J Control Release. 2020 Nov 16;:
Authors: Anderson JM, Grainger DW
Abstract
Sung Wan Kim's initial efforts as an independent investigator were focused on improving the understanding of the early events in blood/material interactions with the goal to develop blood compatible materials for application in medical devices and prostheses. These initial efforts were centered around blood protein adsorption on biomaterials and related mechanisms of thrombus formation (thrombosis). Ultimately, Sung Wan's efforts were expanded to studies of the non-thrombogenic nature of heparinized biomaterials, prostaglandin biomaterials, and block copolymer systems. These studies were supported by two NIH grants for 22 and 19 years, respectively, and a NIH Career Development Award. Moreover, these studies resulted in over 140 peer-reviewed publications and training of many students and postdoctoral scientists. The intent of this paper is to identify key concepts, papers, and contributions by Sung Wan and his colleagues that fall within the four aforementioned research categories. In this context, many of Sung Wan's early efforts contributed directly to Utah's biomaterials efforts and the Total Artificial Heart program at the time, while providing the foundation for the productive international Triangle Collaboration as well as his following work in polymer-controlled drug releasing systems.
PMID: 33212119 [PubMed - as supplied by publisher]
J Appl Physiol (1985). 2020 Nov 19;:
Authors: Bunsawat K, Ratchford SM, Alpenglow JK, Park SH, Jarrett CL, Stehlik J, Smith AS, Richardson RS, Wray DW
Abstract
The PARADIGM-HF trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan, but the physiologic processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF. We prospectively studied patients with HFrEF (n=11, 10M/1F, left ventricular ejection fraction 27±8%) on optimal, guideline-directed medical treatment who were subsequently prescribed sacubitril-valsartan (open-label, uncontrolled, and unblinded). Peripheral vascular function (brachial artery flow-mediated dilation (FMD, conduit vessel function) and reactive hyperemia (RH, microvascular function)), functional capacity (six-minute walk test (6MWT) distance), and the pro-inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) were obtained at baseline and again at 1, 2, and 3 months of treatment. %FMD improved after 1 month of treatment, and this favorable response persisted for months 2 and 3 (baseline: 3.25±1.75%; 1mo: 5.23±2.36%; 2mo: 5.81±1.79%; 3mo: 6.35±2.77%), while RH remained unchanged. 6MWT distance increased at months 2 and 3 (baseline: 420±92 m; 1mo: 436±98 m; 2mo: 465±115 m; 3mo: 460±110 m), and there was a sustained reduction in TNF-α (baseline: 2.38±1.35 pg/mL; 1mo: 2.06±1.52 pg/mL; 2mo: 1.95±1.34 pg/mL; 3mo: 1.92±1.37 pg/mL) and a reduction in IL-18 at months 3 (baseline: 654±150 pg/mL; 1mo: 595±140 pg/mL; 2mo: 601±176 pg/mL; 3mo: 571±127 pg/mL). This study provides new evidence for the potential of this new drug class to improve conduit vessel function, functional capacity, and inflammation in patients with HFrEF.
PMID: 33211601 [PubMed - as supplied by publisher]
Authors: Gardner M, Turner JE, Youssef OA, Cheshier S
Abstract
Tumor-associated macrophages (TAMs) have recently emerged as potentially crucial therapeutic targets for cancer. Thus, the development of macrophage-mediated phagocytosis assays is vital for preclinical drug screening of different tumor cells. This assay can be used to evaluate the effect of anti-cancer therapy, such as immunotherapy, radiotherapy, and chemotherapy, on different tumor cells. Here, we describe the in-vitro phagocytosis assay in detail. As an example of immunotherapy treatment, we used a monoclonal antibody to block an anti-phagocytic signal (CD47) to evaluate the assay using human brain tumor cells and monocyte-derived macrophages. We also demonstrated that this assay can be used to evaluate the effect of different irradiation doses on the phagocytosis of brain tumor cells. This functional assay is fast, accurate, and highly reproducible. Furthermore, the results successfully demonstrate that anti-CD47 antibodies and irradiation can enhance the macrophage-mediated phagocytosis of brain tumors.
PMID: 33209523 [PubMed]
Nat Metab. 2020 Nov 18;:
Authors: Zhang Y, Taufalele PV, Cochran JD, Robillard-Frayne I, Marx JM, Soto J, Rauckhorst AJ, Tayyari F, Pewa AD, Gray LR, Teesch LM, Puchalska P, Funari TR, McGlauflin R, Zimmerman K, Kutschke WJ, Cassier T, Hitchcock S, Lin K, Kato KM, Stueve JL, Haff L, Weiss RM, Cox JE, Rutter J, Taylor EB, Crawford PA, Lewandowski ED, Des Rosiers C, Abel ED
Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PMID: 33208925 [PubMed - as supplied by publisher]
Sci Rep. 2020 Nov 18;10(1):20133
Authors: Kim V, Jeong S, Zhao H, Kesimer M, Boucher RC, Wells JM, Christenson SA, Han MK, Dransfield M, Paine R, Cooper CB, Barjaktarevic I, Bowler R, Curtis JL, Kaner RJ, O'Beirne SL, O'Neal WK, Rennard SI, Martinez FJ, Woodruff PG
Abstract
COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane. GCD was divided into tertiles based on log10 transformed values. Log10GCD was greater in current smokers compared to former smokers. Those with classically defined CB or SGRQ defined CB had a greater log10 GCD compared to those without CB. Current smoking was independently associated with tertile 3 (high log10GCD) whereas CB was not in multivariable regression when adjusting for lung function and demographics. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.
