Publications by authors named "Eun Shin"

465 Publications

Anatomy of comorbidity complexity of COVID-19: the case of hospitalized South Korean patients.

Epidemiol Health 2021 May 7:e2021035. Epub 2021 May 7.

Department of Medicine, Division of Hematology & Oncology, University of Tennessee Health Science Center, TN, USA.

Objectives: We aimed to examine how comorbidities are associated with outcome (illness severity or death) in hospitalized COVID-19 patients.

Methods: We use data provided by Korea Disease Control & Prevention Agency, National Medical Center, which include the clinical and epidemiological patient data of all patients hospitalized with COVID-19, who were discharged on, or prior to, April 30, 2020, in South Korea. We conducted comorbidity network and multinomial logistic regression analyses to identify risk factors associated with the severity of and mortality from COVID-19 disease. The outcome variable is the categorized clinical severity scores (CSS): mild case (O2 treatment not needed), severe case (O2 treatment needed), and death.

Results: A total of 5,771 patients were included. In the fully adjusted model, chronic kidney disease (CKD); odds ratio, 2.59 [95% CI, 1.19 to 5.61] and chronic obstructive pulmonary disease (COPD); odds ratio, 3.19 [95% CI, 1.35 to 7.52] were significantly associated with case severity. The following were associated with an increased risk of death: CKD; odds ratio, 5.35 [95% CI, 2.00 to 14.31], Heart failure (HF) odds ratio, 3.15 [95% CI, 1.22 to 8.15], malignancy odds ratio, 3.38 [95% CI, 1.59 to 7.17], dementia odds ratio, 2.62 [95% CI, 1.45 to 4.73], and diabetes odds ratio, 2.26 [95% CI, 1.46 to 3.49]. Asthma and hypertension were associated with an increased risk of death, although this was not statistically significant.

Conclusion: Underlying diseases have different contributions to the severity of COVID-19 disease. To efficiently allocated limited medical resources, underlying comorbidities should be closely monitored, particularly chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD), heart failure (HF) in the past.
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http://dx.doi.org/10.4178/epih.e2021035DOI Listing
May 2021

Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1α (HIF-1α) Inhibitor in Mice.

Molecules 2021 Apr 12;26(8). Epub 2021 Apr 12.

Convergence Medical Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul 05505, Korea.

LW6, an (aryloxyacetylamino)benzoic acid derivative, was recently identified to be an inhibitor of hypoxia-inducible factor-1α (HIF-1α), which is an attractive target for cancer therapeutics. Although LW6 is known to act by inhibiting the accumulation of HIF-1α, pharmacokinetics needs to be evaluated to assess its potential as an anti-tumor agent. Here, we investigated the plasma pharmacokinetics and metabolism of LW6 in mice. LW6 exhibited a small volume of distribution (0.5 ± 0.1 L/kg), and a short terminal half-life (0.6 ± 0.1 h). Following intravenous or oral administration, LW6 was rapidly converted to its active metabolite, (4-adamantan-1-yl-phenoxy)acetic acid (APA). Although LW6 was rapidly absorbed, its oral bioavailability, estimated using values, was low (1.7 ± 1.8%). It was slowly degraded in mouse liver microsomes ( > 1 h) and serum ( > 6 h). About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively. Thus, our results indicated the need to simultaneously consider the active metabolite as well as the parent compound for successful evaluation during lead optimization.
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http://dx.doi.org/10.3390/molecules26082226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070284PMC
April 2021

Novel Long Noncoding RNA miR205HG Functions as an Esophageal Tumor-Suppressive Hedgehog Inhibitor.

Cancers (Basel) 2021 Apr 3;13(7). Epub 2021 Apr 3.

Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.

Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of biological pathways. However, involvement of lncRNAs in the development of BE and EAC has not been well-studied. The aims of the current study were: (1) to study involvement of the lncRNA, , in the development of BE and EAC; (2) to clarify the role of in in vitro and in vivo experiments; and (3) to investigate the mechanism of involving the Hedgehog (Hh) signaling pathway. These experiments revealed that was downregulated in EAC vs. normal esophageal epithelia (NE) as well as in EAC cell lines, and its forced overexpression inhibited EAC cell proliferation and cell cycle progression in vitro. Similarly, overexpression of inhibited xenograft tumor growth in mice In vivo. Finally, we show that one mechanism of action of involves the Hh signaling pathway: and Hh expression levels were inversely correlated in both EAC (r = -0.73) and BE (r = -0.83) tissues, and in vitro studies revealed details of Hh signaling inhibition induced by In conclusion, these findings establish that lncRNA functions as a tumor suppressor in the development of BE and EAC, at least in part through its effect on the Hh signaling pathway.
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http://dx.doi.org/10.3390/cancers13071707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038513PMC
April 2021

Robust and distributed neural representation of action values.

