bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Serum Metabolites to Diagnose Bicuspid Aortic Valve
Authors: Wang Wenshuo , Maimaiti Aikebaier , Zhao Yun , Zhang Lingfei , Tao Hongyue , Nian Hui , Xia Limin , Kong Biao , Wang Chunsheng , Liu Mofang , Wei Lai 
Published: November 2016

AbstractBicuspid aortic valve (BAV) is the most common congenital heart disease. The current study aims to construct a diagnostic model based on metabolic profiling as a non-invasive tool for BAV screening. Blood serum samples were prepared from an estimation group and a validation group, each consisting of 30 BAV patients and 20 healthy individuals, and analyzed by liquid chromatography-mass spectrometry (LC-MS). In total, 2213 metabolites were detected and 41 were considered different. A model for predicting BAV in the estimation group was constructed using the concentration levels of monoglyceride (MG) (18:2) and glycerophospho-N-oleoyl ethanolamine (GNOE). A novel model named Zhongshan (ZS) was developed to amplify the association between BAV and the two metabolites. The area under curve (AUC) of ZS for BAV prediction was 0.900 (0.782–0.967) and was superior to all single-metabolite models when applied to the estimation group. Using optimized cutoff (−0.1634), ZS model had a sensitivity score of 76.7%, specificity score of 90.0%, positive predictive value of 80% and negative predictive value of 85.0% for the validation group. These results support the use of serum-based metabolomics profiling method as a complementary tool for BAV screening in large populations.
Avoidance, escape and microstructural adaptations of the tea green leafhopper to water droplets
Authors: Lin Meizhen , Vasseur Liette , Yang Guang , Gurr Geoff M. , You Minsheng 
Published: November 2016

AbstractRain and dew droplets can dislodge or drown small insects and may be important factors that drive adaptations for avoidance and escape. Studying the microstructure of small insects and insect behaviour can help understand these adaptations. We quantified avoidance behaviour and entrapment of nymphs and adults of the tea green leafhopper (Empoasca onukii) using simulated rainfall onto host plant foliage and made observations of pretarsi and abdomen microstructures. Adults responded rapidly to simulated rainfall and escaped by jumping whilst most young nymphs were washed from water-sprayed leaves though older nymphs tended to remain on leaves and subsequently escaped from water droplets. Adults had denser covering of water-repelling brochosomes on pretarsi and abdomen surface than nymphs, and were able to stand on water film whilst most nymphs had multiple penetrating tarsi. Removal of brochosomes from the abdomen of adults reduced hydrophobicity, demonstrating the hydrophobic significance of brochosomes in the capacity of leafhopper to escape from water droplets. Nymphs exhibited a higher pull-off force than adults. This research is one of the few studies to focus on the wettability and water avoidance of small insect pests and has implications for pest management.
Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia
Authors: Chung Connie , Marson John D. , Zhang Quan-Guang , Kim Jimok , Wu Wei-Hua , Brann Darrell W. , Chen Bo-Shiun 
Published: November 2016

AbstractPost-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity.
Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration
Authors: Zhang Jian-Nan , Michel Uwe , Lenz Christof , Friedel Caroline C. , Köster Sarah , d’Hedouville Zara , Tönges Lars , Urlaub Henning , Bähr Mathias , Lingor Paul , Koch Jan C. 
Published: November 2016

AbstractAxonal degeneration is a key initiating event in many neurological diseases. Focal lesions to axons result in a rapid disintegration of the perilesional axon by acute axonal degeneration (AAD) within several hours. However, the underlying molecular mechanisms of AAD are only incompletely understood. Here, we studied AAD in vivo through live-imaging of the rat optic nerve and in vitro in primary rat cortical neurons in microfluidic chambers. We found that calpain is activated early during AAD of the optic nerve and that calpain inhibition completely inhibits axonal fragmentation on the proximal side of the crush while it attenuates AAD on the distal side. A screening of calpain targets revealed that collapsin response mediator protein-2 (CRMP2) is a main downstream target of calpain activation in AAD. CRMP2-overexpression delayed bulb formation and rescued impairment of axonal mitochondrial transport after axotomy in vitro. In vivo, CRMP2-overexpression effectively protected the proximal axon from fragmentation within 6 hours after crush. Finally, a proteomic analysis of the optic nerve was performed at 6 hours after crush, which identified further proteins regulated during AAD, including several interactors of CRMP2. These findings reveal CRMP2 as an important mediator of AAD and define it as a putative therapeutic target.
A submerged dielectric barrier discharge plasma inactivation mechanism of biofilms produced by Escherichia coli O157:H7, Cronobacter sakazakii, and Staphylococcus aureus
Authors: Khan Muhammad Saiful Islam , Lee Eun-Jung , Kim Yun-Ji 
Published: November 2016

