bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice
Authors: Deng Qingzha , Huang Sunxing , Wen Jinkun , Jiao Yiren , Su Xiaohu , Shi Guang , Huang Junjiu 
Published: April 2020

Abstract
Background
Factors such as poor engraftment, retention, and survival of the transplanted stem cells are deemed to limit their therapeutic efficacy for wound regeneration. Hence, it is necessary to explore these issues in order to resolve them. In this study, we aim to investigate the role of Pluronic F-127 (PF-127) hydrogel plus antioxidant sodium ascorbyl phosphate (SAP) in enhancing Wharton’s jelly mesenchymal stem cell (WJMSC)-mediated effectiveness on full-thickness skin wound healing in mice.

Methods
First, the cytotoxicity of PF-127 and the biological effect of SAP on the survival of WJMSCs were tested in vitro using cell viability and proliferation assays. Next, a cell suspension containing WJMSCs, PF-127, and SAP was topically administered onto an 8-mm diameter excisional full-thickness wound bed. Eight days after transplantation, the mice were sacrificed and the skin tissue was excised for histological and immunohistochemical analysis. Finally, in vivo distribution of transplanted WJMSCs was traced to investigate cell engraftment and the potential therapeutic mechanism.

Results
PF-127 was found to be cytotoxic to WJMSCs while SAP significantly improved the survival of PF-127-embedded WJMSCs. When this combination was topically transplanted onto the wound bed, wound healing was facilitated and dermis regeneration was achieved on the 8th day after surgery, as evidenced by an increase in dermal thickness, newly developed hair follicles, and collagen fiber deposition accompanied by a reduction in scar width. Further, immunohistochemical analysis demonstrated a higher number of anti-inflammatory M2 macrophages, proliferating cells, and newly formed blood vessels in the WJMSCs/PF-127/SAP group relative to all other groups. In addition, in vivo tracking results revealed a highly enhanced engraftment of WJMSCs accumulated in the dermis in the WJMSCs/PF-127/SAP group.

Conclusions
SAP significantly improves the survival of WJMSCs in PF-127 encapsulation. Further, PF-127 plus SAP is an effective combination that enhances WJMSC engraftment in the dermis, which then promotes full-thickness wound healing through potential M2 macrophage formation and angiogenesis.
Review on natural products databases: where to find data in 2020
Authors: Sorokina Maria , Steinbeck Christoph 
Published: April 2020

AbstractNatural products (NPs) have been the centre of attention of the scientific community in the last decencies and the interest around them continues to grow incessantly. As a consequence, in the last 20 years, there was a rapid multiplication of various databases and collections as generalistic or thematic resources for NP information. In this review, we establish a complete overview of these resources, and the numbers are overwhelming: over 120 different NP databases and collections were published and re-used since 2000. 98 of them are still somehow accessible and only 50 are open access. The latter include not only databases but also big collections of NPs published as supplementary material in scientific publications and collections that were backed up in the ZINC database for commercially-available compounds. Some databases, even published relatively recently are already not accessible anymore, which leads to a dramatic loss of data on NPs. The data sources are presented in this manuscript, together with the comparison of the content of open ones. With this review, we also compiled the open-access natural compounds in one single dataset a COlleCtion of Open NatUral producTs (COCONUT), which is available on Zenodo and contains structures and sparse annotations for over 400,000 non-redundant NPs, which makes it the biggest open collection of NPs available to this date.
A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers
Authors: Anjo Sandra I. , dos Santos Patrícia Valério , Rosado Luiza , Baltazar Graça , Baldeiras Inês , Pires Diana , Gomes Andreia , Januário Cristina , Castelo-Branco Miguel , Grãos Mário , Manadas Bruno 
Published: April 2020

Abstract
Background
The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls.

Methods
The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients.

Results
From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis.

