bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Dysfunction and Apoptosis Are Attenuated on κ-Opioid Receptor Activation Through AMPK/GSK-3β Pathway After Myocardial Ischemia and Reperfusion
Authors: Tian Xin , Zhou Yaguang , Wang Yuanbo , Zhang Shumiao , Feng Jiahao , Wang Xu , Guo Haitao , Fan Rong , Feng Na , Jia Min , Gu Xiaoming , Li Juan , Yang Lu , Wang Yueming , Li Jun , Zheng Guoxu , Fu Feng , Pei Jianming 
Published: November 2018

Abstract:
Previous studies have shown that κ-opioid receptor activation possesses cardioprotection against myocardial ischemia and reperfusion (MI/R) injury. The current study was designed to investigate whether mitochondrial dysfunction after MI/R is regulated by the κ-opioid receptor and to further explore the underlying mechanisms involved. MI/R rat model was established in vivo, and a hypoxia and reoxygenation cardiomyocytes model was used in vitro. Mitochondrial morphology and function as well as myocardial apoptosis were determined. Our data indicated that treatment with U50,488H (a selective κ-opioid receptor agonist) not only reduced apoptosis but also significantly improved mitochondrial morphology and function. These effects were blocked by nor-binaltorphimine (nor-BNI, a selective κ-opioid receptor antagonist), Compound C (an AMPK inhibitor), and AR-A014418 (a GSK3β inhibitor). Moreover, in cardiomyocytes, treatment with U50,488H significantly increased the expression in phosphorylation of AMPK and the phosphorylation of GSK3β. Treatment of cardiomyocytes with AMPKα siRNA decreased the phosphorylation of AMPK and GSK3β. Moreover, AMPK activation resulted in the phosphorylation of GSK3β. Our findings suggested that U50,488H exerted cardioprotective effects by improving mitochondrial morphology and function against MI/R injury through activation of the κ-opioid receptor–mediated AMPK/GSK3β pathway.
New Mass Spectrometric Approaches for the Quantitative Evaluation of Anticancer Drug Levels in Treated Patients
Authors: D'Aronco Sara , D'Angelo Edoardo , Crotti Sara , Traldi Pietro , Agostini Marco 
Published: November 2018

Abstract:
Alternatively to the well-consolidated liquid chromatography coupled to tandem mass spectrometry approach used for the evaluation of anticancer drug concentrations in treated patients, new mass spectrometric methods have been proposed and tested recently. They exhibited faster analysis time and, at first sight, simpler instrumental approaches. However, results obtained by these methods require an in-depth evaluation, because of their strong dependence on the experimental set-up. In this short review, the quantification of irinotecan, sunitinib, and 6-α-hydroxy paclitaxel (the main metabolite of paclitaxel) by laser desorption ionization techniques (matrix-assisted laser desorption/ionization, nanostructure-assisted laser desorption/ionization, and surface-assisted laser desorption/ionization) is reported and discussed, showing the advantages but also the drawbacks of the methods. The matrix-assisted laser desorption/ionization approach led to the most reliable results, and the cross-validation for the quantitative analysis of irinotecan indicates that this method can be fruitfully used for therapeutic drug monitoring and pharmacokinetic studies. Another recently proposed technique, paper spray mass spectrometry, has been tested for the quantitative measurement of imatinib in plasma samples. Even if the approach is, at first sight, really simple, the parameterization of the analytical and instrumental aspects has required many efforts to reach satisfactory results. What it should be expected in the future is the evaluation of these methods, not only in scientific environments dedicated to instrument development, but also in clinical chemistry laboratories, to evaluate their effectiveness and to give new and valid tools for TDM and for other qualitative or quantitative measurements of biomedical interest.
Efficacy of Luliconazole Against Broad-Range Filamentous Fungi Including Fusarium solani Species Complex Causing Fungal Keratitis
Authors: Todokoro Daisuke , Suzuki Takashi , Tamura Takashi , Makimura Koichi , Yamaguchi Hideyo , Inagaki Katsuhiro , Akiyama Hideo 
Published: November 2018

Purpose:
Fungal keratitis can be difficult to medically treat. Topical antifungals are usually applied empirically as the initial option in treating fungal keratitis. Natamycin (NAT) and/or voriconazole (VRCZ) have been widely used in the treatment of fungal keratitis. However, Fusarium solani species complex (FSSC), which are the dominant species of fungal keratitis, are resistant to VRCZ. This study investigated in vitro efficacy of luliconazole (LLCZ), a new imidazole antifungal, against FSSC and other filamentous fungi.

