Digital Commons Network^™

Cumulative Exposure To Long Working Hours And Occurrence Of Ischemic Heart Disease: Evidence From The Constances Cohort At Inception, Marc Fadel, Jian Li, Grace Sembajwe, Diana Gagliardi, Fernando Pico, Anna Ozguler, Bradley A Evanoff, Michel Baer, Akizumi Tsutsumi, Sergio Iavicoli, Annette Leclerc, Yves Roquelaure, Johannes Siegrist, Alexis Descatha

Open Access Publications

Background Long-working hours (LWH) are a probable risk factor for ischemic heart diseases (IHD); however, no previous study has considered duration of exposure to LWH when addressing this topic. We aimed to determine the association between cumulative exposure to LWH and IHD while accounting for relevant confounders. Methods and Results In this retrospective study, we included all baseline participants from the French population-based cohort CONSTANCES. Part-time employees and those who reported a cardiac event in the 5 years before LWH exposure were excluded. From self-administered questionnaires and clinical examinations, we obtained participants' age, sex, body mass index, occupational status, smoking …

Oligomerization Of The Vesicular Stomatitis Virus Phosphoprotein Is Dispensable For Mrna Synthesis But Facilitates Rna Replication, Louis-Marie Bloyet, Benjamin Morin, Vesna Brusic, Erica Gardner, Robin A. Ross, Tegy Vadakkan, Tomas Kirchhausen, Sean P. J. Whelan

Open Access Publications

Nonsegmented negative-strand (NNS) RNA viruses possess a ribonucleoprotein template in which the genomic RNA is sequestered within a homopolymer of nucleocapsid protein (N). The viral RNA-dependent RNA polymerase (RdRP) resides within an approximately 250-kDa large protein (L), along with unconventional mRNA capping enzymes: a GDP:polyribonucleotidyltransferase (PRNT) and a dual-specificity mRNA cap methylase (MT). To gain access to the N-RNA template and orchestrate the L

Modulation Of Extracellular Isg15 Signaling By Pathogens And Viral Effector Proteins, Caleb D Swaim, Larissa A Canadeo, Kristen J Monte, Swati Khanna, Deborah J Lenschow, Jon M Huibregtse

Open Access Publications

ISG15 is a ubiquitin-like modifier that also functions extracellularly, signaling through the LFA-1 integrin to promote interferon (IFN)-γ release from natural killer (NK) and T cells. The signals that lead to the production of extracellular ISG15 and the relationship between its two core functions remain unclear. We show that both epithelial cells and lymphocytes can secrete ISG15, which then signals in either an autocrine or paracrine manner to LFA-1-expressing cells. Microbial pathogens and Toll-like receptor (TLR) agonists result in both IFN-β-dependent and -independent secretion of ISG15, and residues required for ISG15 secretion are mapped. Intracellular ISGylation inhibits secretion, and viral …

Sting Gain-Of-Function Disrupts Lymph Node Organogenesis And Innate Lymphoid Cell Development In Mice, Brock G Bennion, Teresa L Ai, Wei Qian, Amber M Menos, Cathrine A Miner, Prabhakar S Andhey, Derek J Platt, Jennifer K Bando, Erin R Wang, Elisha D O Roberson, Maxim N Artyomov, Marco Colonna, Jonathan J Miner, Et Al

Open Access Publications

STING gain-of-function causes autoimmunity and immunodeficiency in mice and STING-associated vasculopathy with onset in infancy (SAVI) in humans. Here, we report that STING gain-of-function in mice prevents development of lymph nodes and Peyer's patches. We show that the absence of secondary lymphoid organs is associated with diminished numbers of innate lymphoid cells (ILCs), including lymphoid tissue inducer (LTi) cells. Although wild-type (WT) α4β7

Validation Of Parkinson's Disease-Related Questionnaires In South Africa, Gill Nelson, Ntombizodwa Ndlovu, Nicola Christofides, Tintswalo M Hlungwani, Irene Faust, Brad A Racette

Open Access Publications

Background: There are very few epidemiological studies investigating Parkinson's disease (PD) in Africa. The hundreds of local languages and dialects make traditional screening and clinical evaluation tools difficult to use.

Objective: The objective of the study was to validate two commonly used PD questionnaires in an African population.

