bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Do People Begin to Meditate and Why Do They Continue?
Authors: Sedlmeier Peter , Theumer Jan
Published: April 2020

Objectives

Studies that have examined why people begin to meditate and why they stay with it are few and inconclusive. We looked at these questions in two comprehensive exploratory studies.

Methods

In study 1, meditation teachers were asked why participants in their courses might begin to meditate and why they might continue to do so. A qualitative analysis of their responses, together with suggestions from the literature, yielded 77 distinct reasons that were applicable to both beginners and advanced meditators. In study 2, 245 meditators (49 who had practiced for less than 1 year) rated how strongly these reasons applied to themselves. Exploratory factor analyses of the reasons both to begin and to continue meditation were conducted.

Results

We found a large number of different categories that go beyond those identified in previous research. Reasons changed with increasing meditation practice, although spiritual goals tended to become more important only for practitioners with a spiritual background.

Conclusions

Our results indicate that reasons for meditating are much more diverse than previously assumed and that they are influenced by practitioners’ spiritual background and their personality characteristics.
Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice
Authors: Trout Amanda L. , Kahle Michael P. , Roberts Jill M. , Marcelo Aileen , de Hoog Leon , Boychuk Jeffery A. , Grupke Stephen L. , Berretta Antonio , Gowing Emma K. , Boychuk Carie R. , Gorman Amanda A. , Edwards Danielle N. , Rutkai Ibolya , Biose Ifechukwude J. , Ishibashi-Ueda Hatsue , Ihara Masafumi , Smith Bret N. , Clarkson Andrew N. , Bix Gregory J.
Published: April 2020

The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods. Furthermore, perlecan deficient mice had significantly less neuroblast precursor cells after experimental stroke. Seven-day delayed domain V administration enhanced neurogenesis and restored peri-infarct excitatory synaptic drive to neocortical layer 2/3 pyramidal neurons after experimental stroke. Domain V’s effects were inhibited by blockade of α2β1 integrin, suggesting the importance of α2β1 integrin to neurogenesis and domain V neurogenic effects. Our results demonstrate that perlecan plays a previously unrecognized role in post-stroke neurogenesis and that delayed DV administration after experimental stroke enhances neurogenesis and improves recovery in an α2β1 integrin-mediated fashion. We conclude that domain V is a clinically relevant neuroprotective and neuroreparative novel stroke therapy with a broad therapeutic window.
Effects of annealing and firing in wet hydrogen on the dielectric breakdown strengths of alumina ceramics
Authors: Du Jishi , Tang Binghua , Liu Wei , Zhang Tao , Peng Jiagen , Chen Hu , Lei Yangjun
Published: April 2020

Annealing and firing in wet hydrogen are widely used steps in the processing alumina.ceramic insulators that may affect their dielectric breakdown strengths (DBS). In this study, the effects of annealing (at 1300 °C for 7 h) and firing in wet hydrogen on the DBS of alumina ceramics (all sintered at 1650 °C) were studied, and the underlying mechanisms were analyzed by material characterizations. Annealing reduced the DBS of the 95% alumina ceramics due to the inter-granular phase crystallization, and the reduction in the DBS could be correlated to the reduction in mechanical strength. In contrast, annealing improved the DBS of the 99% alumina ceramic without intergranular phase transformation. Firing in wet hydrogen at 1500 °C caused the DBS increment, which can be ascribed to the reduction in the concentrations of point defects and electrical carriers.
P-E hysteresis loop going slim in Ba0.3Sr0.7TiO3-modified Bi0.5Na0.5TiO3 ceramics for energy storage applications
Authors: Li Dongxu , Shen Zong-Yang , Li Zhipeng , Luo Wenqin , Wang Xingcai , Wang Zhumei , Song Fusheng , Li Yueming
Published: April 2020

