bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy activated via GRP78 to alleviate endoplasmic reticulum stress for cell survival in blue light-mediated damage of A2E-laden RPEs
Authors: Feng Jingyang , Chen Yuhong , Lu Bing , Sun Xiangjun , Zhu Hong , Sun Xiaodong 
Published: December 2019

Abstract
Background
Retinal pigment epithelium cells (RPEs) are critical for maintaining retinal homeostasis. Accumulation of age-related lipofuscin, N-retinylidene-N-retinylethanolamine (A2E), makes RPEs vulnerable to blue light-mediated damage, which represents an initial cause of some retinal degenerative diseases. This study investigated the activation of autophagy and the signaling pathway involved in glucose-related protein 78 (GRP78) induced autophagy in blue light-mediated damage of A2E-laden RPEs. In addition, we explored whether autophagy could play a protective role by alleviating endoplasmic reticulum (ER) stress to promote RPEs survival.

Methods
RPEs were incubated with 25 μM A2E for 2 h and exposed to blue light for 20 min. The expression of ER stress-related apoptotic proteins, CHOP and caspase-12, as well as autophagy marker LC3 were measured by western blot analysis. Autophagosomes were observed by both transmission electron microscopy and immunofluorescence assays. GRP78 interference performed by short hairpin RNA (shRNA) was used to identify the signaling pathway involved in GRP78 induced autophagy. Cell death was assessed using TUNEL analysis.

Results
Treatment with A2E and blue light markedly increased the expression of ER stress-related apoptotic molecules CHOP and caspase-12. The activation of autophagy was recognized by observing autophagosomes at ultrastructural level. Additionally, punctate distributions of LC3 immunofluorescence and enhanced conversions of LC3-I to LC3-II were found in A2E and blue light-treated RPEs. Moreover, GRP78 interference reduced AMPK phosphorylation and promoted mTOR activity, thereby downregulating autophagy. In addition, the inhibition of autophagy made RPEs vulnerable to A2E and blue light damage. In contrast, the autophagy inducer rapamycin alleviated ER stress to promote RPEs survival.

Conclusions
GRP78 activates autophagy via AMPK/mTOR in blue light-mediated damage of A2E-laden RPEs in vitro. Autophagy may be a vital endogenous cytoprotective process to alleviate stress for RPEs survival in retinal degenerative diseases.
The effect of oral contraceptive pills on the macula, the retinal nerve fiber layer, the ganglion cell layer and the choroidal thickness
Authors: Shaaban Yasmine Maher , Badran Tamer Abdel Fattah 
Published: December 2019

Abstract
Backgroun
To evaluate the effect of oral contraceptive pills (OCP) on the macula, the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the choroidal thickness (CT).

Methods
In this prospective observational cross-sectional study, 60 eyes of 30 healthy women taking monophasic OCP (0.03 mg ethinylestradiol and 0.15 mg levonorgestrel) for contraception for at least 1 year were compared with 60 eyes of a control group of 30 healthy women who were not taking any OCP. Spectral-Domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macula, the RNFL, the GCL, and the CT. Measurements were taken in the follicular phase (day 3) of the last menstrual cycle in all women. The body mass index (BMI) scores of all participants were also recorded.

Results
No disparity in terms of age and BMI between both groups was observed (p = 0.444, p = 0.074, respectively). All the macular parameters measurements were considerably lower in the OCP group compared to the control group (p < 0.001). Also, the RNFL thickness, the GCL thickness, and the CT were all significantly thinner in the OCP group (p < 0.001).

Conclusions
The use of OCP can cause significant changes in the retina and choroid thickness over 1 year period. The women who are using OCP for a longer duration could have some eye problems. OCT should be routinely done for follow up. Further long term studies are required, using different preparations of OCP. It is important to find out when this thickness alterations can be clinically significant or symptomatic and if these changes are reversible or not.
A new method for quantitative detection of Lactobacillus casei based on casx gene and its application
Authors: Pang Xiaoyang , Jia Ziyang , Lu Jing , Zhang Shuwen , Zhang Cai , Zhang Min , Lv Jiaping 
Published: December 2019

Abstract
Background
The traditional method of bacterial identification based on 16S rRNA is a widely used and very effective detection method, but this method still has some deficiencies, especially in the identification of closely related strains. A high homology with little differences is mostly observed in the 16S sequence of closely related bacteria, which results in difficulty to distinguish them by 16S rRNA-based detection method. In order to develop a rapid and accurate method of bacterial identification, we studied the possibility of identifying bacteria with other characteristic fragments without the use of 16S rRNA as detection targets.