Methods: The PD Screening Questionnaire (PDSQ) and Parkinson's Disease Questionnaire (PDQ-39) were modified and translated into Afrikaans, Setswana, and isiZulu and administered to a sample of healthy local residents. We assessed the internal consistencies and cluster characteristics of the questionnaires, using a Cronbach's alpha test and exploratory factor analysis. The questionnaires were …

Replication Of Associations With Psychotic-Like Experiences In Middle Childhood From The Adolescent Brain Cognitive Development (Abcd) Study, Nicole R Karcher, Rachel L Loewy, Mark Savill, Shelli Avenevoli, Rebekah S Huber, Tony J Simon, Ingrid N Leckliter, Kenneth J Sher, Deanna M Barch

Open Access Publications

The fields of psychology and psychiatry are increasingly recognizing the importance of replication efforts. The current study aimed to replicate previous findings examining the construct validity and psychometric properties of a psychotic-like experiences (PLEs) measure in middle childhood using an independent subset of the baseline Adolescent Brain Cognitive Development (ABCD) sample. Using a remainder baseline sample of 7013 nine- to eleven-year-old children with complete data, we examined measurement invariance across race/ethnicity and sex, and examined the associations between the Prodromal Questionnaire Brief-Child Version (PQ-BC) and other measures of PLEs, internalizing symptoms, neuropsychological test performance, and developmental milestones, to determine whether …

A Survey-Based Analysis Of The Academic Job Market, Jason D. Fernandes, Sarvenaz Sarabipour, Christopher T. Smith, Natalie M. Niemi, Nafisa M. Jadavji, Ariangela J. Kozik, Alex S. Holehouse, Vikas Pejaver, Orsolya Symmons, Alexandre W. Bisson Filho, Amanda Haage

Open Access Publications

Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success - including funding, number of publications or journals published in - were unable to completely …

The Neurons That Mistook A Hat For A Face, Michael J. Arcaro, Carlos Ponce, Margaret Livingstone

Open Access Publications

Despite evidence that context promotes the visual recognition of objects, decades of research have led to the pervasive notion that the object processing pathway in primate cortex consists of multiple areas that each process the intrinsic features of a few particular categories (e.g. faces, bodies, hands, objects, and scenes). Here we report that such category-selective neurons do not in fact code individual categories in isolation but are also sensitive to object relationships that reflect statistical regularities of the experienced environment. We show by direct neuronal recording that face-selective neurons respond not just to an image of a face, but also …

Phospho-Ser784-Vcp Is Required For Dna Damage Response And Is Associated With Poor Prognosis Of Chemotherapy-Treated Breast Cancer, Cuige Zhu, Anna Rogers, Karama Asleh, Jennifer Won, Dongxia Gao, Samuel Leung, Shan Li, Kiran R Vij, Jian Zhu, Jason M Held, Zhongsheng You, Torsten O Nielsen, Jieya Shao

Open Access Publications

Spatiotemporal protein reorganization at DNA damage sites induced by genotoxic chemotherapies is crucial for DNA damage response (DDR), which influences treatment response by directing cancer cell fate. This process is orchestrated by valosin-containing protein (VCP), an AAA+ ATPase that extracts polyubiquinated chromatin proteins and facilitates their turnover. However, because of the essential and pleiotropic effects of VCP in global proteostasis, it remains challenging practically to understand and target its DDR-specific functions. We describe a DNA-damage-induced phosphorylation event (Ser

Safety And Efficacy Of Co-Administered Diethylcarbamazine, Albendazole And Ivermectin During Mass Drug Administration For Lymphatic Filariasis In Haiti: Results From A Two-Armed, Open-Label, Cluster-Randomized, Community Study, Christine Dubray, Anita Sircar, Madsen Beau De Rochars, Joshua Bogus, Abdel N. Direny, Jean Romuald Ernest, Carl Fayette, Charles W. Goss, Marisa Hast, Katiuscia O'Brian, Guy Emmanuel Pavilus, Daniel Frantz Sabin, Ryan Wiegand, Gary J. Weil, Jean Frantz Lemoine

Open Access Publications

No abstract provided.

Radiological Society Of North America (Rsna) 3d Printing Special Interest Group (Sig) Clinical Situations For Which 3d Printing Is Considered An Appropriate Representation Or Extension Of Data Contained In A Medical Imaging Examination: Abdominal, Hepatobiliary, And Gastrointestinal Conditions, David H Ballard, Et Al

Open Access Publications

BACKGROUND: Medical 3D printing has demonstrated value in anatomic models for abdominal, hepatobiliary, and gastrointestinal conditions. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides appropriateness criteria for abdominal, hepatobiliary, and gastrointestinal 3D printing indications.

METHODS: A literature search was conducted to identify all relevant articles using 3D printing technology associated with a number of abdominal pathologic processes. Each included study was graded according to published guidelines.

