bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the Nrf2/HO-1 pathway by curcumin inhibits oxidative stress in human nasal fibroblasts exposed to urban particulate matter
Authors: Kim Ji-Sun , Oh Jeong-Min , Choi Hyunsu , Kim Sung Won , Kim Soo Whan , Kim Byung Guk , Cho Jin Hee , Lee Joohyung , Lee Dong Chang 
Published: March 2020

Abstract
Background
Particulate matter (PM) can cause various negative acute and chronic diseases of the respiratory system, including the upper airways. Curcumin has been reported to have anti-inflammatory and anti-oxidative effects; therefore, we investigated the effects of curcumin on nasal fibroblasts exposed to urban PM (UPM).

Methods
Samples of inferior turbinate tissue were obtained from six patients. Flow cytometry was used to assess the levels of reactive oxygen species (ROS) following the treatment of nasal fibroblasts with UPM and/or curcumin. We evaluated the effects of UPM and/or curcumin on the expression of phosphorylated ERK, Nrf2, HO-1, and SOD2 in fibroblasts by Western blotting.

Results
When UPM was applied to nasal fibroblasts, ROS production was significantly increased in a dose-dependent manner. UPM-exposed fibroblasts caused the activation of ERK to increase HO-1 expression and decrease SOD2 expression. Treatment with curcumin reduced the UPM-mediated increase in ROS; this decrease in ROS occurred in a dose-dependent manner. The UPM-induced activation of ERK was inhibited by curcumin. Nrf2 production was also promoted to increase the expression of HO-1 and SOD2 by curcumin.

Conclusion
Curcumin reduced ROS production caused by UPM in human nasal fibroblasts in a dose-dependent manner, suggesting that curcumin has anti-oxidative effects and may be useful in the treatment of nasal diseases caused by UPM, such as allergic and chronic rhinitis.
Neonatal care and community-level treatment seeking for possible severe bacterial infection (PSBI) in Amhara, Ethiopia
Authors: Asfaha Meron D. , Comeau Dawn L. , Spangler Sydney A. , Spratt Brandon L. , Alamineh Lamesgin , Gobezayehu Abebe G. , Cranmer John N. 
Published: March 2020

Abstract
Background
In Ethiopia, neonatal mortality accounts for approximately 54% of under-five deaths with the majority of these deaths driven by infections. Possible Severe Bacterial Infection (PSBI) in neonates is a syndromic diagnosis that non-clinical health care providers use to identify and treat newborns with signs of sepsis. In low- and middle–income countries, referral to a hospital may not be feasible due to transportation, distance or finances. Growing evidence suggests health extension workers (HEWs) can identify and manage PSBI at the community level when referral to a hospital is not possible. However, community-based PSBI care strategies have not been widely scaled-up. This study aims to understand general determinants of household-level care as well as household care seeking and decision-making strategies for neonatal PSBI symptoms.

Methods
We conducted eleven focus group discussions (FGDs) to explore illness recognition and care seeking intentions from four rural kebeles in Amhara, Ethiopia. FGDs were conducted among mothers, fathers and households with recruitment stratified among households that have had a newborn with at least one symptom of PSBI (Symptomatic Group), and households that have had a newborn regardless of the child’s health status (Community Group). Data were thematically analyzed using MAXQDA software.

Results
Mothers were described as primary caretakers of the newborn and were often appreciated for making decisions for treatment, even when the father was not present. Type of care accessed was often dependent on conceptualization of the illness as simple or complex. When symptoms were not relieved with clinical care, or treatments at facilities were perceived as ineffective, alternative methods were sought. Most participants identified the health center as a reliable facility. While designed to be the first point of access for primary care, health posts were not mentioned as locations where families seek clinical treatment.

