bluuebunny/crossref_metadata_2025_split huggingface dataset:
HMGB1/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia
Authors: Zhang Shutian , Hu Li , Jiang Jialun , Li Hongji , Wu Qin , Ooi Kokwin , Wang Jijiang , Feng Yi , Zhu Danian , Xia Chunmei 
Published: January 2020

Abstract
Background
Microglial mediated neuroinflammation in the rostral ventrolateral medulla (RVLM) plays roles in the etiology of stress-induced hypertension (SIH). It was reported that autophagy influenced inflammation via immunophenotypic switching of microglia. High-mobility group box 1 (HMGB1) acts as a regulator of autophagy and initiates the production of proinflammatory cytokines (PICs), but the underlying mechanisms remain unclear.

Methods
The stressed mice were subjected to intermittent electric foot shocks plus noises administered for 2 h twice daily for 15 consecutive days. In mice, blood pressure (BP) and renal sympathetic nerve activity (RSNA) were monitored by noninvasive tail-cuff method and platinum-iridium electrodes placed respectively. Microinjection of siRNA-HMGB1 (siHMGB1) into the RVLM of mice to study the effect of HMGB1 on microglia M1 activation was done. mRFP-GFP-tandem fluorescent LC3 (tf-LC3) vectors were transfected into the RVLM to evaluate the process of autolysosome formation/autophagy flux. The expression of RAB7, lysosomal-associated membrane protein 1 (LAMP1), and lysosomal pH change were used to evaluate lysosomal function in microglia. Mitophagy was identified by transmission electron microscopic observation or by checking LC3 and MitoTracker colocalization under a confocal microscope.

Results
We showed chronic stress increased cytoplasmic translocations of HMGB1 and upregulation of its receptor RAGE expression in microglia. The mitochondria injury, oxidative stress, and M1 polarization were attenuated in the RVLM of stressed Cre-CX3CR1/RAGEfl/fl mice. The HMGB1/RAGE axis increased at the early stage of stress-induced mitophagy flux while impairing the late stages of mitophagy flux in microglia, as revealed by decreased GFP fluorescence quenching of GFP-RFP-LC3-II puncta and decreased colocalization of lysosomes with mitochondria. The expressions of RAB7 and LAMP1 were decreased in the stressed microglia, while knockout of RAGE reversed these effects and caused an increase in acidity of lysosomes. siHMGB1 in the RVLM resulted in BP lowering and RSNA decreasing in SIH mice. When the autophagy inducer, rapamycin, is used to facilitate the mitophagy flux, this treatment results in attenuated NF-κB activation and reduced PIC release in exogenous disulfide HMGB1 (ds-HMGB1)-stimulated microglia.

Conclusions
Collectively, we demonstrated that inhibition of the HMGB1/RAGE axis activation led to increased stress-induced mitophagy flux, hence reducing the activity of microglia-mediated neuroinflammation and consequently reduced the sympathetic vasoconstriction drive in the RVLM.
Isotalatizidine, a C19-diterpenoid alkaloid, attenuates chronic neuropathic pain through stimulating ERK/CREB signaling pathway-mediated microglial dynorphin A expression
Authors: Shao Shuai , Xia Huan , Hu Min , Chen Chengjuan , Fu Junmin , Shi Gaona , Guo Qinglan , Zhou Yu , Wang Wenjie , Shi Jiangong , Zhang Tiantai 
Published: January 2020

Abstract
Background
Isotalatizidine is a representative C19-diterpenoid alkaloid extracted from the lateral roots of Aconitum carmichaelii, which has been widely used to treat various diseases on account of its analgesic, anti-inflammatory, anti-rheumatic, and immunosuppressive properties. The aim of this study was to evaluate the analgesic effect of isotalatizidine and its underlying mechanisms against neuropathic pain.

Methods
A chronic constrictive injury (CCI)-induced model of neuropathic pain was established in mice, and the limb withdrawal was evaluated by the Von Frey filament test following isotalatizidine or placebo administration. The signaling pathways in primary or immortalized microglia cells treated with isotalatizidine were analyzed by Western blotting and immunofluorescence.