(Ba0.3Sr0.7)x(Bi0.5Na0.5)1-xTiO3(BSxBNT,x= 0.3–V0.8) ceramics were prepared to investigate their structure, dielectric and ferroelectric properties. BSxBNT ceramics possess pure perovskite structure accompanied from a tetragonal symmetry to pseudo-cubic one with the increase ofxvalue, being confirmed by X-ray diffraction (XRD) and Raman results. TheTmcorresponding to a temperature in the vicinity of maximum dielectric constant gradually decreases from 110 °C (x= 0.3) to -45 °C (x= 0.8), acrossTm= 36 °C (x= 0.5) with a maximum dielectric constant (ɛr= 5920 @1 kHz) around room temperature. The saturated polarizationPsgradually while the remnant polarization Pr sharply decreases with the increase ofxvalue, making theP-Ehysteresis loop of BSxBNT ceramics goes slim. A maximum difference betweenPsandPr(Ps-Pr) is obtained for BSxBNT ceramics withx= 0.5, at which a high recoverable energy density (Wrec= 1.04 J/cm3) is achieved under an applied electric field of 100 kV/cm with an efficiency ofη= 77%. Meanwhile, the varied temperatureP-Eloops, fatigue measurements, and electric breakdown characteristics for the sample withx= 0.5 indicate that it is promising for pulsed power energy storage capacitor candidate materials.
Determination of polarization states in (K,Na)NbO3 lead-free piezoelectric crystal
Authors: Zhang Mao-Hua , Hu Chengpeng , Zhou Zhen , Tian Hao , Thong Hao-Cheng , Liu Yi Xuan , Xu Xing-Yu , Xi Xiao-Qing , Li Jing-Feng , Wang Ke
Published: April 2020

Polarization switching in lead-free (K0.40Na0.60)NbO3 (KNN) single crystals was studied by switching spectroscopy piezoresponse force microscopy (SS-PFM). Acquisition of multiple hysteresis loops on a closely spaced square grid enables polarization switching parameters to be mapped in real space. Piezoresponse amplitude and phase hysteresis loops show collective symmetric/asymmetric characteristics, affording information regarding the switching behavior of different domains. As such, the out-of-plane polarization states of the domains, including amplitudes and phases can be determined. Our results could contribute to a further understanding of the relationships between polarization switching and polarization vectors at the nanoscale, and provide a feasible method to correlate the polarization hysteresis loops in a domain under an electric field with the polarization vector states.
Effect of sintering temperature in argon atmosphere on microstructure and properties of 3D printed alumina ceramic cores
Authors: Li He , Liu Yongsheng , Liu Yansong , Zeng Qingfeng , Hu Kehui , Lu Zhigang , Liang Jingjing
Published: April 2020

Alumina ceramics with different sintering temperatures in argon atmosphere were obtained using stereolithography-based 3D printing. The effects of sintering temperature on microstructure and physical and mechanical properties were investigated. The results show that the average particle size, shrinkage, bulk density, crystallite size, flexural strength, Vickers hardness, and nanoindentation hardness increased with the increase in sintering temperature, whereas the open porosity decreased with increasing sintering temperature. No change was observed in phase composition, chemical bond, atomic ratio, and surface roughness. For the sintered samples, the shrinkage in Z direction is much greater than that in X or Y direction. The optimum sintering temperature in argon atmosphere is 1350 °C with a shrinkage of 3.0%, 3.2%, and 5.5% in X, Y, and Z directions, respectively, flexural strength of 26.7 MPa, Vickers hardness of 198.5 HV, nanoindentation hardness of 33.1 GPa, bulk density of 2.5 g/cm3, and open porosity of 33.8%. The optimum sintering temperature was 70 °C higher than that sintering in air atmosphere when achieved the similar properties.
Mit zweierlei Maß gemessen – Kalkulierte Ambivalenz in rechtspopulistischen Repräsentationen von Geschlechterverhältnissen
Authors: Reisigl Martin
Published: April 2020

Kalkulierte Ambivalenz ist ein rhetorisches Prinzip, das in Parteiprogrammen, in der politischen Werbung, in konsensorientierten Kommunikationstypen wie Gedenkreden, in diplomatischen Text- und Diskursarten sowie halbherzigen Entschuldigungen gerne verwendet wird. Es dient dazu, die Vereinbarkeit von gegensätzlichen politischen sowie ideologischen Interessen und Positionen zu suggerieren, mehrere Gruppen von Wähler*innen gleichzeitig zu adressieren, Tabus zu brechen, ohne die Verantwortung übernehmen zu müssen, und die Festlegung auf eine eindeutige Position zu vermeiden. Sie kann das Ergebnis der Mitwirkung unterschiedlicher Personen an der Textarbeit sein. Der Beitrag geht darauf ein, wie das Prinzip im rechten oppositionellen ebenso wie im Regierungspopulismus der FPÖ bei der Darstellung von Geschlechterverhältnissen angewandt wird, um die traditionelle Männerpartei als frauenfreundlichere Partei erscheinen zu lassen.
Un agent abyssinien et deux rois indiens à La Mecque: Interactions autour du droit islamique auxve siècle
Authors: Kooria Mahmood
Published: April 2020