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Republic of Korea.

Studies in rats, monkeys, and humans have found action-value signals in multiple regions of the brain. These findings suggest that action-value signals encoded in these brain structures bias choices toward higher expected rewards. However, previous estimates of action-value signals might have been inflated by serial correlations in neural activity and also by activity related to other decision variables. Here, we applied several statistical tests based on permutation and surrogate data to analyze neural activity recorded from the striatum, frontal cortex, and hippocampus. The results show that previously identified action-value signals in these brain areas cannot be entirely accounted for by concurrent serial correlations in neural activity and action value. We also found that neural activity related to action value is intermixed with signals related to other decision variables. Our findings provide strong evidence for broadly distributed neural signals related to action value throughout the brain.
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http://dx.doi.org/10.7554/eLife.53045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104958PMC
April 2021

A Clinical Risk Score to Predict In-hospital Mortality from COVID-19 in South Korea.

J Korean Med Sci 2021 Apr 19;36(15):e108. Epub 2021 Apr 19.

Division of Cardiology, Department of Internal Medicine, Ulsan Medical Center, Ulsan, Korea.

Background: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19.

Methods: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score). The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves.

Results: The incidence of mortality was 4.3% in both the development and validation set. A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85-0.91) and 0.97 (95% CI, 0.84-0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com).

Conclusion: This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.
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http://dx.doi.org/10.3346/jkms.2021.36.e108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055508PMC
April 2021

Nanoaggregates Derived from Amyloid-beta and Alpha-synuclein Characterized by Sequential Quadruple Force Mapping.

Nano Lett 2021 May 12;21(9):3789-3797. Epub 2021 Apr 12.

Department of Chemistry, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang 37673, Republic of Korea.

Overlapping of Alzheimer's disease and Parkinson's disease is associated with the formation of hetero-oligomers derived from amyloid-beta and alpha-synuclein. However, the structural identity of the hetero-oligomer has yet to be elucidated, particularly at high resolution. Here, with atomic force microscopy, the surface structure of hetero-oligomer was examined with four AFM tips tethering one of the selected antibodies recognizing N-terminus or C-terminus of each peptide. All aggregates were found to be hetero-oligomers, and probability of recognizing the termini is higher than that for the homo-oligomers, suggesting that the termini of the former have a greater tendency to be located at the surface or the termini have more freedom to be recognized, probably through loose packing. The methodology in this study provides us with a new approach to elucidate the structure of such aggregates at the single-molecule level, allowing the exploration of other intrinsically disordered proteins frequently found in nature.
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http://dx.doi.org/10.1021/acs.nanolett.1c00058DOI Listing
May 2021

Nuclear Factor Erythroid 2-related Factor 2 Knockout Suppresses the Development of Aggressive Colorectal Cancer Formation Induced by Azoxymethane/Dextran Sulfate Sodium-Treatment in Female Mice.

J Cancer Prev 2021 Mar;26(1):41-53

Laboratory of Immunology, Division of Biotechnology Review and Research-III, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.

Colon tumors develop more frequently in male than in female. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays differential roles in the stage of tumorigenesis. The purpose of this study was to investigate the role of Nrf2 on colitis-associated tumorigenesis using Nrf2 knockout (KO) female mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO female mice were sacrificed at week 2 and 16 after AOM injection. Severity of colitis, tumor incidence, and levels of inflammatory mediators were evaluated in AOM/DSS-treated WT and Nrf2 KO mice. Furthermore, qRT-PCR, Western blot abnalysis, and ELISA were performed in colon tissues. At week 2, AOM/DSS-induced colon tissue damages were significantly greater in Nrf2 KO than in WT mice. At week 16, tumor numbers (> 2 mm size) were significantly lower in both the proximal and distal colon in Nrf2 KO compared to WT. The overall incidences of adenoma/cancer of the proximal colon and submucosal invasive cancer of the distal colon were reduced by Nrf2 KO. The mRNA and protein expression levels of NF-κB-related mediators (i.e., iNOS and COX-2) and Nrf2-related antioxidants (i.e., heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit) were significantly lower in the Nrf2 KO than in WT mice. Interestingly, the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was higher in AOM/DSS-treated Nrf2 KO than in WT mice. Our results support the oncogenic effect of Nrf2 in the later stage of carcinogenesis and upregulation of tumor suppressor 15-PGDH might contribute to the repression of colitis-associated tumorigenesis in Nrf2 KO female mice.
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http://dx.doi.org/10.15430/JCP.2021.26.1.41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020176PMC
March 2021

Metabolite Profiling and Characterization of LW6, a Novel HIF-1α Inhibitor, as an Antitumor Drug Candidate in Mice.

