHQ-2/PHQ-9 modality was verbally administered by nursing staff at the time of patient intake as part of a universal screening initiative. Chi-square analysis was used to determine the univariate associations of performed depression screening with variables of language, ethnicity, gender and number of office visits. …

Napoli-1 Phase 3 Study Of Liposomal Irinotecan In Metastatic Pancreatic Cancer: Final Overall Survival Analysis And Characteristics Of Long-Term Survivors, Andrea Wang-Gillam, Richard A Hubner, Jens T Siveke, Daniel D Von Hoff, Bruce Belanger, Floris A De Jong, Beloo Mirakhur, Li-Tzong Chen

Open Access Publications

BACKGROUND: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial.

PATIENTS AND METHODS: Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) …

White Matter Damage, Neuroinflammation, And Neuronal Integrity In Hand, Aljoharah Alakkas, David B Clifford, Et Al.

2010-2019 OA Pubs

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds …

Association Between Reductions Of Number Of Cigarettes Smoked Per Day And Mortality Among Older Adults In The United States, Maki Inoue-Choi, Patricia Hartge, Yikyung Park, Christian C Abnet, Neal D Freedman

2010-2019 OA Pubs

Many smokers do not quit but instead reduce the number of cigarettes they smoke per day (CPD) over their lifetime. Yet the associations of such changes in CPD with health risks are unclear. We examined the association of changes in CPD with subsequent death in the period 2004-2011 among 253,947 participants of the National Institutes of Health-AARP Diet and Health Study. Using a questionnaire assessing responders' history of smoking cigarettes, we identified cigarette smokers who quit, decreased, maintained, or increased their CPD between ages 25-29 and 50-59 years. Hazard ratios and 95% confidence intervals were obtained from multivariable adjusted Cox …

Characteristics Of Late Fatal Infections After Allogeneic Hematopoietic Cell Transplantation., Maxim Norkin, Bronwen E. Shaw, Ruta Brazauskas, Heather R. Tecca, Helen L. Leather, Juan Gea-Banacloche, Rammurti T. Kamble, Zachariah Defilipp, David A. Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly A. Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M. Badawy, Hillard M. Lazarus, Neel Bhatt, Biljana Horn, Saurabh Chhabra, Kristin M. Page, Betty Hamilton, Gerhard C. Hildebrandt, Jean A. Yared, Vaibhav Agrawal, Amer M. Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F. Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim A. Ahmed, Harry C. Schouten, Jane L. Liesveld, Nandita Khera, Amir Steinberg, Ami J. Shah, Melhem Solh, David I. Marks, Witold Rybka, Mahmoud Aljurf, Andrew C. Dietz, Usama Gergis, Biju George, Sachiko Seo, Mary E D Flowers, Minoo Battiwalla, Bipin N. Savani, Marcie L. Riches, John R. Wingard

Manuscripts, Articles, Book Chapters and Other Papers

We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% …

Genetic Associations Of Hemoglobin In Children With Chronic Kidney Disease In The Pedigfr Consortium, Meredith A Atkinson, Rui Xiao, Anna Köttgen, Elke Wühl, Craig S Wong, Matthias Wuttke, Aysun K Bayazit, Salim Çalişkan, Bradley A Warady, Franz Schaefer, Susan L Furth

Pediatrics Research and Scholarship

BACKGROUND: Genome-wide association studies (GWAS) in healthy populations have identified variants associated with erythrocyte traits, but genetic causes of hemoglobin variation in children with CKD are incompletely understood.

METHODS: The Pediatric Investigation of Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE), and Cardiovascular Comorbidity in Children with CKD (4C). We performed cross-sectional and longitudinal association studies of single-nucleotide polymorphisms (SNPs) in 1125 patients.

RESULTS: Children of European (n = 725) or …

Prevalence, Underlying Causes, And Preventability Of Sepsis-Associated Mortality In Us Acute Care Hospitals, Chanu Rhee, Travis M. Jones, Yasir Hamad, Anupam Pande, Jack Varon, Cara O'Brien, Deverick J Anderson, David K. Warren, Raymund B. Dantes, Lauren Epstein, Michael Klompas

Open Access Publications

Importance: Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown.