Results
Intrathecal injection of isotalatizidine attenuated the CCI-induced mechanical allodynia in a dose-dependent manner. At the molecular level, isotalatizidine selectively increased the phosphorylation of p38 and ERK1/2, in addition to activating the transcription factor CREB and increasing dynorphin A production in cultured primary microglia. However, the downstream effects of isotalatizidine were abrogated by the selective ERK1/2 inhibitor U0126-EtOH or CREB inhibitor of KG-501, but not by the p38 inhibitor SB203580. The results also were confirmed in in vivo experiments.

Conclusion
Taken together, isotalatizidine specifically activates the ERK1/2 pathway and subsequently CREB, which triggers dynorphin A release in the microglia, eventually leading to its anti-nociceptive action.
A microRNA signature of toxic extrasynaptic N-methyl-D-aspartate (NMDA) receptor signaling
Authors: Bas-Orth Carlos , Koch Mirja , Lau David , Buchthal Bettina , Bading Hilmar 
Published: January 2020

AbstractThe cellular consequences of N-Methyl-D-Aspartate receptor (NMDAR) stimulation depend on the receptors’ subcellular localization. Synaptic NMDARs promote plasticity and survival whereas extrasynaptic NMDARs mediate excitotoxicity and contribute to cell death in neurodegenerative diseases. The mechanisms that couple activation of extrasynaptic NMDARs to cell death remain incompletely understood. We here show that activation of extrasynaptic NMDARs by bath application of NMDA or L-glutamate leads to the upregulation of a group of 19 microRNAs in cultured mouse hippocampal neurons. In contrast, none of these microRNAs is induced upon stimulation of synaptic activity. Increased microRNA expression depends on the pri-miRNA processing enzyme Drosha, but not on de novo gene transcription. These findings suggest that toxic NMDAR signaling involves changes in the expression levels of particular microRNAs.
Performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of ovarian cancer: a systematic review and meta-analysis
Authors: Li Kexin , Pei Yuqing , Wu Yue , Guo Yi , Cui Wei 
Published: January 2020

Abstract
Background
To evaluate the diagnostic performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for ovarian cancer.

Patients and methods
A thorough research was conducted in PubMed, Web of Science and Embase (until November 2018) to identify studies evaluating the accuracy of MALDI-TOF-MS for ovarian cancer. Using Meta-Disc1.4, Review Manager 5.3 and Stata 15.1 software to analyze the pooled results: sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals (CI). The summary receiver operating characteristic curves (SROC) and area under the curve (AUC) show the overall performance of MALDI-TOF-MS.

Results
Eighteen studies were included in the meta-analysis. Methodological quality analysis of the included studies showed that these articles were at low risk of bias and applicability concerns in total. Summary estimates of the diagnostic parameters were as follows: sensitivity, 0.77 (95% CI: 0.73–0.80); specificity, 0.72 (95% CI: 0.70–0.74), PLR, 2.80 (95% CI: 2.41–3.24); NLR, 0.30 (95% CI: 0.22–0.40) and DOR, 10.71 (95% CI: 7.81–14.68). And the AUC was 0.8336. Egger’s test showed no significant publication bias in this meta-analysis.

Conclusion
In conclusion, MALDI-TOF-MS shows a good ability for diagnosing ovarian cancer. Further evaluation and optimization of standardized procedures are necessary for complete relying on MALDI-TOF-MS to diagnose ovarian cancer.
Clinical guided computer tomography decisions are advocated in potentially severely injured trauma patients: a one-year audit in a level 1 trauma Centre with long pre-hospital times
Authors: Bågenholm Anna , Dehli Trond , Eggen Hermansen Stig , Bartnes Kristian , Larsen Marthe , Ingebrigtsen Tor 
Published: January 2020

Abstract
Background
The International Commission on Radiological Protection’s (ICRP) justification principles state that an examination is justified if the potential benefit outweighs the risk for radiation harm. Computer tomography (CT) contributes 50% of the radiation dose from medical imaging, and in trauma patients, the use of standardized whole body CT (SWBCT) increases. Guidelines are lacking, and reviews conclude conflictingly regarding the benefit. We aimed to study the degree of adherence to ICRP’s level three justification, the individual dose limitation principle, in our institution.