Molecules 2021 Mar 30;26(7). Epub 2021 Mar 30.

Asan Medical Center, Asan Institute for Life Sciences, Seoul 05505, Korea.

A novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6.
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http://dx.doi.org/10.3390/molecules26071951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037336PMC
March 2021

A Data Science Approach to Analyze the Association of Socioeconomic and Environmental Conditions With Disparities in Pediatric Surgery.

Front Pediatr 2021 12;9:620848. Epub 2021 Mar 12.

Department of Pediatrics, Center for Biomedical Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States.

Scientific evidence confirm that significant racial disparities exist in healthcare, including surgery outcomes. However, the causal pathway underlying disparities at preoperative physical condition of children is not well-understood. This research aims to uncover the role of socioeconomic and environmental factors in racial disparities at the preoperative physical condition of children through multidimensional integration of several data sources at the patient and population level. After the data integration process an unsupervised k-means algorithm on neighborhood quality metrics was developed to split 29 zip-codes from Memphis, TN into good and poor-quality neighborhoods. An unadjusted comparison of African Americans and white children showed that the prevalence of poor preoperative condition is significantly higher among African Americans compared to whites. No statistically significant difference in surgery outcome was present when adjusted by surgical severity and neighborhood quality. The socioenvironmental factors affect the preoperative clinical condition of children and their surgical outcomes.
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http://dx.doi.org/10.3389/fped.2021.620848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994338PMC
March 2021

GREB1: An evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer.

Sci Adv 2021 Mar 17;7(12). Epub 2021 Mar 17.

Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research, Singapore 138673, Singapore.

What covalent modifications control the temporal ubiquitination of ERα and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERα-inducible enzyme, catalyzes O-GlcNAcylation of ERα at residues T553/S554, which stabilizes ERα protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERα results in reduced cellular ERα levels and insensitivity to estrogen. Higher expression in ERα breast cancer is associated with greater survival in response to tamoxifen, an ERα agonist. Mice lacking exhibit growth and fertility defects reminiscent of phenotypes in ERα-null mice. In summary, this study identifies GREB1, a protein with an evolutionarily conserved domain related to DNA-modifying glycosyltransferases of bacteriophages and kinetoplastids, as the first inducible and the only other (apart from OGT) O-GlcNAc glycosyltransferase in mammalian cytoplasm and ERα as its first substrate.
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http://dx.doi.org/10.1126/sciadv.abe2470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968844PMC
March 2021

Addition of Cellulose Nanofibers to Control Surface Roughness for Hydrophobic Ceramic Coatings.

J Nanosci Nanotechnol 2021 Aug;21(8):4492-4497

Korea Packaging Center, Korea Institute of Industrial Technology, 2F, IT301, Bucheon Techno Park, Ssangyong 3cha, Apt, 397, Seokcheon-ro, Bucheon-si, Gyeonggi-do, 14449, Republic of Korea.

Hydrophobic ceramic coatings are used for a variety of applications. Generally, hydrophobic coating surfaces are obtained by reducing the surface energy of the coating material or by forming a highly textured surface. Reducing the surface energy of the coating material requires additional costs and processing and changes the surface properties of the ceramic coating. In this study, we introduce a simple method to improve the hydrophobicity of ceramic coatings by implementing a textured surface without chemical modification of the surface. The ceramic coating solution was first prepared by adding cellulose nanofibers (CNFs) and then applied to a polypropylene (PP) substrate. The surface roughness increased as the amount of added CNFs increased, increasing the water contact angle of the surface. When the amount of CNFs added was corresponding to 10% of the solid content, the surface roughness average of the area was 43.8 m. This is an increase of approximately 140% from 3.1 m (the value of the surface roughness of the surface without added CNFs). In addition, the water contact angle of the coating with added CNF increased to 145.0°, which was 46% higher than that without the CNFs. The hydrophobicity of ceramic coatings with added CNFs was better because of changes in the surface topography. After coating and drying, the CNFs randomly accumulated inside the ceramic coating layer, forming a textured surface. Thus, hydrophobicity was improved by implementing a rugged ceramic surface without revealing the surface of the CNFs inside the ceramic layer.
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http://dx.doi.org/10.1166/jnn.2021.19430DOI Listing
August 2021

Ethnic Difference of Thrombogenicity in Patients with Cardiovascular Disease: a Pandora Box to Explain Prognostic Differences.

Korean Circ J 2021 Mar;51(3):202-221

Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.