Résumés

Durant le premier millénaire de l’islam, la plus grande faculté de droit(madrasa)de La Mecque fut créée par un souverain bengali. Connue sous le nom d’université Banjāliyya, elle devint l’un des instituts les plus importants de la ville. Une deuxième université fut fondée deux décennies plus tard par un autre sultan bengali, né et élevé en hindou. Cet article revient en détail sur la création et l’histoire de ces deux universités et sur les implications en matière d’interactions juridiques pour l’historiographie existante sur le Moyen-Orient, l’islam d’Asie du Sud et l’océan Indien. Le premier projet d’établissement, mené à bien par un agent abyssin, montre comment le droit a fourni des fondements et un langage communs qui permirent aux musulmans asiatiques, africains et arabes d’échanger et d’harmoniser leurs desseins culturels, économiques, politiques et diplomatiques. Les représentations liées aux projets juridiques ouvraient des possibilités qui n’auraient autrement pas été envisageables et qui dépassaient le droit en tant que doctrine religieuse. Cette histoire d’un triangle d’interactions afro-arabo-asiatique amène à repenser ce que nous savions sur l’islam prémoderne et le droit islamique. Au lieu de considérer les Arabes comme les seuls exportateurs de l’islam et de son droit et les croyants d’Asie et d’Afrique comme de simples récepteurs, il faut accepter la réalité d’échanges réciproques existant depuis les périodes prémodernes. L’histoire des facultés de droit bengalies à La Mecque éclaire sur ces interconnexions afro-arabo-asiatiques et sur leur rôle dans la formation de l’islam d’Asie du Sud en particulier et de l’océan Indien en général.
Subthalamic Nucleus Stimulation in Pediatric Isolated Dystonia: A 10-Year Follow-up
Authors: Xu Wenying , Li Hongxia , Zhang Chencheng , Sun Bomin , Wu Yiwen , Li Dianyou
Published: April 2020

Objective:

To evaluate the short-term and long-term clinical effectiveness and safety of subthalamic nucleus deep brain stimulation (STN-DBS) for medically intractable pediatric isolated dystonia.

Methods:

Using a longitudinal retrospective design, we assessed the clinical outcomes of nine patients who underwent STN-DBS for treatment-refractory pediatric isolated dystonia one decade ago (mean age at surgery: 15.9 ± 4.5 years). The primary clinical outcome used was assessed by retrospective video analyses of patients’ dystonia symptoms using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Clinical assessments were performed at baseline, 1-year follow-up (1-yr FU), and 10-year follow-up (10-yr FU). Adverse side effects, including surgery-related, device-related, and stimulation-related effects, were also documented.

Results:

After STN-DBS surgery, the mean improvement in the BFMDRS motor score was 77.1 ± 26.6% at 1-yr FU and 90.4 ± 10.4% at 10-yr FU. Similarly, the mean BFMDRS disability score was improved by 69.5 ± 13.6% at 1-yr FU and by 86.5 ± 13.9% at 10-yr FU. The clinical improvements gained at 10-yr FU were significantly larger than those observed at 1-yr FU. Negative correlations were found between the duration of disease to age at surgery ratio (DD/AS) and the improvements in the BFMDRS motor score and total score at 1-yr FU and 10-yr FU.

Conclusion:

To our knowledge, this study provides the first clinical evidence for the short- and long-term effectiveness and safety of STN-DBS for pediatric isolated dystonia. Additionally, putative evidence is provided that earlier STN-DBS intervention in patients with refractory pediatric isolated dystonia may improve short- and long-term clinical outcomes.
Effect of antibiotic time-outs on modification of antibiotic prescriptions in nursing homes
Authors: Liao Chi-Yin , Nace David A. , Crnich Christopher J. , Bahrainian Mozhdeh , Ford James H.
Published: April 2020

Background:

Antibiotic overuse and misuse is a common problem in nursing homes. Antibiotic time-out (ATO) interventions have led to improvements in antibiotic uses in hospitals, but their impact in nursing homes remain understudied.

Objective:

To evaluate the impact of a stewardship intervention, promoting use of ATOs on the frequency and types of antibiotic change events (ACEs) in nursing homes.

Design:

Controlled before-and-after intervention study.

Setting:

Nursing homes in Wisconsin and Pennsylvania.

Method:

Data on antibiotic prescriptions in 11 nursing homes were collected for 25 months. We categorized ACEs as (1) early discontinuation, (2) class modification, or (3) administration modification. Class modification ACEs were further classified based on whether the change narrowed, expanded, or had no effect on bacterial spectrum coverage. Analyses were performed using a difference-in-difference (DiD) approach.