Conclusions
This study describes socio-contextual drivers for PSBI treatment at the community level. Future programming should consider the role community members have in planning interventions to increase demand for neonatal care at primary facilities. Encouragement of health post utilization could further allow for heightened accessibility-acceptability of a simplified PSBI regimen.
Pragmatic adaptation of implementation research measures for a novel context and multiple professional roles: a factor analysis study
Authors: Smith Justin D. , Rafferty Miriam R. , Heinemann Allen W. , Meachum Mariah K. , Villamar Juan , Lieber Richard L. , Brown C. Hendricks 
Published: March 2020

Abstract
Background
Although some advances have been made in recent years, the lack of measures remains a major challenge in the field of implementation research. This results in frequent adaptation of implementation measures for different contexts—including different types of respondents or professional roles—than those for which they were originally developed and validated. The psychometric properties of these adapted measures are often not rigorously evaluated or reported. In this study, we examined the internal consistency, factor structure, and structural invariance of four well-validated measures of inner setting factors across four groups of respondents. The items in these measures were adapted as part of an evaluation of a large-scale organizational change in a rehabilitation hospital, which involved transitioning to a new building and a new model of patient care, facilitated by a significant redesign of patient care and research spaces.

Methods
Items were tailored for the context and perspective of different respondent groups and shortened for pragmatism. Confirmatory factor analysis was then used to test study hypotheses related to fit, internal consistency, and invariance across groups.

Results
The survey was administered to approximately 1208 employees; 785 responded (65% response rate) across the roles of clinician, researcher, leader, support staff, or dual clinician and researcher. For each of the four scales, confirmatory factor analysis demonstrated adequate fit that largely replicated the original measure. However, a few items loaded poorly and were removed from the final models. Internal consistencies of the final scales were acceptable. For scales that were administered to multiple professional roles, factor structures were not statistically different across groups, indicating structural invariance.

Conclusions
The four inner setting measures were robust for use in this new context and across the multiple stakeholder groups surveyed. Shortening these measures did not significantly impair their measurement properties; however, as this study was cross sectional, future studies are required to evaluate the predictive validity and test-retest reliability of these measures. The successful use of adapted measures across contexts, across and between respondent groups, and with fewer items is encouraging, given the current emphasis on designing pragmatic implementation measures.
Perspectives on program mis-implementation among U.S. local public health departments
Authors: Allen Peg , Jacob Rebekah R. , Parks Renee G. , Mazzucca Stephanie , Hu Hengrui , Robinson Mackenzie , Dobbins Maureen , Dekker Debra , Padek Margaret , Brownson Ross C. 
Published: March 2020

Abstract
Background
Public health resources are limited and best used for effective programs. This study explores associations of mis-implementation in public health (ending effective programs or continuing ineffective programs) with organizational supports for evidence-based decision making among U.S. local health departments.

Methods
The national U.S. sample for this cross-sectional study was stratified by local health department jurisdiction population size. One person was invited from each randomly selected local health department: the leader in chronic disease, or the director. Of 600 selected, 579 had valid email addresses; 376 completed the survey (64.9% response). Survey items assessed frequency of and reasons for mis-implementation. Participants indicated agreement with statements on organizational supports for evidence-based decision making (7-point Likert).

Results
Thirty percent (30.0%) reported programs often or always ended that should have continued (inappropriate termination); organizational supports for evidence-based decision making were not associated with the frequency of programs ending. The main reason given for inappropriate termination was grant funding ended (86.0%). Fewer (16.4%) reported programs often or always continued that should have ended (inappropriate continuation). Higher perceived organizational supports for evidence-based decision making were associated with less frequent inappropriate continuation (odds ratio = 0.86, 95% confidence interval 0.79, 0.94). All organizational support factors were negatively associated with inappropriate continuation. Top reasons were sustained funding (55.6%) and support from policymakers (34.0%).

Conclusions
Organizational supports for evidence-based decision making may help local health departments avoid continuing programs that should end. Creative mechanisms of support are needed to avoid inappropriate termination. Understanding what influences mis-implementation can help identify supports for de-implementation of ineffective programs so resources can go towards evidence-based programs.
Assessing medical impoverishment and associated factors in health care in Ethiopia
Authors: Obse Amarech G. , Ataguba John E. 
Published: March 2020

