Digital Commons Network^™

Slo2.1/Nalcn A Sodium Signaling Complex That Regulates Uterine Activity, Juan J Ferreira, Chinwendu Amazu, Lis C Puga-Molina, Xiaofeng Ma, Sarah K England, Celia M Santi

Open Access Publications

Depolarization of the myometrial smooth muscle cell (MSMC) resting membrane potential is necessary for the uterus to transition from a quiescent state to a contractile state. The molecular mechanisms involved in this transition are not completely understood. Here, we report that a coupled system between the Na

Visual Prototypes In The Ventral Stream Are Attuned To Complexity And Gaze Behavior, Olivia Rose, James Johnson, Binxu Wang, Carlos R Ponce

Open Access Publications

Early theories of efficient coding suggested the visual system could compress the world by learning to represent features where information was concentrated, such as contours. This view was validated by the discovery that neurons in posterior visual cortex respond to edges and curvature. Still, it remains unclear what other information-rich features are encoded by neurons in more anterior cortical regions (e.g., inferotemporal cortex). Here, we use a generative deep neural network to synthesize images guided by neuronal responses from across the visuocortical hierarchy, using floating microelectrode arrays in areas V1, V4 and inferotemporal cortex of two macaque monkeys. We hypothesize …

Dasatinib And Dexamethasone Followed By Hematopoietic Cell Transplantation For Adults With Ph-Positive All, Matthew J. Wieduwilt, Geoffrey L. Uy, Et Al

Open Access Publications

No abstract provided.

Matched Cohort Study Of Germline Brca Mutation Carriers With Triple Negative Breast Cancer In Brightness, Otto Metzger-Filho, Katharine Collier, Sarah Asad, Mark Watson, Et Al

Open Access Publications

No abstract provided.

Directed Flow Of Beta Band Communication During Reorienting Of Attention Within The Dorsal Attention Network, Sara Spadone, Miroslaw Wyczesany, Stefania Della Penna, Maurizio Corbetta, Paolo Capotosto

Open Access Publications

No abstract provided.

Synaptic Zn 2+ Potentiates The Effects Of Cocaine On Striatal Dopamine Neurotransmission And Behavior, Juan L. Gomez, Marco Pignatelli, Et Al

Open Access Publications

No abstract provided.

Staphylococcus Aureus Injection Drug Use-Associated Bloodstream Infections Are Propagated By Community Outbreaks Of Diverse Lineages, Laura R Marks, Juan J Calix, John A Wildenthal, Meghan A Wallace, Sanjam S Sawhney, Eric M Ransom, Michael J Durkin, Jeffrey P Henderson, Carey-Ann D Burnham, Gautam Dantas

Open Access Publications

Background: The ongoing injection drug use (IDU) crisis in the United States has been complicated by an emerging epidemic of

Methods: We performed a case-control study comparing

Results: Here we show that patients with IDU-BSI experience longer durations of bacteremia and have lower medical therapy completion rates. In phylogenetic analyses, 45/154 and 1/91 contemporaneous IDU-BSI and non-IDU BSI staphylococcal isolates, respectively, group into multiple, unique clonal clusters, revealing that pathogen community transmission distinctively spurs IDU-BSI. Lastly, multiple

Conclusions: We identify clonal expansion of multiple

Cd36 Maintains The Gastric Mucosa And Associates With Gastric Disease, Miriam Jacome-Sosa, Zhi-Feng Miao, Vivek S Peche, Edward F Morris, Ramkumar Narendran, Kathryn M Pietka, Dmitri Samovski, Hei-Yong G Lo, Terri Pietka, Latisha Love-Gregory, Nada A Abumrad, Et Al

Open Access Publications

The gastric epithelium is often exposed to injurious elements and failure of appropriate healing predisposes to ulcers, hemorrhage, and ultimately cancer. We examined the gastric function of CD36, a protein linked to disease and homeostasis. We used the tamoxifen model of gastric injury in mice null for Cd36 (Cd36

Cytokine Exposure Mediates Transcriptional Activation Of The Orphan Nuclear Receptor Nur77 In Hematopoietic Cells, Orsola Di Martino, Haixia Niu, Gayla Hadwiger, Margaret A Ferris, John S Welch

Open Access Publications

The orphan nuclear receptor Nur77 is an immediate-early response gene that based on tissue and cell context is implicated in a plethora of cellular processes, including proliferation, differentiation, apoptosis, metabolism, and inflammation. Nur77 has a ligand-binding pocket that is obstructed by hydrophobic side groups. Naturally occurring, cell-endogenous ligands have not been identified, and Nur77 transcriptional activity is thought to be regulated through posttranslational modification and modulation of protein levels. To determine whether Nur77 is transcriptionally active in hematopoietic cells in vivo, we used an upstream activating sequence (UAS)-GFP transgenic reporter. We found that Nur77 is transcriptionally inactive in vivo in …

