bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Use of a General Equilibrium Method to Assess the Value of a Malaria Vaccine: An Application to Ghana
Authors: Yerushalmi Erez , Hunt Priscillia , Hoorens Stijn , Sauboin Christophe , Smith Richard
Published: December 2019

Background. Malaria is an important health and economic burden in sub-Saharan Africa. Conventional economic evaluations typically consider only direct costs to the health care system and government budgets. This paper quantifies the potential impact of malaria vaccination on the wider economy, using Ghana as an example. Methods. We used a computable general equilibrium model of the Ghanaian economy to estimate the macroeconomic impact of malaria vaccination in children under the age of 5, with a vaccine efficacy of 50% against clinical malaria and 20% against malaria mortality. The model considered changes in demography and labor productivity, and projected gross domestic product (GDP) over a time frame of 30 years. Vaccine coverage ranging from 20% to 100% was compared with a baseline with no vaccination. Results. Malaria vaccination with 100% coverage was projected to increase the GDP of Ghana over 30 years by US$6.93 billion (in 2015 prices) above the baseline without vaccination, equivalent to an increase in annual GDP growth of 0.5%. Projected GDP per capita would increase in the first year due to immediate reductions in time lost from work by adults caring for children with malaria, then decrease for several years as reductions in child mortality increase the number of dependent children, then show a sustained increase after Year 11 due to long-term productivity improvements in adults resulting from fewer malaria episodes in childhood. Conclusion. Investing in improving childhood health by vaccinating against malaria could result in substantial long-term macroeconomic benefits when these children enter the workforce as adults. These macroeconomic benefits are not captured by conventional economic evaluations and constitute an important potential benefit of vaccination.
A Systematic Review of the Incremental Costs of Implementing a New Vaccine in the Expanded Program of Immunization in Sub-Saharan Africa
Authors: Brew Joe , Sauboin Christophe
Published: December 2019

Background. The World Health Organization is planning a pilot introduction of a new malaria vaccine in three sub-Saharan African countries. To inform considerations about including a new vaccine in the vaccination program of those and other countries, estimates from the scientific literature of the incremental costs of doing so are important. Methods. A systematic review of scientific studies reporting the costs of recent vaccine programs in sub-Saharan countries was performed. The focus was to obtain from each study an estimate of the cost per dose of vaccine administered excluding the acquisition cost of the vaccine and wastage. Studies published between 2000 and 2018 and indexed on PubMed could be included and results were standardized to 2015 US dollars (US$). Results. After successive screening of 2119 titles, and 941 abstracts, 58 studies with 80 data points (combinations of country, vaccine type, and vaccination approach–routine v. campaign) were retained. Most studies used the so-called ingredients approach as costing method combining field data collection with documented unit prices per cost item. The categorization of cost items and the extent of detailed reporting varied widely. Across the studies, the mean and median cost per dose administered was US$1.68 and US$0.88 with an interquartile range of US$0.54 to US$2.31. Routine vaccination was more costly than campaigns, with mean cost per dose of US$1.99 and US$0.88, respectively. Conclusion. Across the studies, there was huge variation in the cost per dose delivered, between and within countries, even in studies using consistent data collection tools and analysis methods, and including many health facilities. For planning purposes, the interquartile range of US$0.54 to US$2.31 may be a sufficiently precise estimate.
Teaching Root Cause Analysis Using Simulation: Curriculum and Outcomes
Authors: Aboumrad Maya , Neily Julia , Watts Bradley V
Published: December 2019

Background:

Clinicians are key drivers for improving health care quality and safety. However, some may lack experience in quality improvement and patient safety (QI/PS) methodologies, including root cause analysis (RCA).

Objective:

The Department of Veterans Affairs (VA) sought to develop a simulation approach to teach clinicians from the VA’s Chief Resident in Quality and Safety program about RCA. We report the use of experiential learning to teach RCA, and clinicians’ preparedness to conduct and teach RCA post-training. We provide curriculum details and materials to be adapted for widespread use.

Methods:

The course was designed to meet the learning objectives through simulation. We developed course materials, including presentations, a role-playing case, and an elaborate RCA case. Learning objectives included (1) basic structure of RCA, (2) process flow diagramming, (3) collecting information for RCA, (4) cause and effect diagramming, and (5) identifying actions and outcomes. We administered a voluntary, web-based survey in November 2016 to participants (N = 114) post-training to assess their competency with RCA.

Results:

A total of 93 individuals completed the survey of the 114 invited to participate, culminating an 82% response rate. Nearly all respondents (99%, N = 92) reported feeling at least moderately to extremely prepared to conduct and teach RCA post-training. Most respondents reported feeling very to extremely prepared to conduct and teach RCA (77%, N = 72).

