bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of economic crisis on mental health: a 10-year challenge
Authors: Marazziti Donatella , Avella Maria T. , Mucci Nicola , Della Vecchia Alessandra , Ivaldi Tea , Palermo Stefania , Mucci Federico 
Published: April 2020

AbstractThe worldwide economic crisis of the last decade, and still unresolved, led to a great recession involving all major economies. Since economic factors may influence mental wellbeing, not surprisingly a rise in poor mental health was observed in different countries, while representing a great challenge to psychiatric interventions. This paper aims at reviewing the available English literature focusing on the impact of the current economic crisis on mental health, with a special focus on depression and suicide. Available studies indicate that consequences of economic crisis, such as unemployment, increased workload or work reorganization, and reduced staff and wages, may constitute important stressing factors with a negative impact on mental health. Although data are not easily comparable in different countries, depression seems to be the most common psychiatric disorders especially in middle-aged men. Even suicide rates seem to be increased in men, mainly in countries with no public welfare or poor family relationships. All these findings require a careful attention from both governments that cut resources on public health instead of investing in it, and psychiatric associations that should implement appropriate strategies to face and to manage this sort of depression epidemic driven by economic crisis. Again, as available data suggest that the impact of the crisis might have been attenuated in countries with higher spending in social protection, they clearly urge policy makers to take into account possible health externalities associated to inadequate social protection systems.
Temporal and Spectral Studies by XMM‐Newton of Jupiter's X‐ray Auroras During a Compression Event
Authors: Wibisono A. D. , Branduardi‐Raymont G. , Dunn W. R. , Coates A. J. , Weigt D. M. , Jackman C. M. , Yao Z. H. , Tao C. , Allegrini F. , Grodent D. , Chatterton J. , Gerasimova A. , Kloss L. , Milović J. , Orlandiayni L. , Preidl A.‐K. , Radler C. , Summhammer L. , Fleming D. 
Published: April 2020

AbstractWe report the temporal and spectral results of the first XMM‐Newton observation of Jupiter's X‐ray auroras during a clear magnetospheric compression event on June 2017 as confirmed by data from the Jovian Auroral Distributions Experiment (JADE) instrument onboard Juno. The northern and southern auroras were visible twice and thrice respectively as they rotated in and out of view during the ∼23‐hr (almost 2.5 Jupiter rotations) long XMM‐Newton Jovian‐observing campaign. Previous auroral observations by Chandra and XMM‐Newton have shown that the X‐ray auroras sometimes pulse with a regular period. We applied wavelet and fast Fourier transforms (FFTs) on the auroral light curves to show that, following the compression event, the X‐ray auroras exhibited a recurring 23‐ to 27‐min periodicity that lasted over 12.5 hr (longer than a Jupiter rotation). This periodicity was observed from both the northern and southern auroras, suggesting that the emission from both poles was caused by a shared driver. The soft X‐ray component of the auroras is due to charge exchange processes between precipitating ions and neutrals in Jupiter's atmosphere. We utilized the Atomic Charge Exchange (ACX) spectral package to produce solar wind and iogenic plasma models to fit the auroral spectra in order to identify the origins of these ions. For this observation, the iogenic model gave the best fit, which suggests that the precipitating ions are from iogenic plasma in Jupiter's magnetosphere.
Covariate-adjusted analysis of the Phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma
Authors: Briggs Andrew , Daniele Bruno , Dick Katherine , Evans Thomas R. Jeffry , Galle Peter R. , Hubner Richard A. , Lopez Carlos , Siebert Uwe , Tremblay Gabriel 
Published: April 2020

Abstract
Background
In the Phase 3 REFLECT trial in patients with unresectable hepatocellular carcinoma (uHCC), the multitargeted tyrosine kinase inhibitor, lenvatinib, was noninferior to sorafenib in the primary outcome of overall survival. Post-hoc review revealed imbalances in prognostic variables between treatment arms. Here, we re-analyse overall survival data from REFLECT to adjust for the imbalance in covariates.

