bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data-driven discovery of a novel sepsis pre-shock state predicts impending septic shock in the ICU
Authors: Liu Ran , Greenstein Joseph L. , Granite Stephen J. , Fackler James C. , Bembea Melania M. , Sarma Sridevi V. , Winslow Raimond L. 
Published: April 2019

AbstractSeptic shock is a life-threatening condition in which timely treatment substantially reduces mortality. Reliable identification of patients with sepsis who are at elevated risk of developing septic shock therefore has the potential to save lives by opening an early window of intervention. We hypothesize the existence of a novel clinical state of sepsis referred to as the “pre-shock” state, and that patients with sepsis who enter this state are highly likely to develop septic shock at some future time. We apply three different machine learning techniques to the electronic health record data of 15,930 patients in the MIMIC-III database to test this hypothesis. This novel paradigm yields improved performance in identifying patients with sepsis who will progress to septic shock, as defined by Sepsis- 3 criteria, with the best method achieving a 0.93 area under the receiver operating curve, 88% sensitivity, 84% specificity, and median early warning time of 7 hours. Additionally, we introduce the notion of patient-specific positive predictive value, assigning confidence to individual predictions, and achieving values as high as 91%. This study demonstrates that early prediction of impending septic shock, and thus early intervention, is possible many hours in advance.
Sex-specific differences in spring and autumn migration in a northern large herbivore
Authors: Debeffe Lucie , Rivrud Inger Maren , Meisingset Erling L. , Mysterud Atle 
Published: April 2019

AbstractOngoing global warming is now affecting migratory cycles in a large variety of taxa in seasonally variable environments. Disruption of migratory systems can cause population decline and affect ecosystem function across the globe. It is therefore urgent to understand the drivers of migration and how the different fitness limitations of the sexes affect migration, but studies seldom considered the full annual cycle. We analysed the annual migration cycle of 237 red deer (Cervus elaphus) in Norway and investigate how different seasonal limitations affected the variation in a suite of migration characteristics. We found fundamental differences in migration phenology between seasons, and migratory traits were much more variable in males. Spring migratory movements were characterized by longer distance roamed, lower speed, lasted longer, more frequent use of stopovers, timing was more synchronized and coincided with onset of plant growth, and with higher daily activity levels. Timing of autumn migration was more variable and not closely related to cease of plant growth. Our study emphasizes the benefits of studying the full annual cycle to gain further insight into the migration process, and how understanding the limitations of the full annual migration process of both sexes is critical for conservation purposes.
Hand-Fabricated CNT/AgNPs Electrodes using Wax-on-Plastic Platforms for Electro-Immunosensing Application
Authors: Chen Sensen , Qamar Ahmad Z. , Asefifeyzabadi Narges , Funneman Madison , Taki Motahareh , Elliot Lee , Kinsel Mary E. , Kinsel Gary R. , Shamsi Mohtashim H. 
Published: April 2019

AbstractFabrication of inexpensive and flexible electronic and electrochemical sensors is in high demand for a wide range of biochemical and biomedical applications. We explore hand fabrication of CNT modified AgNPs electrodes using wax-on-plastic platforms and their application in electrochemical immunosensing. Wax patterns were printed on polyethylene terephthalate-based substrates to laydown templates for the electrodes. Hand painting was employed to fabricate a silver conductive layer using AgNPs ink applied in the hydrophilic regions of the substrate surrounded by wax. CNT was drop cast on top of the working electrodes to improve their electrochemical signal. The device layers were characterized by scanning electron microscopy. The electrochemical performance of the hand fabricated AgNPs and CNT/AgNPs electrodes was tested using cyclic voltammetry, differential pulse voltammetry, and amperometry. The electrochemical response of CNT/AgNPs electrodes was relatively faster, higher, and more selective than unmodified AgNPs sensing electrodes. Finally, the hand-painted CNT/AgNPs electrodes were applied to detect carcinoembryonic antigen (CEA) by measuring the end-product of immunoassay performed on magnetic particles. The detection limit for CEA was found to be 0.46 ng/mL.
Bioproduction of pure, kilobase-scale single-stranded DNA
Authors: Shepherd Tyson R. , Du Rebecca R. , Huang Hellen , Wamhoff Eike-Christian , Bathe Mark 
Published: April 2019