Conclusions
In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.
Income and food Engel curves in Rwanda: a household microdata analysis
Authors: Nsabimana Aimable , Bali Swain Ranjula , Surry Yves , Ngabitsinze Jean Chrysostome 
Published: April 2020

AbstractFood insecurity and malnutrition are still major challenges for large proportions of households in Sub-Saharan Africa. The empirical literature on food demand, however, suggests mixed evidence on the roles of income and other socio-economic attributes on food demand. This study analyzes the food demand among households in Rwanda, based on nationally representative household expenditures and demographic (EICV4, 2013/14) survey data. The results show that poor households consume merely food containing higher carbohydrates and starches. Further, the study finds that the majority of rural households spend almost nothing on micronutrients from animal products, suggesting that effective targeted food policy interventions for poor and rural households may play an important role in reducing the incidence of malnutrition through improving food diets.
MetaEuk—sensitive, high-throughput gene discovery, and annotation for large-scale eukaryotic metagenomics
Authors: Levy Karin Eli , Mirdita Milot , Söding Johannes 
Published: April 2020

AbstractBackgroundMetagenomics is revolutionizing the study of microorganisms and their involvement in biological, biomedical, and geochemical processes, allowing us to investigate by direct sequencing a tremendous diversity of organisms without the need for prior cultivation. Unicellular eukaryotes play essential roles in most microbial communities as chief predators, decomposers, phototrophs, bacterial hosts, symbionts, and parasites to plants and animals. Investigating their roles is therefore of great interest to ecology, biotechnology, human health, and evolution. However, the generally lower sequencing coverage, their more complex gene and genome architectures, and a lack of eukaryote-specific experimental and computational procedures have kept them on the sidelines of metagenomics.ResultsMetaEuk is a toolkit for high-throughput, reference-based discovery, and annotation of protein-coding genes in eukaryotic metagenomic contigs. It performs fast searches with 6-frame-translated fragments covering all possible exons and optimally combines matches into multi-exon proteins. We used a benchmark of seven diverse, annotated genomes to show that MetaEuk is highly sensitive even under conditions of low sequence similarity to the reference database. To demonstrate MetaEuk’s power to discover novel eukaryotic proteins in large-scale metagenomic data, we assembled contigs from 912 samples of the Tara Oceans project. MetaEuk predicted >12,000,000 protein-coding genes in 8 days on ten 16-core servers. Most of the discovered proteins are highly diverged from known proteins and originate from very sparsely sampled eukaryotic supergroups.ConclusionThe open-source (GPLv3) MetaEuk software (https://github.com/soedinglab/metaeuk) enables large-scale eukaryotic metagenomics through reference-based, sensitive taxonomic and functional annotation.
Holistic tactical-level planning in liner shipping: an exact optimization approach
Authors: Pasha Junayed , Dulebenets Maxim A. , Kavoosi Masoud , Abioye Olumide F. , Theophilus Oluwatosin , Wang Hui , Kampmann Raphael , Guo Weihong 
Published: April 2020

AbstractEffective liner shipping is important for the global seaborne trade. The volume of cargoes transported by liner shipping has been increasing over the past decades. Liner shipping companies face three levels of decision problems, including strategic, tactical, and operational problems. The tactical-level decisions are commonly made every three to 6 months. These decisions include: (1) port service frequency determination; (2) fleet deployment; (3) sailing speed optimization; and (4) vessel schedule design. Most of the concurrent liner shipping studies have addressed the tactical-level decision problems separately. Even though a few studies have proposed joint planning models that capture multiple decision problems at the same time, none of the conducted studies has integrated all the four tactical-level decision problems. To address this gap in the state-of-the-art, this study presents a holistic optimization model that addresses all the tactical-level liner shipping decision problems, aiming to maximize the total profit obtained from liner shipping services. The key route service cost components, found in the liner shipping literature, are considered in this study, which include: (1) vessel operational cost; (2) vessel chartering cost; (3) port handling cost; (4) port late arrival cost; (5) fuel consumption cost; (6) container inventory costs in sea and at ports of call; and (7) emission costs in sea and at ports of call. An exact optimization approach is adopted for the developed mathematical model. The computational experiments, conducted for a set of Asia-North America liner shipping routes, showcase the efficiency of the proposed approach and offer some important managerial insights.
Development of a multiplicative, multi-attribute utility function and eight single-attribute utility functions for the Health Utilities Index Mark 3 in Japan
Authors: Noto Shinichi , Shiroiwa Takeru , Kobayashi Makoto , Murata Tatsunori , Ikeda Shunya , Fukuda Takashi 
Published: April 2020