Methods
Univariable and multivariable adjustments were undertaken for a candidate set of covariate values that a physician panel indicated could be prognostically associated with overall survival in uHCC. The values included baseline variables observed pre- and post-randomisation. Univariable analyses were based on a stratified Cox model. The multivariable analysis used a “forwards stepwise” Cox model.

Results
Univariable analysis identified alpha-fetoprotein (AFP) as the most influential variable. The chosen multivariable Cox model analysis resulted in an estimated adjusted hazard ratio for lenvatinib of 0.814 (95% CI: 0.699–0.948) when only baseline variables were included. Adjusting for post-randomisation treatment variables further increased the estimated superiority of lenvatinib.

Conclusions
Covariate adjustment of REFLECT suggests that the original noninferiority trial likely underestimated the true effect of lenvatinib on overall survival due to an imbalance in baseline prognostic covariates and the greater use of post-treatment therapies in the sorafenib arm.

Trial registration
Trial number: NCT01761266 (Submitted January 2, 2013).
Prognostic impact of ACTN4 gene copy number alteration in hormone receptor-positive, HER2-negative, node-negative invasive breast carcinoma
Authors: Sugano Teppei , Yoshida Masayuki , Masuda Mari , Ono Makiko , Tamura Kenji , Kinoshita Takayuki , Tsuda Hitoshi , Honda Kazufumi , Gemma Akihiko , Yamada Tesshi 
Published: April 2020

Abstract
Background
Most patients with hormone receptor (HR)-positive, human epidermal growth factor receptor type 2 (HER2)-negative breast cancer can be cured by surgery and endocrine therapy, but a significant proportion suffer recurrences. Actinin-4 is associated with cancer invasion and metastasis, and its genetic alteration may be used for breast cancer prognostication.

Methods
The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridisation (FISH) in two independent cohorts totalling 597 patients (336 from Japan and 261 from the USA) with HR-positive, HER2-negative, node-negative breast cancer.

Results
In the Japanese cohort, multivariate analysis revealed that a copy number increase (CNI) of ACTN4 was an independent factor associated with high risks of recurrence (P = 0.01; hazard ratio (HR), 2.95) and breast cancer death (P = 0.014; HR, 4.27). The prognostic significance of ACTN4 CNI was validated in the US cohort, where it was the sole prognostic factor significantly associated with high risks of recurrence (P = 0.04; HR, 2.73) and death (P = 0.016; HR, 4.01).

Conclusions
Copy number analysis of a single gene, ACTN4, can identify early-stage luminal breast cancer patients with a distinct outcome. Such high-risk patients may benefit from adjuvant chemotherapy.
Deep CO2 in the end-Triassic Central Atlantic Magmatic Province
Authors: Capriolo Manfredo , Marzoli Andrea , Aradi László E. , Callegaro Sara , Dal Corso Jacopo , Newton Robert J. , Mills Benjamin J. W. , Wignall Paul B. , Bartoli Omar , Baker Don R. , Youbi Nasrrddine , Remusat Laurent , Spiess Richard , Szabó Csaba 
Published: April 2020

AbstractLarge Igneous Province eruptions coincide with many major Phanerozoic mass extinctions, suggesting a cause-effect relationship where volcanic degassing triggers global climatic changes. In order to fully understand this relationship, it is necessary to constrain the quantity and type of degassed magmatic volatiles, and to determine the depth of their source and the timing of eruption. Here we present direct evidence of abundant CO2in basaltic rocks from the end-Triassic Central Atlantic Magmatic Province (CAMP), through investigation of gas exsolution bubbles preserved by melt inclusions. Our results indicate abundance of CO2and a mantle and/or lower-middle crustal origin for at least part of the degassed carbon. The presence of deep carbon is a key control on the emplacement mode of CAMP magmas, favouring rapid eruption pulses (a few centuries each). Our estimates suggest that the amount of CO2that each CAMP magmatic pulse injected into the end-Triassic atmosphere is comparable to the amount of anthropogenic emissions projected for the 21stcentury. Such large volumes of volcanic CO2likely contributed to end-Triassic global warming and ocean acidification.
A simple contagion process describes spreading of traffic jams in urban networks
Authors: Saberi Meead , Hamedmoghadam Homayoun , Ashfaq Mudabber , Hosseini Seyed Amir , Gu Ziyuan , Shafiei Sajjad , Nair Divya J. , Dixit Vinayak , Gardner Lauren , Waller S. Travis , González Marta C. 
Published: April 2020

