Digital Commons Network^™

Genome-Wide Meta-Analysis For Alzheimer's Disease Cerebrospinal Fluid Biomarkers, Iris E Jansen, Muhammad Ali, Yun Ju Sung, Carlos Cruchaga, Duber Gomez-Fonseca, Et Al.

2020-Current year OA Pubs

Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for …

A Report Of 2 Cases Of The Use Of The Inari Flowtriever System In The Treatment Of Pulmonary Embolism, Richard Pham, Alexander Sasha Ushinsky, Naganathan Mani, Pavan K Kavali

2020-Current year OA Pubs

The FlowTriever System (Inari Medical, Irvine, California) is the first FDA-approved mechanical thrombectomy device used for treatment of pulmonary embolism. This device enables nonsurgical removal of pulmonary blood clots without the use of thrombolytic medication and its associated risks. We report 2 cases of successful application of the Inari FlowTriever in treatment of pulmonary embolism and right atrial thrombus.

A Comparison Of Methods To Harmonize Cortical Thickness Measurements Across Scanners And Sites, Delin Sun, Evan Gordon, Et Al.

2020-Current year OA Pubs

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME

Trim-Nhl Protein, Nhl-2, Modulates Cell Fate Choices In The C. Elegans Germ Line, John L. Brenner, Erin M. Jyo, Ariz Mohammad, Paul Fox, Vovanti Jones, Elaine Mardis, Tim Schedl, Eleanor M. Maine

2020-Current year OA Pubs

Many tissues contain multipotent stem cells that are critical for maintaining tissue function. In Caenorhabditis elegans, germline stem cells allow gamete production to continue in adulthood. In the gonad, GLP-1/Notch signaling from the distal tip cell niche to neighboring germ cells activates a complex regulatory network to maintain a stem cell population. GLP-1/Notch signaling positively regulates production of LST-1 and SYGL-1 proteins that, in turn, interact with a set of PUF/FBF proteins to positively regulate the stem cell fate. We previously described sog (suppressor of glp-1 loss of function) and teg (tumorous enhancer of glp-1 gain of function) genes that …

Facial Paresis As The First Sign In Atypical Facioscapulohumeral Muscular Dystrophy, Nneoma S. Wamkpah, John J. Chi

2020-Current year OA Pubs

No abstract provided.

A Preclinical And Phase Ib Study Of Palbociclib Plus Nab-Paclitaxel In Patients With Metastatic Adenocarcinoma Of The Pancreas, Manuel Hidalgo, Kian-Huat Lim, Et Al.

2020-Current year OA Pubs

PURPOSE: To assess the preclinical efficacy, clinical safety and efficacy, and MTD of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

EXPERIMENTAL DESIGN: Preclinical activity was tested in patient-derived xenograft (PDX) models of PDAC. In the open-label, phase I clinical study, the dose-escalation cohort received oral palbociclib initially at 75 mg/day (range, 50‒125 mg/day; modified 3+3 design; 3/1 schedule); intravenous nab-paclitaxel was administered weekly for 3 weeks/28-day cycle at 100‒125 mg/m

RESULTS: Palbociclib plus nab-paclitaxel was more effective than gemcitabine plus nab-paclitaxel in three of four PDX models tested; the combination was not inferior to paclitaxel plus …

Durable Melanoma Control Following Disseminated Talimogene Laherparepvec Herpetic Infection, Leonid Shmuylovich, Aubriana M Mcevoy, Ryan C Fields, Leonel Hernandez-Aya, George Ansstas, David Y Chen

2020-Current year OA Pubs

No abstract provided.

Implementation Of An Electronic, Secure, Web-Based Application To Support Routine Hand Hygiene Observation With Immediate Direct Feedback And Anonymized Benchmarking, Simon Simonet, Jonas Marschall, Rolf Kuhn, Matthias Schlegel, Christian R Kahlert

2020-Current year OA Pubs

A secure web-based electronic tool was developed and implemented to record adherence to hand hygiene during routine care and to provide direct feedback including anonymized benchmarking. It was found suitable for documenting hand hygiene improvements in a local campaign and following rollout to other institutions in 2013, the tool is currently used in >100 hospitals in Switzerland and will play a major part in upcoming national hand hygiene campaigns.

Risk-Adjusted Safety Analysis Of The Oral Jak2/Irak1 Inhibitor Pacritinib In Patients With Myelofibrosis, Naveen Pemmaraju, Claire Harrison, Vikas Gupta, Srdan Verstovsek, Bart Scott, Stephen T Oh, Francesca Palandri, Haifa Kathrin Al-Ali, Marta Sobas, Mary Frances Mcmullin, Ruben Mesa, Sarah Buckley, Karisse Roman-Torres, Alessandro Vannucchi, Abdulraheem Yacoub

2020-Current year OA Pubs

The safety profile of the novel oral JAK2/IRAK1 inhibitor pacritinib in patients with cytopenic myelofibrosis was described in the Phase 2 PAC203 and Phase 3 PERSIST-2 studies. To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk-adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia.