Methods:
A total of 18 Fusarium isolates and 7 others were grown on potato dextrose agar at 30 and 37°C. For Fusarium, species identification and phylogenetic tree analysis were performed based on elongation factor-1α (EF-1α) DNA sequencing. The broth microdilution method was used for antifungal susceptibility testing of 11 antifungal drugs including LLCZ.

Results:
The 18 identified Fusarium isolates belonged to FSSC (n = 13), Fusarium oxysporum species complex (FOSC; n = 2), Fusarium chlamydosporum species complex (FCSC; n = 1), Fusarium incarnatum-equiseti species complex (FIESC; n = 1), and Fusarium fujikuroi species complex (FFSC; n = 1). We further divided 13 FSSC isolates into 3 clades, FSSC5 (n = 8), FSSC3 + 4 (n = 4), and FSSC9-a (n = 1), with 8 FSSC strains growing at 37°C. LLCZ showed lowest minimum inhibitory concentrations (MICs) against all tested filamentous fungi, with a MIC90 against the Fusarium species of 0.06 μg/mL, whereas MIC90 for NAT and VRCZ were 4 and 8 μg/mL, respectively.

Conclusions:
LLCZ has the strongest in vitro antifungal activity among all drugs used against broad-range filamentous fungi including FSSC. LLCZ may potentially be a new medical treatment option for fungal keratitis.
Urticaria Multiforme
Authors: Maynard Kristi 
Published: November 2018

ABSTRACT
Urticaria multiforme is a rare, hypersensitivity reaction that occurs in infants and small children. Because of its rare occurrence, many providers are unable to accurately identify the rash and associated symptoms to unnecessary laboratory and histological testing or misdiagnosis. This article highlights the case of an 11-month-old female infant with urticaria multiforme. It explores the identification, diagnosis, and current treatment recommendations.
Self-Management Problem-Solving Tools for Lower-Limb Prosthesis Wearers: Mobile App Usability and Acceptability Study
Authors: Lee Daniel Joseph , Veneri Diana A. , Goodworth Adam D. 
Published: November 2018

ABSTRACT

Introduction
The ability to self-manage and problem solve effectively is an important component of managing chronic conditions. For individuals with limb loss, problem solving the fit of their prosthetic socket is crucial to being able to functionally ambulate with a prosthetic leg. This study evaluates and compares two innovative problem-solving tools designed to empower prosthesis wearers in self-managing their socket fit.

Materials and Methods
Fourteen paper-based problem-solving decision trees were integrated into a mobile health app displayed on an iPad. Thirty prosthesis wearers performed a total of six trials split between the two conditions (paper-based and mobile app).Technical effectiveness, efficiency, and acceptability were assessed during and after participants used each tool to problem solve real-life scenarios. Technical effectiveness was a measure of the number of errors, whereas efficiency was a measure of the amount of time needed to complete each trial. Acceptability was measured using Likert-like questionnaires and semistructured interviews.

Results
Results demonstrated significantly better efficiency (paper-based = 124.22 seconds on average, app = 108.76 seconds; P = 0.0076) and technical effectiveness (paper-based = 0.66 errors on average, app = 0.2 errors; P < 0.001) for the app. Age and education were correlated with the outcomes.