Results
We analyzed the potential of using cas (CRISPR-associated proteins) gene as a target for bacteria detection. We found that certain fragment located in the casx gene was species-specific and could be used as a specific target gene. Based on these fragments, we established a TaqMan MGB Real-time PCR method for detecting bacteria. We found that the method used in this study had the advantages of high sensitivity and good specificity.

Conclusions
The casx gene-based method of bacterial identification could be used as a supplement to the conventional 16 s rRNA-based detection method. This method has an advantage over the 16 s rRNA-based detection method in distinguishing the genetic relationship between closely-related bacteria, such as subgroup bacteria, and can be used as a supplement to the 16 s rRNA-based detection method.
Abiraterone and MDV3100 inhibits the proliferation and promotes the apoptosis of prostate cancer cells through mitophagy
Authors: Han Jingli , Zhang Junhua , Zhang Wei , Zhang Dalei , Li Ying , Zhang Jinsong , Zhang Yaqun , Diao Tongxiang , Cui Luwei , Li Wenqing , Xiao Fei , Liu Ming , Zou Lihui 
Published: December 2019

AbstractBackgroundAbiraterone and MDV3100 are two effective anticancer agents for prostate cancer, however, the mechanism of their downstream action remains undefined.MethodsA dual fluorescent biosensor plasmid was transfected in LNCaP cells to measure mitophagy. The DNA of LNCaP cells was extracted and performed with quantitative real-time PCR to detect mitochondrial DNA copy number. JC-1 staining was utilized to detect the mitochondrial membrane potential and electron microscope was performed to analyze mitochondrial morphology. Moreover, the protein levels of mitochondrial markers and apoptotic markers were detected by western blot. At last, the proliferation and apoptosis of LNCaP cells were analyzed with CCK-8 assay and flow cytometry after abiraterone or MDV3100 treatment.ResultsMitophagy was induced by abiraterone and MDV3100 in LNCaP cells. The low expression level of mitochondrial DNA copy number and mitochondrial depolarization were further identified in the abiraterone or MDV3100 treatment groups compared with the control group. Besides, severe mitochondria swelling and substantial autophagy-lysosomes were observed in abiraterone- and MDV3100-treated LNCaP cells. The expression of mitochondria-related proteins, frataxin, ACO2 and Tom20 were significantly downregulated in abiraterone and MDV3100 treated LNCaP cells, whereas the expression level of inner membrane protein of mitochondria (Tim23) was significantly upregulated in the same condition. Moreover, the proliferation of LNCaP cells were drastically inhibited, and the apoptosis of LNCaP cells was increased in abiraterone or MDV3100 treatment groups. Meanwhile, the addition of mitophagy inhibitor Mdivi-1 (mitochondrial division inhibitor 1) could conversely elevate proliferation and constrain apoptosis of LNCaP cells.ConclusionsOur results prove that both abiraterone and MDV3100 inhibit the proliferation, promote the apoptosis of prostate cancer cells through regulating mitophagy. The promotion of mitophagy might enhance the efficacy of abiraterone and MDV3100, which could be a potential strategy to improve chemotherapy with these two reagents.
Genotypes and phenotypes of resistance in Ecuadorian Plasmodium falciparum
Authors: Valenzuela Gabriela , Castro L. Enrique , Valencia-Zamora Julio , Vera-Arias Claudia A. , Rohrbach Petra , Sáenz Fabián E. 
Published: December 2019

Abstract
Background
Malaria continues to be endemic in the coast and Amazon regions of Ecuador. Clarifying current Plasmodium falciparum resistance in the country will support malaria elimination efforts. In this study, Ecuadorian P. falciparum parasites were analysed to determine their drug resistance genotypes and phenotypes.