Arterial and venous atherothrombotic events are finely regulated processes involving a complex interplay between vulnerable blood, vulnerable vessel, and blood stasis. Vulnerable blood ('thrombogenicity') comprises complex interactions between cellular components and plasma factors (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors). The extent of thrombogenicity may determine the progression of atheroma and the clinical manifestation of atherothrombotic events, with the highest thrombogenicity in African Americans and lowest in East Asians. Inherent thrombogenicity may influence clinical efficacy and safety of specific antithrombotic treatments in high-risk patients, which may in part explain the observation that East Asian patients have reduced anti-ischemic benefits and elevated bleeding risk with antithrombotic therapy compared to Caucasian patients. In this review, we discuss available evidence regarding the racial differences in thrombogenicity and its impact on clinical outcomes among patients with atherosclerotic cardiovascular disease.
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http://dx.doi.org/10.4070/kcj.2020.0537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925962PMC
March 2021

Guidelines on management of pancreatic cysts detected in high-risk individuals: An evaluation of the 2017 Fukuoka guidelines and the 2020 International Cancer of the Pancreas Screening (CAPS) consortium statements.

Pancreatology 2021 Apr 2;21(3):613-621. Epub 2021 Feb 2.

Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address:

Background: Objectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI.

Methods: Using prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts.

Results: 356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria.

Conclusions: In HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI.
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http://dx.doi.org/10.1016/j.pan.2021.01.017DOI Listing
April 2021

Implant survival and risk factor analysis in regenerated bone: results from a 5-year retrospective study.

J Periodontal Implant Sci 2020 Dec;50(6):379-391

Department of Periodontology, Periodontal-Implant Clinical Research Institute, School of Dentistry, Kyung Hee University, Seoul, Korea.

Purpose: The aims of this study were to evaluate the 5-year cumulative survival rate (CSR) of implants placed with guided bone regeneration (GBR) compared to implants placed in native bone, and to identify factors contributing to implant failure in regenerated bone.

Methods: This retrospective cohort study included 240 patients who had implant placement either with a GBR procedure (regenerated bone group) or with pristine bone (native bone group). Data on demographic features (age, sex, smoking, and medical history), location of the implant, implant-specific features, and grafting procedures and materials were collected. The 5-year CSRs in both groups were estimated using Kaplan-Meier analysis. Risk factors for implant failure were analyzed with a Cox proportional hazards model.

Results: In total, 264 implants in the native bone group and 133 implants in the regenerated bone group were analyzed. The 5-year CSRs were 96.4% in the regenerated bone group and 97.5% in the native bone group, which was not a significant difference. The multivariable analysis confirmed that bone status was not an independent risk factor for implant failure. However, smoking significantly increased the failure rate (hazard ratio, 10.7; =0.002).

Conclusions: The 5-year CSR of implants placed in regenerated bone using GBR was comparable to that of implants placed in native bone. Smoking significantly increased the risk of implant failure in both groups.
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http://dx.doi.org/10.5051/jpis.2002140107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758304PMC
December 2020

Risk factors for lymph node metastasis and survival of patients with nonampullary duodenal carcinoid tumors treated with endoscopic therapy versus surgical resection: analysis of the Surveillance, Epidemiology, and End Results program.

Gastrointest Endosc 2021 Feb 15. Epub 2021 Feb 15.

Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA.

Background And Aims: Endoscopic therapy (ET) has been used to treat nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in size, but data on long-term outcomes are limited. In addition, management of 11- to 19-mm NAD-NETs is not well defined because of variable estimates of risk of metastasis. We aimed to determine the prevalence and risk factors of metastasis of NAD-NETs ≤19 mm and evaluate the long-term survival of patients after ET as compared with radical surgery.

Methods: The Surveillance Epidemiology and End Result database was used to identify 1243 patients with T1-2 histologically confirmed NAD-NETs ≤19 mm in size. Cancer-specific survival (CSS) and overall survival (OS) were calculated.

Results: Overall, 4.8% of cases had metastasis at the time of diagnosis, with lower prevalence in ≤10-mm lesions (3.1%) versus 11- to 19-mm lesions (11.7%, P < .001). The risk factors for metastases included invasion to the muscularis propria (odds ratio, 25.95; 95% confidence interval, 9.01-76.70), age <65 years (odds ratio, 1.93), submucosal involvement (odds ratio, 3.1), and 11 to 19 mm in size (vs ≤10 mm). In patients with well- to moderately differentiated T1-2N0M0 NAD-NETs ≤19 mm confined to the mucosa/submucosa who underwent ET or surgery, the 5-year CSS was 100%. The 5-year OS was similar between the ≤10-mm and 11- to 19-mm groups (86.6% vs 91.0%, P = .31) and the ET and surgery groups (87.4% vs 87.5%, P = .823).

Conclusions: In NAD-NETs, invasion to the muscularis propria is the strongest risk factor for metastasis. In the absence of metastasis, in lesions with well/moderate differentiation and without muscle invasion, ET is adequate for NAD-NETs ≤10 mm and is a viable option for 11- to 19-mm lesions.
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http://dx.doi.org/10.1016/j.gie.2020.12.012DOI Listing
February 2021

Ameliorative effect of persimmon (Diospyros kaki) in cognitively impaired diabetic mice.