Conclusions:

Experiential learning involving simulations may be effective to improve clinicians’ competency in QI/PS practices, including RCA. Further research is warranted to understand how the training affects clinicians’ capacity to participate in real RCA teams post-training, as well as applicability to other disciplines and interdisciplinary teams.
Euler–Lagrange approach to investigate respiratory anatomical shape effects on aerosol particle transport and deposition
Authors: Islam Mohammad S , Saha Suvash C , Sauret Emilie , Ong Hui , Young Paul , Gu YT
Published: December 2019

An accurate knowledge of the pulmonary aerosol particle transport in the realistic lung is essential to deliver the therapeutic particle to the targeted site of the bifurcating airways. The available in silico studies have enriched the knowledge of the aerosol transport and deposition (TD) in the lung; however, the absolute TD data in the realistic lung airway are still elusive. Therefore, in this study, a 3-D geometry of the human lung central airway is developed from the computed tomography (CT) images. A CT scan-based modified lung geometry with a smooth surface and nonrealistic Weibel’s lung geometry is also generated. The coal mine exhausted aerosol TD in the upper airway is investigated. The Euler–Lagrange (E-L) method for particle tracking and ANSYS Fluent solver are used to carry out the entire investigation. The effective diameter method is employed to define the shape-specific particles and is integrated with the E-L method. The anatomical shape effects on the deposition patterns are investigated for different deposition parameter. The numerical results illustrated that the airway geometry, particle shape, particle diameter, and breathing flow rates significantly influence the aerosol TD pattern in the upper airway. The present study reports that airway tracheal wall is the new deposition hot spot for the CT-based geometry instead of bifurcating area for the idealized model, which might be helpful for zone-specific drug delivery to the respiratory airways.
Graph input representations for machine learning applications in urban network analysis
Authors: Pagani Alessio , Mehrotra Abhinav , Musolesi Mirco
Published: December 2019

Understanding and learning the characteristics of network paths has been of particular interest for decades and has led to several successful applications. Such analysis becomes challenging for urban networks as their size and complexity are significantly higher compared to other networks. The state-of-the-art machine learning techniques allow us to detect hidden patterns and, thus, infer the features associated with them. However, very little is known about the impact on the performance of such predictive models by the use of different input representations. In this paper, we design and evaluate six different graph input representations (i.e. representations of the network paths), by considering the network’s topological and temporal characteristics, for being used as inputs for machine learning models to learn the behavior of urban network paths. The representations are validated and then tested with a real-world taxi journeys dataset predicting the tips of using a road network of New York. Our results demonstrate that the input representations that use temporal information help the model to achieve the highest accuracy (root mean-squared error of 1.42$).
The development of urban mega-projects in China: A case study of Nantong’s metro project
Authors: Zhou Shutian , Zhai Guofang , Lu Yuwen , Shi Yijun
Published: December 2019

Since there has been a huge amount of transport infrastructure projects being proposed, planned and constructed over the past decades in China, this article aims to reveal the substantial dynamics of China’s rapid development of urban mega-projects. It analyzes Nantong’s metro project to use it as a case study – how it was being justified, approved and implemented, and what were the key driving forces within the whole process through official justifications and key informant interview materials. The urban metro system is supposedly an approach to achieve urban development objectives, a tool for growth and a way to a better urban life. We find inter-city competition as an underlying driving force that initiates such urban mega-projects with certain weight given to economic indicators in project appraisals within a largely local government-led and public-invested process. Furthermore, domestic economic performance and changing policy interventions also exert significant influence on project approval and long-term project development. Our findings echo some Western literature on mega-projects development and urban competition, while revealing other features and emerging issues relating to project initiation, proposal examination and implementation specific to the Chinese context.
Integrating urban analysis, generative design, and evolutionary optimization for solving urban design problems
Authors: Koenig Reinhard , Miao Yufan , Aichinger Anna , Knecht Katja , Konieva Kateryna
Published: December 2019

To better support urban designers in planning sustainable, resilient, and livable urban environments, new methods and tools are needed. A variety of computational approaches have been proposed, including different forms of spatial analysis to evaluate the performance of design proposals, or the automated generation of urban design proposals based on specific parameters. However, most of these propositions have produced separate tools and disconnected workflows. In the context of urban design optimization procedures, one of the main challenges of integrating urban analytics and generative methods is a suitable computational representation of the urban design problem. To overcome this difficulty, we present a holistic data representation for urban fabrics, including the layout of street networks, parcels, and buildings, which can be used efficiently with evolutionary optimization algorithms. We demonstrate the use of the data structure implemented for the software Grasshopper for Rhino3D as part of a flexible, modular, and extensible optimization system that can be used for a variety of urban design problems and is able to reconcile potentially contradicting design goals in a semi-automated design process. The proposed optimization system aims to assist a designer by populating the design space with options for more detailed exploration. We demonstrate the functionality of our system using the example of an urban master-design project for the city of Weimar.
Sanitizing Heritage—Hydraulic Water Supply and the Erosion of the Traditional Water Management System in Colonial Bombay City (1860–1947)
Authors: Kelkar Madhu
Published: December 2019