AbstractScalable production of kilobase single-stranded DNA (ssDNA) with sequence control has applications in therapeutics, gene synthesis and sequencing, scaffolded DNA origami, and archival DNA memory storage. Biological production of circular ssDNA (cssDNA) using M13 addresses these needs at low cost. However, one unmet goal is to minimize the essential protein coding regions of the exported DNA while maintaining its infectivity and production purity to produce sequences less than 3,000 nt in length, relevant to therapeutic and materials science applications. Toward this end, synthetic miniphage with inserts of custom sequence and size offers scalable, low-cost synthesis of cssDNA at milligram and higher scales. Here, we optimize growth conditions using an E. coli helper strain combined with a miniphage genome carrying only an f1 origin and a β-lactamase-encoding (bla) antibiotic resistance gene, enabling isolation of pure cssDNA with a minimum sequence genomic length of 1,676 nt, without requiring additional purification from contaminating DNA. Low-cost scalability of isogenic, custom-length cssDNA is demonstrated for a sequence of 2,520 nt using a bioreactor, purified with low endotoxin levels (<5 E.U./ml). We apply these exonuclease-resistant cssDNAs to the self-assembly of wireframe DNA origami objects and to encode digital information on the miniphage genome for biological amplification.
Metabolites can regulate stem cell behavior through the STAT3/AKT pathway in a similar trend to that under hypoxic conditions
Authors: Jeong Gun-Jae , Kang Donglim , Kim Ae-Kyeong , Han Kyu-Hyun , Jeon Hye Ran , Kim Dong-ik 
Published: April 2019

AbstractStem cell therapy has long been considered a promising mode of treatment for many incurable diseases. Human mesenchymal stem cells (hMSCs) have provided the most promising results to date for regenerative medicine. Nevertheless, due to several obstacles such as difficulty in sourcing and characterizing hMSCs, they remain largely unavailable for clinical use. The signaling requirements for maintaining stem cell function have been studied widely, but little is known about how metabolism contributes to stem cell function. hMSCs have been shown to promote therapeutic efficacy in hypoxic conditions through metabolic conversion. According to published studies, certain metabolites are able to convert stem cell metabolism from oxidative phosphorylation to glycolysis. In this study, we selected several metabolites (fructose-1,6-bisphosphate (FBP), Phosphoenolpyruvic acid (PEP) and sodium oxalate (OXA)) to examine the relation between metabolites and stem cell functions. In addition, we investigated the ability of selected metabolites to induce rapid expansion of this cell population. Our results indicate that selected metabolites stimulate stem cell proliferation by induce glycolytic metabolism via AKT/STAT signaling.
Designed Mutations Alter the Binding Pathways of an Intrinsically Disordered Protein
Authors: Wu Di , Zhou Huan-Xiang 
Published: April 2019

AbstractMany cellular functions, including signaling and regulation, are carried out by intrinsically disordered proteins (IDPs) binding to their targets. Experimental and computational studies have now significantly advanced our understanding of these binding processes. In particular, IDPs that become structured upon binding typically follow a dock-and-coalesce mechanism, whereby the docking of one IDP segment initiates the process, followed by on-target coalescence of remaining IDP segments. Multiple dock-and-coalesce pathways may exist, but one may dominate, by relying on electrostatic attraction and molecular flexibility for fast docking and fast coalescing, respectively. Here we critically test this mechanistic understanding by designing mutations that alter the dominant pathway. This achievement marks an important step toward precisely manipulating IDP functions.
Body distribution of stable copper isotopes during the progression of cholestatic liver disease induced by common bile duct ligation in mice
Authors: Costas-Rodríguez Marta , Van Campenhout Sanne , Hastuti Agustina A M B , Devisscher Lindsey , Van Vlierberghe Hans , Vanhaecke Frank 
Published: April 2019