AbstractThe spread of traffic jams in urban networks has long been viewed as a complex spatio-temporal phenomenon that often requires computationally intensive microscopic models for analysis purposes. In this study, we present a framework to describe the dynamics of congestion propagation and dissipation of traffic in cities using a simple contagion process, inspired by those used to model infectious disease spread in a population. We introduce two macroscopic characteristics for network traffic dynamics, namely congestion propagation rate β and congestion dissipation rate μ. We describe the dynamics of congestion spread using these new parameters embedded within a system of ordinary differential equations, similar to the well-known susceptible-infected-recovered (SIR) model. The proposed contagion-based dynamics are verified through an empirical multi-city analysis, and can be used to monitor, predict and control the fraction of congested links in the network over time.
Gating mechanism of elongating β-ketoacyl-ACP synthases
Authors: Mindrebo Jeffrey T. , Patel Ashay , Kim Woojoo E. , Davis Tony D. , Chen Aochiu , Bartholow Thomas G. , La Clair James J. , McCammon J. Andrew , Noel Joseph P. , Burkart Michael D. 
Published: April 2020

AbstractCarbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs and choreograph a ping-pong mechanism, often in an iterative fashion. Here, we report crystal structures of substrate mimetic bearing ACPs in complex with the elongating KSs from Escherichia coli, FabF and FabB, in order to better understand the stereochemical features governing substrate discrimination by KSs. Complemented by molecular dynamics (MD) simulations and mutagenesis studies, these structures reveal conformational states accessed during KS catalysis. These data taken together support a gating mechanism that regulates acyl-ACP binding and substrate delivery to the KS active site. Two active site loops undergo large conformational excursions during this dynamic gating mechanism and are likely evolutionarily conserved features in elongating KSs.
Examining the surface evolution of LaTiOxNy an oxynitride solar water splitting photocatalyst
Authors: Lawley Craig , Nachtegaal Maarten , Stahn Jochen , Roddatis Vladimir , Döbeli Max , Schmidt Thomas J. , Pergolesi Daniele , Lippert Thomas 
Published: April 2020

AbstractLaTiOxNy oxynitride thin films are employed to study the surface modifications at the solid-liquid interface that occur during photoelectrocatalytic water splitting. Neutron reflectometry and grazing incidence x-ray absorption spectroscopy were utilised to distinguish between the surface and bulk signals, with a surface sensitivity of 3 nm. Here we show, contrary to what is typically assumed, that the A cations are active sites that undergo oxidation at the surface as a consequence of the water splitting process. Whereas, the B cations undergo local disordering with the valence state remaining unchanged. This surface modification reduces the overall water splitting efficiency, but is suppressed when the oxynitride thin films are decorated with a co-catalyst. With this example we present the possibilities of surface sensitive studies using techniques capable of operando measurements in water, opening up new opportunities for applications to other materials and for surface sensitive, operando studies of the water splitting process.
Predictive values of lung cancer alarm symptoms in the general population: a nationwide cohort study
Authors: Haastrup Peter F. , Jarbøl Dorte E. , Balasubramaniam Kirubakaran , Sætre Lisa M. S. , Søndergaard Jens , Rasmussen Sanne 
Published: April 2020