Abstract
Background
The Health Utilities Index Mark 3 (HUI3) is a generic multi-attribute, preference-based system for assessing health-related quality of life. It is widely used overseas as an outcome measure and for estimating quality-adjusted life years. We aimed to estimate a multi-attribute and eight single-attribute utility functions for the HUI3 system based on community preferences in Japan. We conducted two preference surveys in this study. The first survey was designed to estimate a model of utility function and collect preference scores, and the second survey was designed to evaluate predictive validity of the utility function and provide independent scores. Values obtained from the feeling thermometer and standard gamble scores obtained from using a chance board were included in the preference scale. We recruited 1043 respondents (age: 20–79 years) from five cities in Japan through the general population classified by sex and age groups. Respondents were further randomly divided into a modeling group (n = 774) and a direct group (n = 263).

Results
We acquired the estimation for eight single-attribute and a global multi-attribute utility function. The minimum expected multi-attribute utility score was − 0.002. The intraclass correlation coefficient between the directly measured utility score and the score generated by multi-attribute function in terms of 53 health conditions was 0.742.

Conclusions
The HUI3 scoring function developed in Japan has a strong theoretical and empirical basis. It will be useful in future to predict the directly measured score of health technology assessments in Japan.
Layered obfuscation: a taxonomy of software obfuscation techniques for layered security
Authors: Xu Hui , Zhou Yangfan , Ming Jiang , Lyu Michael 
Published: April 2020

AbstractSoftware obfuscation has been developed for over 30 years. A problem always confusing the communities is what security strength the technique can achieve. Nowadays, this problem becomes even harder as the software economy becomes more diversified. Inspired by the classic idea of layered security for risk management, we propose layered obfuscation as a promising way to realize reliable software obfuscation. Our concept is based on the fact that real-world software is usually complicated. Merely applying one or several obfuscation approaches in an ad-hoc way cannot achieve good obscurity. Layered obfuscation, on the other hand, aims to mitigate the risks of reverse software engineering by integrating different obfuscation techniques as a whole solution. In the paper, we conduct a systematic review of existing obfuscation techniques based on the idea of layered obfuscation and develop a novel taxonomy of obfuscation techniques. Following our taxonomy hierarchy, the obfuscation strategies under different branches are orthogonal to each other. In this way, it can assist developers in choosing obfuscation techniques and designing layered obfuscation solutions based on their specific requirements.
Integrative bioinformatics analysis reveals miR-494 and its target genes as predictive biomarkers of trastuzumab-resistant breast cancer
Authors: Hermawan Adam , Putri Herwandhani 
Published: April 2020

Abstract
Background
The focus of trastuzumab resistance biomarkers in recent decades has been on epigenetic and non-coding RNA-based mechanisms. In this study, the potential of miR-494 and its target genes as predictive biomarkers for breast cancer (BC) resistance to trastuzumab was identified. The microarray data were obtained from the GEO database, including GSE101841, GSE75669, and GSE66305. Data processing was conducted using GEO2R to obtain differentially expressed genes (DEGs).

Results
The data analysis using GEO2R revealed that DEGs from GSE101841 and GSE75669 consisted of 3 and 135 upregulated miRNAs, respectively. On the other hand, the same analysis revealed 8 and 226 downregulated miRNAs for DEGs from GSE101841 and GSE75669, respectively. A Venn diagram showed that one miR was detectable in serum and tissue samples, namely miR-494. The miR-494 target was predicted using the miRecords database and resulted in 69 target genes. A Venn diagram between miR-494 target genes from miRecords and the mRNA array from GSE66305 revealed three potential targets of CNR1, RBM39, and ZNF207. A Kaplan–Meier survival plot showed that BC patients with a high miR-494 level and a low ZNF207 mRNA level had significantly worse overall survival. Validation of target genes in BC samples and trastuzumab-resistant and -sensitive BC cells with GEPIA and ONCOMINE highlighted the potential of CNR1, RBM39, and ZNF207 as predictive biomarkers of trastuzumab resistance in BC cells.

