Digital Commons Network^™

19f Nmr Reveals The Conformational Properties Of Free Thrombin And Its Zymogen Precursor Prethrombin-2, Eliza A. Ruben, Prafull S. Gandhi, Zhiwei Chen, Sarah K. Koester, Gregory T. Dekoster, Carl Frieden, Enrico Di Cera

Open Access Publications

No abstract provided.

Using Polygenic Scores For Identifying Individuals At Increased Risk Of Substance Use Disorders In Clinical And Population Samples, Peter B. Barr, Emma C. Johnson, Andrey Anokhin, Arpana Agrawal, Et Al.

Open Access Publications

No abstract provided.

The Chromatin Remodeling Enzyme Chd4 Regulates Genome Architecture In The Mouse Brain, Jared V. Goodman, Tomoko Yamada, Yue Yang, Lingchun Kong, Dennis Y. Wu, Guoyan Zhao, Harrison W. Gabel, Azad Bonni

Open Access Publications

No abstract provided.

Kir B Donors Improve The Outcome For Aml Patients Given Reduced Intensity Conditioning And Unrelated Donor Transplantation, Daniel Weisdorf, Todd A. Fehniger, Et Al.

Open Access Publications

No abstract provided.

A Phase 1 Trial Of Itacitinib, A Selective Jak1 Inhibitor, In Patients With Acute Graft-Versus-Host Disease, Mark A. Schroeder, Karl Staser, Jaebok Choi, Leah Gehrs, John F. Dipersio, Et Al.

Open Access Publications

No abstract provided.

Inhibition Of The Translesion Synthesis Polymerase Rev1 Exploits Replication Gaps As A Cancer Vulnerability, Sumeet Nayak, Jennifer A Calvo, Ke Cong, Min Peng, Emily Berthiaume, Jessica Jackson, Angela M Zaino, Alessandro Vindigni, M Kyle Hadden, Sharon B Cantor

Open Access Publications

The replication stress response, which serves as an anticancer barrier, is activated not only by DNA damage and replication obstacles but also oncogenes, thus obscuring how cancer evolves. Here, we identify that oncogene expression, similar to other replication stress-inducing agents, induces single-stranded DNA (ssDNA) gaps that reduce cell fitness. DNA fiber analysis and electron microscopy reveal that activation of translesion synthesis (TLS) polymerases restricts replication fork slowing, reversal, and fork degradation without inducing replication gaps despite the continuation of replication during stress. Consistent with gap suppression (GS) being fundamental to cancer, we demonstrate that a small-molecule inhibitor targeting the TLS …

Precise Breakpoint Detection In A Patient With 9p- Syndrome, Jeffrey Ng, Eleanor Sams, Dustin Baldridge, Milinn Kremitzki, Daniel J Wegner, Tina Lindsay, Robert Fulton, F Sessions Cole, Tychele N Turner

Open Access Publications

We present a case of 9p- syndrome with a complex chromosomal event originally characterized by the classical karyotype approach as 46,XX,der(9)t(9;13)(p23;q13). We used advanced technologies (Bionano Genomics genome imaging and 10× Genomics sequencing) to characterize the location of the translocation and accompanying deletion on Chromosome 9 and duplication on Chromosome 13 with single-nucleotide breakpoint resolution. The translocation breakpoint was at Chr 9:190938 and Chr 13:50850492, the deletion at Chr 9:1-190938, and the duplication at Chr 13:50850492-114364328. We identified genes in the deletion and duplication regions that are known to be associated with this patient's phenotype (e.g.,

The Clonal Evolution Of Metastatic Colorectal Cancer, Ha X Dang, Bradley A Krasnick, Julie G Grossman, Matthew S Strand, Jin Zhang, Christopher A Miller, Robert S Fulton, S Peter Goedegebuure, Catrina C Fronick, Malachi Griffith, David E Larson, Brian D Goetz, Jason R Walker, William G Hawkins, Steven M Strasberg, Kian H Lim, Timothy J Ley, Christopher A Maher, Ryan C Fields, Et Al

Open Access Publications

Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed …

Understanding Antibiotic Prophylaxis Prescribing In Pediatric Surgical Specialties, Sara M Malone, Natalie S Seigel, Jason G Newland, Jacqueline M Saito, Virginia R Mckay

Open Access Publications

BACKGROUND: Overuse of antibiotics has caused secondary poor outcomes and has led to a current rate of antibiotic resistant infections that constitutes a public health crisis. In pediatric surgical specialties, children continue to receive unnecessary antibiotics.