Result:

Of 2,647 antibiotic events initiated in study nursing homes, 376 (14.2%) were associated with an ACE. The overall proportion of ACEs did not significantly differ between intervention and control nursing homes. Early discontinuation ACEs increased in intervention nursing homes (DiD, 2.5%; P = .01), primarily affecting residents initiated on broad-spectrum antibiotics (DiD, 2.9%; P < .01). Class modification ACEs decreased in intervention nursing homes but remained unchanged in control nursing homes.

Conclusion:

The impact of an ATO intervention in study nursing homes was mixed with increases in early discontinuation ACEs offset by reductions in class modification ACEs. More research on the potential value of ATO interventions in nursing homes is warranted.
Variability in antifungal stewardship strategies among Society for Healthcare Epidemiology of America (SHEA) Research Network facilities
Authors: Fitzpatrick Margaret A. , Albarillo Fritzie , Santarossa Maressa , Evans Charlesnika T. , Suda Katie J.
Published: April 2020

Objective:

To characterize antifungal stewardship among antimicrobial stewardship programs (ASPs) at a diverse range of hospitals and to correlate antifungal stewardship with hospital characteristics.

Design:

Cross-sectional survey.

Participants:

ASP physician and/or pharmacist members at Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN) hospitals.

Methods:

An electronic survey administered August–September 2018 via the SRN to 111 hospitals. The χ2 test was used to test associations between ASP and hospital characteristics and use of antifungal stewardship strategies.

Results:

Of 111 hospitals, 45 (41%) responded; most were academic medical centers (65%) caring for stem-cell patients (73.3%) and solid-organ transplant patients (80.0%). Most hospitals have large, well-established ASPs: 60% had >5 team members and 68.9% had a duration ≥6 years. In 43 hospitals (95.6%), ASPs used antifungal stewardship strategies, most commonly prospective audit and feedback (73.3%) by a pharmacist (71.4%). Half of ASPs (51.1%) created guidelines for invasive fungal infection (IFI) management. Most hospitals (71.1%) offered rapid laboratory tests to diagnose IFI, but polymerase chain reaction (PCR) testing and antifungal susceptibility testing varied. Also, 29 ASPs (64.4%) perform surveillance of antifungal utilization, but only 9 (31%) reported to the CDC National Healthcare Safety Network. ASP size, duration, and presence of transplant populations were not associated with a higher likelihood of using antifungal stewardship strategies (P > .05 for all).

Conclusions:

The use of antifungal stewardship strategies was high at SRN hospitals, but they mainly involved audit and feedback. ASPs should be encouraged (1) to disseminate guidelines for IFI management, (2) to promote access to laboratory tests for rapid and accurate IFI diagnosis, and (3) to perform surveillance for antifungal utilization with reporting to the CDC.
School belonging in adolescents: Psychometric properties of the School Belongingness Scale in Iranian students
Authors: Arslan Gökmen , Asanjarani Faramarz , Bakhtiari Saeede , Hajkhodadadi Fatemeh
Published: April 2020

The purpose of the present study is to investigate the initial psychometric properties and cultural adaptation of the School Belongingness Scale (SBS) in a sample of Iranian adolescents. Participants included 324 students, ranging in age between 12 and 18 years ( M = 14.68, SD = 1.39). Confirmatory factor analysis indicated that responses to the Farsi version of the SBS were characterised by a two-factor measurement model, and latent variable path analysis results revealed this measurement model was predictive of adolescents’ responses to measures of social, emotional, and behavioural problems (e.g., emotional problems, conduct problems), academic achievement, and prosocial behaviour. These results provide initial evidence suggesting that the scale is psychometrically adequate to measure Iranian students’ sense of belonging at school.
Hidden diversity of small predators: new thorny lacewings from mid-Cretaceous amber from northern Myanmar (Neuroptera: Rhachiberothidae: Paraberothinae)
Authors: Nakamine Hiroshi , Yamamoto Shûhei , Takahashi Yui
Published: April 2020

