Digital Commons Network^™

Clip And Massively Parallel Functional Analysis Of Celf6 Reveal A Role In Destabilizing Synaptic Gene Mrnas Through Interaction With 3' Utr Elements, Michael A Rieger, Dana M King, Haley Crosby, Yating Liu, Barak A Cohen, Joseph D Dougherty

Open Access Publications

CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, …

Comparison Of Upper Respiratory Viral Load Distributions In Asymptomatic And Symptomatic Children Diagnosed With Sars-Cov-2 Infection In Pediatric Hospital Testing Programs, Larry K Kociolek, Bijal A Parikh, Ariel Hernandez-Leyva, Et Al

Open Access Publications

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL …

Longitudinal Care Cascade Outcomes Among People Eligible For Antiretroviral Therapy Who Are Newly Linking To Care In Zambia: A Multistate Analysis, Aaloke Mody, David V Glidden, Ingrid Eshun-Wilson, Kombatende Sikombe, Sandra Simbeza, Njekwa Mukamba, Paul Somwe, Laura K Beres, Jake Pry, Carolyn Bolton-Moore, Nancy Padian, Charles B Holmes, Izukanji Sikazwe, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Retention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time.

METHODS: We analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last …

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m

Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators

Open Access Publications

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of …

Comparative Evaluation Of Clinical Manifestations And Risk Of Death In Patients Admitted To Hospital With Covid-19 And Seasonal Influenza: Cohort Study, Yan Xie, Benjamin Bowe, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

No abstract provided.

Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley

Open Access Publications

The protozoan parasite

Evaluating The Implementation Of The Switch® School Wellness Intervention And Capacity-Building Process Through Multiple Methods, Gabriella M Mcloughlin, Priscila Candal, Spyridoula Vazou, Joey A Lee, David A Dzewaltowski, Richard R Rosenkranz, Lorraine Lanningham-Foster, Douglas A Gentile, Laura Liechty, Senlin Chen, Gregory J Welk

2020-Current year OA Pubs

BACKGROUND: School wellness programming is important for promoting healthy lifestyles and academic achievement in youth; however, research is needed on methods that can help schools implement and sustain such programs on their own. The purpose of this study was to investigate factors within and outside the school environment that influenced school capacity for implementation and potential sustainability of wellness programming.

METHODS: As part of the School Wellness Integration Targeting Child Health (SWITCH®) intervention, elementary school wellness teams (N = 30) were guided through a capacity-building process focused on promoting the adoption of healthy lifestyle behaviors in students. Data on implementation …

Comparing The Effects Of Hiv Self-Testing To Standard Hiv Testing For Key Populations: A Systematic Review And Meta-Analysis, T Charles Witzel, Ingrid Eshun-Wilson, Muhammad S Jamil, Nerissa Tilouche, Carmen Figueroa, Cheryl C Johnson, David Reid, Rachel Baggaley, Nandi Siegfried, Fiona M Burns, Alison J Rodger, Peter Weatherburn

2020-Current year OA Pubs

BACKGROUND: We update a previous systematic review to inform new World Health Organization HIV self-testing (HIVST) recommendations. We compared the effects of HIVST to standard HIV testing services to understand which service delivery models are effective for key populations.

METHODS: We did a systematic review of randomised controlled trials (RCTs) which compared HIVST to standard HIV testing in key populations, published from 1 January 2006 to 4 June 2019 in PubMed, Embase, Global Index Medicus, Social Policy and Practice, PsycINFO, Health Management Information Consortium, EBSCO CINAHL Plus, Cochrane Library and Web of Science. We extracted study characteristic and outcome data …

Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin

Open Access Publications

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the …

Humoral Immune Responses Mediate The Development Of A Restrictive Phenotype Of Chronic Lung Allograft Dysfunction, Keizo Misumi, David S Wheeler, Yoshiro Aoki, Michael P Combs, Russell R Braeuer, Ryuji Higashikubo, Wenjun Li, Daniel Kreisel, Ragini Vittal, Jeffrey Myers, Amir Lagstein, Natalie M Walker, Carol F Farver, Vibha N Lama