U2af1 Is A Haplo-Essential Gene Required For Hematopoietic Cancer Cell Survival In Mice, Brian A Wadugu, Sridhar Nonavinkere Srivatsan, Amanda Heard, Michael O Alberti, Matthew Ndonwi, Jie Liu, Sarah Grieb, Joseph Bradley, Jin Shao, Tanzir Ahmed, Cara L Shirai, Ajay Khanna, Christopher A Miller, Matthew J Walter, Et Al

Open Access Publications

Somatic mutations in the spliceosome gene U2AF1 are common in patients with myelodysplastic syndromes. U2AF1 mutations that code for the most common amino acid substitutions are always heterozygous, and the retained WT allele is expressed, suggesting that mutant hematopoietic cells may require the residual WT allele to be viable. We show that hematopoiesis and RNA splicing in U2af1 heterozygous knockout mice were similar to those in control mice, but that deletion of the WT allele in U2AF1(S34F) heterozygous mutant-expressing hematopoietic cells (i.e., hemizygous mutant) was lethal. These results confirm that U2AF1 mutant hematopoietic cells are dependent on the expression of …

8-Azaadenosine And 8-Chloroadenosine Are Not Selective Inhibitors Of Adar, Kyle A Cottrell, Luisangely Soto Torres, Michael G Dizon, Jason D Weber

Open Access Publications

The RNA editing enzyme ADAR, is an attractive therapeutic target for multiple cancers. Through its deaminase activity, ADAR edits adenosine to inosine in dsRNAs. Loss of ADAR in some cancer cell lines causes activation of the type I interferon pathway and the PKR translational repressor, leading to inhibition of proliferation and stimulation of cell death. As such, inhibition of ADAR function is a viable therapeutic strategy for many cancers. However, there are no FDA approved inhibitors of ADAR. Two small molecules have been previously shown to inhibit ADAR or reduce its expression: 8-azaadenosine and 8-chloroadenosine. Here we show that neither …

Long-Term Prognosis And Educational Determinants Of Brain Network Decline In Older Adult Individuals, Micaela Y Chan, Liang Han, Claudia A Carreno, Ziwei Zhang, Rebekah M Rodriguez, Megan Larose, Jason Hassenstab, Gagan S Wig

Open Access Publications

Older adults with lower education are at greater risk for dementia. It is unclear which brain changes lead to these outcomes. Longitudinal imaging-based measures of brain structure and function were examined in adult individuals (baseline age, 45-86 years; two to five visits per participant over 1-9 years). College degree completion differentiates individual-based and neighborhood-based measures of socioeconomic status and disadvantage. Older adults (~65 years and over) without a college degree exhibit a pattern of declining large-scale functional brain network organization (resting-state system segregation) that is less evident in their college-educated peers. Declining brain system segregation predicts impending changes in dementia …

Tai Chi For Cancer Survivors: A Systematic Review Toward Consensus-Based Guidelines, Lin Yang, Kerri Winters-Stone, Benny Rana, Chao Cao, Linda E Carlson, Kerry S Courneya, Christine M Friedenreich, Kathryn H Schmitz

Open Access Publications

To manage acute, long-term, and late effects of cancer, current guidelines recommend moderate-to-vigorous intensity aerobic and resistance exercise. Unfortunately, not all cancer survivors are able or willing to perform higher intensity exercise during difficult cancer treatments or because of other existing health conditions. Tai Chi is an equipment-free, multicomponent mind-body exercise performed at light-to-moderate intensity that may provide a more feasible alternative to traditional exercise programs for some cancer survivors. This systematic review evaluated the therapeutic efficacy of Tai Chi across the cancer care continuum. We searched MEDLINE/PubMed, Embase, SCOPUS, and CINAHL databases for interventional studies from inception to 18 …

Diagnostics To Support Elimination Of Lymphatic Filariasis-Development Of Two Target Product Profiles, Kimberly Y. Won, Gary J. Weil, Et Al

Open Access Publications

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs …

First Clinical Experience Of Correcting Phantom-Based Image Distortion Related To Gantry Position On A 0.35t Mr-Linac, Benjamin C Lewis, Jaeik Shin, Benjamin Quinn, Enzo Barberi, Domenic Sievert, Jin Sung Kim, Taeho Kim