RESULTS: Evidence-based appropriateness guidelines are provided for the following areas: intra-hepatic masses, hilar cholangiocarcinoma, biliary stenosis, biliary stones, gallbladder pathology, pancreatic cancer, …

Cd56 Regulates Human Nk Cell Cytotoxicity Through Pyk2, Justin T. Gunesch, Amera L. Dixon, Tasneem A.M. Ebrahim, Melissa M. Berrien-Elliott, Swetha Tatineni, Tejas Kumar, Everardo Hegewisch-Solloa, Todd A. Fehniger, Emily M. Mace

Open Access Publications

Human natural killer (NK) cells are defined as CD56

Multidimensional Imaging Of Liver Injury Repair In Mice Reveals Fundamental Role Of The Ductular Reaction, Kenji Kamimoto, Yasuhiro Nakano, Kota Kaneko, Atsushi Miyajima, Tohru Itoh

Open Access Publications

Upon severe and/or chronic liver injury, ectopic emergence and expansion of atypical biliary epithelial-like cells in the liver parenchyma, known as the ductular reaction, is typically induced and implicated in organ regeneration. Although this phenomenon has long been postulated to represent activation of facultative liver stem/progenitor cells that give rise to new hepatocytes, recent lineage-tracing analyses have challenged this notion, thereby leaving the pro-regenerative role of the ductular reaction enigmatic. Here, we show that the expanded and remodelled intrahepatic biliary epithelia in the ductular reaction constituted functional and complementary bile-excreting conduit systems in injured parenchyma where hepatocyte bile canalicular networks …

Assessment Of Antibiotic-Resistant Organism Transmission Among Rooms Of Hospitalized Patients, Healthcare Personnel, And The Hospital Environment Utilizing Surrogate Markers And Selective Bacterial Cultures, Jennie H Kwon, Kimberly Reske, Caroline A O'Neil, Candice Cass, Sondra Seiler, Meghan A Wallace, Tiffany Hink, Stephen Y Liang, Victoria J Fraser, Carey-Ann D Burnham, Erik R Dubberke

Open Access Publications

OBJECTIVE: To assess potential transmission of antibiotic-resistant organisms (AROs) using surrogate markers and bacterial cultures.

DESIGN: Pilot study.

SETTING: A 1,260-bed tertiary-care academic medical center.

PARTICIPANTS: The study included 25 patients (17 of whom were on contact precautions for AROs) and 77 healthcare personnel (HCP).

METHODS: Fluorescent powder (FP) and MS2 bacteriophage were applied in patient rooms. HCP visits to each room were observed for 2-4 hours; hand hygiene (HH) compliance was recorded. Surfaces inside and outside the room and HCP skin and clothing were assessed for fluorescence, and swabs were collected for MS2 detection by polymerase chain reaction (PCR) …

Wide Complex Tachycardia Differentiation: A Reappraisal Of The State-Of-The-Art, Anthony H Kashou, Peter A Noseworthy, Christopher V Desimone, Abhishek J Deshmukh, Samuel J Asirvatham, Adam M May

Open Access Publications

The primary goal of the initial ECG evaluation of every wide complex tachycardia is to determine whether the tachyarrhythmia has a ventricular or supraventricular origin. The answer to this question drives immediate patient care decisions, ensuing clinical workup, and long-term management strategies. Thus, the importance of arriving at the correct diagnosis cannot be understated and has naturally spurred rigorous research, which has brought forth an ever-expanding abundance of manually applied and automated methods to differentiate wide complex tachycardias. In this review, we provide an in-depth analysis of traditional and more contemporary methods to differentiate ventricular tachycardia and supraventricular wide complex …

Stage-Specific Requirement For Eomes In Mature Nk Cell Homeostasis And Cytotoxicity, Julia A Wagner, Pamela Wong, Timothy Schappe, Melissa M Berrien-Elliott, Celia Cubitt, Natalia Jaeger, Madeline Lee, Cassie R Keppel, Nancy D Marin, Jennifer A Foltz, Lynne Marsala, Carly C Neal, Ryan P Sullivan, Stephanie E Schneider, Molly P Keppel, Nermina Saucier, Megan A Cooper, Todd A Fehniger