Open Access Publications

Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human …

Medicine And Surgery Residents' Perspectives On The Impact Of Covid-19 On Graduate Medical Education., Tanvi Rana, Christopher Hackett, Timothy Quezada, Abhishek Chaturvedi, Veli Bakalov, Jody Leonardo, Sandeep Rana

COVID-19 Papers, Posters, and Presentations

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents' professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or …

Epidemiology Of Covid-19 And Predictors Of Outcome In Nigeria: A Single-Center Study., Olayinka Rasheed Ibrahim, Bello Muhammed Suleiman, Suleiman Bello Abdullahi, Taofeek Oloyede, Abdallah Sanda, Maruf Sanusi Gbadamosi, Bashir Olajide Yusuf, Rabilu Yandoma Iliyasu, Lawal Magaji Ibrahim, Adamu Danladi Dawud, Sulaiman Saidu Bashir, Nwawueze Efam Okonta, Wasinda Francis Umar, Abiodun Gbenga Tekobo, Muhammadu Sani Abubakar, Bashir Taiye Aminu, Shuaibu Onoruoyiza Ibrahim, Rasaq Olaosebikan, Olugbenga Ayodeji Mokuolu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a paucity of information regarding the epidemiology and outcome of COVID-19 from low/middle-income countries, including from Nigeria. This single-center study described the clinical features, laboratory findings, and predictors of in-hospital mortality of COVID-19 patients. Patients admitted between April 10, 2020 and June 10, 2020 were included. Forty-five patients with a mean age of 43 (16) years, predominantly male (87%), presented with fever (38%), cough (29%), or dyspnea (24%). In-hospital mortality was 16%. The independent predictors of mortality were hypoxemia (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.3-5.1) and creatinine > 1.5 mg/dL (aOR: 4.3; 95% CI: 1.9-9.8).

The Impact Of The Diabetes Management Incentive On Diabetes-Related Services: Evidence From Ontario, Canada., Thaksha Thavam, Rose Anne Devlin, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

Financial incentives have been introduced in several countries to improve diabetes management. In Ontario, the most populous province in Canada, a Diabetes Management Incentive (DMI) was introduced to family physicians practicing in patient enrollment models in 2006. This paper examines the impact of the DMI on diabetes-related services provided to individuals with diabetes in Ontario. Longitudinal health administrative data were obtained for adults diagnosed with diabetes and their family physicians. The study population consisted of two groups: DMI group (patients enrolled with a family physician exposed to DMI for 3 years), and comparison group (patients affiliated with a family physician …

Sequence Analysis In Bos Taurus Reveals Pervasiveness Of X-Y Arms Races In Mammalian Lineages, Jennifer F Hughes, Colin Kremitzki, Catrina Fronick, Tina A Graves-Lindsay, Lucinda Fulton, Wesley C Warren, Richard K Wilson, Et Al.

2020-Current year OA Pubs

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of

Participatory Video As A Novel Recovery-Oriented Intervention In Early Psychosis: A Pilot Study., Arlene G Macdougall, Sahana Kukan, Elizabeth Price, Sarah Glen, Richelle Bird, Laura Powe, Joshua C. Wiener, Paul H Lysaker, Kelly K Anderson, Ross Mg Norman

Epidemiology and Biostatistics Publications

BACKGROUND: Personal narrative plays an important role in the process of recovery from psychotic illnesses. Participatory video is a novel, active intervention that can be used as a tool for fostering narrative development among people with psychosis.

AIM: To assess the feasibility, acceptability and potential clinical utility of participatory video as an innovative tool for promoting recovery in early psychosis.