J Food Biochem 2021 Jan 16;45(1):e13581. Epub 2020 Dec 16.

Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Republic of Korea.

The effects of ethanolic extract of Diospyros kaki (EED) on diabetic cognitive impairment were investigated in high-fat diet (HFD)-induced mouse. After HFD was fed to mouse for 16 weeks, EED was administrated to mouse for 4 weeks. EED reduced fasting blood glucose level and improved cognitive and behavioral dysfunction. EED improved serum biomarkers related to lipid and liver damage better than positive control (PC). In addition, EED ameliorated impaired cholinergic system, increased oxidative stress as well as mitochondrial dysfunction compared with HFD group. In the molecular study, EED downregulated the phosphorylation of c-Jun N-terminal kinase (p-JNK), which phosphorylates the serine residue of insulin receptor substrate-1 (IRS-1pSer). Finally, various physiological compounds such as tannin-based ingredients were identified using UPLC-QTOF/MS . These results suggest that EED can help improve cognitive impairment caused by HFD. PRACTICAL APPLICATIONS: Recently, cognitive impairment caused by type 2 diabetes mellitus (T2DM) has become a problem. T2DM, mainly derived from HFD, is characterized by hyperglycemia, which is associated with insulin resistance. In this study, EED not only improved hyperglycemia and insulin resistance, but also restored diabetes-related cognitive dysfunction in HFD-induced diabetic mice. Finally, the decrease in cholinergic and antioxidant systems related to cognitive impairment was recovered by consumption of EED via improvement of insulin signaling pathway. Therefore, this study suggests that persimmon (Diospyros kaki) containing diverse physiological compounds has potential and industrial value as a functional food material for cognitive improvement.
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http://dx.doi.org/10.1111/jfbc.13581DOI Listing
January 2021

Propolis Suppresses UV-Induced Photoaging in Human Skin through Directly Targeting Phosphoinositide 3-Kinase.

Nutrients 2020 Dec 10;12(12). Epub 2020 Dec 10.

Department of Biotechnology, Yonsei University, Seoul 03722, Korea.

Propolis is a resinous substance generated by bees using materials from various plant sources. It has been known to exhibit diverse bioactivities including anti-oxidative, anti-microbial, anti-inflammatory, and anti-cancer effects. However, the direct molecular target of propolis and its therapeutic potential against skin aging in humans is not fully understood. Herein, we investigated the effect of propolis on ultraviolet (UV)-mediated skin aging and its underlying molecular mechanism. Propolis suppressed UV-induced matrix metalloproteinase (MMP)-1 production in human dermal fibroblasts. More importantly, propolis treatment reduced UV-induced MMP-1 expression and blocked collagen degradation in human skin tissues, suggesting that the anti-skin-aging activity of propolis can be recapitulated in clinically relevant conditions. While propolis treatment did not display any noticeable effects against extracellular signal-regulated kinase (ERK), p38, and c-jun -terminal kinase (JNK) pathways, propolis exerted significant inhibitory activity specifically against phosphorylations of phosphoinositide-dependent protein kinase-1 (PDK1) and protein kinase B (Akt). Kinase assay results demonstrated that propolis can directly suppress phosphoinositide 3-kinase (PI3K) activity, with preferential selectivity towards PI3K with p110α and p110δ catalytic subunits over other kinases. The content of active compounds was quantified, and among the compounds identified from the propolis extract, caffeic acid phenethyl ester, quercetin, and apigenin were shown to attenuate PI3K activity. These results demonstrate that propolis shows anti-skin-aging effects through direct inhibition of PI3K activity.
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http://dx.doi.org/10.3390/nu12123790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764066PMC
December 2020

Early Surgical and Long-term Oncological Outcomes of Totally Laparoscopic Near-total Gastrectomy in >150 Cases.

Surg Laparosc Endosc Percutan Tech 2020 Dec;30(6):529-533

Departments of Surgery.

Background: This study aimed to examine the early surgical outcomes and long-term oncological safety of totally laparoscopic near-total gastrectomy for the treatment of upper-third early gastric cancer.

Materials And Methods: We retrospectively collected and analyzed the data of 167 consecutive patients who underwent totally laparoscopic near-total gastrectomy for upper-third early gastric cancer between January 2008 and May 2018. Data on clinical characteristics and surgical outcomes, including operation time, length of postoperative hospital stay, pathologic findings, and postoperative complications, were obtained. We also analyzed recurrence-free and overall survival rates to evaluate the oncological outcomes.