The traditional urban water management systems of Bombay (Mumbai) city consisted of tanks and wells constructed by charitable people of all creeds. But the entry of hydraulic engineering techniques, via the construction of Vihar Lake in 1860, ostensibly to supply pure and plentiful water heralded their doom. The modern but intrinsically flawed water supply system, unplanned urban development and the ensuing insanitation aggravated cholera and malaria epidemics, endemic to the city, threatening its imperial trade. This, and the desire to create sanitized colonies through town planning, encouraged Bombay municipality to attack the city’s tanks and wells, vilified as sources of pollution, despite protests of the local people. Based on an examination of archival sources, this article traces the history of colonial Bombay’s water management policy from 1860 and examines its impact on the city’s water inheritance, up to Indian independence in 1947. It aims to raise awareness levels about the potential importance of the surviving heritage, at a time when the spectre of insanitation and water scarcity haunts Mumbai.
Intersecting hazards, intersectional identities: A baseline Critical Environmental Justice analysis of US homelessness
Authors: Goodling Erin
Published: December 2019

Lacking access to stable shelter, infrastructure, and services, houseless people are exposed to a range of environmental hazards. Yet, environmental justice scholars have only begun to consider how environmental justice issues impact unsheltered people. In dialogue with Critical Environmental Justice (EJ) Studies and geographies of homelessness research, and drawing on seven years of participant observation and a national phone survey of 47 houseless community representatives, this paper begins to chart a baseline Critical EJ analysis of homelessness. I argue that understanding the environmental justice experiences of houseless people requires attention not only to direct exposure to hazards, but also to criminalization. Police sweeps in downtown and residential areas push people into toxic spaces; when houseless communities express concerns, they risk further eviction. In this way, cities overwhelmingly respond to hazard exposure with displacement, creating a cycle of criminalization, dangerous living conditions, and serial forced removals. Moreover, examining such intersecting hazards and their impacts through a Black feminist lens of intersectionality reveals how systemic violence vis-à-vis environmental hazards is multiplied and magnified for houseless people along lines of race, gender, age, disability status, and so on. By bringing Critical EJ and geographies of homelessness into conversation, with particular attention to intersectional impacts, scholars and organizers can better attend to the complex suite of issues that differentially shape the lives of houseless people and inspire resistance.
Genome-Wide Association Analysis of the Genetic Basis for Sheath Blight Resistance in Rice
Authors: Zhang Fan , Zeng Dan , Zhang Cong-Shun , Lu Jia-Ling , Chen Teng-Jun , Xie Jun-Ping , Zhou Yong-Li
Published: December 2019

Background

Sheath blight (ShB), caused by Rhizoctonia solani Kühn, is one of the most destructive rice diseases. Developing ShB-resistant rice cultivars represents the most economical and environmentally sound strategy for managing ShB.

Results

To characterize the genetic basis for ShB resistance in rice, we conducted association studies for traits related to ShB resistance, namely culm length (CL), lesion height (LH), and relative lesion height (RLH). Combined a single locus genome-wide scan and a multi-locus method using 2,977,750 single-nucleotide polymorphisms to analyse 563 rice accessions, we detected 134, 562, and 75 suggestive associations with CL, LH, and RLH, respectively. The adjacent signals associated with RLH were merged into 27 suggestively associated loci (SALs) based on the estimated linkage disequilibrium blocks. More than 44% of detected RLH-SALs harboured multiple QTLs/genes associated with ShB resistance, while the other RLH-SALs were putative novel ShB resistance loci. A total of 261 ShB resistance putative functional genes were screened from 23 RLH-SALs according to bioinformatics and haplotype analyses. Some of the annotated genes were previously reported to encode defence-related and pathogenesis-related proteins, suggesting that quantitative resistance to ShB in rice is mediated by SA- and JA-dependent signalling pathways.

Conclusions

Our findings may improve the application of germplasm resources as well as knowledge-based ShB management and the breeding of ShB-resistant rice cultivars.
Challenges and Perspectives in Homology-Directed Gene Targeting in Monocot Plants
Authors: Van Vu Tien , Sung Yeon Woo , Kim Jihae , Doan Duong Thi Hai , Tran Mil Thi , Kim Jae-Yean
Published: December 2019

Continuing crop domestication/redomestication and modification is a key determinant of the adaptation and fulfillment of the food requirements of an exploding global population under increasingly challenging conditions such as climate change and the reduction in arable lands. Monocotyledonous crops are not only responsible for approximately 70% of total global crop production, indicating their important roles in human life, but also the first crops to be challenged with the abovementioned hurdles; hence, monocot crops should be the first to be engineered and/or de novo domesticated/redomesticated. A long time has passed since the first green revolution; the world is again facing the challenge of feeding a predicted 9.7 billion people in 2050, since the decline in world hunger was reversed in 2015. One of the major lessons learned from the first green revolution is the importance of novel and advanced trait-carrying crop varieties that are ideally adapted to new agricultural practices. New plant breeding techniques (NPBTs), such as genome editing, could help us succeed in this mission to create novel and advanced crops. Considering the importance of NPBTs in crop genetic improvement, we attempt to summarize and discuss the latest progress with major approaches, such as site-directed mutagenesis using molecular scissors, base editors and especially homology-directed gene targeting (HGT), a very challenging but potentially highly precise genome modification approach in plants. We therefore suggest potential approaches for the improvement of practical HGT, focusing on monocots, and discuss a potential approach for the regulation of genome-edited products.
Nanomedicine review: clinical developments in liposomal applications
Authors: Beltrán-Gracia Esteban , López-Camacho Adolfo , Higuera-Ciapara Inocencio , Velázquez-Fernández Jesús B , Vallejo-Cardona Alba A
Published: December 2019