Conclusions
The mobile app demonstrated significantly better outcomes as compared with the paper-based decision trees. Both the mobile app and paper-based tool had high acceptability; however, the mobile app was found to be significantly easier to use and less confusing than the paper-based version of the decision trees. Further study is required to assess the efficacy of the decision trees to manage a prosthetic fit issue in an individual who is currently having difficult managing a prosthetic socket fit issue.
Comparison of chitinase-3-like protein 1, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 index with shear-wave elastography
Authors: Mushtaq Saadiya , Ghani Eijaz , Azam Khalid , Hussain Tabinda 
Published: November 2018

Background
In the past, there has been an exponential increase in the potential biomarkers that can be used for staging of liver fibrosis. In light of intraobserver and intralobular variations, criticism has been directed at liver biopsy, and its efficacy has been challenged. Shear-wave elastography (SWE) has become a routine method for pre-assessment of liver fibrosis. Serum markers such as chitinase-3-like protein 1 (CHI3L1) also known as YKL-40, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (Fib-4) index have been researched as potential alternates to detect liver fibrosis.

Study
A total of 150 enrolled patients with chronic hepatitis underwent serum analysis to estimate CHI3L1 or YKL-40 level, aspartate aminotransferase-to-platelet ratio index, and Fib-4 index. These patients also underwent SWE.

Results
The distribution of fibrosis grade according to SWE was F0: 46 patients, F1: 31 patients, F2: 16 patients, F3: four patients, and F4: 53 patients. Receiver operating characteristic curve analysis for F0–F1 versus F2–F3, F0–F1 versus F4, and F2–F3 versus F4 gave area under curve values of 0.56 (P>0.05), 0.76 (P<0.01), and 0.75, respectively (P<0.01) for aspartate aminotransferase-to-platelet ratio index; of 0.65 (P<0.05), 0.78 (P<0.01), and 0.7, respectively (P<0.05) for Fib-4 index; and 0.98, 0.99, and 0.95, respectively (P<0.01 for all) for CHI3L1.

Conclusion
CHI3L1 could be used as a preliminary tool to assess mild/absent fibrosis from significant fibrosis and cirrhosis.
Health Information and the Quality and Safety of Care for People With Disability: An Analysis of Australian Reports of Reviewable Deaths in Residential Care
Authors: Dahm Maria R. , Georgiou Andrew , Balandin Susan , Hill Sophie , Hemsley Bronwyn 
Published: November 2018

Objective
Many Australians with disability live in residential care and require assistance to manage their health information across hybrid care settings encompassing residential care, primary and tertiary care, and allied health. In this study, we examined case study reports on people with disability living in residential care in New South Wales, Australia to (a) identify threats to the quality of care and safety for this vulnerable patient group in relation to health documentation and information infrastructure and (b) evaluate the applicability of a conceptual health information infrastructure model.

Methods
All 99 case studies were extracted from eight New South Wales Ombudsmen reports of reviewable deaths for a directed content analysis applying a conceptual model of health information infrastructure in residential care.

Results
Ninety-one percent of case studies (n = 90) contained information relation to documentation. Forty-seven percent of case studies (n = 47) linked failures in documentation to risk of death, and 12% (n = 12) described best practice use of documentation. Threats to quality of care and safety related to poor “coordination” of information, including information not being implemented, poor “communication” across services, and discrepancies between “policy and practice” in health management.

Conclusions
The conceptual model demonstrated how “coordination” and “communication” of health information relate to tensions between “policy and practice,” influencing the safety and quality of care for people with disability in residential care. The model was a good fit to investigate how health information infrastructure may affect the quality of residential care and could inform holistic digital solutions to deliver safer, integrated, and higher quality care for people with disability.
Phenome-wide Investigation of Health Outcomes Associated with Genetic Predisposition to Loneliness
Authors: Abdellaoui Abdel , Sanchez-Roige Sandra , Sealock Julia , Treur Jorien L. , Dennis Jessica , Fontanillas Pierre , Elson Sarah ,   The 23andme Research Team, Nivard Michel , Fung Ip Hill , der Zee Matthijs van , Baselmans Bart , Hottenga Jouke Jan , Willemsen Gonneke , Mosing Miriam , Yu Li , Pedersen Nancy L. , Amin Najaf , van Duijn Cornelia M , Szilagyi Ingrid , Tiemeier Henning , Neumann Alexander , Verweij Karin , Cacioppo Stephanie , Cacioppo John T. , Davis Lea K. , Palmer Abraham A. , Boomsma Dorret I. 
Published: November 2018