Objective: To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals.

Design, Setting, and Participants: Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, …

An Observational Study Of End-Tidal Carbon Dioxide Trends In General Anesthesia, Annemarie Akkermans, Judith A R Van Waes, Aleda Thompson, Amy Shanks, Linda M Peelen, Michael F Aziz, Daniel A Biggs, William C Paganelli, Jonathan P Wanderer, Daniel L Helsten, Sachin Kheterpal, Wilton A Van Klei, Leif Saager

Open Access Publications

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO

METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO

RESULTS: Both TWA-AUC and median ETCO

CONCLUSIONS: Between 2008 and 2016, intraoperative ETCO

Clinical Evaluation Of Exercise Capacity In Adults With Systemic Right Ventricle, Beata Rog, Kinga Salapa, Magdalena Okolska, Natalia Dluzniewska, Piotr Werynski, Piotr Podolec, Lidia Tomkiewicz-Pajak

The Texas Heart Institute Journal

The right ventricle provides systemic circulation in individuals with congenitally corrected transposition of the great arteries (CCTGA) and in those with complete transposition who have had an atrial switch repair (DTGA). The aim of this study was to evaluate how the systemic right ventricle adapts to increased workload and oxygen demand during exercise. From November 2005 through December 2015, 3,358 adult patients with congenital heart disease were treated at our institution; we identified 48 (26 females, 22 males; median age, 25.4 ± 8.1 yr) who met the study criteria; 37 had DTGA and atrial switch repair, and 11 had CCTGA. …

Preventing A Catastrophe: Increasing Awareness Of Loeys-Dietz Syndrome, Bradley S Kane, Kamran Shamsa

The Texas Heart Institute Journal

Loeys-Dietz syndrome is a genetic disorder that predisposes patients to aortic aneurysms. If left untreated, the natural history of the associated aortopathy often culminates in fatal aortic dissection. We describe the case of a 21-year-old man who was diagnosed with Loeys-Dietz syndrome after 2 family members died of aortic dissection. This case highlights the importance of increased physician awareness of this syndrome, which can play a crucial role in preventing premature sudden cardiac death caused by aortic catastrophe.

Penetrating Atherosclerotic Ulcer Of The Ascending Aorta Found Incidentally In A 71-Year-Old Man, Antonino M Grande, Dario Di Perna, Adele Valentini, Eloisa Arbustini

The Texas Heart Institute Journal

No abstract provided.

Adgrl3 (Lphn3) Variants Predict Substance Use Disorder, Mauricio Arcos-Burgos, Jorge I. Vélez, Ariel F. Martinez, Marta Ribasés, Josep A. Ramos-Quiroga, Cristina Sánchez-Mora, Vanesa Richarte, Carlos Roncero, Bru Cormand, Noelia Fernández-Castillo, Miguel Casas, Francisco Lopera, David A. Pineda, Juan D. Palacio, Johan E. Acosta-López, Martha L. Cervantes-Henriquez, Manuel G. Sánchez-Rojas, Pedro J. Puentes-Rozo, Brooke S. G. Molina, Mta Cooperative Group, Margaret T. Boden, Deeann Wallis, Brett Lidbury, Saul Newman, Simon Easteal, James Swanson, Hardip Patel, Nora Volkow, Maria T. Acosta, Francisco X. Castellanos, Jose De Leon

Psychiatry Faculty Publications

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we …

Multiancestry Genome-Wide Association Study Of Lipid Levels Incorporating Gene-Alcohol Interactions, Paul S. De Vries, Yun J. Sung, Karen Schwander, Aldi T. Kraja, Mary F. Feitosa, Lisa De Las Fuentes, Renee De Mutsert, C Charles Gu, Yize Li, Treva K. Rice, Lihua Wang, Christine Williams, Mary K. Wojczynski, Michael A. Province, Dabeeru C. Rao, Et Al

Open Access Publications

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test …

Elbow Angle Modulates Corticospinal Excitability To The Resting Biceps Brachii At Both Spinal And Supraspinal Levels, Siobhan C. Dongés, Janet L. Taylor, James L. Nuzzo

Research outputs 2014 to 2021

NEW FINDINGS:

What is the central question of this study?