Open Access Publications

Natural killer (NK) cells are cytotoxic innate lymphoid cells (ILCs) that mediate antiviral and antitumor responses and require the transcriptional regulator Eomesodermin (Eomes) for early development. However, the role of Eomes and its molecular program in mature NK cell biology is unclear. To address this, we develop a tamoxifen-inducible, type-1-ILC-specific (Ncr1-targeted) cre mouse and combine this with Eomes-floxed mice. Eomes deletion after normal NK cell ontogeny results in a rapid loss of NK cells (but not ILC1s), with a particularly profound effect on penultimately mature stage III NK cells. Mechanisms responsible for stage III reduction include increased apoptosis and impaired …

Survival Benefit Associated With Early Detection Of Spontaneous Bacterial Peritonitis In Veteran Inpatients With Cirrhotic Ascites, Luke Townsend, Pierre Blais, Alex Huh, Leela Nayak, Jill E Elwing, Gregory S Sayuk

Open Access Publications

Background: Spontaneous bacterial peritonitis (SBP) is common in hospitalized cirrhotic patients with ascites and carries high mortality. This study aimed to determine whether early diagnostic paracentesis (EDP) <12 h of hospitalization conveys an intermediate-term (6-month) survival benefit in cirrhotic patients diagnosed with SBP.

Methods: Consecutive US veterans with cirrhosis diagnosed with SBP over 13 years at a single VA medical center were reviewed retrospectively. Kaplan-Meyer analyses assessed the effects of EDP on survival.

Results: A total of 79 cirrhotic patients were diagnosed with SBP (61.8 ± 8.8 years,

Conclusions: EDP is associated with improved 6-month mortality in cirrhotic patients with ascites. In this veteran cohort, EDP was as important as MELD as a predictor of intermediate-term …

Systematic Validation Of Variants Of Unknown Significance In App, Psen1 And Psen2, Simon Hsu, Anna A Pimenova, Kimberly Hayes, Juan A Villa, Matthew J Rosene, Madhavi Jere, Alison M Goate, Celeste M Karch

Open Access Publications

Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. More than 200 pathogenic mutations have been identified in amyloid-β precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Additionally, common and rare variants occur within APP, PSEN1, and PSEN2 that may be risk factors, protective factors, or benign, non-pathogenic polymorphisms. Yet, to date, no single study has carefully examined the effect of all of the variants of unknown significance reported in APP, PSEN1 and PSEN2 on Aβ isoform levels in vitro. In this study, we analyzed Aβ isoform levels by ELISA in a …

Potent, Specific Mepicides For Treatment Of Zoonotic Staphylococci, Rachel L. Edwards, Isabel Heueck, Soon Goo Lee, Ishaan T. Shah, Justin J. Miller, Andrew J. Jezewski, Marwa O. Mikati, Xu Wang, Robert C. Brothers, Kenneth M. Heidel, Damon M. Osbourn, Carey-Ann D. Burnham, Sophie Alvarez, Stephanie A. Fritz, Cynthia S. Dowd, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) …

Impact Of Left Ventricular Assist Device Implantation On Mitral Regurgitation: An Analysis From The Momentum 3 Trial, Manreet K Kanwar, Keshava Rajagopal, Akinobu Itoh, Scott C Silvestry, Nir Uriel, Joseph C Cleveland, Christopher T Salerno, Douglas Horstmanshof, Daniel J Goldstein, Yoshifumi Naka, Stephen Bailey, Igor D Gregoric, Joyce Chuang, Poornima Sood, Mandeep R Mehra

Open Access Publications

BACKGROUND: Mitral regurgitation (MR) determines pathophysiology and outcome in advanced heart failure. The impact of left ventricular assist device (LVAD) placement on clinically significant MR and its contribution to long-term outcomes has been sparsely evaluated.

METHODS: We evaluated the effect of clinically significant MR on patients implanted in the MOMENTUM 3 trial with either the HeartMate II (HMII) or the HeartMate 3 (HM3) at 2 years. Clinical significance was defined as moderate or severe grade MR determined by site-based echocardiograms.

RESULTS: Of 927 patients with LVAD implants without a prior or concomitant mitral valve procedure, 403 (43.5%) had clinically significant …

Strategies To Optimize Icu Liberation (A To F) Bundle Performance In Critically Ill Adults With Coronavirus Disease 2019, John W Devlin, Hollis R O'Neal Jr, Christopher Thomas, Mary Ann Barnes Daly, Joanna L Stollings, David R Janz, E Wesley Ely, John C Lin

Open Access Publications

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, …

Efficacy Of Bezlotoxumab In Participants Receiving Metronidazole, Vancomycin, Or Fidaxomicin For Treatment Of Clostridioides (Clostridium) Difficile Infection, Erik R. Dubberke, Dale N. Gerding, Ciarán P. Kelly, Kevin W. Garey, Galia Rahav, Audrey Mosley, Robert Tipping, Mary Beth Dorr

Open Access Publications

Background: In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of

Methods: In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups.