AbstractA submerged dielectric barrier discharge plasma reactor (underwater DBD) has been used to inactivate biofilm produced by three different food-borne pathogens, namelyEscherichia coliO157:H7 (ATCC 438),Cronobacter sakazakii(ATCC 29004), andStaphylococcus aureus(KCCM 40050). The inactivation that were obtained after 90 minutes of plasma operation were found to measure 5.50 log CFU/coupon, 6.88 log CFU/coupon and 4.20 log CFU/coupon forEscherichia coliO157:H7 (ATCC 438),Cronobacter sakazakii(ATCC 29004), andStaphylococcus aureus(KCCM 40050), respectively. Secondary Electron Images (SEI) obtained from Field Emission Scanning Electron Microscopy (FE-SEM) show the biofilm morphology and its removal trend by plasma operation at different time intervals. An attenuated total reflectance Fourier transform infrared (ATR-FTIR) measurement was performed to elucidate the biochemical changes that occur on the bacterial cell and extracellular polymeric substance (EPS) of biofilm during the plasma inactivation process. The ATR-FTIR measurement shows the gradual reduction of carbohydrates, proteins, and lipid and DNA peak regions with increased plasma exposure time. The presence of an EPS layer on the upper surface of the biofilm plays a negative and significant role in its removal from stainless steel (SS) coupons.
Effects of seasonal meteorological variables on E. coli persistence in livestock faeces and implications for environmental and human health
Authors: Oliver David M. , Page Trevor 
Published: November 2016

AbstractAgriculture contributes significant volumes of livestock faeces to land. Understanding how faecal microbes respond to shifts in meteorological patterns of contrasting seasons is important in order to gauge how environmental (and human health) risks may alter under a changing climate. The aim of this study was to: (i) quantify the temporal pattern of E. coli growth within dairy faeces post defecation; and (ii) derive E. coli seasonal population change profiles associated with contrasting environmental drivers. Evaluation of the die-off dynamics of E. coli revealed that a treatment mimicking drought and warming conditions significantly enhanced persistence relative to E. coli in faeces that were exposed to field conditions, and that this pattern was consistent across consecutive years. The internal temperature of faeces was important in driving the rate of change in the E. coli population in the immediate period post defecation, with most E. coli activity (as either die-off or growth) occurring at low dry matter content. This study highlighted that the use of seasonal E. coli persistence profiles should be approached with caution when modelling environmental and human health risks given the increased likelihood of atypical seasonal meteorological variables impacting on E. coli growth and die-off.
Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease’s active site cysteine residue
Authors: Rausalu Kai , Utt Age , Quirin Tania , Varghese Finny S. , Žusinaite Eva , Das Pratyush Kumar , Ahola Tero , Merits Andres 
Published: November 2016

AbstractChikungunya virus (CHIKV), genus Alphavirus, family Togaviridae, has a positive-stand RNA genome approximately 12 kb in length. In infected cells, the genome is translated into non-structural polyprotein P1234, an inactive precursor of the viral replicase, which is activated by cleavages carried out by the non-structural protease, nsP2. We have characterized CHIKV nsP2 using both cell-free and cell-based assays. First, we show that Cys478 residue in the active site of CHIKV nsP2 is indispensable for P1234 processing. Second, the substrate requirements of CHIKV nsP2 are quite similar to those of nsP2 of related Semliki Forest virus (SFV). Third, substitution of Ser482 residue, recently reported to contribute to the protease activity of nsP2, with Ala has almost no negative effect on the protease activity of CHIKV nsP2. Fourth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 completely abolished RNA replication in CHIKV and SFV trans-replication systems. In contrast, trans-replicases with Ser482 to Ala mutation were similar to wild type counterparts. Fifth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 abolished the rescue of infectious virus from CHIKV RNA transcripts while Ser482 to Ala mutation had no effect. Thus, CHIKV nsP2 is a cysteine protease.
Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome
Authors: Sakata Kazuya , Araki Kimi , Nakano Hiroyasu , Nishina Takashi , Komazawa-Sakon Sachiko , Murai Shin , Lee Grace E. , Hashimoto Daisuke , Suzuki Chigure , Uchiyama Yasuo , Notohara Kenji , Gukovskaya Anna S. , Gukovsky Ilya , Yamamura Ken-ichi , Baba Hideo , Ohmuraya Masaki 
Published: November 2016