Background

In recent years, disease treatment has evolved strategies that require increase in pharmaceutical agent’s efficacy and selectivity while decreasing their toxicity in normal tissues. These requirements have led to the development of nanoscale liposome systems for drug release. This review focuses on lipid features, pharmacological properties of liposomal formulations and the clinical studies of their application.

Main body

Several lipids are available, but their properties could affect pharmacological or clinical efficiency of drug formulations. Many liposomal formulations have been developed and are currently on the market. Proper selection of lipid is essential for the pharmacological effect to be improved. Most of the formulations use mainly zwitterionic, cationic or anionic lipids, PEG and/or cholesterol, which have different effects on stability, pharmacokinetics and delivery of the drug formulation. Clinical trials have shown that liposomes are pharmacologically and pharmacokinetically more efficient than drug-alone formulations in treating acute myeloid leukemia, hepatitis A, pain management, ovary, gastric breast and lung cancer, among others.

Conclusion

Liposomal formulations are less toxic than drugs alone and have better pharmacological parameters. Although they seem to be the first choice for drug delivery systems for various diseases, further research about dosage regimen regarding dose and time needs to be carried out.
A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays
Authors: Guerreiro Alexandra , Chatterton Nicholas , Crabb Eleanor M. , Golding Jon P.
Published: December 2019

Background

A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element nanoparticles has been made. Here, we directly compare the irradiation-induced (10 Gy of 6-MV X-ray photon) production of hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the following metal oxide nanoparticles: Al2O3, SiO2, Sc2O3, TiO2, V2O5, Cr2O3, MnO2, Fe3O4, CoO, NiO, CuO, ZnO, ZrO2, MoO3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb4O7, Dy2O3, Er2O3 and HfO2. We also examine DNA damage due to these NPs in unirradiated and irradiated conditions.

Results

Without any X-rays, several NPs produced more radicals than water alone. Thus, V2O5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO2 NPs produced around 10-times more superoxide anions and Tb4O7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V2O5 NPs produced nearly 10-times more hydroxyl radicals than water. Changes in radical concentrations were determined by subtracting unirradiated values from irradiated values. These were then compared with irradiation-induced changes in water only. Irradiation-specific increases in hydroxyl radical were seen with most NPs, but these were only significantly above the values of water for V2O5, while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO2 showed a trend of irradiation-specific increase in superoxides, while V2O5, MnO2, CoO, CuO, MoO3 and Tb4O7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V2O5, NiO, CuO, MoO3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO2, Fe3O4 and CoO were slightly protective against irradiation-induced DNA damage.

Conclusions

Beyond identifying promising metal oxide NP radiosensitisers and radioprotectors, our broad comparisons reveal unexpected differences that suggest the surface chemistry of NP radiosensitisers is an important criterion for their success.
Deriving a Boolean dynamics to reveal macrophage activation with in vitro temporal cytokine expression profiles
Authors: Ramirez Ricardo , Herrera Allen Michael , Ramirez Joshua , Qian Chunjiang , Melton David W. , Shireman Paula K. , Jin Yu-Fang
Published: December 2019

Background

Macrophages show versatile functions in innate immunity, infectious diseases, and progression of cancers and cardiovascular diseases. These versatile functions of macrophages are conducted by different macrophage phenotypes classified as classically activated macrophages and alternatively activated macrophages due to different stimuli in the complex in vivo cytokine environment. Dissecting the regulation of macrophage activations will have a significant impact on disease progression and therapeutic strategy. Mathematical modeling of macrophage activation can improve the understanding of this biological process through quantitative analysis and provide guidance to facilitate future experimental design. However, few results have been reported for a complete model of macrophage activation patterns.

Results

We globally searched and reviewed literature for macrophage activation from PubMed databases and screened the published experimental results. Temporal in vitro macrophage cytokine expression profiles from published results were selected to establish Boolean network models for macrophage activation patterns in response to three different stimuli. A combination of modeling methods including clustering, binarization, linear programming (LP), Boolean function determination, and semi-tensor product was applied to establish Boolean networks to quantify three macrophage activation patterns. The structure of the networks was confirmed based on protein-protein-interaction databases, pathway databases, and published experimental results. Computational predictions of the network evolution were compared against real experimental results to validate the effectiveness of the Boolean network models.