Methods
This is a retrospective clinical audit. We included all 144 patients admitted with trauma team activation to our regional Level 1 trauma centre in 2015. Injuries were categorized according to the Abbreviated Injury Scale (AIS) codes. Time variables, vital parameters and interventions were registered. We categorized patients into trauma admission SWBCT, selective CT or no CT examination strategy groups. We used descriptive statistics and regression analysis of predictors for CT examination strategy.

Results
The 144 patients (114 (79.2%) males) had a median age of 31 (range 0–91) years. 105 (72.9%) had at least one AIS ≥ 2 injury, 26 (18.1%) in more than two body regions. During trauma admission, at least one vital parameter was abnormal in 46 (32.4%) patients, and 73 (50.7%) underwent SWBCT, 43 (29.9%) selective CT and 28 (19.4%) no CT examination. No or only minor injuries were identified in 17 (23.3%) in the SWBCT group. Two (4.6%) in the selective group were examined with a complement CT, with no new injuries identified. A significantly (p < 0.001) lower proportion of children (61.5%) than adults (89.8%) underwent CT examination despite similar injury grades and use of interventions. In adjusted regression analysis, patients with a high-energy trauma mechanism had significantly (p = 0.028) increased odds (odds ratio = 4.390, 95% confidence interval 1.174–16.413) for undergoing a SWBCT.

Conclusion
The high proportion of patients with no or only minor injuries detected in the SWBCT group and the significantly lower use of CT among children, indicate that use of a selective CT examination strategy in a higher proportion of our patients would have approximated the ICRP’s justification level three, the individual dose limitation principle, better.
Molecular diversity of Bulinus species in Madziwa area, Shamva district in Zimbabwe: implications for urogenital schistosomiasis transmission
Authors: Mutsaka-Makuvaza Masceline Jenipher , Zhou Xiao-Nong , Tshuma Cremance , Abe Eniola , Manasa Justen , Manyangadze Tawanda , Allan Fiona , Chinómbe Nyasha , Webster Bonnie , Midzi Nicholas 
Published: January 2020

AbstractBackgroundBulinusspecies are freshwater snails that transmit the parasitic trematodeSchistosoma haematobium. Despite their importance, the diversity of these intermediate host snails and their evolutionary history is still unclear in Zimbabwe.Bulinus globosusandB. truncatuscollected from a urogenital schistosomiasis endemic region in the Madziwa area of Zimbabwe were characterized using molecular methods.MethodsMalacological survey sites were mapped and snails were collected from water contact sites in four communities in the Madziwa area, Shamva district for a period of one year, at three-month intervals.Schistosoma haematobiuminfections in snails were determined by cercarial shedding and the partial mitochondrial cytochromecoxidase subunit 1 gene (cox1) was used to investigate the phylogeny and genetic variability of theBulinusspp. collected.ResultsAmong the 1570Bulinusspp. snails collected, 30 (1.9%)B. globosuswere shedding morphologically identified schistosomes. None of theB. truncatussnails were shedding. The mitochondrialcox1 data from 166 and 16 samples forB. globosusandB. truncatus, respectively, showed genetically diverse populations within the two species. Twelvecox1 haplotypes were found from the 166B. globosussamples and three from the 16B. truncatussamples with phylogenetic analysis showing that the haplotypes fall into well-supported clusters within their species groups. BothB. truncatusandB. globosusclustered into two distinct lineages. Overall, significant negative values for both Tajima’s D statistic and the Fu’s Fs statistic were observed forB. globosusandB. truncatus.ConclusionsThe study provided new insights into the levels of genetic diversity withinB. globosusand additional information onB. truncatuscollected from a small geographical area in Zimbabwe. Low prevalence levels of infection observed in the snails may reflect the low transmission level of urogenital schistosomiasis in the area. Our results contribute towards the understanding of the distribution and population genetic structure ofBulinusspp. supporting the mapping of the transmission or risk of transmission of urogenital schistosomiasis, particularly in Zimbabwe.
An unsupervised learning approach to identify novel signatures of health and disease from multimodal data
Authors: Shomorony Ilan , Cirulli Elizabeth T. , Huang Lei , Napier Lori A. , Heister Robyn R. , Hicks Michael , Cohen Isaac V. , Yu Hung-Chun , Swisher Christine Leon , Schenker-Ahmed Natalie M. , Li Weizhong , Nelson Karen E. , Brar Pamila , Kahn Andrew M. , Spector Timothy D. , Caskey C. Thomas , Venter J. Craig , Karow David S. , Kirkness Ewen F. , Shah Naisha 
Published: January 2020