Open Access Publications

MR-guided radiotherapy requires strong imaging spatial integrity to deliver high quality plans and provide accurate dose calculation. The MRI system, however, can be compromised by the integrated linear accelerator (Linac), resulting in inaccurate imaging isocenter position and geometric distortion. Dependence on gantry position further complicates the correction of distortions. This work presents a new clinical application of a commercial phantom and software system that quantifies isocenter alignment and geometric distortion, as well as providing a deformation vector field (DVF). A large distortion phantom and a smaller grid phantom were imaged at multiple gantry angles from 0 to 330° on a …

Cardiac Stereotactic Ablative Radiotherapy For Control Of Refractory Ventricular Tachycardia: Initial Uk Multicentre Experience, Justin Lee, Clifford Robinson, Phillip Cuculich, Geoffrey Hugo, Et Al

Open Access Publications

BACKGROUND: Options for patients with ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or catheter ablation remain limited. Stereotactic radiotherapy has been described as a novel treatment option.

METHODS: Seven patients with recurrent refractory VT, deemed high risk for either first time or redo invasive catheter ablation, were treated across three UK centres with non-invasive cardiac stereotactic ablative radiotherapy (SABR). Prior catheter ablation data and non-invasive mapping were combined with cross-sectional imaging to generate radiotherapy plans with aim to deliver a single 25 Gy treatment. Shared planning and treatment guidelines and prospective peer review were used.

RESULTS: Acute suppression of VT …

Validation Of Ad8-Philippines (Ad8-P): A Brief Informant-Based Questionnaire For Dementia Screening In The Philippines, Jacqueline C Dominguez, John C Morris, Et Al

Open Access Publications

Aim: This study was aimed at validating the Filipino version of AD8 (AD8-P).

Methods: Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for …

Patients With Definite And Inconclusive Evidence Of Reflux According To Lyon Consensus Display Similar Motility And Esophagogastric Junction Characteristics, Mentore Ribolsi, Edoardo Savarino, Benjamin Rogers, Arvind Rengarajan, Marco Della Coletta, Matteo Ghisa, Michele Cicala, C Prakash Gyawali

Open Access Publications

Background/Aims: The role of esophageal high-resolution manometry (HRM) within Lyon consensus phenotypes, especially patients with inconclusive gastroesophageal reflux disease (GERD) evidence, has not been fully investigated. In this multicenter, observational study we aim to compare HRM parameters in patients with GERD stratified according to the Lyon consensus.

Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH (MII-pH) studies performed off proton pump inhibitor therapy in patients with esophageal GERD symptoms were reviewed. Lyon consensus criteria identified pathological GERD, reflux hypersensitivity, functional heartburn, and inconclusive GERD. Patients, with inconclusive GERD were further subdivided into 2 groups based on total reflux …

The Application Of Exercise Training For Diabetic Peripheral Neuropathy, Clifton J. Holmes, Mary K. Hastings

Open Access Publications

Diabetic peripheral neuropathy (DPN) is the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes. It is associated with pain, paresthesia, sensory loss, muscle atrophy with fat infiltration, and muscular dysfunction typically starting distally in the feet and progressing proximally. Muscle deterioration within the leg and foot can lead to muscle dysfunction, reduced mobility, and increases the risk of disability, ulceration, and amputation. Exercise training is an established method for increasing the different components of physical fitness, including enhancing body composition and improving neuromuscular strength. A number of experimental studies …

A Novel Class Of Tmprss2 Inhibitors Potently Block Sars-Cov-2 And Mers-Cov Viral Entry And Protect Human Epithelial Lung Cells, Matthew Mahoney, Vishnu C Damalanka, Michael A Tartell, Anne E Mayer Bridwell, Jorine Voss, Partha Karmakar, Paul W Rothlauf, Cassandra E Thompson, Christina L Stallings, Sean P J Whelan, James W Janetka, Et Al

Open Access Publications

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat. Lead compound MM3122 (4) has an IC

Comparative Genomics Of Mycobacterium Avium Complex Reveals Signatures Of Environment-Specific Adaptation And Community Acquisition, Eric C Keen, Joohee Choi, Meghan A Wallace, Michelle Azar, Carlos R Mejia-Chew, Shail B Mehta, Thomas C Bailey, Lindsay J Caverly, Carey-Ann D Burnham, Gautam Dantas

Open Access Publications

Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize …

Neutralizing Monoclonal Antibodies That Target The Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection Against Sars-Cov-2 Infection In Syrian Hamsters, Wen Su, Sin Fun Sia, Aaron J Schmitz, Traci L Bricker, Tyler N Starr, Allison J Greaney, Jackson S Turner, Bassem M Mohammed, Zhuoming Liu, Ka Tim Choy, Tamarand L Darling, Astha Joshi, Ka Man Cheng, Alvina Y L Wong, Houda H Harastani, John M Nicholls, Sean P J Whelan, Jesse D Bloom, Hui-Ling Yen, Ali H Ellebedy, Adrianus C M Boon