Conclusion

Three macrophage activation core evolution maps were established based on the Boolean networks using Matlab. Cytokine signatures of macrophage activation patterns were identified, providing a possible determination of macrophage activations using extracellular cytokine measurements.
Osa-miR7695 enhances transcriptional priming in defense responses against the rice blast fungus
Authors: Sánchez-Sanuy Ferran , Peris-Peris Cristina , Tomiyama Shiho , Okada Kazunori , Hsing Yue-Ie , San Segundo Blanca , Campo Sonia
Published: December 2019

Background

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level in eukaryotes. In rice, MIR7695 expression is regulated by infection with the rice blast fungus Magnaporthe oryzae with subsequent down-regulation of an alternatively spliced transcript of natural resistance-associated macrophage protein 6 (OsNramp6). NRAMP6 functions as an iron transporter in rice.

Results

Rice plants grown under high iron supply showed blast resistance, which supports that iron is a factor in controlling blast resistance. During pathogen infection, iron accumulated in the vicinity of M. oryzae appressoria, the sites of pathogen entry, and in cells surrounding infected regions of the rice leaf. Activation-tagged MIR7695 rice plants (MIR7695-Ac) exhibited enhanced iron accumulation and resistance to M. oryzae infection. RNA-seq analysis revealed that blast resistance in MIR7695-Ac plants was associated with strong induction of defense-related genes, including pathogenesis-related and diterpenoid biosynthetic genes. Levels of phytoalexins during pathogen infection were higher in MIR7695-Ac than wild-type plants. Early phytoalexin biosynthetic genes, OsCPS2 and OsCPS4, were also highly upregulated in wild-type rice plants grown under high iron supply.

Conclusions

Our data support a positive role of miR7695 in regulating rice immunity that further underpin links between defense and iron signaling in rice. These findings provides a basis to better understand regulatory mechanisms involved in rice immunity in which miR7695 participates which has a great potential for the development of strategies to improve blast resistance in rice.
MicroRNA-mRNA expression profiles and their potential role in cadmium stress response in Brassica napus
Authors: Fu Ying , Mason Annaliese S. , Zhang Yaofeng , Lin Baogang , Xiao Meili , Fu Donghui , Yu Huasheng
Published: December 2019

Background

Oilseed rape is an excellent candidate for phytoremediation of cadmium (Cd) contaminated soils given its advantages of high biomass, fast growth, moderate metal accumulation, ease of harvesting, and metal tolerance, but the cadmium response pathways in this species (Brassica napus) have yet to be fully elucidated. A combined analysis of miRNA and mRNA expression to infer Cd-induced regulation has not been reported inB. napus.

Results

We characterized concurrent changes in miRNA and mRNA profiles in the roots and shoots ofB. napusseedlings after 10 days of 10 mg/L Cd2+treatment. Cd treatment significantly affected the expression of 22 miRNAs belonging to 11 families in the root and 29 miRNAs belonging to 14 miRNA families in the shoot. Five miRNA families (MIR395, MIR397, MIR398, MIR408 and MIR858) and three novel miRNAs were differentially expressed in both tissues. A total of 399 differentially expressed genes (DEGs) in the root and 389 DEGs in the shoot were identified, with very little overlap between tissue types. Eight anti-regulation miRNA-mRNA interaction pairs in the root and eight in the shoot were identified in response to Cd and were involved in key plant stress response pathways: for example, four genes targeted by miR398 were involved in a pathway for detoxification of superoxide radicals. Cd stress significantly impacted the photosynthetic pathway. Transcription factor activation, antioxidant response pathways and secondary metabolic processes such as glutathione (GSH) and phenylpropanoid metabolism were identified as major components for Cd-induced response in both roots and shoots.

Conclusions

Combined miRNA and mRNA profiling revealed miRNAs, genes and pathways involved in Cd response which are potentially critical for adaptation to Cd stress inB. napus. Close crosstalk between several Cd-induced miRNAs and mRNAs was identified, shedding light on possible mechanisms for response to Cd stress in underground and aboveground tissues inB. napus. The pathways, genes, and miRNAs identified here will be valuable targets for future improvement of cadmium tolerance inB. napus.
Novel findings to the biosynthetic pathway of magnoflorine and taspine through transcriptomic and metabolomic analysis of Croton draco (Euphorbiaceae)
Authors: Canedo-Téxon Anahí , Ramón-Farias Feliza , Monribot-Villanueva Juan Luis , Villafán Emanuel , Alonso-Sánchez Alexandro , Pérez-Torres Claudia Anahí , Ángeles Guillermo , Guerrero-Analco José Antonio , Ibarra-Laclette Enrique
Published: December 2019

Background

Croton dracois an arboreal species and its latex as well as some other parts of the plant, are traditionally used in the treatment of a wide range of ailments and diseases. Alkaloids, such as magnoflorine, prevent early atherosclerosis progression while taspine, an abundant constituent of latex, has been described as a wound-healer and antitumor-agent. Despite the great interest for these and other secondary metabolites, no omics resources existed for the species and the biosynthetic pathways of these alkaloids remain largely unknown.