AbstractBackgroundModern medicine is rapidly moving towards a data-driven paradigm based on comprehensive multimodal health assessments. Integrated analysis of data from different modalities has the potential of uncovering novel biomarkers and disease signatures.MethodsWe collected 1385 data features from diverse modalities, including metabolome, microbiome, genetics, and advanced imaging, from 1253 individuals and from a longitudinal validation cohort of 1083 individuals. We utilized a combination of unsupervised machine learning methods to identify multimodal biomarker signatures of health and disease risk.ResultsOur method identified a set of cardiometabolic biomarkers that goes beyond standard clinical biomarkers. Stratification of individuals based on the signatures of these biomarkers identified distinct subsets of individuals with similar health statuses. Subset membership was a better predictor for diabetes than established clinical biomarkers such as glucose, insulin resistance, and body mass index. The novel biomarkers in the diabetes signature included 1-stearoyl-2-dihomo-linolenoyl-GPC and 1-(1-enyl-palmitoyl)-2-oleoyl-GPC. Another metabolite, cinnamoylglycine, was identified as a potential biomarker for both gut microbiome health and lean mass percentage. We identified potential early signatures for hypertension and a poor metabolic health outcome. Additionally, we found novel associations between a uremic toxin,p-cresol sulfate, and the abundance of the microbiome generaIntestinimonasand an unclassified genus in theErysipelotrichaceaefamily.ConclusionsOur methodology and results demonstrate the potential of multimodal data integration, from the identification of novel biomarker signatures to a data-driven stratification of individuals into disease subtypes and stages—an essential step towards personalized, preventative health risk assessment.
Non-intrusive load monitoring and decomposition method based on decision tree
Authors: Lin Jiang , Ding Xianfeng , Qu Dan , Li Hongyan 
Published: January 2020

AbstractIn order to realize the problems of non-intrusive load monitoring and decomposition (NILMD) from two aspects of load identification and load decomposition, based on the load characteristics of the database, this paper firstly analyzes and identifies the equipment composition of mixed electrical equipment group by using the load decision tree algorithm. Then, a 0–1 programming model for the equipment status identification is established, and the Particle Swarm Optimization (PSO) is used to solve the model for equipment state recognition, and the equipment operating state in the equipment group is identified. Finally, a simulation experiment is carried out for the partial data of Question A in the 6th “teddy cup” data mining challenge competition.
On solutions of a class of three-point fractional boundary value problems
Authors: Bai Zhanbing , Cheng Yu , Sun Sujing 
Published: January 2020

AbstractExistence results for the three-point fractional boundary value problem
$$\begin{aligned}& D^{\alpha}x(t)= f \bigl(t, x(t), D^{\alpha-1} x(t) \bigr),\quad 0< t< 1, \\& x(0)=A, \qquad x(\eta)-x(1)=(\eta-1)B, \end{aligned}$$ Dαx(t)=f(t,x(t),Dα−1x(t)),0<t<1,x(0)=A,x(η)−x(1)=(η−1)B, are presented, where $A, B\in\mathbb{R}$A,B∈R, $0<\eta<1$0<η<1, $1<\alpha\leq2$1<α≤2. $D^{\alpha}x(t)$Dαx(t) is the conformable fractional derivative, and $f: [0, 1]\times\mathbb{R}^{2}\to\mathbb{R}$f:[0,1]×R2→R is continuous. The analysis is based on the nonlinear alternative of Leray–Schauder.
Governance of sustainability in the German biogas sector—adaptive management of the Renewable Energy Act between agriculture and the energy sector
Authors: Thrän Daniela , Schaubach Kay , Majer Stefan , Horschig Thomas 
Published: January 2020