Open Access Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection. Also, their mechanism of action

Human Monoclonal Antibodies Against Ns1 Protein Protect Against Lethal West Nile Virus Infection, Alex W Wessel, Michael P Doyle, Taylor B Engdahl, Jessica Rodriguez, James E Crowe, Michael S Diamond

Open Access Publications

Envelope protein-targeted vaccines for flaviviruses are limited by concerns of antibody-dependent enhancement (ADE) of infections. Nonstructural protein 1 (NS1) provides an alternative vaccine target that avoids this risk since this protein is absent from the virion. Beyond its intracellular role in virus replication, extracellular forms of NS1 function in immune modulation and are recognized by host-derived antibodies. The rational design of NS1-based vaccines requires an extensive understanding of the antigenic sites on NS1, especially those targeted by protective antibodies. Here, we isolated human monoclonal antibodies (MAbs) from individuals previously naturally infected with WNV, mapped their epitopes using structure-guided mutagenesis, and …

Comparison Of 2-Year Outcomes With Car T Cells (Zuma-1) Vs Salvage Chemotherapy In Refractory Large B-Cell Lymphoma, Sattva S. Neelapu, Nancy L. Bartlett, Et Al

Open Access Publications

No abstract provided.

Surgical Strategy For The Management Of Cervical Deformity Is Based On Type Of Cervical Deformity, Han Jo Kim, Munish Gupta, Et Al

Open Access Publications

OBJECTIVES: Cervical deformity morphotypes based on type and location of deformity have previously been described. This study aimed to examine the surgical strategies implemented to treat these deformity types and identify if differences in treatment strategies impact surgical outcomes. Our hypothesis was that surgical strategies will differ based on different morphologies of cervical deformity.

METHODS: Adult patients enrolled in a prospective cervical deformity database were classified into four deformity types (Flatneck (FN), Focal kyphosis (FK), Cervicothoracic kyphosis (CTK) and Coronal (C)), as previously described. We analyzed group differences in demographics, preoperative symptoms, health-related quality of life scores (HRQOLs), and surgical …

The Content And Quality Of Publicly Available Information About Congenital Diaphragmatic Hernia: Descriptive Study, Frank Coyle Soltys, Kimi Spilo, Mary C Politi

Open Access Publications

BACKGROUND: Congenital diaphragmatic hernia (CDH) diagnosis in an infant is distressing for parents. Parents often feel unable to absorb the complexities of CDH during prenatal consultations and use the internet to supplement their knowledge and decision making.

OBJECTIVE: We aimed to examine the content and quality of publicly available, internet-based CDH information.

METHODS: We conducted internet searches across 2 popular search engines (Google and Bing). Websites were included if they contained CDH information and were publicly available. We developed a coding instrument to evaluate websites. Two coders (FS and KS) were trained, achieved interrater reliability, and rated remaining websites independently. …

Relationship Between Quality Of Life Indicators And Cardiac Status Indicators In Chemotherapy Patients, Blaž Matija Geršak, Andreja Kukec, Henning Steen, Moritz Montenbruck, Maja Šoštarič, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Sorin Giusca, Grigorios Korosoglou, Pia Wülfing, Susan Dent, Daniel Lenihan

Open Access Publications

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients.

METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. …

Alternative Pre-Mrna Splicing Of The Mu Opioid Receptor Gene, Oprm1: Insight Into Complex Mu Opioid Actions, Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan

Open Access Publications

Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene,

Aducanumab For Alzheimer Disease: The Amyloid Hypothesis Moves From Bench To Bedside, Erik S. Musiek, Teresa Gomez-Isla, David M Holtzman

Open Access Publications

No abstract provided.

Plasmid-Encoded H-Ns Controls Extracellular Matrix Composition In A Modern Acinetobacter Baumannii Urinary Isolate, Saida Benomar, Gisela Di Venanzio, Mario F Feldman

Open Access Publications

Acinetobacter baumannii is emerging as a multidrug-resistant (MDR) nosocomial pathogen of increasing threat to human health worldwide. The recent MDR urinary isolate UPAB1 carries the plasmid pAB5, a member of a family of large conjugative plasmids (LCPs). LCPs encode several antibiotic resistance genes and repress the type VI secretion system (T6SS) to enable their dissemination, employing two TetR transcriptional regulators. Furthermore, pAB5 controls the expression of additional chromosomally encoded genes, impacting UPAB1 virulence. Here, we show that a pAB5-encoded H-NS transcriptional regulator represses the synthesis of the exopolysaccharide PNAG and the expression of a previously uncharacterized three-gene cluster that encodes …