Results

To gain insights into the pathways involved in magnoflorine and taspine biosynthesis byC. dracoand identify the key enzymes in these processes, we performed an integrated analysis of the transcriptome and metabolome in the major organs (roots, stem, leaves, inflorescences, and flowers) of this species. Transcript profiles were generated through high-throughput RNA-sequencing analysis while targeted and high resolution untargeted metabolomic profiling was also performed. The biosynthesis of these compounds appears to occur in the plant organs examined, but intermediaries may be translocated from the cells in which they are produced to other cells in which they accumulate.

Conclusions

Our results provide a framework to better understand magnoflorine and taspine biosynthesis inC. draco. In addition, we demonstrate the potential of multi-omics approaches to identify candidate genes involved in the biosynthetic pathways of interest.
Case report - coronary vasospasm in transplanted heart: a puzzling phenomenon
Authors: Pagnoni M. , Regamey J. , Adjedj J. , Rogati G. , Muller O. , Tozzi P.
Published: December 2019

Background

Coronary artery spasm (CAS) is an underdiagnosed disease especially in heart transplant patients, and in those patients the etiology and pathophysiology remain largely unknown, although it has been associated with cardiac allograft vasculopathy or graft rejection.

Case presentation

We report the case of a heart-transplant patient whose cardiac graft experienced two coronary vasospasms: the first before transplantation, and the other at one-month of a postoperative course complicated by primary graft failure.

Conclusion

Our case illustrates that a transplanted heart predisposed with coronary vasospasm may suffer from early relapse in the recipient despite of complete post-surgical autonomic denervation. Exacerbated endothelial dysfunction of the donor heart after transplant, with the addition of systemic factors in the recipient may be involved in the genesis of this puzzling phenomenon.
Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial
Authors: Cai Hua , Qin Yue-Lan , Shi Ze-Ya , Chen Jin-Hui , Zeng Min-Jie , Zhou Wei , Chen Ru-Qun , Chen Zhi-Yuan
Published: December 2019

Background

Alternate-day fasting (ADF) is a novel diet therapy that may achieve reduction in body weight and improvement of dyslipidaemia, but the impact of this diet on patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. The aim of this study was to evaluate the effects of ADF on the body weight and lipid profile of individuals with NAFLD.

Methods

NAFLD patients (n = 271) were randomised to the ADF group, time-restricted feeding (TRF) group, or the control group and subjected to the respective diet for 12 weeks. Anthropometric measurements (body weight, fat mass/fat-free mass) were performed, and plasma lipids were analysed enzymatically.

Results

Within 4 weeks, the body weight decreased significantly (P < 0.001) in the ADF group by 4.56 ± 0.41 kg (6.1 ± 0.5%) and the TRF group by 3.62 ± 0.65 kg (4.83 ± 0.9%) compared to the control group, and it decreased even more after 12 weeks in both groups (ADF: − 4.04 ± 0.54 kg, 5.4 ± 0.7%; TRF: − 3.25 ± 0.67 kg, 4.3 ± 0.9%). Fat mass was significantly reduced by ADF (− 3.49 ± 0.37 kg; 11 ± 1.2%) and TRF (− 2.91 ± 0.41 kg; 9.6 ± 1.3%), with ADF leading to a further reduction in fat mass after 12 weeks (− 3.48 ± 0.38 kg; 11 ± 1.2%). Total cholesterol was significantly decreased at both time points in the ADF group (− 0.91 ± 0.07 mmol/L; 18.5 ± 1.5%) compared to the control and TRF groups. Both ADF (− 0.64 ± 0.06 mmol/L; 25 ± 1.9%) and TRF (0.58 ± 0.07 mmol/L; 20 ± 1.7%) achieved a significant reduction in serum triglycerides (P < 0.001) after 12 weeks. Changes in fat free mass, HDL, LDL, fasting insulin, glucose, liver stiffness, and systolic or diastolic blood pressure did not differ between the groups.

Conclusions

ADF appears to be an effective diet therapy for individuals with NAFLD that can achieve weight loss and improvement of dyslipidaemia within a relatively short period of time (4 to 12 weeks). Potential preventive effects of ADF on cardiovascular disease need to be confirmed by future investigations.

Trial registration

ChiCTR1900024411, this trial was retrospectively registered on July 10, 2019.
Evaluation of GeneXpert MTB/RIF system performances in the diagnosis of extrapulmonary tuberculosis
Authors: Mechal Youness , Benaissa Elmostafa , El mrimar Nadia , Benlahlou Yassine , Bssaibis Fatna , Zegmout Adil , Chadli Mariama , Malik Yashpal S. , Touil Nadia , Abid Ahmed , Maleb Adil , Elouennass Mostafa
Published: December 2019

Background

Tuberculosis represents a serious public health problem and a significant diagnostic and therapeutic challenge worldwide. Molecular diagnostic techniques are crucial in the World Health Organization’s new tuberculosis control strategy.

This study aims to evaluate the performance of GeneXpert MTB/RIF (Cepheid Sunnyvale, CA, United States) in diagnosis of extra-pulmonary tuberculosis then compare it’s performance in detecting Rifampicin resistance to GenoType MTBDRplus (HAIN Life Sciences, Nehren, Germany).

