Digital Commons Network^™

Driving Factors Of Preterm Birth Risk In Adolescents, Marta J. Perez, Jen J. Chang, Lorene A. Temming, Ebony B. Carter, Julia D. López, Methodius G. Tuuli, George A. Macones, Molly J. Stout

Open Access Publications

No abstract provided.

Brainstorm: A Multi-Institutional Phase 1/2 Study Of Rrx-001 In Combination With Whole Brain Radiation Therapy For Patients With Brain Metastases, Michelle M Kim, Christina I Tsien, Et Al

Open Access Publications

PURPOSE: To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response.

METHODS AND MATERIALS: Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m

RESULTS: Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The …

Switching Warfarin To Direct Oral Anticoagulants In Atrial Fibrillation: Insights From The Ncdr Pinnacle Registry, Christopher T Sciria, Thomas M Maddox, Et Al

Open Access Publications

BACKGROUND: Previous studies examining the use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) have largely focused on patients newly initiating therapy. Little is known about the prevalence/patterns of switching to DOACs among AF patients initially treated with warfarin.

HYPOTHESIS: To examine patterns of anticoagulation among patients chronically managed with warfarin upon the availability of DOACs and identify patient/practice-level factors associated with switching from chronic warfarin therapy to a DOAC.

METHODS: Prospective cohort study of AF patients in the NCDR PINNACLE registry prescribed warfarin between May 1, 2008 and May 1, 2015. Patients were followed at least 1 year …

A Color Flow Tract In Ultrasound-Guided Random Renal Core Biopsy Predicts Complications, Marie-Helene Gagnon, Michael F. Lin, Samantha Lancia, Amber Salter, Motoyo Yano

Open Access Publications

OBJECTIVES: To determine patient and procedural risk factors for major complications in ultrasound (US)-guided random renal core biopsy.

METHODS: Random renal biopsies performed by radiologists in the US department at a single institution between 2014 and 2018 were retrospectively reviewed. The patient's age, sex, race, and estimated glomerular filtration rate (eGFR) were recorded. The biopsy approach, needle gauge, length of cores, number of throws, and presence of a color flow tract were recorded. Outcome data included minor and major complications. Associations between variables were tested with χ

RESULTS: A total of 231 biopsies (167 native and 64 allografts) were reviewed. …

The Effect Of Thermal Therapy On The Blood-Brain Barrier And Blood-Tumor Barrier, Bhuvic Patel, Peter H Yang, Albert H Kim

Open Access Publications

The blood-brain and blood-tumor barriers represent highly specialized structures responsible for tight regulation of molecular transit into the central nervous system. Under normal circumstances, the relative impermeability of the blood-brain barrier (BBB) protects the brain from circulating toxins and contributes to a brain microenvironment necessary for optimal neuronal function. However, in the context of tumors and other diseases of central nervous system, the BBB and the more recently appreciated blood-tumor barrier (BTB) represent barriers that prevent effective drug delivery. Overcoming both barriers to optimize treatment of central nervous system diseases remains the subject of intense scientific investigation. Although many newer …

Defining The Substrate For Ventricular Tachycardia Ablation: The Impact Of Rhythm At The Time Of Mapping, Danesh K Kella, Seth H Sheldon, Amit Noheria, Deepak Padmanabhan, Thomas Munger, Samuel J Asirvatham, Suraj Kapa

Open Access Publications

BACKGROUND: Voltage mapping is critical to define substrate during ablation. In ventricular tachycardia, abnormal potentials may be targets. However, wavefront of activation could impact local signal characteristics. This may be particularly true when comparing sinus rhythm versus paced rhythms. We sought to determine how activation wavefront impacts electrogram characteristics.

METHODS: Patients with ischemic cardiomyopathy, ventricular tachycardia, and without fascicular or bundle branch block were included. Point by point mapping was done and at each point, one was obtained during an atrial paced rhythm and one during a right ventricular paced rhythm. Signals were adjudicated after ablation to define late potentials, …

Histopathology And Selective Biomarker Expression In Human Meibomian Glands, Lixing W Reneker, Rebecca T Irlmeier, Ying-Bo Shui, Ying Liu, Andrew J W Huang

Open Access Publications

BACKGROUND/AIMS: Meibomian gland dysfunction (MGD) is the most common form of evaporative dry eye disease, but its pathogenesis is poorly understood. This study examined the histopathological features of meibomian gland (MG) tissue from cadaver donors to identify potential pathogenic processes that underlie MGD in humans.