AbstractThe loss-of-function mutations of serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with human chronic pancreatitis, but the underlying mechanisms remain unknown. We previously reported that mice lackingSpink3, the murine homologue of humanSPINK1, die perinatally due to massive pancreatic acinar cell death, precluding investigation of the effects of SPINK1 deficiency. To circumvent perinatal lethality, we have developed a novel method to integrate humanSPINK1gene on the X chromosome using Cre-loxP technology and thus generated transgenic mice termed “X-SPINK1“. Consistent with the fact that one of the two X chromosomes is randomly inactivated,X-SPINK1mice exhibit mosaic pattern ofSPINK1expression. Crossing ofX-SPINK1mice withSpink3+/−mice rescued perinatal lethality, but the resultingSpink3−/−;XXSPINK1mice developed spontaneous pancreatitis characterized by chronic inflammation and fibrosis. The results show that mice lacking a gene essential for cell survival can be rescued by expressing this gene on the X chromosome. TheSpink3−/−;XXSPINK1mice, in which this method has been applied to partially restore SPINK1 function, present a novel genetic model of chronic pancreatitis.
Roles of endoplasmic reticulum stress-mediated apoptosis in M1-polarized macrophages during mycobacterial infections
Authors: Lim Yun-Ji , Yi Min-Hee , Choi Ji-Ae , Lee Junghwan , Han Ji-Ye , Jo Sung-Hee , Oh Sung-Man , Cho Hyun Jin , Kim Dong Woon , Kang Min-Woong , Song Chang-Hwa 
Published: November 2016

AbstractAlteration of macrophage function has an important regulatory impact on the survival of intracellular mycobacteria. We found that macrophages infected with attenuated Mycobacterium tuberculosis (Mtb) strain H37Ra had elevated expression of M1-related molecules, whereas the M2 phenotype was dominant in macrophages infected with virulent Mtb H37Rv. Further, the TLR signalling pathway played an important role in modulating macrophage polarization against Mtb infection. Interestingly, endoplasmic reticulum (ER) stress was significantly increased in M1 polarized macrophages and these macrophages effectively removed intracellular Mtb, indicating that ER stress may be an important component of the host immune response to Mtb in M1 macrophages. This improved understanding of the mechanisms that regulate macrophage polarization could provide new therapeutic strategies for tuberculosis.
Profiling ribonucleotide and deoxyribonucleotide pools perturbed by gemcitabine in human non-small cell lung cancer cells
Authors: Guo Jian-Ru , Chen Qian-Qian , Lam Christopher Wai Kei , Wang Cai-Yun , Wong Vincent Kam Wai , Chang Zee-Fen , Zhang Wei 
Published: November 2016

AbstractIn this study, we investigated the dosage effect of gemcitabine, an inhibitor of ribonucleotide reductase (RR), on cellular levels of ribonucleotides and deoxyribonucleotides using high performance liquid chromatography-electrospray ionization tandem mass spectrometric method. As anticipated, after 4-h incubation of non-small cell lung cancer (A549) cells with gemcitabine at 0.5 and 2 μM, there were consistent reductions in levels of deoxyribonucleoside diphosphates (dNDP) and their corresponding deoxyribonucleoside triphosphates (dNTP). However, after 24-h exposure to 0.5 μM gemcitabine, the amounts of dNTP were increased by about 3 fold, whereas cells after 24-h 2 μM gemcitabine treatment exhibited deoxycytidine diphosphate (dCDP), deoxyadenosine diphosphate (dADP) and deoxyguanosine diphosphate (dGDP) levels less than 50% of control values, with deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP) returning to the control level. Using cell cycle analysis, we found that 24-h incubation at 0.5 μM gemcitabine resulted in a significant increase in S phase arrest, while 2 μM treatment increased G0/G1 population. Our data demonstrated the correlation between the level of RR and the increased levels of dNTPs in the group of 0.5 μM treatment for 24-h with a markedly reduced level of dFdCTP. Accordingly, we proposed that the dosage of dFdC could determine the arrested phase of cell cycle, in turn affecting the recovery of dNTPs pools.
Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC–MS-based metabonomics
Authors: Zheng P , Chen J-J , Zhou C-J , Zeng L , Li K-W , Sun L , Liu M-l , Zhu D , Liang Z-H , Xie P 
Published: November 2016