Abstract
Patients with chronic liver disease from different aetiologies show a light serum Cu isotopic composition compared to the reference population, with the enrichment in the 63Cu isotope correlating with the severity of the disease. However, the mechanisms underlying Cu isotope fractionation at the onset and during progression of the disease are still unclear. In this work, a common bile duct ligation (CBDL) murine model was used to investigate the effect of cholestasis-induced liver disease on the Cu isotopic composition. Wild type male and female mice underwent surgical ligation of the common bile duct and were sacrificed 2, 4 and 6 weeks, and 4, 6 and 8 weeks after the surgical intervention, respectively. The age- and gender-matched control mice underwent sham surgery. Disease progression was evaluated using serum bilirubin levels, hepatic pro-inflammatory chemokine levels and Metavir fibrosis score. CBDL-operated mice show an overall body enrichment in the light isotope 63Cu. The Cu isotopic composition of organs, bone and serum becomes gradually lighter compared to the sham-operated mice with increasing severity of the disease. The light Cu isotopic composition of the CBDL-operated mice might result from an altered Cu intake and/or excretion. As the intestinal uptake of dietary Cu is largely mediated by transporters of Cu(i), mRNA and protein expression levels of two major metal transporters (CTR1 and DMT1) and Cu reductases (STEAP proteins and duodenal cytochrome B) were examined in the duodenal tissues as potential factors inducing Cu isotope fractionation. However, no significant differences in protein expression levels were observed between the CBDL- and sham-operated mice.
CrmA orthologs from diverse poxviruses potently inhibit caspases-1 and -8, yet cleavage site mutagenesis frequently produces caspase-1-specific variants
Authors: Bloomer David T. , Kitevska-Ilioski Tanja , Pantaki-Eimany Delara , Ji Yanhao , Miles Mark A. , Heras Begona , Hawkins Christine J. 
Published: April 2019

Abstract
Poxviruses encode many proteins that enable them to evade host anti-viral defense mechanisms. Spi-2 proteins, including Cowpox virus CrmA, suppress anti-viral immune responses and contribute to poxviral pathogenesis and lethality. These proteins are ‘serpin’ protease inhibitors, which function via a pseudosubstrate mechanism involving initial interactions between the protease and a cleavage site within the serpin. A conformational change within the serpin interrupts the cleavage reaction, deforming the protease active site and preventing dissociation. Spi-2 proteins like CrmA potently inhibit caspases-1, -4 and -5, which produce proinflammatory cytokines, and caspase-8, which facilitates cytotoxic lymphocyte-mediated target cell death. It is not clear whether both of these functions are equally perilous for the virus, or whether only one must be suppressed for poxviral infectivity and spread but the other is coincidently inhibited merely because these caspases are biochemically similar. We compared the caspase specificity of CrmA to three orthologs from orthopoxviruses and four from more distant chordopoxviruses. All potently blocked caspases-1, -4, -5 and -8 activity but exhibited negligible inhibition of caspases-2, -3 and -6. The orthologs differed markedly in their propensity to inhibit non-mammalian caspases. We determined the specificity of CrmA mutants bearing various residues in positions P4, P3 and P2 of the cleavage site. Almost all variants retained the ability to inhibit caspase-1, but many lacked caspase-8 inhibitory activity. The retention of Spi-2 proteins’ caspase-8 specificity during chordopoxvirus evolution, despite this function being readily lost through cleavage site mutagenesis, suggests that caspase-8 inhibition is crucial for poxviral pathogenesis and spread.
MiR-205 suppresses epithelial–mesenchymal transition and inhibits tumor growth of human glioma through down-regulation of HOXD9
Authors: Dai Bin , Zhou Guanghua , Hu Zhiqiang , Zhu Guangtong , Mao Beibei , Su Haiyang , Jia Qingbin 
Published: April 2019