Conclusion
Taken together, these results suggest that miR-494 plays a role in the mechanism of BC resistance to trastuzumab by involving its target genes CNR1, RBM39, and ZNF207.
A Novel Phenotype Combining Primary Ovarian Insufficiency Growth Retardation and Pilomatricomas With MCM8 Mutation
Authors: Heddar Abdelkader , Beckers Dominique , Fouquet Baptiste , Roland Dominique , Misrahi Micheline 
Published: April 2020

AbstractContextPrimary Ovarian insufficiency (POI) affects 1% of women aged &lt;40 years and leads most often to definitive infertility with adverse health outcomes. Very recently, genes involved in deoxyribonucleic acid (DNA) repair have been shown to cause POI.ObjectiveTo identify the cause of a familial POI in a consanguineous Turkish family.DesignExome sequencing was performed in the proposita and her mother. Chromosomal breaks were studied in lymphoblastoid cell lines treated with mitomycin (MMC).Setting and patientsThe proposita presented intrauterine and postnatal growth retardation, multiple pilomatricomas in childhood, and primary amenorrhea. She was treated with growth hormone (GH) from age 14 to 18 years.ResultsWe identified a novel nonsense variant in exon 9 of the minichromosome maintenance complex component 8 gene (MCM8) NM_001281522.1: c0.925C &gt; T/p.R309* yielding either a truncated protein or nonsense-mediated messenger ribonucleic acid decay.The variant was homozygous in the daughter and heterozygous in the mother. MMC induced DNA breaks and aberrant metaphases in the patient’s lymphoblastoid cells. The mother’s cells had intermediate but significantly higher chromosomal breaks compared with a control.ConclusionWe describe a novel phenotype of syndromic POI related to a novel truncating MCM8 variant. We show for the first time that spontaneous tumors (pilomatricomas) are associated with an MCM8 genetic defect, making the screening of this gene necessary before starting GH therapy in patients with POI with short stature, especially in a familial or consanguineous context. Appropriate familial monitoring in the long term is necessary, and fertility preservation should be considered in heterozygous siblings to avoid rapid follicular atresia.
Cost and cost-effectiveness analysis of treatment for child undernutrition in low- and middle-income countries: A systematic review
Authors: Njuguna Rebecca G , Berkley James A , Jemutai Julie 
Published: April 2020

Background: Undernutrition remains highly prevalent in low- and middle-income countries, with sub-Saharan Africa and Southern Asia accounting for majority of the cases. Apart from the health and human capacity impacts on children affected by malnutrition, there are significant economic impacts to households and service providers. The aim of this study was to determine the current state of knowledge on costs of child undernutrition treatment to households, health providers, organizations and governments in low and middle-income countries (LMICs).Methods: We conducted a systematic review of peer-reviewed studies in LMICs up to September 2019. We searched online databases including PubMed-Medline, Embase, Popline, Econlit and Web of Science. We identified additional articles through bibliographic citation searches. Only articles including costs of child undernutrition treatment were included.Results:We identified a total of 6436 articles, and only 50 met the eligibility criteria. Most included studies adopted institutional/program (45%) and health provider (38%) perspectives. The studies varied in the interventions studied and costing methods used with treatment costs reported ranging between US$0.44 and US$1344 per child. The main cost drivers were personnel, therapeutic food and productivity loss.Conclusion: There is a need to assess the burden of direct and indirect costs of child undernutrition to households and communities in order to plan, identify cost-effective solutions and address issues of cost that may limit delivery, uptake and effectiveness. Standardized methods and reporting in economic evaluations would facilitate interpretation and provide a means for comparing costs and cost-effectiveness of interventions.
Impatience and Time Inconsistency in Discounting Models
Authors: Yoon Haewon 
Published: April 2020

Extant theories of intertemporal choice entangle two aspects of time preference: impatience and time inconsistency. Impatient people focus on present consumption without worrying too much about the future; they may spend freely and avoid exercise. An outsider might question their choices, but impatient people do not experience conflict over those choices. By contrast, people who are time-inconsistent intend to save and exercise, but they fail to do so when temptation is proximate. Such individuals are conflicted; their preferences today differ from their preferences tomorrow. I characterize the interaction between impatience and time inconsistency in three leading models of temporal discounting that go beyond the exponential model, which does not predict time inconsistency at any level of impatience. The quasi-hyperbolic model predicts that time inconsistency increases with patience, whereas the hyperbolic model makes the opposite prediction. The constant-sensitivity model predicts that time inconsistency peaks at a moderate level of impatience. The results of an experiment using real monetary consequences with delays of up to one year align most closely with the prediction of the constant-sensitivity model. This paper was accepted by Yuval Rottenstreich, judgment and decision making.