Results: The mean operation time was 149.44±37.59 minutes; none of the patients required conversion to laparotomy during surgery. The average postoperative hospital stay was 7.57±5.69 days. On final pathologic analysis, the mean proximal resection margin was 1.97±1.68 cm. No patients had an involved proximal resection margin. Twenty-seven patients (16.17%) had postoperative complications; of them, 6 patients (3.59%) had Clavien-Dindo classification grade 3 or higher complications, all within 1 month. The median follow-up duration was 54.35 months. The 3- and 5-year recurrence-free survival rates were 98.3% and 97.1%, respectively. The overall survival rate was 97.1% at both 3 and 5 years.

Conclusions: Our study shows that totally laparoscopic near-total gastrectomy is a safe and feasible procedure for treating the upper-third early gastric cancer. Further, in the current study, the procedure demonstrated a favorable oncological outcome for a relatively long follow-up period and large sample size.
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http://dx.doi.org/10.1097/SLE.0000000000000823DOI Listing
December 2020

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes.

Yonsei Med J 2020 Dec;61(12):1004-1012

Department of Cardiology, Peking University Shougang Hospital, Shijingshan District, Beijig, China.

Purpose: Dissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.

Materials And Methods: A total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).

Results: The cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, =0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, =0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.

Conclusion: The presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).
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http://dx.doi.org/10.3349/ymj.2020.61.12.1004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700881PMC
December 2020

The Need for a Better-Designed Study of the Outcomes of Endoscopic Management of Bile Leak.

Clin Endosc 2020 Nov 13;53(6):633-635. Epub 2020 Nov 13.

Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.

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http://dx.doi.org/10.5946/ce.2020.263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719423PMC
November 2020

Dielectric Elastomers UV-Cured from Poly(dimethylsiloxane) Solution in Vinyl Acetate.

Polymers (Basel) 2020 Nov 11;12(11). Epub 2020 Nov 11.

Human Enhancement & Assistive Technology Research Section, Electronics and Telecommunications Research Institute, 218 Gajeong-ro, Yuseong-gu, Daejeon 34129, Korea.

Poly(dimethylsiloxane) (PDMS) has been extensively used as an electroactive polymer material because it exhibits not only excellent moldability but also mechanical properties sufficient enough for electroactive performance despite low dielectric permittivity. Its low dielectric property is due to its molecular non-polarity. Here, we introduce a polar group into a PDMS elastomer by using vinyl acetate (VAc) as a crosslinker to improve the dielectric permittivity. We synthesized a high-molecular weight PDMS copolymer containing vinyl groups, namely poly(dimethylsiloxane--methylvinylsiloxane) (VPDMS), and prepared several of the VPDMS solutions in VAc. We obtained transparent PDMS films by UV curing of the solution layers. Electromechanical actuation-related physical properties of one of the UV-cured films were almost equivalent to or superior to those of platinum-catalyzed hydrosilylation-cured PDMS films. In addition, saponification of the UV-cured film significantly improved the electrical and mechanical properties (ɛ' ~ 44.1 pF/m at 10 kHz, E ~ 350 kPa, ɛ ~ 320%). The chemical introduction of VAc into PDMS main chains followed by saponification would offer an efficacious method of enhancing the electroactive properties of PDMS elastomers.
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http://dx.doi.org/10.3390/polym12112660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697987PMC
November 2020

Alterations in the Duodenal Fluid Microbiome of Patients With Pancreatic Cancer.

Clin Gastroenterol Hepatol 2020 Nov 5. Epub 2020 Nov 5.

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address:

Background & Aims: The tumor microbiome of patients with pancreas ductal adenocarcinoma (PDAC) includes bacteria normally present in the upper gastrointestinal tract. If the predominant source of intratumoral bacteria in patients with PDAC is retrograde migration from the duodenum, duodenal fluid could be a representative biospecimen for determining microbiome profiles of patients with PDAC or at risk of developing PDAC.

Methods: We performed a case-control study comparing bacterial and fungal (16S and 18S rRNA) profiles of secretin-stimulated duodenal fluid collections from 308 patients undergoing duodenal endoscopy including 134 normal pancreas control subjects, 98 patients with pancreatic cyst(s) and 74 patients with PDAC.

Results: Alterations in duodenal fluid microbiomes with diminished alpha diversity were significantly associated with age >70 and proton pump inhibitor use. Patients with PDAC had significantly decreased duodenal microbial alpha diversity compared with age-matched control subjects with normal pancreata and those with pancreatic cyst(s). There was evidence of enrichment of Bifidobacterium genera in the duodenal fluid of patients with PDAC compared with control subjects and those with pancreatic cyst(s). There were also enrichment of duodenal fluid Fusobacteria and Rothia bacteria among patients with PDAC with short-term survival. Duodenal fluid microbiome profiles were not significantly different between control subjects and patients with pancreatic cyst(s).