Methods
Molecular analyses were performed to search for mutations in known resistance markers (Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, k13). Pfmdr1 copy number was determined by qPCR. PFMDR1 transporter activity was characterized in live parasites using live cell imaging in combination with the Fluo-4 transport assay. Chloroquine, quinine, lumefantrine, mefloquine, dihydroartemisinin, and artemether sensitivities were measured by in vitro assays.

Results
The majority of samples from this study presented the CVMNT genotype for Pfcrt (72–26), NEDF SDFD mutations in Pfmdr1 and wild type genotypes for Pfdhfr, Pfdhps and k13. The Ecuadorian P. falciparum strain ESM-2013 showed in vitro resistance to chloroquine, but sensitivity to quinine, lumefantrine, mefloquine, dihydroartemisinin and artemether. In addition, transport of the fluorochrome Fluo-4 from the cytosol into the digestive vacuole (DV) of the ESM-2013 strain was minimally detected in the DV. All analysed samples revealed one copy of Pfmdr1.

Conclusion
This study indicates that Ecuadorian parasites presented the genotype and phenotype for chloroquine resistance and were found to be sensitive to SP, artemether-lumefantrine, quinine, mefloquine, and dihydroartemisinin. The results suggest that the current malaria treatment employed in the country remains effective. This study clarifies the status of anti-malarial resistance in Ecuador and informs the P. falciparum elimination campaigns in the country.
Households forgoing healthcare as a measure of financial risk protection: an application to Liberia
Authors: Gabani Jacopo , Guinness Lorna 
Published: December 2019

AbstractIntroductionAccess to Liberia’s health system is reliant on out-of-pocket (OOP) health expenditures which may prevent people from seeking care or result in catastrophic health expenditure (CHE). CHE and impoverishment due to OOP, which are used by the World Bank and World Health Organization as the sole measures of financial risk protection, are limited: they do not consider households who, following a health shock, do not incur expenditure because they cannot access the healthcare services they need (i.e., households forgoing healthcare (HFH) services). This paper attempts to overcome this limitation and improve financial risk protection by measuring HFH incidence and comparing it with CHE standard measures using household survey data from Liberia.MethodsData from the Liberia Household Income and Expenditure Survey 2014 were analysed. An OOP health expenditure is catastrophic when it exceeds a total or non-food household expenditure threshold. A CHE incidence curve, representing CHE incidence at different thresholds, was developed. To overcome CHE limitations, an HFH incidence measure was developed based on CHE, OOP and health shocks data: households incurring health shocks and having negligible OOP were considered to have forgone healthcare. HFH incidence was compared with standard CHE measures.ResultsCHE incidence and intensity levels depend on the threshold used. Using a 30% non-food expenditure threshold, CHE incidence is 2.1% (95% CI: 1.7–2.5%) and CHE intensity is 37.4% (95% CI: 22.7–52.0%). CHE incidence is approximately in line with other countries, while CHE intensity is higher than in other countries. CHE pushed 1.6% of households below the food poverty line in 2014. HFH incidence is approximately 4 times higher than CHE (8.0, 95% CI, 7.2–8.9%).ConclusionLack of financial risk protection is a significant problem in Liberia and it may be underestimated by CHE: this study confirms that HFH incidence can complement CHE measures in providing a complete picture of financial risk protection and demonstrates a simple method that includes measures of healthcare forgone as part of standard CHE analyses. This paper provides a new methodology to measure HFH incidence and highlights the need to consider healthcare forgone in analyses of financial risk protection, as well as the need for further development of these measures.
CPT1a gene expression reverses the inflammatory and anti-phagocytic effect of 7-ketocholesterol in RAW264.7 macrophages
Authors: Calle Priscila , Muñoz Angeles , Sola Anna , Hotter Georgina 
Published: December 2019