METHODS: Ten outpatients of an early psychosis intervention programme were recruited to participate in 13 biweekly workshops to plan, film and produce documentary-style videos of their experiences. Feasibility was measured through recruitment and retention. Acceptability was measured through workshop attendance …

Evolution Of The Epigenetic Landscape In Childhood B Acute Lymphoblastic Leukemia And Its Role In Drug Resistance, Shella Saint Fleur-Lominy, Nikki A. Evensen, Teena Bhatla, Gunjan Sethia, Sonali Narang, Jun H. Choi, Xiaotu Ma, Jun J. Yang, Stephen Kelly, Elizabeth Raetz, Richard C. Harvey, Cheryl Willman, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown, Kylie M. Getz, Cem Meydan, Christopher E. Mason, Aristotelis Tsirigos, William Carroll

Pathology Research and Scholarship

Although B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children and while highly curable, it remains a leading cause of cancer-related mortality. The outgrowth of tumor subclones carrying mutations in genes responsible for resistance to therapy has led to a Darwinian model of clonal selection. Previous work has indicated that alterations in the epigenome might contribute to clonal selection, yet the extent to which the chromatin state is altered under the selective pressures of therapy is unknown. To address this, we performed chromatin immunoprecipitation, gene expression analysis, and enhanced reduced representation bisulfite sequencing on a cohort of …

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

Antibody Profiling Of Patients With Prostate Cancer Reveals Differences In Antibody Signatures Among Disease Stages, Hemanth K Potluri, Tun Lee Ng, Michael A Newton, Jin Zhang, Christopher A Maher, Peter S Nelson, Douglas G Mcneel

2020-Current year OA Pubs

BACKGROUND: Previous studies of prostate cancer autoantibodies have largely focused on diagnostic applications. So far, there have been no reports attempting to more comprehensively profile the landscape of prostate cancer-associated antibodies. Specifically, it is unknown whether the quantity of antibodies or the types of proteins recognized change with disease progression.

METHODS: A peptide microarray spanning the amino acid sequences of the gene products of 1611 prostate cancer-associated genes was synthesized. Serum samples from healthy male volunteers (n=15) and patients with prostate cancer (n=85) were used to probe the array. These samples included patients with various clinical stages of disease: newly …

The Impact Of Uncorrected Mild Aortic Insufficiency At The Time Of Left Ventricular Assist Device Implantation, Yuki Tanaka, Tomohiro Nakajima, Irene Fischer, Fei Wan, Kunal Kotkar, Marc R Moon, Ralph J Damiano Jr, Muhammad F Masood, Akinobu Itoh

2020-Current year OA Pubs

OBJECTIVE: The study objective was to investigate the progression of uncorrected mild aortic insufficiency and its impact on survival and functional status after left ventricular assist device implantation.

METHODS: We retrospectively reviewed 694 consecutive patients who underwent implantation of a continuous-flow left ventricular assist device between January 2006 and March 2018. Pre-left ventricular assist device transthoracic echocardiography identified 111 patients with mild aortic insufficiency and 493 patients with trace or no aortic insufficiency. To adjust for differences in preoperative factors, propensity score matching was used, resulting in 101 matched patients in each of the mild aortic insufficiency and no aortic …

A Randomized, Placebo-Controlled Trial Evaluating Effects Of Lebrikizumab On Airway Eosinophilic Inflammation And Remodelling In Uncontrolled Asthma (Clavier), Cary D Austin, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate-to-severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.

OBJECTIVE: To report safety and efficacy results from enrolled participants with available data from CLAVIER.

METHODS: We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm

RESULTS: There was a baseline …

The Correlation Between Neonatal Intensive Care Unit Safety Culture And Quality Of Care, Jochen Profit, Paul J Sharek, Xin Cui, Courtney C Nisbet, Eric J Thomas, Daniel S Tawfik, Henry C Lee, David Draper, J Bryan Sexton

Journal Articles

OBJECTIVES: Key validated clinical metrics are being used individually and in aggregate (Baby-MONITOR) to monitor the performance of neonatal intensive care units (NICUs). The degree to which perceptions of key components of safety culture, safety climate, and teamwork are related to aspects of NICU quality of care is poorly understood. The objective of this study was to test whether NICU performance on key clinical metrics correlates with caregiver perceptions of safety culture.