Conclusion: Patients with PDAC have alterations in their duodenal fluid microbiome profiles compared with patients with pancreatic cysts and those with normal pancreata. ClinicalTrials.gov, Number: NCT02000089.
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http://dx.doi.org/10.1016/j.cgh.2020.11.006DOI Listing
November 2020

Multifocal Cryoballoon Ablation for Eradication of Barrett's Esophagus-Related Neoplasia: A Prospective Multicenter Clinical Trial.

Am J Gastroenterol 2020 11;115(11):1879-1890

Division of Gastroenterology, University of North Carolina, Chapel Hill, North Carolina, USA.

Introduction: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE.

Methods: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year.

Results: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR.

Discussion: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).
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http://dx.doi.org/10.14309/ajg.0000000000000822DOI Listing
November 2020

Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017.

Cancer Lett 2021 01 28;497:221-228. Epub 2020 Oct 28.

The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Recent research on genomic profiling of pancreatic ductal adenocarcinoma (PDAC) has identified many potentially actionable alterations. However, the feasibility of using genomic profiling to guide routine clinical decision making for PDAC patients remains unclear. We retrospectively reviewed PDAC patients between October 2013 and December 2017, who underwent treatment at the Johns Hopkins Hospital and had clinical tumor next-generation sequencing (NGS) through commercial resources. Ninety-two patients with 93 tumors tested were included. Forty-eight (52%) patients had potentially curative surgeries. The median time from the tissue available to the NGS testing ordered was 229 days (interquartile range 62-415). A total of three (3%) patients had matched targeted therapies based on genomic profiling results. Genomic profiling guided personalized treatment for PDAC patients is feasible, but the percentage of patients who receive targeted therapy is low. The main challenges are ordering NGS testing early in the clinical course of the disease and the limited evidence of using a targeted approach in these patients. A real-time department level genomic testing ordering system in combination with an evidence-based flagging system for potentially actionable alterations could help address these shortcomings.
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http://dx.doi.org/10.1016/j.canlet.2020.10.039DOI Listing
January 2021

Hexagonal and Monoclinic Phases of LaOCO Nanoparticles and Their Phase-Related CO Behavior.

Nanomaterials (Basel) 2020 Oct 19;10(10). Epub 2020 Oct 19.

School of Chemical Engineering, University of Ulsan, Daehakro 93, Nam-gu, Ulsan 44610, Korea.

In this study, we prepared hexagonal and monoclinic phases of LaOCO nanoparticles by different wet preparation methods and investigated their phase-related CO behavior through field-emission scanning microscopy, high-resolution transmission electron microscopy, Fourier transform infrared, thermogravimetric analysis, CO-temperature programmed desorption, and linear sweeping voltammetry of CO electrochemical reduction. The monoclinic LaOCO phase was synthesized by a conventional precipitation method via La(OH)CO when the precipitation time was longer than 12 h. In contrast, the hydrothermal method produced only the hexagonal LaOCO phase, irrespective of the hydrothermal reaction time. The La(OH) phase was determined to be the initial phase in both preparation methods. During the precipitation, the La(OH) phase was transformed into La(OH)CO owing to the continuous supply of CO from air whereas the hydrothermal method of a closed system crystallized only the La(OH) phase. Based on the CO-temperature programmed desorption and thermogravimetric analysis, the hexagonal LaOCO nanoparticles (HL-12h) showed a higher surface CO adsorption and thermal stability than those of the monoclinic LaOCO (PL-12h). The crystalline structures of both LaOCO phases predicted by the density functional theory calculation explained the difference in the CO behavior on each phase. Consequently, HL-12h showed a higher current density and a more positive onset potential than PL-12h in CO electrochemical reduction.
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http://dx.doi.org/10.3390/nano10102061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603085PMC
October 2020

17β-Estradiol strongly inhibits azoxymethane/dextran sulfate sodium-induced colorectal cancer development in Nrf2 knockout male mice.

Biochem Pharmacol 2020 12 15;182:114279. Epub 2020 Oct 15.

Tumor Microenvironment Global Core Research Center, Seoul National University College of Pharmacy, Seoul, South Korea.