AbstractBackgroundAbout 5% of the global population, predominantly in low- and middle-income countries, is forced into poverty because of out-of-pocket (OOP) health spending. In most countries in sub-Saharan Africa, the share of OOP health spending in current health expenditure exceeds 35%, increasing the likelihood of impoverishment. In Ethiopia, OOP payments remained high at 37% of current health expenditure in 2016. This study assesses the impoverishment resulting from OOP health spending in Ethiopia and the associated factors.MethodsThis paper uses data from the Ethiopian Household Consumption Expenditure Survey (HCES) 2010/11. The HCES covered 10,368 rural and 17,664 urban households. OOP health spending includes spending on various outpatient and inpatient services. Impoverishing impact of OOP health spending was estimated by comparing poverty estimates before and after OOP health spending. A probit model was used to assess factors that are associated with impoverishment.ResultsUsing the Ethiopian national poverty line of Birr 3781 per person per year (equivalent to US$2.10 per day), OOP health spending pushed about 1.19% of the population (i.e. over 957,169 individuals) into poverty. At the regional level, impoverishment ranged between 2.35% in Harari and 0.35% in Addis Ababa. Living in rural areas (highland, moderate, or lowland) increased the likelihood of impoverishment compared to residing in an urban area. Households headed by males and adults with formal education are less likely to be impoverished by OOP health spending, compared to their counterparts.ConclusionIn Ethiopia, OOP health spending impoverishes a significant number of the population. Although the country had piloted and initiated many reforms, e.g. the fee waiver system and community-based health insurance, a significant proportion of the population still lacks financial protection. The estimates of impoverishment from out-of-pocket payments reported in this paper do not consider individuals that are already poor before paying out-of-pocket for health services. It is important to note that this population may either face deepening poverty or forgo healthcare services if a need arises. More is therefore required to provide financial protection to achieve universal health coverage in Ethiopia, where the informal sector is relatively large.
Persistent DNA damage triggers activation of the integrated stress response to promote cell survival under nutrient restriction
Authors: Clementi Elena , Inglin Larissa , Beebe Erin , Gsell Corina , Garajova Zuzana , Markkanen Enni 
Published: March 2020

Abstract
Background
Base-excision repair (BER) is a central DNA repair mechanism responsible for the maintenance of genome integrity. Accordingly, BER defects have been implicated in cancer, presumably by precipitating cellular transformation through an increase in the occurrence of mutations. Hence, tight adaptation of BER capacity is essential for DNA stability. However, counterintuitive to this, prolonged exposure of cells to pro-inflammatory molecules or DNA-damaging agents causes a BER deficiency by downregulating the central scaffold protein XRCC1. The rationale for this XRCC1 downregulation in response to persistent DNA damage remains enigmatic. Based on our previous findings that XRCC1 downregulation causes wide-ranging anabolic changes, we hypothesised that BER depletion could enhance cellular survival under stress, such as nutrient restriction.

Results
Here, we demonstrate that persistent single-strand breaks (SSBs) caused by XRCC1 downregulation trigger the integrated stress response (ISR) to promote cellular survival under nutrient-restricted conditions. ISR activation depends on DNA damage signalling via ATM, which triggers PERK-mediated eIF2α phosphorylation, increasing translation of the stress-response factor ATF4. Furthermore, we demonstrate that SSBs, induced either through depletion of the transcription factor Sp1, responsible for XRCC1 levels, or through prolonged oxidative stress, trigger ISR-mediated cell survival under nutrient restriction as well. Finally, the ISR pathway can also be initiated by persistent DNA double-strand breaks.

Conclusions
Our results uncover a previously unappreciated connection between persistent DNA damage, caused by a decrease in BER capacity or direct induction of DNA damage, and the ISR pathway that supports cell survival in response to genotoxic stress with implications for tumour biology and beyond.
In vitro screening antiviral activity of Thai medicinal plants against porcine reproductive and respiratory syndrome virus
Authors: Arjin Chaiwat , Pringproa Kidsadagon , Hongsibsong Surat , Ruksiriwanich Warintorn , Seel-audom Mintra , Mekchay Supamit , Sringarm Korawan 
Published: March 2020

AbstractBackgroundPorcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) results in economic losses in the swine industry globally. Several studies have investigated the use of plant extracts in the prevention and control of PRRS outbreaks. Thai medicinal plants may be useful for treating PRRSV infection in pigs. Therefore, we investigated the in vitro anti-PRRSV and antioxidant properties of seven Thai medicinal plants:Caesalpinia sappanLinn.,Garcinia mangostanaLinn.,Houttuynia cordata,Perilla frutescens,Clinacanthus nutans,Phyllanthus emblica, andTiliacora triandra.ResultsUsing antiviral screening, we observed thatT. triandraextract strongly inhibited PRRSV infectivity in MARC-145 cells [virus titer 3.5 median tissue culture infective dose (TCID50)/ml (log10)] at 24 h post-infection, whereasC. sappanextract strongly inhibited PRRSV replication [virus titer 2.5 TCID50/ml (log10)] at 72 h post-infection.C. sappanextract had the highest total phenolic content [220.52 mM gallic acid equivalent/g] and lowest half-maximal inhibitory concentration [1.17 mg/ml in 2,2-diphenyl-1-picrylhydrazyl and 2.58 mg/ml in 2,2-azino-bis (3-ethylbenzothiazo-line-6-sulfonic acid) diammonium salt].ConclusionT. triandraextract could inhibit PRRSV infectivity, whereasC. sappanextract was the most effective in inhibiting PRRSV replication in MARC-145 cells. This study elucidates the antiviral activities of Thai medicinal plant extracts in vivo. The results promise that Thai medicinal plant extracts, particularlyT. triandraandC. sappanextracts, can be developed into pharmaceutical drugs for the prevention of PRRS in pigs.
Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model
Authors: Varghese Rency S. , Zhou Yuan , Barefoot Megan , Chen Yifan , Di Poto Cristina , Balla Abdalla Kara , Oliver Everett , Sherif Zaki A. , Kumar Deepak , Kroemer Alexander H. , Tadesse Mahlet G. , Ressom Habtom W. 
Published: March 2020

Abstract
Background
The established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies.

Methods
The HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level.

Results
mRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TCGA data are previously reported in the literature and overlap in regulation and function, new pairs have been identified that may contribute to the discovery of novel targets.

Conclusion
The results strongly support the hypothesis that miRNAs are important regulators of mRNAs in HCC. Furthermore, these results emphasize the biological relevance of studying miRNA-mRNA pairs.
Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis
Authors: Zhang Xiaoyu , Xu Yingying , Yamaguchi Kenji , Hu Jinping , Zhang Lianbo , Wang Jianfeng , Tian Jifeng , Chen Wanying 
Published: March 2020

Abstract
Background
Colorectal cancer (CRC) is a malignant tumor, and the overall prognosis of patients with advanced CRC is still unsatisfactory. Circular RNAs (circRNAs) vesicle-associated membrane protein-associated protein A (circVAPA) could act as an underlying biomarker in CRC. This study aimed to explore the mechanism of circVAPA in the regulation of CRC growth.

Methods
CircVAPA level was measured in CRC tumor tissues. The expression levels of circVAPA, VAPA mRNA, microRNA-125a (miR-125a), and cAMP response element binding 5 (CREB5) in CRC cells were detected by RT-qPCR. Cell cycle progression, migration and invasion, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by flow cytometry, transwell assays and Seahorse XF96 Glycolysis Analyzer, severally. The levels of glucose uptake, lactate and ATP production were examined by Glucose Uptake Colorimetric Assay kit, Lactate Assay kit and ATP Colorimetric Assay kit, respectively. The interaction between miR-125a and circVAPA or CREB5 was predicted by Starbase or DIANA TOOL, and verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.

Results
CircVAPA level was up-regulated in CRC tumor tissues. Expression levels of circVAPA and CREB5 were increased, and miR-125a was decreased in CRC cells. CircVAPA knockdown repressed CRC cells cycle progression, migration, invasion and glycolysis. CircVAPA acted as a miR-125a sponge to regulate CREB5 expression. Rescue assay confirmed that miR-125a deletion or CREB5 overexpression weakened the inhibitory effect of circVAPA knockdown on CRC growth.

Conclusion
Our studies disclosed that circVAPA knockdown suppressed CRC cells cycle progression, migration, invasion and glycolysis partly by modulating miR-125a/CREB5 axis, suggesting a potential therapeutic strategy for CRC treatment.
Effects of body condition on the insulin resistance, lipid metabolism and oxidative stress of lactating dairy cows
Authors: Wu Jiajin , Liu Jianxin , Wang Diming 
Published: March 2020

Abstract
Background
Overconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated.

Methods
The objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment.

Results
The concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups.

Conclusions
Results of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.