AbstractHumans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. While it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition towards loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we conducted a genome-wide association (GWAS) meta-analysis of loneliness (N=475,661), report 12 associated loci (two novel) and significant genetic correlations with 34 other complex traits. The polygenic basis for loneliness was significantly enriched for evolutionary constrained genes and genes expressed in specific brain tissues: (frontal) cortex, cerebellum, anterior cingulate cortex, and substantia nigra. We built polygenic scores based on this GWAS meta-analysis to explore the genetic association between loneliness and health outcomes in an independent sample of 18,498 individuals for whom electronic health records were available. A genetic predisposition towards loneliness predicted cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, effect of body fat on loneliness, and a similar weaker causal effect of BMI. Our results provide a framework for ongoing studies of the genetic basis of loneliness and its role in mental and physical health.
Drop-In Biofuel production by using fatty acid photodecarboxylase from Chlorella variabilis in the oleaginous yeast Yarrowia lipolytica
Authors: Bruder Stefan , Moldenhauer Eva Johanna , Lemke Robert Denis , Ledesma-Amaro Rodrigo , Kabisch Johannes 
Published: November 2018

AbstractBackgroundOleaginous yeasts are potent hosts for the renewable production of lipids and harbor great potential for derived products, such as biofuels. Several promising processes have been described that produce hydrocarbon drop-in biofuels based on fatty acid decarboxylation and fatty aldehyde decarbonylation. Unfortunately, besides fatty aldehyde toxicity and high reactivity, the most investigated enzyme, aldehyde-deformylating oxygenase, shows unfavorable catalytic properties which hindered high yields in previous metabolic engineering approaches.ResultsTo demonstrate an alternative alkane production pathway for oleaginous yeasts, we describe the production of diesel-like, odd-chain alkanes and alkenes, by heterologously expressing a recently discovered light-driven oxidase from Chlorella variabilis (CvFAP) in Yarrowia lipolytica. Initial experiments showed that only strains engineered to have an increased pool of free fatty acids showed to be susceptible to sufficient decarboxylation. Providing these strains with glucose and light in a synthetic medium resulted in titers of 10.9 mg/L of hydrocarbons. Using custom 3D printed labware for lighting bioreactors, and an automated pulsed glycerol fed-batch strategy, intracellular titers of 58.7 mg/L were achieved.ConclusionsOleaginous yeasts such as Yarrowia lipolytica can transform renewable resources such as glycerol into fatty acids and lipids. By heterologously expressing a fatty acid photodecarboxylase from the algae Chlorella variabilis hydrocarbons were produced in several scales from microwell plate to 400 ml bioreactors. The developed bioprocess shows a route to the renewable production of hydrocarbons for a variety of applications ranging from representing a substrate for further enzymatic or chemical modification or as a drop-in biofuel blend.Short abstractOleaginous yeasts are potent hosts for the renewable production of lipids, fatty acids and derived products such as biofuels. Here, we describe, the production of odd-numbered alkanes and alkenes with a length of 17 and 15 carbons by expression of a fatty acid photodecarboxylase (CvFAP) from Chlorella variabilis in different Yarrowia lipolytica strains under different regimes of blue light exposure in several scales from microwell plate to 400 ml bioreactors.
Cell-intrinsic Wnt4 controls early cDC1 commitment and suppresses development of pathogen-specific Type 2 immunity
Authors: Hung Li-Yin , Ji Yingbiao , Christian David A. , Herbine Karl R. , Pastore Christopher F. , Herbert De’Broski R. 
Published: November 2018