AbstractWe aimed to firstly determine the 1-year predictive values of lung cancer alarm symptoms in the general population and to analyse the proportion of alarm symptoms reported prior to diagnosis, and secondly analyse how smoking status and reported contact with general practitioners (GPs) regarding lung cancer alarm symptoms influence the predictive values. The study was a nationwide prospective cohort study of 69,060 individuals aged ≥40 years, randomly selected from the Danish population. Using information gathered in a survey regarding symptoms, lifestyle and healthcare-seeking together with registry information on lung cancer diagnoses in the subsequent year, we calculated the predictive values and likelihood ratios of symptoms that might be indicative of lung cancer. Furthermore, we analysed how smoking status and reported contact with GPs regarding the alarm symptoms affected the predictive values. We found that less than half of the patients had reported an alarm symptom six months prior to lung cancer diagnosis. The positive predictive values of the symptoms were generally very low, even for patients reporting GP contact regarding an alarm symptom. The highest predictive values were found for dyspnoea, hoarseness, loss of appetite and for current heavy smokers. The negative predictive values were high, all close to 100%. Given the low positive predictive values, our findings emphasise that diagnostic strategies should not focus on single, specific alarm symptoms, but should perhaps focus on different clusters of symptoms. For patients not experiencing alarm symptoms, the risk of overlooking lung cancer is very low.
The Na/K-ATPase α1 and c-Src form signaling complex under native condition: A crosslinking approach
Authors: Nie Ying , Bai Fang , Chaudhry Muhammad A. , Pratt Rebecca , Shapiro Joseph I. , Liu Jiang 
Published: April 2020

AbstractThe protein-protein interactions amongst the Na/K-ATPase α1 subunit, c-Src, and caveolin-1 (cav-1) are essential for the Na/K-ATPase signaling functions. However, there are arguments concerning the interaction model. The present study aims to clarify the interactions amongst the endogenous native proteins in live cells under native resting condition. Under native condition, Blue Native-PAGE and Blue Native-PAGE/SDS-PAGE 2D analyses demonstrated co-existence of the α1 subunit and c-Src in same protein complex, as well as a direct interaction between the α1 subunit and c-Src. By comparison of cleavable and non-cleavable cysteine-cysteine crosslinked samples, capillary immunoblotting analysis demonstrated that depletion of Src kinase family members (c-Src, Yes, and Fyn) or cav-1 clearly reduced the interactions of the α1 subunit with proteins, but depletion of cav-1 did not affect the interaction of c-Src with the α1 subunit. The data indicated that there are direct interactions between the α1 subunit and c-Src as well as between the α1 subunit and cav-1, but argued about the interaction between c-Src and cav-1 under the condition. Furthermore, the data also indicated the existence of different protein complexes containing the α1 subunit and c-Src, which might have different signaling functions.
GWAS revealed a novel resistance locus on chromosome 4D for the quarantine disease Karnal bunt in diverse wheat pre-breeding germplasm
Authors: Singh Sukhwinder , Sehgal D. , Kumar S. , Arif M. A. R. , Vikram P. , Sansaloni C. P. , Fuentes-Dávila G. , Ortiz C. 
Published: April 2020

AbstractThis study was initiated to identify genomic regions conferring resistance to Karnal Bunt (KB) disease in wheat through a genome-wide association study (GWAS) on a set of 179 pre-breeding lines (PBLs). A GWAS of 6,382 high-quality DArTseq SNPs revealed 15 significant SNPs (P-value <10−3) on chromosomes 2D, 3B, 4D and 7B that were associated with KB resistance in individual years. In particular, two SNPs (chromosome 4D) had the maximumR2values: SNP 1114200 | F | 0–63:T > C at 1.571 cM andR2of 12.49% and SNP 1103052 | F | 0–61:C > A at 1.574 cM andR2of 9.02%. These two SNPs displayed strong linkage disequilibrium (LD). Anin silicoanalysis of SNPs on chromosome 4D identified two candidate gene hits, TraesCS4D02G352200 (TaNox8; an NADPH oxidase) and TraesCS4D02G350300 (a rhomboid-like protein belonging to family S54), with SNPs 1103052 | F | 0–61:C > A and 1101835 | F | 0–5:C > A, respectively, both of which function in biotic stress tolerance. The epistatic interaction analysis revealed significant interactions among 4D and 7B loci. A pedigree analysis of confirmed resistant PBLs revealed thatAegilopsspecies is one of the parents and contributed the D genome in these resistant PBLs. These identified lines can be crossed with any elite cultivar across the globe to incorporate novel KB resistance identified on 4B.
Otoferlin gene editing in sheep via CRISPR-assisted ssODN-mediated Homology Directed Repair
Authors: Menchaca A. , dos Santos-Neto P. C. , Souza-Neves M. , Cuadro F. , Mulet A. P. , Tesson L. , Chenouard V. , Guiffès A. , Heslan J. M. , Gantier M. , Anegón I. , Crispo M. 
Published: April 2020