Methods

Samples from pulmonary and/or extra-pulmonary origins were analysed in a 21 months retrospective study. Samples were sent to the bacteriology laboratory forMycobacterium tuberculosisdetection using conventional bacteriological and molecular methods (GeneXpert MTB/RIF and MTBDRplus). Sensitivity and specificity were calculated for the stained smear and GeneXpert according to culture (Gold Standard) as well as for GeneXpert MTB/RIF in both negative and positive microscopy tuberculosis cases. Data’s statistical analysis was performed with SPSS13.0 software.

Results

Seven hundred fourteen patients’ samples were analysed; the average age was 47.21 ± 19.98 years with a male predominance (66.4%). Out of 714 samples: 285 were from pulmonary and 429 were from extra-pulmonary origins. The positivity rates for microscopy, GeneXpert MTB/RIF and culture were 12.88, 20.59 and 15.82%, respectively. These rates were 18.9, 23.85 and 20.35% for pulmonary samples and 9.71, 18.41 and 12.82% for extra-pulmonary samples, respectively. The sensitivity and specificity of GeneXpert MTB/RIF were almost the same in both pulmonary and extra-pulmonary samples (78.2 and 90.4%) and (79,3 and 90.3%) respectively.

Rifampicin resistance rate found by GeneXpert MTB/RIF was 0.84%. Comparison of Rifampicin resistance obtained by GeneXpert MTB/RIF and Genotype MTBDRplus, showed 100% agreement between the two techniques for studied samples.

Conclusions

This confirms GeneXpert MTB/RIF advantage for tuberculosis diagnosis, particularly extra-pulmonary tuberculosis with negatively stained smear. The performance of GeneXpert and Genotype MTBDRplus are similar in detection of Rifampicin resistance. However, variability of detection performance according to tuberculosis endemicity deserves more attention in the choice of screening techniques of Rifampicin resistance, hence the interest of conducting comparative studies of detection performance under low and medium endemicity on large samples of tuberculosis populations.
Cumulative incidence and mortality of infective endocarditis in Siriraj hospital–Thailand: a 10-year retrospective study
Authors: Angsutararux Taksaon , Angkasekwinai Nasikarn
Published: December 2019

Background

To investigate the cumulative incidence of and factors associated with mortality among patients with infective endocarditis (IE) at Thailand’s largest national tertiary referral center.

Methods

Medical charts of adult patients diagnosed with IE by Duke criteria at Siriraj Hospital during January 2005 to May 2015 were retrospectively reviewed.

Results

Of 380 patients, 66.3% had definite IE, and 81.3% had native valve IE (NVE). Cumulative IE incidence was 5.67/1000 admissions. The most common pathogens were viridans group streptococci (VGS) (39.7%), methicillin-sensitive Staphylococcus aureus (MSSA) (13.1%), and beta-hemolytic streptococci (11.5%) in NVE; and, MSSA (20.3%), VGS (20.3%), and Enterococcus spp. (16.9%) in prosthetic valve (PVE) or device-related IE (DRIE). Overall in-hospital mortality was 18.4%. Mortality was significantly higher in PVE/DRIE than in NVE (26.8% vs. 16.5%, p = 0.047). End-stage renal disease (ESRD) (aOR: 9.43, 95% CI: 2.36–37.70), diabetes mellitus (DM) (aOR: 2.81, 95% CI: 1.06–7.49), neurological complication (aOR: 14.16, 95% CI: 5.11–39.22), congestive heart failure (aOR: 4.32, 95% CI: 1.91–9.75), hospital-acquired infection (aOR: 3.78, 95% CI: 1.66–8.57), renal complication (aOR: 3.12, 95%CI: 1.32–7.37), and other complication during admission (aOR: 3.28, 95% CI: 1.41–7.61) were independently associated with mortality.

Conclusions

The incidence of IE, and the mortality rate among those diagnosed with IE are both increasing in Thailand – particularly among those with PVE or DRIE. End-stage renal disease, diabetes mellitus, and development of IE-related complications during admission were found to be independent predictors of mortality.
House-hold contact tuberculosis screening adherence and associated factors among tuberculosis patients attending at health facilities in Gondar town, northwest, Ethiopia
Authors: Shiferaw Dessie Alemnew , Mekonnen Habtamu Sewunet , Abate Addisu Taye
Published: December 2019

Background

Contacting patients with tuberculosis have a substantial risk of developing the disease. Household contact screening has recently been recommended as a strategy to enhance case detection in high-burden countries. But there is no enough information in Gondar town regarding household contact screening practice among TB patients.

Methods

An institution-based cross-sectional study was conducted from March 1 to 30, 2019 on 404 tuberculosis patients attending at health facilities in Gondar Town. Epi-Info version 7 for data entry and SPSS version 20 for data analysis were used. Descriptive statistics were carried out to illustrate the means, standard deviations, and frequencies. Bivariable and multivariable logistic regression analyses were used to identify significantly associated variables with the dependent variable.