Abstract
Epithelial–mesenchymal transition (EMT) plays a pivotal role in cancer progression. Hsa-miR-205 is considered one of the fundamental regulators of EMT. In the present study, we found that miR-205 was down-regulated in glioma tissues and human glioma cells U87 and U251. Meanwhile, miR-205 overexpression enhanced E-cadherin, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, miR-205 suppressed tumor growth. Additionally, HOXD9 was confirmed as a direct target of miR-205. Suppression of HOXD9 by miR-205 was demonstrated by luciferase reporter assay, quantitative real time-PCR analysis, and western blot. Moreover, we observed a negative correlation between miR-205 and HOXD9 in human glioma tissues. In summary, our findings demonstrated that miR-205 suppresses glioma tumor growth, invasion, and reverses EMT through down-regulating its target HOXD9.
MPSSS impairs the immunosuppressive function of cancer-associated fibroblasts via the TLR4-NF-κB pathway
Authors: Xu Yuwei , Ma Jing , Zheng Qilin , Wang Yuanyuan , Hu Minghua , Ma Fangli , Qin Zhihai , Lei Ningjing , Tao Ning 
Published: April 2019

Abstract
The polysaccharides MPSSS was extracted from Lentinus edodes and has been reported to effectively inhibit tumor growth and eliminate the function of myeloid-derived immune suppressor cell-mediated T cell inhibition, thus improving the efficacy of cancer therapy. The exploration of how MPSSS affects the functions of cancer-associated fibroblasts (CAFs) will provide a new perspective for understanding the antitumor effects of MPSSS. In the present study, prostate CAFs were selected as target cells to study whether MPSSS affected cell proliferation and function. The results showed that MPSSS did not directly inhibit the growth of prostate CAFs but interfered with CAF-mediated T cell inhibition and affected the immunosuppressive function of prostate CAFs. Mechanistic studies were further performed and showed that MPSSS activated key node proteins in the NF-κB pathway that were dependent on MyD88, and a TLR4 inhibitor blocked the changes in these proteins and the effect of MPSSS. We hypothesize that MPSSS can activate the MyD88-dependent TLR4-NF-κB signaling pathway to change the function of CAFs. In conclusion, these results demonstrate that MPSSS can not only effectively inhibit the growth of prostate cancer as we previously reported but also alter the function of prostate CAFs by activating the TLR4-NF-κB pathway, providing a new strategy for the comprehensive treatment of tumors.
Oleic acid ameliorates palmitic acid-induced ER stress and inflammation markers in naive and cerulein-treated exocrine pancreas cells
Authors: Ben-Dror Karin , Birk Ruth 
Published: April 2019

Abstract
Dietary fat overload (typical to obesity) increases the risk of pancreatic pathologies through mechanisms yet to be defined. We previously showed that saturated dietary fat induces pancreatic acinar lipotoxicity and cellular stress. The endoplasmic reticulum (ER) of exocrine pancreas cells is highly developed and thus predisposed to stress. We studied the combination of saturated and unsaturated FAs in metabolic and pancreatitis like cerulein (CER)-induced stress states on cellular ER stress.
Exocrine pancreas AR42J and rat primary exocrine acinar cells underwent acute (24 h) challenge with different FAs (saturated, monounsaturated) at different concentrations (250 and 500 µM) and in combination with acute CER-induced stress, and were analyzed for fat accumulation, ER stress unfolded protein response (UPR) and immune and enzyme markers. Acute exposure of AR42J and pancreatic acinar cells to different FAs and their combinations increased triglyceride accumulation. Palmitic acid significantly dose-dependently enhanced the UPR, immune factors and pancreatic lipase (PL) levels, as demonstrated by XBP1 splicing and elevation in UPR transcripts and protein levels (Xbp1,Atf6, Atf4, Chop, Tnfα, Tgfβ and Il-6). Exposure to high palmitic levels in a CER-induced stress state synergistically increased ER stress and inflammation marker levels. Exposure to oleic acid did not induce ER stress and PL levels and significantly decreased immune factors in an acute CER-induced stress state. Combination of oleic and palmitic acids significantly reduced the palmitic-induced ER stress, but did not affect the immune factor response. We show that combination of monounsaturated and saturated FAs protects from exocrine pancreatic cellular ER stress in both metabolic and CER-induced stress.
Anti-Toxoplasmaactivity of silver nanoparticles green synthesized withPhoenix dactyliferaandZiziphus spina-christiextracts which inhibits inflammation through liver regulation of cytokines in Balb/c mice
Authors: Alajmi Reem A. , AL-Megrin Wafa A. , Metwally Dina , AL-Subaie Hind , Altamrah Nourah , Barakat Ashraf M. , Abdel Moneim Ahmed E. , Al-Otaibi Tahani T. , El-Khadragy Manal 
Published: April 2019