Results: Of 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and …

Growth Velocity In Children With Environmental Enteric Dysfunction Is Associated With Specific Bacterial And Viral Taxa Of The Gastrointestinal Tract In Malawian Children, Chandni Desai, Scott A. Handley, Rachel Rodgers, Cynthia Rodriguez, Maria I. Ordiz, Mark J. Manary, Lori R. Holtz

Open Access Publications

Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of …

The Impact Of Four Years Of Semiannual Treatments With Albendazole Alone On Lymphatic Filariasis And Soil-Transmitted Helminth Infections: A Community-Based Study In The Democratic Republic Of The Congo, Sébastien D. S. Pion, Cédric B. Chesnais, Naomi P. Awaca-Uvon, Johnny Vlaminck, Anlimou Abdou, Billy Kunyu-Shako, Godefroy Kuyangisa Simuna, Jean-Paul Tambwe, Gary J. Weil, Michel Boussinesq

Open Access Publications

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow.

METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo …

Trends In Frequency Of Sexual Activity And Number Of Sexual Partners Among Adults Aged 18 To 44 Years In The Us, 2000-2018, Peter Ueda, Catherine H. Mercer, Cyrus Ghaznavi, Debby Herbenick

Open Access Publications

Importance: Sexual relationships are important for well-being and health. Recent trends in sexual activity among US adults are unknown.

Objectives: To examine trends in reported frequency of sexual activity and number of sexual partners by sex and age and the association between measures of sexual activity and sociodemographic variables.

Design, Setting, and Participants: In this survey study, repeat, cross-sectional analyses of participants aged 18 to 44 years from 10 rounds of the General Social Survey (2000-2018), a US nationally representative survey, were performed for men and women separately.

Main Outcomes and Measures: Sexual frequency in the past year (sexual inactivity, …

Clinical Trial Design And Development Work Group Within The Quantitative Imaging Network, Ella F. Jones, John M. Buatti, Hui-Kuo Shu, Richard L. Wahl, Brenda F. Kurland, Hannah M. Linden, David A. Mankoff, Daniel L. Rubin, Darrell Tata, Robert J. Nordstrom, Lubomir Hadjiyski, Matthias Holdhoff, Lawrence H. Schwartz

Open Access Publications

The Clinical Trial Design and Development Working Group within the Quantitative Imaging Network focuses on providing support for the development, validation, and harmonization of quantitative imaging (QI) methods and tools for use in cancer clinical trials. In the past 10 years, the Group has been working in several areas to identify challenges and opportunities in clinical trials involving QI and radiation oncology. The Group has been working with Quantitative Imaging Network members and the Quantitative Imaging Biomarkers Alliance leadership to develop guidelines for standardizing the reporting of quantitative imaging. As a validation platform, the Group led a multireader study to …

Repository Corticotropin Injection For Active Rheumatoid Arthritis Despite Aggressive Treatment: A Randomized Controlled Withdrawal Trial., Roy Fleischmann, Daniel E Furst, Erin Connolly-Strong, Jingyu Liu, Julie Zhu, Richard Brasington

Open Access Publications

INTRODUCTION: The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs).

METHODS: All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) < 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports.

RESULTS: Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; …

Update On T Cells In The Virally Infected Brain: Friends And Foes, Shenjian Ai, Robyn S Klein

Open Access Publications

PURPOSE OF REVIEW: The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated.

RECENT FINDINGS: The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including …

Racial Disparities In Calculated Risk For Bronchopulmonary Dysplasia: A Dataset, Zachary A Vesoulis, Christopher C Mcpherson, Halana V Whitehead

Open Access Publications

Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication of prematurity and is associated with significant morbidity or death. Early use of systemic corticosteroids may alter the trajectory of the disease and improve outcomes. A BPD Outcomes estimator, developed by the NICHD using a large population dataset, can be used to calculate individual risk. Risk above a certain threshold may indicate that the benefits of corticosteroids outweigh the risks. Empiric analysis of this calculator by systematic entry of synthetic patient information reveals a marked racial disparity; black infants have lower risk of moderate/severe BPD due to a higher risk of death …

Bosutinib For Pretreated Patients With Chronic Phase Chronic Myeloid Leukemia: Primary Results Of The Phase 4 Byond Study, Andreas Hochhaus, Camille Abboud, Et Al

Open Access Publications

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of …