AbstractWomen are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography–mass spectrometry (GC–MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their respective healthy controls (HCs). Twenty seven women and 36 men related differentially expressed metabolites were identified in MDD. Fourteen metabolites were changed in both women and men MDD subjects. Significantly, the women-specific (m-Hydroxyphenylacetate, malonate, glycolate, hypoxanthine, isobutyrate and azelaic acid) and men-specific (tyrosine, N-acetyl-d-glucosamine, N-methylnicotinamide, indoxyl sulfate, citrate and succinate) marker panels were further identified, which could differentiate men and women MDD patients from their respective HCs with higher accuracy than previously reported sex-nonspecific marker panels. Our findings demonstrate that men and women MDD patients have distinct metabonomic signatures and sex-specific biomarkers have promising values in diagnosing MDD.
Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system
Authors: Man K K C , Coghill D , Chan E W , Lau W C Y , Hollis C , Liddle E , Banaschewski T , McCarthy S , Neubert A , Sayal K , Ip P , Wong I C K 
Published: November 2016

AbstractPrevious studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined, and the possibility of confounding factors has not been excluded. Patients aged 6–19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System (2001–2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20,586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10,000 patient-years. No increased risk was found during MPH-exposed compared with non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53–1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17–9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment.
Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis
Authors: Suvitaival T , Mantere O , Kieseppä T , Mattila I , Pöhö P , Hyötyläinen T , Suvisaari J , Orešič M 
Published: November 2016

AbstractPsychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. In this study, we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients. We applied comprehensive metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. While corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline, that is, lipids known to be associated with increased liver fat. Our study suggests that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain.
High step‐up dual full‐bridge ZVS DC–DC converter with improved integrated magnetics and new resonant switched capacitor cell
Authors: Taheri Meghdad , Milimonfared Jafar , Abbasi Arand Bijan , Salehi Dobakhshari Sina 
Published: November 2016

A high voltage gain dual interleaved full bridge converter with Zero Voltage Switching (ZVS), improved integrated magnetics, and a new resonant Switched ‐Capacitor‐Cell (RSC) is presented. By taking the advantage of a new resonant switched capacitor cell and transformers with low turn‐ratio as well as low leakage inductances, the desired high output voltage can be obtained. Furthermore, the output diodes operate in Zero Current Switching (ZCS) condition, and switches are maintained under ZVS condition over the whole range of output load variations. In addition, switches turn off near zero current leading to high overall efficiency. An interleaved approach (multi‐cell) is adopted over a single cell to increase the power handling capacity. Furthermore, transformers of dual cells are integrated into a single UU core which cuts down the total volume of the converter as well as the total core loss. Since secondary windings have opposite polarities, there exists no DC flux, and the top and bottom RSC cells operate in 180 degree out of phase. Taking the aforementioned characteristics into consideration, the proposed converter has a good performance for high voltage applications. Experimental results of a 3 kw prototype with an output voltage of 16 kV validate the features of this topology.
Spontaneous Intestinal Perforation: The Long-Term Outcome
Authors: Feng Xiang-Nan , Chan Kin , Mou Jennifer , Tam Yuk , Lee Kim , Houben Christoph 
Published: November 2016

Background/Purpose Evaluating the long-term outcome of spontaneous intestinal perforation (SIP).
Methods We studied all patients treated for SIP at our institution between January 1, 2005 and December 31, 2014.
Results Twenty-three infants (13 males) with a median gestational age of 26 (range: 23–32) weeks and a median weight of 825 (range: 560–1,965) g composed this cohort. Seventeen (74%) infants had an extremely low birth weight (ELBW); nine (39%) infants were the result of multiple pregnancies.Patent ductus arteriosus (PDA) was present in 16 (70%) infants. Cyclooxygenase inhibitors were administered in 12 (52%) infants.Ten infants (seven males, 44%) were diagnosed with intraventricular hemorrhage (IVH), which was identified in the majority (8/10) at a median of 9 (range: 1–11) days prior to the perforation.All patients presented with pneumoperitoneum and underwent a laparotomy at a median age of 9 (range: 2–16) days. Twenty-one patients had an ileal perforation. A temporary stoma was placed in 21 patients, whereas two got primary anastomosis. Two (8.7%) male infants died. During the long-term follow-up period (median 6 years), six (five males) (26%) infants developed moderate to severe disabilities in combination with cerebral palsy. No surgical complications were observed.
Conclusion The most important risk factor for SIP is ELBW (75%). The distal ileum is the most frequent site of perforation (88%). Approximately 40% develop IVH most often prior to the SIP. Moderate to severe neurologic disabilities are seen in more than a quarter of the children. Disability and mortality affect mostly the male sex. Long-term risks of surgical complications are very low.