Thorny lacewings (Rhachiberothidae) are currently distributed only within Africa, whereas they are prevalent in the fossil record of various Cretaceous ambers across the Northern Hemisphere, with a handful of the fossil records from some Eocene European ambers. Four rhachiberothid species in four extinct genera are known from the mid-Cretaceous amber of northern Myanmar. Here, we report further examples of the remarkable palaeodiversity of this group from the same amber deposit, adding the four new fossil genera and seven new species:Acanthoberotha cuspisgen. et sp. nov.,Astioberotha falcipesgen. et sp. nov.,Stygioberotha siculiferagen. et sp. nov.,Uranoberotha chariessagen. et sp. nov.,Creagroparaberotha cuneatasp. nov.,Micromantispa galeatasp. nov. andM.spicatasp. nov. Based on a series of well-preserved specimens, we discuss the fine details of the raptorial forelegs and genital segments, which may be important for elucidating the phylogenetic relationships among genera. Our findings reveal an unexpectedly diverse assemblage of thorny lacewings in the Cretaceous System, highlighting the morphologically diverse rhachiberothids in Burmese amber. The discovery of seven additional rhachiberothid species in Myanmar amber suggests the potential for much higher diversity and abundance of the Cretaceous rhachiberothids than previously documented. Furthermore, morphological variation in the raptorial forelegs was found to be extremely diverse among the Burmese amber paraberothines, especially in terms of the size, number and shape of spines (or spine-like setae) on the inner edges of protibia, and the morphological structure of the probasitarsus.
The Samurai Bond: Credit Supply, Market Access, and Structural Transformation in Pre-War Japan
Authors: Basco Sergi , Tang John P.
Published: April 2020

While credit supply growth is associated with exacerbating financial crises, its impact on long-run growth is unclear. Market access similarly has ambiguous economic effects over time. Using regional variation in bond payments to samurai and the introduction of railways in nineteenth century Japan, we find that together they are associated with persistent redistributive effects between regions and sectors. Areas with higher bond value and railway access experienced tertiary sector growth and primary sector shrinkage, with analogous results in sectoral labor shares. This interaction between credit supply and market access facilitated structural transformation but had little long-run net growth impact.
Ultimate attainment in heritage language speakers: Syntactic and morphological knowledge of Italian accusative clitics
Authors: Romano Francesco Bryan
Published: April 2020

The acquisition of a heritage language, normally the weaker language of early bilinguals, has been oftentimes defined as incomplete, especially for morphosyntax. As a result, these early bilinguals resemble late bilinguals more than native language speakers, calling into question the role of age of exposure. The effects of syntactic complexity on knowledge of morphosyntactic structures, however, have not been sufficiently considered hitherto. This study investigates age of exposure and syntactic complexity by comparing heritage, second language, and native language speakers on knowledge of Italian accusative clitics in three structures. An oral structural priming task and a speeded grammaticality judgment task find a discrepancy in the level of ultimate attainment heritage speakers reach for syntax and morphology. While their abstract representation of clitic structures approximates that of native language speakers more closely, their morphological knowledge of clitics aligns with second language speakers, suggesting early exposure has tangible effects only on syntactic knowledge. In turn, syntactic complexity affects the representation of clitic structures in a predictable manner, but is inconsequential to explicit knowledge of morphological forms in monolingual and bilingual speakers. Lack of age of exposure effects in the morphological domain are attributed to interface vulnerability.
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

The 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

We 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

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

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

Large 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

The 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

Carbon-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

LaTiOxNy 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

We 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

The 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

This 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.
Author Correction: The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study
Authors: Rashad Sherif , Saqr Khalid M. , Fujimura Miki , Niizuma Kuniyasu , Tominaga Teiji
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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

Different 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

Protein 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

Microbial 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.
RETRACTED ARTICLE: Fire and summer temperatures work together breaking physical seed dormancy
Authors: Luna Belén
Published: April 2020

Fire and high summer soil temperatures can break physical seed dormancy in Mediterranean fire-prone ecosystems. Their independent effect is somewhat recognized but both factors may act together with a synergistic effect yet unknown. This study aims to determine the isolated and combined effects of fire and summer temperatures on the release of physical seed dormancy in Cistaceae species. Fire and summer temperature treatments were applied in a factorial experiment to seeds of 12 species of Cistaceae. Seeds previously exposed or not to a heat shock (fire simulation) were kept for 1 or 2 months at constant or alternating temperatures (summer temperatures simulation). Additionally, I compared the effect of exposing the seeds to a heat shock before or after they had been subjected to the summer temperatures. Heat shock increased germination of all species, but summer temperatures produced different results. When seeds were exposed to summer temperatures after heat shock, germination decreased. This negative effect disappeared when heat shock was simulated at the end of the summer temperatures. Fire and summer temperatures modulate timing of germination in Cistaceae with a joint control on post-fire regeneration. Cycling of sensitivity to physical dormancy release may be the mechanism to explain this fine-tuning, which would ensure germination when environmental conditions are suitable for growth. These results contribute to our understanding of vegetation dynamics and postfire regeneration in Mediterranean ecosystems.