Implementation Of Telemedicine Infectious Diseases Consultation In A Rural Hospital Using The Active Implementation Framework, Jason P Burnham, Stephanie A Fritz, Graham A Colditz

2020-Current year OA Pubs

In this pilot study, guided by the Active Implementation Framework, telemedicine infectious diseases consultation was provided to hospitalized inpatients at a rural Missouri hospital. Measured outcomes included the implementation outcomes of feasibility, acceptability, appropriateness, and fidelity, as well as clinical outcomes of readmissions and death.

A Phase I First-In-Human Study Of Abbv-383, A B-Cell Maturation Antigen × Cd3 Bispecific T-Cell Redirecting Antibody, In Patients With Relapsed/Refractory Multiple Myeloma, Anita D'Souza, Ravi Vij, Et Al.

2020-Current year OA Pubs

PURPOSE: ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.

METHODS: Patients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest …

American Cochlear Implant Alliance Task Force Guidelines For Clinical Assessment And Management Of Adult Cochlear Implantation For Single-Sided Deafness, Margaret T. Dillon, Armine Kocharyan, Ghazal S. Daher, Matthew L. Carlson, William H. Shapiro, Hillary A. Snapp, Jill B. Firszt

2020-Current year OA Pubs

The indications for cochlear implantation have expanded to include individuals with profound sensorineural hearing loss in the impaired ear and normal hearing (NH) in the contralateral ear, known as single-sided deafness (SSD). There are additional considerations for the clinical assessment and management of adult cochlear implant candidates and recipients with SSD as compared to conventional cochlear implant candidates with bilateral moderate to profound sensorineural hearing loss. The present report reviews the current evidence relevant to the assessment and management of adults with SSD. A systematic review was also conducted on published studies that investigated outcomes of cochlear implant use on …

Ascertainment Of Vaccination Status By Self-Report Versus Source Documentation: Impact On Measuring Covid-19 Vaccine Effectiveness, Meagan Stephenson, Jennie H Kwon, Et Al

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, self-reported COVID-19 vaccination might facilitate rapid evaluations of vaccine effectiveness (VE) when source documentation (e.g., immunization information systems [IIS]) is not readily available. We evaluated the concordance of COVID-19 vaccination status ascertained by self-report versus source documentation and its impact on VE estimates.

METHODS: Hospitalized adults (≥18 years) admitted to 18 U.S. medical centers March-June 2021 were enrolled, including COVID-19 cases and SARS-CoV-2 negative controls. Patients were interviewed about COVID-19 vaccination. Abstractors simultaneously searched IIS, medical records, and other sources for vaccination information. To compare vaccination status by self-report and documentation, we estimated percent agreement …

Distinct Stimulus-Dependent Neutrophil Dynamics Revealed By Real-Time Imaging Of Intestinal Mucosa After Acute Injury, Veronica Azcutia, Matthias Kelm, Seonyoung Kim, Anny-Claude Luissint, Sven Flemming, Lisa Abernathy-Close, Vincent B Young, Asma Nusrat, Mark J Miller, Charles A Parkos

2020-Current year OA Pubs

Clinical symptoms in many inflammatory diseases of the intestine are directly related to neutrophil (PMN) migration across colonic mucosa and into the intestinal lumen, yet in-vivo studies detailing this process are lacking. Using real-time intravital microscopy and a new distal colon loop model, we report distinct PMN migratory dynamics in response to several models of acute colonic injury. PMNs exhibited rapid swarming responses after mechanically induced intestinal wounds. Similar numbers of PMNs infiltrated colonic mucosa after wounding in germ-free mice, suggesting microbiota-independent mechanisms. By contrast, acute mucosal injury secondary to either a treatment of mice with dextran sodium sulfate or …

Diagnosis And Management Of Functional Tic-Like Phenomena, Irene A Malaty, Seonaid Anderson, Shannon M Bennett, Cathy L Budman, Barbara J Coffey, Keith A Coffman, Erica Greenberg, Joseph F Mcguire, Kirsten R Müller-Vahl, Michael S Okun, Julio Quezada, Amy Robichaux-Viehoever, Kevin J. Black

2020-Current year OA Pubs

Over the past 3 years, a global phenomenon has emerged characterized by the sudden onset and frequently rapid escalation of tics and tic-like movements and phonations. These symptoms have occurred not only in youth known to have tics or Tourette syndrome (TS), but also, and more notably, in youth with no prior history of tics. The Tourette Association of America (TAA) convened an international, multidisciplinary working group to better understand this apparent presentation of functional neurological disorder (FND) and its relationship to TS. Here, we review and summarize the literature relevant to distinguish the two, with recommendations to clinicians for …