STUDY DESIGN: Cross-sectional study of 6253 very low-birth-weight infants in 44 NICUs. We measured clinical quality via the Baby-MONITOR and its nine risk-adjusted and standardized subcomponents (antenatal corticosteroids, …

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

Patient Factors Influencing Acute Gluten Reactions And Cytokine Release In Treated Coeliac Disease., Jason A Tye-Din, A James M Daveson, Kaela E Goldstein, Holly L Hand, Kristin M Neff, Gautam Goel, Leslie J Williams, Kenneth E Truitt, Robert P Anderson, Anthony Dimariono (Reset Ced Study Group)

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Patients with coeliac disease (CD) commonly report a variety of adverse symptoms to gluten, but descriptions of the symptomatic response in the literature may have been confounded by the presence of food components such as fermentable carbohydrates (FODMAPs) causing symptoms of irritable bowel syndrome independent of gluten. In recent unmasked and masked low FODMAP gluten challenge studies in small groups of treated CD patients, nausea and vomiting were shown to be the key symptoms associated with serum interleukin (IL)-2 release. Our objective was to utilise a large and diverse cohort of people with CD undertaking a standardised gluten food …

Carfilzomib, Lenalidomide, And Dexamethasone Plus Transplant In Newly Diagnosed Multiple Myeloma, Jagoda K Jasielec, Ravi Vij, Et Al.

2020-Current year OA Pubs

In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point …

Altered Capicua Expression Drives Regional Purkinje Neuron Vulnerability Through Ion Channel Gene Dysregulation In Spinocerebellar Ataxia Type 1, Ravi Chopra, David D Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison, Haoran Huang, Hillary P Handler, Luke J Man, Warunee Dansithong, Daniel R Scoles, Stefan M Pulst, Harry T Orr, Vikram G Shakkottai

2020-Current year OA Pubs

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, …

Central Nervous System Pathology In Preclinical Mps Iiib Dogs Reveals Progressive Changes In Clinically Relevant Brain Regions, Martin T Egeland, Marta M Tarczyluk-Wells, Melissa M Asmar, Evan G Adintori, Roger Lawrence, Elizabeth M Snella, Jackie K Jens, Brett E Crawford, Jill C M Wait, Emma Mccullagh, Jason Pinkstaff, Jonathan D Cooper, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24-30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain …

A Phase 1b Study Of Afm13 In Combination With Pembrolizumab In Patients With Relapsed Or Refractory Hodgkin Lymphoma, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a …

Functional Genomic Analyses Uncover Apoe-Mediated Regulation Of Brain And Cerebrospinal Fluid Beta-Amyloid Levels In Parkinson Disease, Laura Ibanez, Jorge A Bahena, Chengran Yang, Umber Dube, Fabiana H G Farias, John P Budde, Kristy Bergmann, Carol Brenner-Webster, John C Morris, Richard J Perrin, Nigel J Cairns, John O'Donnell, Rebecca Miller, Albert A Davis, Paul Kotzbauer, Meghan C Campbell, Joel S Perlmutter, Oscar Harari, Carlos Cruchaga, Bruno A Benitez, Et Al.

2020-Current year OA Pubs

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta

Full-Length Trkb Variant In Nsclc Is Associated With Brain Metastasis, Mariangela Lombardi, Michela D'Ascanio, Stefania Scarpino, Davide Scozzi, Marco Giordano, Leopoldo Costarelli, Enrico Rathina Raj, Rita Mancini, Giuseppe Cardillo, Vittorio Cardaci, Marta Innammorato, Andrea Vecchione, Alberto Ricci

Open Access Publications

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their …