AbstractBiomass is an integral part of the energy system being not only used in the chemical industry, but also as a basic raw material for the bio-economy sector, which is promoted worldwide. However, its potential can only be exploited sustainably if biomass is cultivated and governed appropriately. Consequently, governance systems are needed to ensure sustainability throughout the bioenergy value chain to maximise the benefits and minimise possible negative impacts. This study investigates how sustainability is put into effect in the German biogas market, the largest biogas market worldwide. The development of Germany’s biogas market is described according to the structure of a four-phase market model of Heuss: the introduction, expansion, maturing, and stagnation phase. Within each of these market phases, the most important German legislation for development of the biogas market was analysed, namely the Renewable Energy Act and legislation addressing associated sustainability issues. The development of the biogas market was controlled and steered by the adaptive Renewable Energy Act, particularly by incentivising cultivation of energy crops. Efforts to promote sustainability started during the transition from market expansion to market consolidation. The effects of these efforts on greenhouse gas emission reductions have been monitored and reported for more than 15 years, but assessment of other aspects of sustainability has varied. In general, legislation regulating the agriculture sector was changed to address new sustainability concerns with some delay. Sustainable development of the agricultural biogas market requires elements of governance, including adaptive legislation within the energy sector as well as monitoring and regular reporting of environmental impacts and related developments in areas of the agriculture sector, such as meat production. Rapid growth of capacity in the biogas sector combined with a significant increase in meat production, dependent on increased fodder production, created risks to sustainability. It can be concluded that the sustainable development of biogas requires additional instruments, possibly national regulation, in addition to legislation applied to the broader agricultural sector.
Smartphones in mental health: a critical review of background issues, current status and future concerns
Authors: Bauer Michael , Glenn Tasha , Geddes John , Gitlin Michael , Grof Paul , Kessing Lars V. , Monteith Scott , Faurholt-Jepsen Maria , Severus Emanuel , Whybrow Peter C. 
Published: January 2020

AbstractThere has been increasing interest in the use of smartphone applications (apps) and other consumer technology in mental health care for a number of years. However, the vision of data from apps seamlessly returned to, and integrated in, the electronic medical record (EMR) to assist both psychiatrists and patients has not been widely achieved, due in part to complex issues involved in the use of smartphone and other consumer technology in psychiatry. These issues include consumer technology usage, clinical utility, commercialization, and evolving consumer technology. Technological, legal and commercial issues, as well as medical issues, will determine the role of consumer technology in psychiatry. Recommendations for a more productive direction for the use of consumer technology in psychiatry are provided.
Fabrication of novel polymer-modified graphene-based electrochemical sensor for the determination of mercury and lead ions in water and biological samples
Authors: Raril Chenthattil , Manjunatha Jamballi G. 
Published: January 2020

AbstractBackgroundThis paper presents the application of polyglycine-modified graphene paste electrode (PGMGPE) for the electrochemical detection of Hg (II) and Pb (II) ions in the water and biological samples.MethodThe developed electrode was characterized by field emission scanning electron microscopy. Electrochemical techniques such as cyclic voltammetry and differential pulse voltammetry were used to study the behavior of metal ions.ResultsThe modification process improves the electrochemical behavior of heavy metal ions. The peak current varied linearly with the increase of the concentration leading to a detection limit of 6.6 μM (Hg (II)) and 0.8 μM (Pb (II)), respectively.ConclusionThe developed electrode exhibits good sensitivity, selectivity, stability, and lower detection limit, and was successfully applied to the determination of heavy metal ions in water and biological samples with a good recovery range.