Nuclear factor erythroid 2-related factor 2 (Nrf2) has dual effects on inflammation and cancer progression depending on the microenvironment. Estrogens have a protective effect on colorectal cancer (CRC) development. The aim of this study was to investigate CRC development in Nrf2 knockout (KO) mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO male mice were sacrificed at weeks 2 and 16 after AOM injection with/without 17β-estradiol (E2) treatment during week 1. Disease activity index and colon tissue damage at week 2 showed strong attenuation following E2 administration in WT mice but to a lesser extent in Nrf2 KO male mice. At week 16, E2 significantly diminished AOM/DSS-induced adenoma/cancer incidence at distal colon in the Nrf2 KO group, but not in the WT. Furthermore, mRNA or protein levels of NF-κB-related mediators (i.e., iNOS, TNF-α, and IL-1β) and Nrf2-related antioxidants (i.e., NQO1 and HO-1) were significantly lower in the Nrf2 KO group regardless of E2 treatment compared to the WT. The expression of estrogen receptor beta (ERβ) was higher in the Nrf2 KO group than in the WT. In conclusion, estrogen further inhibits CRC by upregulating ERβ-related alternate pathways in the absence of Nrf2.
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http://dx.doi.org/10.1016/j.bcp.2020.114279DOI Listing
December 2020

Anti-Amnesic Effect of Walnut via the Regulation of BBB Function and Neuro-Inflammation in Aβ-Induced Mice.

Antioxidants (Basel) 2020 Oct 12;9(10). Epub 2020 Oct 12.

Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Korea.

This study was conducted to assess the protective effect of walnut ( L.) extract on amyloid beta (Aβ)-induced institute of cancer research (ICR) mice. By conducting a Y-maze, passive avoidance, and Morris water maze tests with amyloidogenic mice, it was found that walnut extract ameliorated behavioral dysfunction and memory deficit. The walnut extract showed a protective effect on the antioxidant system and cholinergic system by regulating malondialdehyde (MDA) levels, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, acetylcholine (ACh) levels, acetylcholinesterase (AChE) activity, and protein expression of AChE and choline acetyltransferase (ChAT). Furthermore, the walnut extract suppressed Aβ-induced abnormality of mitochondrial function by ameliorating reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP contents. Finally, the walnut extract regulated the expression of zonula occludens-1 (ZO-1) and occludin concerned with blood-brain barrier (BBB) function, expression of tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκB), cyclooxygenase-2 (COX-2), and interleukin 1 beta (IL-1β), related to neuroinflammation and the expression of phosphorylated protein kinase B (p-Akt), caspase-3, hyperphosphorylation of tau (p-tau), and heme oxygenase-1 (HO-1), associated with the Aβ-related Akt pathway.
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http://dx.doi.org/10.3390/antiox9100976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600148PMC
October 2020

Positive Psychological Capital Mediates the Association between Burnout and Nursing Performance Outcomes among Hospital Nurses.

Int J Environ Res Public Health 2020 08 18;17(16). Epub 2020 Aug 18.

Department of Nursing, Chunnam Techno University, 113 Daehakro, Okgwamyeon, Gokseong, Jeollanamdo 58128, Korea.

Nursing burnout is associated with reduced nursing performance outcomes. Positive psychological capital is known to play an important role in improving workers' job performance. However, the association among the three variables has rarely been addressed. The purpose of this cross-sectional descriptive study was to explore the association between burnout and nursing performance outcomes among Korean nurses working at a tertiary hospital and the mediating role of psychological capital in this relationship. Recruited through convenience sampling, a total of 285 nurses provided data on their demographic characteristics and completed a structured questionnaire consisting of items from the Professional Quality of Life Scale (burnout), Nursing Performance Scale, and Psychology Capital Questionnaire. Descriptive statistics, student's t-tests, one-way analysis of variance, Pearson's correlation coefficients, and multiple linear regression analyses were used to analyze data. The significance of the mediation effect was obtained using a bootstrap approach with the PROCESS macro. The mean age of participants was 30.51 years, and most participants were females (94.0%) and unmarried (71.6%); more than half (57.5%) experienced a severe workload. The average (±standard deviation) scores of burnout, nursing performance outcomes, and positive psychological capital were 28.77 ± 4.93, 2.98 ± 0.32, and 3.19 ± 0.45, respectively. Burnout was associated with nursing performance among clinical nurses (β = -0.20, < 0.001). Positive psychological capital mediated the association between burnout and nursing performance outcomes (β = 0.41, < 0.001). These findings contribute to the understanding that burnout among nurses could be reduced by increased positive psychological capital, which results in improved performance outcomes. The findings also indicate that interventions to improve positive psychological capital should be developed and implemented for nurses' burnout management and improvement in nursing performance outcomes.
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http://dx.doi.org/10.3390/ijerph17165988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460099PMC
August 2020

Targeting NF-κB Signaling for Multiple Myeloma.

Cancers (Basel) 2020 Aug 6;12(8). Epub 2020 Aug 6.

Cancer Science Institute of Singapore, Singapore 117599, Singapore.

Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease. This paper reviews the evolution of MM therapies, focusing on anti-MM drugs that target the molecular mechanisms of nuclear factor kappa B (NF-κB) signaling. We also provide our perspectives on contemporary research findings and insights for future drug development.
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http://dx.doi.org/10.3390/cancers12082203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463546PMC
August 2020