Corticospinal excitability to biceps brachii is known to modulate according to upper-limb posture. Here, cervicomedullary stimulation was used to investigate potential spinal contributions to elbow angle-dependent changes in corticospinal excitability at rest.

What is the main finding and its importance?

At more extended elbow angles, biceps responses to cervicomedullary stimulation were decreased, whereas cortically evoked responses (normalized to cervicomedullary-evoked responses) were increased. Results suggest decreased spinal excitability but increased cortical excitability as the elbow is placed in a more extended position, an effect that is unlikely to be attributable to …

Assessing The Effect Of Patient To Provider Language Discordance On Depression Screening Utilizing The Patient Health Questionnaire: An Epidemiology Study., Luis A. Murillo, Georgi Alex Grekoff, John C. Sheffield

Reading Hospital Family Medicine Residency

Background: As depression screening becomes a standard in primary care, the question remains of how effective and equitable screening can be implemented to avoid cultural and language-related disparities.

Methods: In this retrospective cohort study, rates of depression screening were compared for 3626 adult patients at a family medicine residency-based health centre in Pennsylvania, USA. The PHQ-2/PHQ-9 modality was verbally administered by nursing staff at the time of patient intake as part of a universal screening initiative. Chi-square analysis was used to determine the univariate associations of performed depression screening with variables of language, ethnicity, gender and number of office visits. …

Shared Heritability And Functional Enrichment Across Six Solid Cancers., Xia Jiang, Hilary K Finucane, Fredrick R Schumacher, Stephanie L Schmit, Jonathan P Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B Kuchenbaecker, Joe Dennis, David V Conti, Graham Casey, Mia M Gaudet, Jeroen R Huyghe, Demetrius Albanes, Melinda C Aldrich, Angeline S Andrew, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Natalia N Antonenkova, Susanne M Arnold, Kristan J Aronson, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Jyotsna Batra, Matthias W Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I Berndt, Heike Bickeböller, Stephanie A Bien, Carl Blomqvist, Stefania Boccia, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Hiltrud Brauch, Hermann Brenner, James D Brenton, Mark N Brook, Joan Brunet, Hans Brunnström, Daniel D Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A Caligo, Ian Campbell, Peter T Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L Carvalho, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, Chu Chen, David C Christiani, Kathleen B M Claes, Frank Claessens, Judith Clements, J Margriet Collée, Marcia Cruz Correa, Fergus J Couch, Angela Cox, Julie M Cunningham, Cezary Cybulski, Kamila Czene, Mary B Daly, Anna Defazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L Donovan, Thilo Dörk, Eric J Duell, Alison M Dunning, Miriam Dwek, Diana M Eccles, Christopher K Edlund, Digna R Velez Edwards, Carolina Ellberg, D Gareth Evans, Peter A Fasching, Robert L Ferris, Triantafillos Liloglou, Jane C Figueiredo, Olivia Fletcher, Renée T Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J Gallinger, Patricia A Ganz, Judy Garber, José A García-Sáenz, Simon A Gayther, Graham G Giles, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Ellen L Goode, Marc T Goodman, Gary E Goodman, Kjell Grankvist, Mark H Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C Hamdy, Robert J Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L Hopper, Richard Houlston, Peter J Hulick, David J Hunter, David G Huntsman, Gregory Idos, Evgeny N Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A Jenkins, Mattias Johansson, Mikael Johansson, Esther M John, Amit D Joshi, Radka Kaneva, Beth Y Karlan, Linda E Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S Kibel, Lambertus A Kiemeney, Jeri Kim, Susanne K Kjaer, Julia A Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A Levine, Li Li, Christopher I Li, Annika Lindblom, Noralane M Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley Mcguffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L Milne, Robert J Macinnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, David E Neal, Andrew R Ness, Susan L Neuhausen, Heli Nevanlinna, Polly A Newcomb, Lisa F Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G Nordestgaard, Robert L Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I Olopade, Andrew F Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y Park, Nora Pashayan, Michael T Parsons, Tanja Pejovic, Kathryn L Penney, Wilbert H M Peters, Catherine M Phelan, Amanda I Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J Ramus, Leon Raskin, Gad Rennert, Hedy S Rennert, Elizabeth J Van Rensburg, Marjorie J Riggan, Harvey A Risch, Angela Risch, Monique J Roobol, Barry S Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P Sandler, Elinor J Sawyer, Matthew B Schabath, Johanna Schleutker, Marjanka K Schmidt, V Wendy Setiawan, Hongbing Shen, Erin M Siegel, Weiva Sieh, Christian F Singer, Martha L Slattery, Karina Dalsgaard Sorensen, Melissa C Southey, Amanda B Spurdle, Janet L Stanford, Victoria L Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J Swerdlow, Eloiza H Tajara, Catherine M Tangen, Adonina Tardon, Jack A Taylor, M Dawn Teare, Manuel R Teixeira, Mary Beth Terry, Kathryn L Terry, Stephen N Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E Toland, Diana Torres, Paul A Townsend, Ruth C Travis, Nadine Tung, Shelley S Tworoger, Cornelia M Ulrich, Nawaid Usmani, Celine M Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M Webb, Clarice R Weinberg, Stephanie Weinstein, Mark C Weissler, Jeffrey N Weitzel, Catharine M L West, Emily White, Alice S Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K Zorn, Jacqueline M Lane, Richa Saxena, Duncan Thomas, Rayjean J Hung, Brenda Diergaarde, James Mckay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A Eeles, Georgia Chenevix-Trench, Paul J Brennan, Christopher A Haiman, Jacques Simard, Douglas F Easton, Stephen B Gruber, Paul D P Pharoah, Alkes L Price, Bogdan Pasaniuc, Christopher I Amos, Peter Kraft, Sara Lindström