AbstractDifferent mutations of the OTOF gene, encoding for otoferlin protein expressed in the cochlear inner hair cells, induces a form of deafness that is the major cause of nonsyndromic recessive auditory neuropathy spectrum disorder in humans. We report the generation of the first large animal model of OTOF mutations using the CRISPR system associated with different Cas9 components (mRNA or protein) assisted by single strand oligodeoxynucleotides (ssODN) to induce homology-directed repair (HDR). Zygote microinjection was performed with two sgRNA targeting exon 5 and 6 associated to Cas9 mRNA or protein (RNP) at different concentrations in a mix with an ssODN template targeting HDR in exon 5 containing two STOP sequences. A total of 73 lambs were born, 13 showing indel mutations (17.8%), 8 of which (61.5%) had knock-in mutations by HDR. Higher concentrations of Cas9-RNP induced targeted mutations more effectively, but negatively affected embryo survival and pregnancy rate. This study reports by the first time the generation of OTOF disrupted sheep, which may allow better understanding and development of new therapies for human deafness related to genetic disorders. These results support the use of CRISPR/Cas system assisted by ssODN as an effective tool for gene editing in livestock.
Two-Level Protein Methylation Prediction using structure model-based features
Authors: Zheng Wei , Wuyun Qiqige , Cheng Micah , Hu Gang , Zhang Yanping 
Published: April 2020

AbstractProtein methylation plays a vital role in cell processing. Many novel methods try to predict methylation sites from protein sequence by sequence information or predicted structural information, but none of them use protein tertiary structure information in prediction. In particular, most of them do not build models for predicting methylation types (mono-, di-, tri-methylation). To address these problems, we propose a novel method, Met-predictor, to predict methylation sites and methylation types using a support vector machine-based network. Met-predictor combines a variety of sequence-based features that are derived from protein sequences with structure model-based features, which are geometric information extracted from predicted protein tertiary structure models, and are firstly used in methylation prediction. Met-predictor was tested on two independent test sets, where the addition of structure model-based features improved AUC from 0.611 and 0.520 to 0.655 and 0.566 for lysine and from 0.723 and 0.640 to 0.734 and 0.643 for arginine. When compared with other state-of-the-art methods, Met-predictor had 13.1% (3.9%) and 8.5% (16.4%) higher accuracy than the best of other methods for methyllysine and methylarginine prediction on the independent test set I (II). Furthermore, Met-predictor also attains excellent performance for predicting methylation types.
A comparative study on flavour components and therapeutic properties of unfermented and fermented defatted soybean meal extract
Authors: Ghanem Kadry Z. , Mahran Mohamed Z. , Ramadan Manal M. , Ghanem Hassan Z. , Fadel Mohamed , Mahmoud Mohamed H. 
Published: April 2020

AbstractMicrobial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography–mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and δ-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362 ± 0.05 and 2.11 ± 0.02 mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763 ± 0.05 and 3.795 ± 0.03 mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331 ± 0.04 and 3.971 ± 0.02 mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 μg/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1 mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1 mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.