High-Speed, Scanned Laser Structuring Of Multi-Layered Eco/Bioresorbable Materials For Advanced Electronic Systems, Quansan Yang, Yameng Xu, Ying Yan, Wilson Z Ray, Mitchell A Pet, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin …

Identification Of Novel Genes And Proteoforms In Angiostrongylus Costaricensis Through A Proteogenomic Approach, Esdras Matheus Gomes Da Silva, Karina Mastropasqua Rebello, Young-Jun Choi, Vitor Gregorio, Alexandre Rossi Paschoal, Makedonka Mitreva, James H Mckerrow, Ana Gisele Da Costa Neves-Ferreira, Fabio Passetti

2020-Current year OA Pubs

RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions.

Defining Cellular Complexity In Human Autosomal Dominant Polycystic Kidney Disease By Multimodal Single Cell Analysis, Yoshiharu Muto, Eryn E Dixon, Yasuhiro Yoshimura, Haojia Wu, Kohei Omachi, Nicolas Ledru, Parker C Wilson, Jeffrey H Miner, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease characterized by progressive expansion of kidney cysts. To better understand the cell types and states driving ADPKD progression, we analyze eight ADPKD and five healthy human kidney samples, generating single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. Activation of proinflammatory, profibrotic signaling pathways are driven by proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts and collecting duct cells. We identify GPRC5A as a marker for cyst-lining collecting duct cells that exhibits increased transcription factor …

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden In Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility, Wei-Yi Lei, Shu-Wei Liang, Taher Omari, Wei-Chuan Chang, Ming-Wun Wong, Jui-Sheng Hung, Chih-Hsun Yi, Tso-Tsai Liu, Lin Lin, C Prakash Gyawali, Chien-Lin Chen

2020-Current year OA Pubs

BACKGROUND/AIMS: Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients.

METHODS: Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR.

RESULTS: Of 85 (56.3% female, mean age: 46.7 …

"We Start Where We Are": A Qualitative Study Of Barriers And Pragmatic Solutions To The Assessment And Reporting Of Implementation Strategy Fidelity, Christopher F Akiba, Byron J Powell, Brian W Pence, Kate Muessig, Carol E Golin, Vivian Go

2020-Current year OA Pubs

BACKGROUND: Fidelity measurement of implementation strategies is underdeveloped and underreported, and the level of reporting is decreasing over time. Failing to properly measure the factors that affect the delivery of an implementation strategy may obscure the link between a strategy and its outcomes. Barriers to assessing and reporting implementation strategy fidelity among researchers are not well understood. The aims of this qualitative study were to identify barriers to fidelity measurement and pragmatic pathways towards improvement.

METHODS: We conducted in-depth interviews among researchers conducting implementation trials. We utilized a theory-informed interview approach to elicit the barriers and possible solutions to implementation …

Myocardial Infarction Size As An Independent Predictor Of Intramyocardial Haemorrhage In Acute Reperfused Myocardial Ischaemic Rats, Rui Xia, Tong Zhu, Yu Zhang, Bo He, Yushu Chen, Lei Wang, Yang Zhou, Jichun Liao, Jie Zheng, Yongmei Li, Fajin Lv, Fabao Gao

2020-Current year OA Pubs

BACKGROUND: In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner.

METHODS: Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1-3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were …

Strategies For De-Implementation Of Low-Value Care-A Scoping Review, Sara Ingvarsson, Henna Hasson, Ulrica Von Thiele Schwarz, Per Nilsen, Byron J Powell, Clara Lindberg, Hanna Augustsson

2020-Current year OA Pubs

BACKGROUND: The use of low-value care (LVC) is a persistent problem that calls for knowledge about strategies for de-implementation. However, studies are dispersed across many clinical fields, and there is no overview of strategies that can be used to support the de-implementation of LVC. The extent to which strategies used for implementation are also used in de-implementing LVC is unknown. The aim of this scoping review is to (1) identify strategies for the de-implementation of LVC described in the scientific literature and (2) compare de-implementation strategies to implementation strategies as specified in the Expert Recommendation for Implementing Change (ERIC) and …

Genetic Addiction Risk And Psychological Profiling Analyses For "Preaddiction" Severity Index, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the

Discovery And Characterization Of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors And Preclinical Safety Assessment Of Ucb7362, Martin A Lowe, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life (

Mindfulness Training For Depressed Older Adults Using Smartphone Technology: Protocol For A Fully Remote Precision Clinical Trial, Abigail Schweiger, Thomas L Rodebaugh, Eric J Lenze, Katie Keenoy, Jason Hassenstab, Jeanne Kloeckner, Torie R Gettinger, Ginger E Nicol

2020-Current year OA Pubs

BACKGROUND: Precision medicine, optimized interventions, and access to care are catchphrases for the future of behavioral treatments. Progress has been slow due to the dearth of clinical trials that optimize interventions' benefits, individually tailor interventions to meet individual needs and preferences, and lead to rapid implementation after effectiveness is demonstrated. Two innovations have emerged to meet these challenges: fully remote trials and precision clinical trials.