AbstractToxoplasmosis constitutes a global infection caused by oblige intracellular apicomplexan protozoan parasite Toxoplasma gondii. Although often asymptomatic, infection can result in more severe, potentially life threatening symptoms particularly in immunocompromised individuals. The present study evaluated the anti-Toxoplasma effects in experimental animals of silver nanoparticles synthesized in combination with extracts of natural plants (Phoenix dactylifera and Ziziphus spina-christi) as an alternative method to standard sulfadiazine drug therapy. Liver functions estimated by and AST and ALT were significantly increased in T. gondii-infected mice compared with the control group as well as hepatic nitric oxide (NO), lipid peroxidation (LPO) levels and caused significant decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione activities in the liver homogenates. Nanoparticles pretreatment prevented liver damage as determined by enzyme activity inhibition, in addition to significant inhibition of hepatic NO levels and significant elevation in liver SOD and CAT activities. Moreover, nanoparticle treatment significantly decreased hepatic LPO and NO concentrations and proinflammatory cytokines but significantly boosted the antioxidant enzyme activity of liver homogenate. In addition, histological examinations showed distinct alterations in the infected compared with untreated control groups. Conversely, nanoparticles pretreatment showed improvement in the histological features indicated by slight infiltration and fibrosis, minimal pleomorphism and less hepatocyte and degeneration. Furthermore, nanoparticles treatment induced a reduction in immunoreactivity to TGF-β and NF-κB in hepatic tissues. Therefore, the present study provides new insights into various natural plants that are used traditionally for the treatment of toxoplasmosis and other parasitic infections, which may be useful as alternative treatment option for T. gondii infections.
CircRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/IGF-1R axis
Authors: Tian Linli , Cao Jing , Jiao Hui , Zhang Jiarui , Ren Xiuxia , Liu Xinyu , Liu Ming , Sun Yanan 
Published: April 2019

Abstract
Background: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA–microRNA (miRNA)–mRNA interaction.
Methods: We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2.
Results: circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro, which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo. Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression.
Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis.
Design of hybrid forward boost converter for renewable energy powered electric vehicle charging applications
Authors: Joseph Peter K. , Devaraj Elangovan 
Published: April 2019

The grid‐connected electric vehicle charging stations are being integrated into renewable energy for preserving the conventional energy resources as well as to ensure sustainable development of the society. In addition to the effortless charging, the sudden demand variations in the grid can be met by the renewable energy storage system in the charging stations. The main challenge in this concept is the unstable nature of renewable energy. As the energy storage system of charging station is directly connected to the renewable energy source like a solar panel, according to the variable and deficient input power condition, the converter should supply a regulated output at the required magnitude. If a conventional converter is used for this purpose, the charging efficiency will be poor for higher gain conditions. This article presents a hybrid forward‐boost converter to overcome this challenge. By maintaining the power transfer efficiency higher, the gain can be varied to supply a regulated voltage, even for very low input conditions in this proposed topology. The maximum overall efficiency of 95% is achieved for a variable input condition of 30–50 V to provide an output voltage of 170 V. The concept is validated by implementing a 150 W hybrid converter.