Articles, Abstracts, and Reports

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r

Developing And Assessing The Feasibility Of A Home-Based Preexposure Prophylaxis Monitoring And Support Program, Aaron J Siegler, Kenneth H Mayer, Albert Y Liu, Rupa R Patel, Lauren M Ahlschlager, Colleen S Kraft, Rossi Fish, Sarah E Wiatrek, Patrick S Sullivan

2010-2019 OA Pubs

We piloted PrEP@Home, a preexposure prophylaxis system of remote laboratory and behavioral monitoring designed to replace routine quarterly follow-up visits with home care to reduce the patient and provider burden. The system was highly acceptable and in-demand for future use, and more than one-third of participants reported greater likelihood of persisting in care if available.

Instability Of The Mitochondrial Alanyl-Trna Synthetase Underlies Fatal Infantile-Onset Cardiomyopathy., Ewen W. Sommerville, Xiao-Long Zhou, Monika Oláhová, Janda L. Jenkins, Liliya Euro, Svetlana Konovalova, Taru Hilander, Angela Pyle, Langping He, Sultan Habeebu, Carol J. Saunders, Anna Kelsey, Andrew A M Morris, Robert Mcfarland, Anu Suomalainen, Gráinne S. Gorman, En-Duo Wang, Isabelle Thiffault, Henna Tyynismaa, Robert W. Taylor

Manuscripts, Articles, Book Chapters and Other Papers

Recessively inherited variants in AARS2 (NM_020745.2) encoding mitochondrial alanyl-tRNA synthetase (mt-AlaRS) were first described in patients presenting with fatal infantile cardiomyopathy and multiple oxidative phosphorylation defects. To date, all described patients with AARS2-related fatal infantile cardiomyopathy are united by either a homozygous or compound heterozygous c.1774C>T (p.Arg592Trp) missense founder mutation that is absent in patients with other AARS2-related phenotypes. We describe the clinical, biochemical and molecular investigations of two unrelated boys presenting with fatal infantile cardiomyopathy, lactic acidosis and respiratory failure. Oxidative histochemistry showed cytochrome c oxidase-deficient fibres in skeletal and cardiac muscle. Biochemical studies showed markedly decreased activities …

Oscillometry And Pulmonary Magnetic Resonance Imaging In Asthma And Copd, Rachel L Eddy, Andrew Westcott, Geoffrey N Maksym, Grace Parraga, Ronald J Dandurand

Medical Biophysics Publications

Developed over six decades ago, pulmonary oscillometry has re-emerged as a noninvasive and effort-independent method for evaluating respiratory-system impedance in patients with obstructive lung disease. Here, we evaluated the relationships between hyperpolarized

Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn L. Skar, David C. Synhorst, Matthew Beaver, Jessica N. Snowden

Manuscripts, Articles, Book Chapters and Other Papers

Background: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.