AbstractWhether conventional dendritic cell (cDC) precursors acquire lineage-specific identity under direction of regenerative secreted glycoproteins within bone marrow niches is entirely unknown. Herein, we demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is both necessary and sufficient for necessary for the full extent of pre-cDC1 specification within bone marrow. Cell-intrinsic Wnt4 deficiency in CD11c+ cells reduced mature cDC1 numbers in BM, spleen, lung, and intestine and, reciprocally, rWnt4 treatment promoted pJNK activation and cDC1 expansion. Lack of cell-intrinsic Wnt4 in mice CD11cCreWnt4flox/flox impaired stabilization of IRF8/cJun complexes in BM and increased the basal frequency of both cDC2 and ILC2 populations in the periphery. Accordingly, CD11c-restricted Wnt4 augmented Type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis accompanied by increased interleukin 5 production relative to CD11cCre controls. Collectively, these data show previously unappreciated role for Wnt4 in DC commitment and pathogen-specific immunity.
A Scube2-Shh feedback loop links morphogen release and spread to morphogen signaling to enable scale invariant patterning of the ventral neural tube
Authors: Collins Zachary M. , Cha Anna , Qin Albert , Ishimatsu Kana , Tsai Tony Y.C. , Swinburne Ian A. , Li Pulin , Megason Sean G. 
Published: November 2018

AbstractTo enable robust patterning, morphogen systems should be resistant to variations in gene expression and tissue size. Here we explore how the Sonic Hedgehog (Shh) morphogen gradient in the ventral neural tube enables scaled patterning in embryos of varying sizes. Using zebrafish eggs that have been surgically reduced in size, we find that ventral neural tube patterning remains proportional in smaller embryos. Intriguingly, a secreted protein implicated in Shh release, Scube2, is expressed in the dorsal-intermediate neural tube far from Shh producing cells. Overexpression ofscube2expands the Shh gradient whereas loss ofscube2causes gradient contraction. Conversely, upregulation of Shh repressesscube2expression while Shh downregulation increasesscube2expression thus establishing a negative feedback loop. This regulatory feedback is necessary for scaling, as demonstrated by its loss inscube2overexpressing embryos. Using mathematical modeling, we show that feedback control on diffusion and release rates of Shh allows the morphogen gradient to be robust to differences in field length and Shh gene dosage. We conclude that Scube2 promotes release and diffusion of Shh to allow gradient scaling in an extension to the expander-repressor model.Summary StatementThe Shh morphogen gradient can scale to different size tissues by feedback between Scube2 mediated release and diffusion of Shh and Shh based inhibition of Scube2 expression
The stem rust fungus Puccinia graminis f. sp. tritici induces centromeric small RNAs during late infection that direct genome-wide DNA methylation
Authors: Sperschneider Jana , Jones Ashley W. , Nasim Jamila , Xu Bo , Jacques Silke , Upadhyaya Narayana M. , Mago Rohit , Figueroa Melania , Singh Karam B. , Stone Eric A. , Schwessinger Benjamin , Wang Ming-Bo , Taylor Jennifer M. , Dodds Peter N. 
Published: November 2018

AbstractBackgroundSilencing of transposable elements (TEs) is essential for maintaining genome stability. Plants use small RNAs (sRNAs) to direct DNA methylation to TEs (RNA-directed DNA methylation; RdDM). Similar mechanisms of epigenetic silencing in the fungal kingdom have remained elusive.ResultsWe use sRNA sequencing and methylation data to gain insight into epigenetics in the dikaryotic fungus Puccinia graminis f. sp. tritici (Pgt), which causes the devastating stem rust disease on wheat. We use Hi-C data to define the Pgt centromeres and show that they are repeat-rich regions (∼250 kb) that are highly diverse in sequence between haplotypes and, like in plants, are enriched for young TEs. DNA cytosine methylation is particularly active at centromeres but also associated with genome-wide control of young TE insertions. Strikingly, over 90% of Pgt sRNAs and several RNAi genes are differentially expressed during infection. Pgt induces waves of functionally diversified sRNAs during infection. The early wave sRNAs are predominantly 21 nts with a 5’ uracil derived from genes. In contrast, the late wave sRNAs are mainly 22 nt sRNAs with a 5’ adenine and are strongly induced from centromeric regions. TEs that overlap with late wave sRNAs are more likely to be methylated, both inside and outside the centromeres, and methylated TEs exhibit a silencing effect on nearby genes.ConclusionsWe conclude that rust fungi use an epigenetic silencing pathway that resembles RdDM in plants. The Pgt RNAi machinery and sRNAs are under tight temporal control throughout infection and might ensure genome stability during sporulation.