AbstractBackgroundMacrophage are specialized cells that contributes to the removal of detrimental contents via phagocytosis. Lipid accumulation in macrophages, whether from phagocytosis of dying cells or from circulating oxidized low-density lipoproteins, alters macrophage biology and functionality. It is known that carnitine palmitoyl transferase 1-a (CPT1a) gene encodes an enzyme involved in fatty acid oxidation and, therefore, lipid content. However, the potential of CPT1a to activate macrophage phagocytic function have not been elucidated.MethodsUsing a murine macrophage cell line, RAW264.7, we determine if intracellular accumulation of 7-ketocholesterol (7-KC) modulates macrophage phagocytic function through CPT1a gene expression. In addition, the effects of CPT1a genetic modification on macrophage phenotype and phagocytosis has been studied.ResultsOur results revealed that CPT1a gene expression decreased by the accumulation of 7-KC at the higher dose of 7-KC. This was concomitant with an impair ability to phagocytize bioparticles and an inflammatory phenotype. GW3965 treatment, which have shown to facilitate the efflux of cholesterol, eliminated the intracellular lipid droplets of 7-KC-laden macrophages, increased the gene expression of CPT1a, diminished the gene expression of the inflammatory marker iNOS and restored macrophage phagocytosis. Furthermore, CPT1a Knockdown per se was detrimental for macrophage phagocytosis whereas transcriptional activation of CPT1a heightened the uptake of bioparticles.ConclusionsAltogether, our findings indicate that downregulation of CPT1a by lipid content modulates macrophage phagocytosis and inflammatory phenotype.
Penalty algorithm adapted for the spectral element discretization of the Darcy equations
Authors: Abdelwahed Mohamed , Chorfi Nejmeddine 
Published: December 2019

AbstractAny spectral element discretization of the Darcy problem can be efficiently solved by applying the penalty method. This method leads to a system of equations with uncoupled unknowns. We prove a posteriori error estimates for a spectral element discretization of the Darcy problem. The proposed algorithm permits the optimization of the penalty parameter as a function of the error indicators.
Protecting the psychological wellbeing of staff exposed to disaster or emergency at work: a qualitative study
Authors: Brooks Samantha K. , Dunn Rebecca , Amlôt Richard , Rubin G. James , Greenberg Neil 
Published: December 2019

Abstract
Background
Disasters are becoming more prevalent across the world and people are frequently exposed to them as part of their occupational groups. It is important for organisations to understand how best to support employees who have experienced a trauma such as a disaster. The purpose of this study was to explore employees’ perceptions of workplace support and help-seeking in the context of a disaster.

Methods
Forty employees in England took part in semi-structured interviews. Thematic analysis was used to extract recurring themes from the data.

Results
Participants reported both positive and negative psychological outcomes of experiencing a disaster or emergency at work. Most had little training in how to prepare for, and cope with, the psychological impact. They perceived stigma around mental health and treatment for psychological issues which often made them reluctant to seek help. Many reported that the psychological support available in the workplace was insufficient and tended to be reactive rather than proactive. Interpersonal relationships at work were viewed as being important sources of support, particularly support from managers. Participants suggested that psychosocial training in the workplace could be beneficial in providing education about mental health, encouraging supportive workplace relationships, and developing listening skills and empathy.

Conclusions
Organisations can take steps to reduce the psychological impact of disasters on employees. This could be done through provision of training workshops incorporating mental health education to reduce stigma, and team-building exercises to encourage supportive workplace relationships.
Ethical considerations about artificial intelligence for prognostication in intensive care
Authors: Beil Michael , Proft Ingo , van Heerden Daniel , Sviri Sigal , van Heerden Peter Vernon 
Published: December 2019

Abstract
Background
Prognosticating the course of diseases to inform decision-making is a key component of intensive care medicine. For several applications in medicine, new methods from the field of artificial intelligence (AI) and machine learning have already outperformed conventional prediction models. Due to their technical characteristics, these methods will present new ethical challenges to the intensivist.