Results

From 412 study populations, 404 were completed the study with 98.06% response rate. The overall household contact TB screening adherence was 47.5% (95% CI: 43.1, 52.5). In the multivariable analysis, having certificate and above educational level (AOR = 2.83, 95% CI:1.40,5.67), having sufficient knowledge about TB (AOR = 8.26, 95% CI:4.34,15.71), being satisfied with health care service (AOR = 3.26, 95% CI:1.58,6.76), health education given by health care workers (AOR = 2.60, 95% CI:1.54,4.40),and having HIV/AIDS co-infection (AOR = 3.54, 95% CI:1.70,7.39), were factors associated with household contact TB screening adherence.

Conclusion

Compared to other previous studies, the current finding was high but it was low as compared with WHO and Ethiopian Ministry of Health recommendations (all persons having TB contact should be screened). Educational status, knowledge on TB, satisfaction with delivered health care service, health education given by HCWs about TB and HIV/AIDS co-infection were factors associated with household contact TB screening practice. Thus, strengthening household TB contact screening and educational programs regarding the risk of getting TB infection from household contacts is crucial.
Free thyroxine level is associated with both relapse rate and poor neurofunction in first-attack Neuromyelitis Optica Spectrum Disorder (NMOSD) patients
Authors: He Qianyi , Li Lifeng , Li Yanfei , Lu Yanhui , Wu Kaimin , Zhang Ruiyi , Teng Junfang , Zhao Jie , Jia Yanjie
Published: December 2019

Background

To investigate whether the serum free thyroxine (FT4) level is a prognostic factor for the first-attack neuromyelitis optica spectrum disorders (NMOSD).

Methods

This retrospective study enrolled 109 patients with first-attack NMOSD. The Expanded Disability Status Scale (EDSS) and the relapse rate were used to evaluate the outcomes. The logistic regression model was used to analyze the independent effects of FT4 on relapse and final EDSS. Kaplan-Meier analysis, scatter plot smoothing method, and two-phase piecewise linear regression model were used to investigate the relationship between the FT4 level and the relapse rate.

Results

Multivariate analysis revealed that serum FT4 level might be a risk factor for both final EDSS (β = 0.17; 95% confidence interval: 0.03–0.32) and the relapse rate (HR = 1.18; 95% confidence interval: 1.05–1.32). Furthermore, 1400 days after the onset, nearly 100% of patients in the high-FT4 group relapsed, while only 40% of the patients in the low-FT4 group relapsed. Finally, we found that the relationship between the FT4 level and the NMOSD relapse rate was nonlinear. The risk of NMOSD relapse increased with the FT4 level up to the inflection point of 12.01 pmol/L (HR = 1.45; 95% confidence interval: 1.06–1.98). When the FT4 level was > 12.01 pmol/L, there was no correlation between the FT4 level and the risk of NMOSD relapse (HR = 1.05; 95% confidence interval: 0.78–1.41).

Conclusion

Serum FT4 level may be a prognostic indicator for the first-attack in patients with NMOSD. High FT4 levels are associated with poor neurofunctions and a high relapse rate in patients with the first-attack in patients with NMOSD.
Plasma volume expansion across healthy pregnancy: a systematic review and meta-analysis of longitudinal studies
Authors: Aguree Sixtus , Gernand Alison D.
Published: December 2019

Background

Plasma volume expansion is an important physiologic change across gestation. High or low expansion has been related to adverse pregnancy outcomes, yet there is a limited understanding of normal/healthy plasma volume expansion. We aimed to evaluate the pattern of plasma volume expansion across healthy pregnancies from longitudinal studies.

Methods

We conducted a systematic review and meta-analysis to identify original studies that measured plasma volume in singleton pregnancies of healthy women. Specifically, we included studies that measured plasma volume at least two times across gestation and one time before or after pregnancy in the same women. PubMed, Web of Science, Cochrane, CINAHL, andclinicaltrials.govdatabases were searched from the beginning of each database to February 2019. We combined data across studies using a random effects model.

Results

Ten observational studies with a total of 347 pregnancies were eligible. Plasma volume increased by 6% (95% CI 3–9) in the first trimester compared to the nonpregnant state. In the second trimester, plasma volume was increased by 18% (95% CI 12–24) in gestational weeks 14–20 and 29% (95% CI 21–36) in weeks 21–27 above the nonpregnant state. In the third trimester, plasma volume was increased by 42% (95% CI 38–46) in weeks 28–34 and 48% (95% CI 44–51) in weeks 35–38. The highest rate of increase occurred in the first half of the second trimester. Included studies were rated from moderate to high quality; 7 out of 10 studies were conducted over 30 years ago.

Conclusions

In healthy pregnancies, plasma volume begins to expand in the first trimester, has the steepest rate of increase in the second trimester, and peaks late in the third trimester. The patterns observed from these studies may not reflect the current population, partly due to the changes in BMI over the last several decades. Additional longitudinal studies are needed to better characterize the range of normal plasma volume expansion across maternal characteristics.