OBJECTIVE: To understand the factors that contribute to pediatric surgeons' decisions regarding the use of perioperative antibiotic prophylaxis.

METHODS: Focus groups included pediatric proceduralists/surgeons from the following specialties: interventional cardiology, otolaryngology, orthopedic surgery, cardiothoracic surgery, and general surgery.

RESULTS: A total of 23 surgeons with a median of 9 years of experience (range, 0.5-29 years) participated in the focus groups that lasted 30-90 minutes …

12-Lox Catalyzes The Oxidation Of 2-Arachidonoyl-Lysolipids In Platelets Generating Eicosanoid-Lysolipids That Are Attenuated By Ipla2Γ Knockout, Xinping Liu, Harold F. Sims, Christopher M. Jenkins, Shaoping Guan, Beverly G. Dilthey, Richard W. Gross

Open Access Publications

No abstract provided.

Automated And Robust Beam Data Validation Of A Preconfigured Ring Gantry Linear Accelerator Using A 1d Tank With Synchronized Beam Delivery And Couch Motions, Nels C Knutson, Matthew C Schmidt, Francisco J Reynoso, Yao Hao, Thomas R Mazur, Eric Laugeman, Geoffrey Hugo, Sasa Mutic, H Harold Li, Wilfred Ngwa, Bin Cai, Erno Sajo

Open Access Publications

PURPOSE: To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions.

MATERIALS AND METHODS: Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers …

Tumor-Associated Macrophages In Osteosarcoma: From Mechanisms To Therapy, Francesca Cersosimo, Silvia Lonardi, Giulia Bernardini, Brian Telfer, Giulio Eugenio Mandelli, Annalisa Santucci, William Vermi, Emanuele Giurisato

Open Access Publications

Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating …

Impact Of Trem2r47h Variant On Tau Pathology-Induced Gliosis And Neurodegeneration, Maud Gratuze, Cheryl Eg Leyns, Andrew D Sauerbeck, Marie-Kim St-Pierre, Monica Xiong, Nayeon Kim, Javier Remolina Serrano, Marie-Ève Tremblay, Terrance T Kummer, Marco Colonna, Jason D Ulrich, David M Holtzman

Open Access Publications

Alzheimer's disease (AD) is characterized by plaques containing amyloid-β (Aβ) and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglia-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2- to 4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicity. However, neocortical Aβ pathology occurs many years before neocortical tau pathology in AD. Thus, it will be important to understand the role of TREM2 in …

Proactive Prevention: Act Now To Disrupt The Impending Non-Communicable Disease Crisis In Low-Burden Populations, Benson Njuguna, Angela Brown, Victor G. Davila-Roman, Et Al.

Open Access Publications

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as "proactive prevention." This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a …

Pain Relief After Surgical Decompression Of The Distal Brachial Plexus, Richard Morgan, Iain Elliot, Vibhu Banala, Christopher Dy, Briana Harris, Elizabeth Anne Ouellette

Open Access Publications

No abstract provided.

Temporary Abdominal Closure Is Associated With Increased Risk For Fungal Intra-Abdominal Infections In Trauma Patients, Christina X. Zhang, Rohit R. Rasane, Qiao Zhang, Ricardo A. Fonseca, Jose A. Aldana, Javier E. Rincon, Maya J. Sorini, Kelly M. Bochicchio, Jennifer M. Leonard, Obeid N. Ilahi, Grant V. Bochicchio

Open Access Publications

No abstract provided.

Risk Factors And Management Options For The Adult Failed Ureteropelvic Junction Obstruction Repair In The Era Of Minimally Invasive And Robotic Approaches: A Comprehensive Literature Review, Alexander K. Chow, Bryan J. Rosenberg, Edward M. Capoccia, Edward E. Cherullo

Open Access Publications

No abstract provided.

Assaying Three-Dimensional Cellular Architecture Using X-Ray Tomographic And Correlated Imaging Approaches, Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick

Open Access Publications

No abstract provided.

Advanced Ultrasound Screening For Temporomandibular Joint (Tmj) Internal Derangement, Saul N. Friedman, Miriam Grushka, Hussam K. Beituni, Madhu Rehman, Hart B. Bressler, Lawrence Friedman

Open Access Publications

No abstract provided.

Complications And Patient-Reported Outcomes After Tram And Diep Flaps: A Systematic Review And Meta-Analysis, Waverly Y. He, Leen El Eter, Pooja Yesantharao, Bethany Hung, Haley Owens, Sarah Persing, Justin M. Sacks

Open Access Publications

No abstract provided.