Results
In addition to the standards of data stewardship in medicine, the selection of datasets and algorithms to create AI prognostication models must involve extensive scrutiny to avoid biases and, consequently, injustice against individuals or groups of patients. Assessment of these models for compliance with the ethical principles of beneficence and non-maleficence should also include quantification of predictive uncertainty. Respect for patients’ autonomy during decision-making requires transparency of the data processing by AI models to explain the predictions derived from these models. Moreover, a system of continuous oversight can help to maintain public trust in this technology. Based on these considerations as well as recent guidelines, we propose a pathway to an ethical implementation of AI-based prognostication. It includes a checklist for new AI models that deals with medical and technical topics as well as patient- and system-centered issues.

Conclusion
AI models for prognostication will become valuable tools in intensive care. However, they require technical refinement and a careful implementation according to the standards of medical ethics.
“Volcanism in the Chugoku region: a review for the first UNESCO field school on Geoenvironmental disaster reduction”
Authors: Auer Andreas 
Published: December 2019

AbstractField studies related to natural hazards are an integral part of any disaster mitigation effort, because geological samples and field records must initially be obtained from the context in which they occur. A sound fieldwork and careful observation and documentation of field relations is crucial for meaningful subsequent laboratory work, further data analysis and modelling. Teaching the necessary practical skills that enable students to recognize natural disaster events in the geological records and to understand circumstances under which they occur is not a trivial task. Some barriers to fieldwork usually exist, especially when the teaching subject focusses on natural disasters. Beside cost and logistics it is often the lack of suitable sites, that serve as instructive examples, displaying the deposits, structures and preserved evidence of natural hazards in the geological record. To students of volcanology, southwest Japan offers an almost unparalleled variety of interesting volcanic successions, including a broad range of different volcanic landforms and deposits that illustrate the various hazards associated with volcanic eruptions. This review will provide a brief overview of the geology of southwest Japan with special emphasis on the igneous and volcanic evolution. It will give participants of the field school a minimum of required background and anybody beyond a quick introduction into one of the most diverse and interesting volcanic field areas in the world.
The Frailty Risk Score predicts length of stay and need for rehospitalization after kidney transplantation in a retrospective cohort: a pilot study
Authors: Schaenman Joanna , Castellon Loren , Liang Emily C. , Nanayakkara Deepa , Abdalla Basmah , Sarkisian Catherine , Goldwater Deena 
Published: December 2019

Abstract
Background
Frailty is a widely used measure in older patients as a predictor of poor outcomes after hospitalization and surgery. There is a growing body of data in kidney transplantation suggesting frailty can predict adverse outcomes. There is interest in using chart review measures of frailty and multimorbidity, as they may be equally predictive as physical measurement. This approach holds promise for patient evaluation, identifying candidates for prehabilitation, and targeting resources towards those anticipated to have an increased rate of clinical challenges after kidney transplantation. Frail patients who are often older may place a large resource and economic burden on transplant programs.

Methods
We applied a previously published chart review–based approach in a retrospective, pilot study to calculate the Frailty Risk Score (FRS) utilizing a cohort of kidney transplant patients. We reviewed concurrent comorbidities using the Charlson comorbidity (CM) score to determine the feasibility and utility of applying this approach in transplant patients to predict post-transplant outcomes such as length of hospitalization and the need for rehospitalization.

Results
Sixty kidney transplant recipients were evaluated by chart review, 23 characterized as older (> = 60) and 37 younger (ages 30–59). Median FRS score was 3 (range 1–7). Higher FRS was significantly associated with increased patient age (high FRS 19% in younger patients, 43% in older patients). Increased CM score was also associated with increased patient age. Patients with a high FRS stayed in the hospital for an average of 8 days, compared with 5.7 days for a low FRS. Patients with high FRS were readmitted an average of 2.9 times compared with an average of 1.1 for those with a low FRS. FRS score remained significant for predicting outcomes after adjustment for patient age.

Conclusion
Elevated FRS prior to transplantation was associated with increased hospital stay and the need for readmission in kidney transplant recipients. This analysis demonstrates the potential strength of chart review in evaluating frailty prior to transplantation, permitting risk stratification and targeting of resources for rehabilitation and close post-transplant monitoring. Frail patients may benefit from targeted “prehabilitation” to attenuate the associated adverse clinical outcomes.