METHODS: Histological analyses was performed on the MGs in the tarsal plates dissected from four cadaver donors, two young and two old adults, including a 36-year-old female (36F) and three males aged 30, 63 and 64 years (30M, 63M and 64M).

RESULTS: The MGs of 36F displayed normal anatomy and structure, whereas the MGs of …

The Endosymbiont Wolbachia Rebounds Following Antibiotic Treatment, Emma L. Gunderson, Young-Jun Choi, Makedonka Mitreva, Et Al.

Open Access Publications

Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi …

Brain Connectivity And Socioeconomic Status At Birth And Externalizing Symptoms At Age 2 Years, Bruce Ramphal, Diana J Whalen, Jeanette K Kenley, Qiongru Yu, Christopher D Smyser, Cynthia E Rogers, Chad M Sylvester

Open Access Publications

Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to …

Phenotypic Profiling In Subjects Heterozygous For 1 Of 2 Rare Variants In The Hypophosphatasia Gene (Alpl), Daniel R Tilden, Jonathan H Sheehan, John H Newman, Jens Meiler, John A Capra, Andrea Ramirez, Jill Simmons, Kathryn Dahir

Open Access Publications

CONTEXT: Hypophosphatasia (HPP) is a syndrome marked by low serum alkaline phosphatase (AlkP) activity as well as musculoskeletal and/or dental disease. While the majority of subjects with HPP carry a pathogenic variant in the

METHODS: Through BioVU, a DNA biobank that pairs individuals' genetic information with their de-identified medical records, we identified subjects with 2 rare variants with distinct reported clinical phenotypes (p.D294A and p.T273M). We then performed a manual review of these subjects' de-identified medical records along with computational modeling of protein structure to construct a genetic, biochemical and clinical phenotype for each subject and variant.

RESULTS: Twenty subjects …

Behavioral And Neural Signatures Of Working Memory In Childhood, Monica D. Rosenberg, Deanna M. Barch, Et Al

Open Access Publications

Working memory function changes across development and varies across individuals. The patterns of behavior and brain function that track individual differences in working memory during human development, however, are not well understood. Here, we establish associations between working memory, other cognitive abilities, and functional MRI (fMRI) activation in data from over 11,500 9- to 10-year-old children (both sexes) enrolled in the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing longitudinal study in the United States. Behavioral analyses reveal robust relationships between working memory, short-term memory, language skills, and fluid intelligence. Analyses relating out-of-scanner working memory performance to memory-related fMRI activation …

Evaluation Of The Biofire Filmarray Pneumonia Panel For Detection Of Viral And Bacterial Pathogens In Lower Respiratory Tract Specimens In The Setting Of A Tertiary Care Academic Medical Center, Daniel M Webber, Meghan A Wallace, C A Burnham, Neil W Anderson

Open Access Publications

Our objective was to evaluate the diagnostic yield and accuracy of the BioFire FilmArray pneumonia panel (BFPP) for identification of pathogens in lower respiratory tract specimens (

Evaluation Of Ng-Test Carba 5 For Rapid Phenotypic Detection And Differentiation Of Five Common Carbapenemase Families: Results Of A Multicenter Clinical Evaluation, Stephen Jenkins, Carey-Ann D. Burnham, Meghan A Wallace, Et Al

Open Access Publications

NG-Test Carba 5 is a rapid

Development Of A Single-Stranded Dna-Binding Protein Fluorescent Fusion Toolbox, Katarzyna Dubiel, Camille Henry, Lisanne M. Spenkelink, Alexander G. Kozlov, Elizabeth A. Wood, Slobodan Jergic, Nicholas E. Dixon, Antoine M. Van Oijen, Michael M. Cox, Timothy M. Lohman, Steven J. Sandler, James L. Keck

Open Access Publications

Bacterial single-stranded DNA-binding proteins (SSBs) bind single-stranded DNA and help to recruit heterologous proteins to their sites of action. SSBs perform these essential functions through a modular structural architecture: the N-terminal domain comprises a DNA binding/tetramerization element whereas the C-terminus forms an intrinsically disordered linker (IDL) capped by a protein-interacting SSB-Ct motif. Here we examine the activities of SSB-IDL fusion proteins in which fluorescent domains are inserted within the IDL of Escherichia coli SSB. The SSB-IDL fusions maintain DNA and protein binding activities in vitro, although cooperative DNA binding is impaired. In contrast, an SSB variant with a fluorescent protein …

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

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 …

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

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 …

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 …

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, …

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 …

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 …

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 …

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 …

Potential Pharmacological Agents For Covid-19, Anita Kotwani, Sumanth Gandra

Open Access Publications

A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At …