Comparative Proteomic Profiling Reveals Mechanisms For Early Spinal Cord Vulnerability In Cln1 Disease, Hemanth R. Nelvagal, Maica Llavero Hurtado, Samantha L. Eaton, Rachel A. Kline, Douglas J. Lamont, Mark S. Sands, Thomas M. Wishart, Jonathan D. Cooper

Open Access Publications

No abstract provided.

Association Between Benzodiazepine Use With Or Without Opioid Use And All-Cause Mortality In The United States, 1999-2015, Kevin Y. Xu, Sarah M. Hartz, Jacob T. Borodovsky, Laura J. Bierut, Richard A. Grucza

Open Access Publications

Importance: Although overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death.

Objective: To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants.

Design, Setting, and Participants: This retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from …

The Landscape Of Novel Therapeutics And Challenges In Glioblastoma Multiforme: Contemporary State And Future Directions, Karam Khaddour, Tanner M Johanns, George Ansstas

Open Access Publications

BACKGROUND: Glioblastoma multiforme is a malignant intracranial neoplasm that constitutes a therapeutic challenge because of the associated high morbidity and mortality given the lack of effective approved medication and aggressive nature of the tumor. However, there has been extensive research recently to address the reasons implicated in the resistant nature of the tumor to pharmaceutical compounds, which have resulted in several clinical trials investigating promising treatment approaches.

METHODS: We reviewed literature published since 2010 from PUBMED and several annual meeting abstracts through 15 September 2020. Selected articles included those relevant to topics of glioblastoma tumor biology, original basic research, clinical …

Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao

Open Access Publications

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have …

Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-Methylpyrimidine-2, 4-Diamine (Th287): A Potential Radiotracer For Measuring And Imaging Mth1, Huaping Chen, Sadia Afrin, Yingqiu Guo, Wenhua Chu, Tammie L S Benzinger, Buck E Rogers, Joel R Garbow, Joel S Perlmutter, Dong Zhou, Jinbin Xu

Open Access Publications

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [

Cd46 And Oncologic Interactions: Friendly Fire Against Cancer, Michelle Elvington, M Kathryn Liszewski, John P Atkinson

Open Access Publications

One of the most challenging aspects of cancer therapeutics is target selection. Recently, CD46 (membrane cofactor protein; MCP) has emerged as a key player in both malignant transformation as well as in cancer treatments. Normally a regulator of complement activation, CD46 is co-expressed as four predominant isoforms on almost all cell types. CD46 is highly overexpressed on a variety of human tumor cells. Clinical and experimental data support an association between increased CD46 expression and malignant transformation and metastasizing potential. Further, CD46 is a newly discovered driver of metabolic processes and plays a role in the intracellular complement system (complosome). …

Using The Systemic Immune-Inflammation Index (Sii) As A Mid-Treatment Marker For Survival Among Patients With Stage-Iii Locally Advanced Non-Small Cell Lung Cancer (Nsclc), Tithi Biswas, Kylie H Kang, Rohin Gawdi, David Bajor, Mitchell Machtay, Charu Jindal, Jimmy T Efird

Open Access Publications

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3-4) is a …

Status Of Theory Use In Self-Care Research, Tiny Jaarsma, Heleen Westland, Ercole Vellone, Kenneth E Freedland, Carin Schröder, Jaap C A Trappenburg, Anna Strömberg, Barbara Riegel

Open Access Publications

BACKGROUND: Theories can provide a foundation to explain behavior, investigate relationships, and to predict the effect of interventions. The aim of the study was to clarify the use of theories in studies testing interventions to promote self-care.

METHOD: A scoping review. PubMed, EMBASE, PsychINFO, and CINAHL were searched from January 2008 through January 2019. Nine common chronic conditions were included. We included studies testing a self-care intervention if they used a randomized controlled trial design. The study was registered in PROSPERO (#123719).

RESULTS: The search retrieved 9309 potential studies, of which 233 were included in the review. In total, 76 …

Chemical Mutagenesis Of A Gpcr Ligand: Detoxifying “Inflammo-Attraction” To Direct Therapeutic Stem Cell Migration, Jean-Pyo Lee, Edward B. Han, Et Al.

Open Access Publications

No abstract provided.

Tumor Microenvironment As A Regulator Of Radiation Therapy: New Insights Into Stromal-Mediated Radioresistance, Varintra E Krisnawan, Jennifer A Stanley, Julie K Schwarz, David G Denardo

Open Access Publications

No abstract provided.