Methods: We conducted a retrospective chart review of children with …

Apo-Opsin Exists In Equilibrium Between A Predominant Inactive And A Rare Highly Active State, Shinya Sato, Beata Jastrzebska, Andreas Engel, Krzysztof Palczewski, Vladimir J. Kefalov

Open Access Publications

Bleaching adaptation in rod photoreceptors is mediated by apo-opsin, which activates phototransduction with effective activity 10

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

A Randomized, Placebo-Controlled Trial Of Fidaxomicin For Prophylaxis Of Clostridium Difficile-Associated Diarrhea In Adults Undergoing Hematopoietic Stem Cell Transplantation, Kathleen M. Mullane, Erik R. Dubberke, Et Al

Open Access Publications

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients.

Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. …

Reward Improves Response Inhibition By Enhancing Attentional Capture, Yanqing Wang, Todd S Braver, Shouhang Yin, Xueping Hu, Xiangpeng Wang, Antao Chen

2010-2019 OA Pubs

Reward plays a crucial role in enhancing response inhibition. While it is generally assumed that the process of response inhibition involves attentional capture and the stopping of action, it is unclear whether this reflects a direct impact of reward on response inhibition or rather an indirect mediation via attentional capture. Here, we employed a revised stop-signal task (SST) that separated these two cognitive elements, by including a continue signal that required the same motor response as in go trials, but also attention to a cue, as in stop trials. We first confirmed the engagement of the right inferior frontal gyrus …

Association Between 5-Year Clinical Outcome In Patients With Nonmedically Evacuated Mild Blast Traumatic Brain Injury And Clinical Measures Collected Within 7 Days Postinjury In Combat, Christine L. Mac Donald, Jason Barber, Jana Patterson, Ann M. Johnson, Sureyya Dikmen, Jesse R. Fann, Nancy Temkin

Open Access Publications

Importance: Although previous work has examined clinical outcomes in combat-deployed veterans, questions remain regarding how symptoms evolve or resolve following mild blast traumatic brain injury (TBI) treated in theater and their association with long-term outcomes.

Objective: To characterize 5-year outcome in patients with nonmedically evacuated blast concussion compared with combat-deployed controls and understand what clinical measures collected acutely in theater are associated with 5-year outcome.

Design, Setting, and Participants: A prospective, longitudinal cohort study including 45 service members with mild blast TBI within 7 days of injury (mean 4 days) and 45 combat deployed nonconcussed controls was carried out. Enrollment …

Ctcf Governs The Identity And Migration Of Mge-Derived Cortical Interneurons., Adrienne Elbert, Daniel Vogt, Ashley Watson, Michael Levy, Yan Jiang, Emilie Brûlé, Megan E Rowland, John Rubenstein, Nathalie G Bérubé

Paediatrics Publications

The CCCTC-binding factor (CTCF) is a central regulator of chromatin topology recently linked to neurodevelopmental disorders such as intellectual disability, autism, and schizophrenia. The aim of this study was to identify novel roles of CTCF in the developing mouse brain. We provide evidence that CTCF is required for the expression of the LIM homeodomain factor LHX6 involved in fate determination of cortical interneurons (CINs) that originate in the medial ganglionic eminence (MGE). Conditional

The Transcriptional Regulator Snon Promotes The Proliferation Of Cerebellar Granule Neuron Precursors In The Postnatal Mouse Brain, Xiaoying Chen, Ayan Chanda, Yoshiho Ikeuchi, Xiaoqing Zhang, Jared V. Goodman, Naveen C. Reddy, Shahriyar P. Majidi, Dennis Y. Wu, Sarah E. Smith, Abigail Godec, Anna Oldenborg, Harrison W. Gabel, Guoyan Zhao, Shirin Bonni, Azad Bonni

Open Access Publications

Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional KO of the transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal male and female mouse brain. In laser capture microdissection …