PMID: 33208859 [PubMed - in process]
Comput Inform Nurs. 2020 Nov 16;:
Authors: Yang R, Plasek JM, Cummins MR, Sward KA
Abstract
Data science skills are increasingly needed by informatics nurses and nurse scientists, but techniques such as machine learning can be daunting for those with clinical, rather than computer science or technical, backgrounds. With the increasing quantity of publicly available population-level datasets, identification of factors that predict clinical outcomes is possible using machine learning algorithms. This study demonstrates how to apply a machine learning approach to nursing-relevant questions, specifically an approach to predict falls among community-dwelling older adults, based on data from the 2014 Behavioral Risk Factor Surveillance System. A random forest algorithm, a common approach to machine learning, was compared to a logistic regression model. Explanations of how to interpret the models and their associated performance characteristics are included to serve as a tutorial to readers. Machine learning methods constitute an increasingly important approach for nursing as population-level data are increasingly being made available to the public.
PMID: 33208628 [PubMed - as supplied by publisher]
Nucleic Acids Res. 2020 11 04;48(19):10877-10889
Authors: Yu Y, Yarrington RM, Stillman DJ
Abstract
The Saccharomyces cerevisiae HO gene is a model regulatory system with complex transcriptional regulation. Budding yeast divide asymmetrically and HO is expressed only in mother cells where a nucleosome eviction cascade along the promoter during the cell cycle enables activation. HO expression in daughter cells is inhibited by high concentration of Ash1 in daughters. To understand how Ash1 represses transcription, we used a myo4 mutation which boosts Ash1 accumulation in both mothers and daughters and show that Ash1 inhibits promoter recruitment of SWI/SNF and Gcn5. We show Ash1 is also required for the efficient nucleosome repopulation that occurs after eviction, and the strongest effects of Ash1 are seen when Ash1 has been degraded and at promoter locations distant from where Ash1 bound. Additionally, we defined a specific nucleosome/nucleosome-depleted region structure that restricts HO activation to one of two paralogous DNA-binding factors. We also show that nucleosome eviction occurs bidirectionally over a large distance. Significantly, eviction of the more distant nucleosomes is dependent upon the FACT histone chaperone, and FACT is recruited to these regions when eviction is beginning. These last observations, along with ChIP experiments involving the SBF factor, suggest a long-distance loop transiently forms at the HO promoter.
PMID: 33010153 [PubMed - indexed for MEDLINE]
Ann Surg. 2020 10;272(4):629-636
Authors: Bucher BT, Shi J, Ferraro JP, Skarda DE, Samore MH, Hurdle JF, Gundlapalli AV, Chapman WW, Finlayson SRG
Abstract
OBJECTIVES: We present the development and validation of a portable NLP approach for automated surveillance of SSIs.
SUMMARY OF BACKGROUND DATA: The surveillance of SSIs is labor-intensive limiting the generalizability and scalability of surgical quality surveillance programs.
METHODS: We abstracted patient clinical text notes after surgical procedures from 2 independent healthcare systems using different electronic healthcare records. An SSI detected as part of the American College of Surgeons' National Surgical Quality Improvement Program was used as the reference standard. We developed a rules-based NLP system (Easy Clinical Information Extractor [CIE]-SSI) for operative event-level detection of SSIs using an training cohort (4574 operative events) from 1 healthcare system and then conducted internal validation on a blind cohort from the same healthcare system (1850 operative events) and external validation on a blind cohort from the second healthcare system (15,360 operative events). EasyCIE-SSI performance was measured using sensitivity, specificity, and area under the receiver-operating-curve (AUC).
RESULTS: The prevalence of SSI was 4% and 5% in the internal and external validation corpora. In internal validation, EasyCIE-SSI had a sensitivity, specificity, AUC of 94%, 88%, 0.912 for the detection of SSI, respectively. In external validation, EasyCIE-SSI had sensitivity, specificity, AUC of 79%, 92%, 0.852 for the detection of SSI, respectively. The sensitivity of EasyCIE-SSI decreased in clean, skin/subcutaneous, and outpatient procedures in the external validation compared to internal validation.
CONCLUSION: Automated surveillance of SSIs can be achieved using NLP of clinical notes with high sensitivity and specificity.
PMID: 32773639 [PubMed - indexed for MEDLINE]
Am J Respir Crit Care Med. 2020 09 15;202(6):885-887
Authors: Baron RM, Christman JW, Liu KD, Matthay MA, Self WH, McVerry BJ, Hite RD, Paine R, Wurfel MM, Shapiro NI, Adams PW, Schmidt EP, Ringwood N
PMID: 32357306 [PubMed - indexed for MEDLINE]
J Heart Lung Transplant. 2019 08;38(8):858-869
Authors: Yin MY, Wever-Pinzon O, Mehra MR, Selzman CH, Toll AE, Cherikh WS, Nativi-Nicolau J, Fang JC, Kfoury AG, Gilbert EM, Kemeyou L, McKellar SH, Koliopoulou A, Vaduganathan M, Drakos SG, Stehlik J
Abstract
BACKGROUND: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS.
METHODS: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes.
RESULTS: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time.
CONCLUSIONS: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant.
PMID: 31072751 [PubMed - indexed for MEDLINE]