OBJECTIVE: This paper provides a detailed description of Mindful MyWay, a study designed to test online mindfulness training in older adults with depression. Consistent with the concept of fully remote trials using a smartphone app, …

Risk Factors And Treatment Strategy For Retinal Vascular Occlusive Diseases, Ryo Terao, Ryosuke Fujino, Tazbir Ahmed

2020-Current year OA Pubs

Retinal occlusive diseases are common diseases that can lead to visual impairment. Retinal artery occlusion and retinal vein occlusion are included in the clinical entity, but they have quite different pathophysiologies. Retinal artery occlusion is an emergent eye disorder. Retinal artery occlusion is mainly caused by thromboembolism, which frequently occurs in conjunction with life-threatening stroke and cardiovascular diseases. Therefore, prompt examinations and interventions for systemic vascular diseases are often necessary for these patients. Retinal vein occlusion is characterized by retinal hemorrhage and ischemia, which may impair visual function via several complications such as macular edema, macular ischemia, vitreous hemorrhage, and …

Self-Renewal Of Macrophages: Tumor-Released Factors And Signaling Pathways, Serena Filiberti, Mariapia Russo, Silvia Lonardi, Mattia Bugatti, William Vermi, Cathy Tournier, Emanuele Giurisato

2020-Current year OA Pubs

Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. During tumor growth, both tissue-resident macrophages and newly recruited monocyte-derived macrophages can give rise to tumor-associated macrophages (TAMs), which have been associated with poor prognosis in most cancers. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating …

Comparison Of Metagenomic Sequencing And The Nanostring Ncounter Analysis System For The Characterization Of Bacterial And Viral Communities In Vaginal Samples, Todd N Wylie, Jane Schrimpf, Haley Gula, Brandi N Herter, Kristine M Wylie

2020-Current year OA Pubs

DNA sequencing assays have been used to characterize the vaginal microbiome and to identify associations with clinical outcomes. The purpose of this study was to evaluate the utility of the NanoString nCounter platform, a more efficient assay compared to sequencing, for the characterization of vaginal microbial communities. A panel of NanoString nCounter probes was designed to detect common vaginal bacteria and viruses with relevance to reproductive health. A defined synthetic community of microbes and 43 clinical samples were interrogated with NanoString nCounter assays and compared to known compositions or metagenomic shotgun sequencing (MSS) results. The NanoString nCounter platform and MSS …

Epidemiology Of Plasmid Lineages Mediating The Spread Of Extended-Spectrum Beta-Lactamases Among Clinical Escherichia Coli, Bejan Mahmud, Meghan A Wallace, Kimberly A Reske, Kelly Alvarado, Carol E Muenks, David A Rasmussen, Carey-Ann D Burnham, Cristina Lanzas, Erik R Dubberke, Gautam Dantas

2020-Current year OA Pubs

The prevalence of extended-spectrum beta-lactamases (ESBLs) among clinical isolates of Escherichia coli has been increasing, with this spread driven by ESBL-encoding plasmids. However, the epidemiology of ESBL-disseminating plasmids remains understudied, obscuring the roles of individual plasmid lineages in ESBL spread. To address this, we performed an in-depth genomic investigation of 149 clinical ESBL-like E. coli isolates from a tertiary care hospital. We obtained high-quality assemblies for 446 plasmids, revealing an extensive map of plasmid sharing that crosses time, space, and bacterial sequence type boundaries. Through a sequence-based network, we identified specific plasmid lineages that are responsible for the dissemination of …

Enteric Pathogen Testing Importance For Children With Acute Gastroenteritis: A Modified Delphi Study, Gillian A M Tarr, Drew J Persson, Phillip I Tarr, Stephen B Freedman

2020-Current year OA Pubs

The application of clinical diagnostics for gastroenteritis in children has implications for a broad collection of stakeholders, impacting clinical care, communicable disease control, and laboratory utilization. To support diagnostic stewardship as gastroenteritis testing options continue to advance, it is critical to understand which enteropathogens constitute priorities for testing across stakeholder groups. Using a modified Delphi technique, we elicited opinions of subject matter experts to determine clinical and public health testing priorities. There was a high level of overall agreement (≥80%) among stakeholders (final round