bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct medical costs of ADHD and its comorbid conditions on basis of a claims data analysis
Authors: Libutzki Berit , Ludwig Saskia , May Melanie , Jacobsen Rasmus Højbjerg , Reif Andreas , Hartman Catharina A.
Published: February 2019

Background:

ADHD is a highly prevalent disease in childhood which often persists into adulthood, then co-occurring with common adult conditions. Especially for adult ADHD, little is known about the costs of ADHD and the additional costs of comorbid conditions.

Aims:

To determine medical costs of ADHD and costs of comorbidities (mood, anxiety and substance use disorders, obesity), including their co-occurrence rates, stratified by age and gender.

Method:

Claims data from a German Statutory Health Insurance database with approximately four million member-records per year were analysed. A total of 25,300 prevalent ADHD patients were identified by means of an ICD-10 GM diagnosis of ADHD. A 1:1 age and gender adjusted reference group without ADHD diagnosis was randomly selected. Total health claims and health care costs related to ADHD were analysed, in addition to more targeted analyses of the occurrence and costs of pre-defined common comorbidities of, in particular, adult ADHD (SUD, mood and anxiety disorders, obesity). Outcomes were mean costs per patient and occurrence rates of comorbid conditions. Surplus costs of a comorbid condition in persons with ADHD relative to costs of this condition in persons without ADHD were calculated. Subgroup analyses were conducted based on age (0–12 years, 13–17 years, 18–30years, 30+ years) and gender.

Results:

Patients with ADHD were €1500 more expensive annually than individuals without ADHD (p < 0.001). Main cost drivers were inpatient care, psychiatrists and psychotherapists. Mood, anxiety, substance use disorders and obesity were significantly more frequent in ADHD patients and additional costs resulting from the comorbid conditions amounted up to €2800. Costs were slightly higher in women than men and increased with age for both genders. In young adults (18–30 years) health care costs dropped notably, especially costs for the medical treatment of ADHD with stimulants and costs for psychiatrists, before rising again in the group of patients over 30 years who had higher comorbidity rates.

Conclusions:

Medical costs for ADHD are substantial, in part through frequently occurring comorbid conditions, and particularly in adulthood, and are likely to further accelerate in the coming years. A gap of care was found, starting with the transition age group of patients over 17 years, as indicated by reduced costs per person during young adulthood, as well as an overall strong drop in administrative prevalence. In the future, approaches to improve the situation of care and reduce costs at the same time, i.e. through managed care programmes, should be implemented and benefit from detailed knowledge on age and gender-specific cost-drivers.
Role of transversal concentration gradient in detonation propagation
Authors: Han Wenhu , Wang Cheng , Law Chung K.
Published: February 2019

The role of a transversal concentration gradient in detonation propagation in a two-dimensional channel filled with an $\text{H}_{2}{-}\text{O}_{2}$ mixture is examined by high-resolution simulation. Results show that, compared to propagation in homogeneous media, a concentration gradient reduces the average detonation velocity because of the delay in reaching downstream reaction equilibrium, leading to a large amount of unreacted $\text{H}_{2}$ and hence significant species fluctuations. The transversal concentration gradient also enhances the cellular detonation instability. Steepening it reduces considerably the number of triple points on the front, lengthens the global detonation front structure on average and consequently increases the deficit of the average detonation velocity. It is further found that the interaction of the leading shock with the transversal concentration gradient influences the formation of local $\text{H}_{2}$ bump and thus the unreacted pocket behind the front, while the transverse wave causes mixing and burning of the residue fuel downstream. Nevertheless, for the steepened concentration gradient, a transverse detonation is present and consumes the fuel in the compressed and preheated zone by the leading shock; consequently, the detonation velocity deficit is not increased significantly for detonation with the single-head propagation mode close to the limit.
Wondrous Depths: Judging the Mind in Nineteenth-Century America
Authors: Evans Catherine L.
Published: February 2019

Susanna L. Blumenthal’sLaw and the Modern Mind: Consciousness and Responsibility in American Legal Culture(2016) is a history of the self in nineteenth-century America. When judges considered a person’s criminal responsibility or civil capacity in court, they created a body of legal and political thought about the self, society, the economy, and American democracy. This essay uses Blumenthal’s book to explore recent work on law and the mind in Britain and North America, and argues that abstract questions about free will, the self, and the mind were part of the everyday jurisprudence of the nineteenth century. Debates about responsibility were also debates about the psychological consequences of capitalism and the borders of personhood and citizenship at a time of rapid economic, political, and social change.
The performance and calibration of the CRAFT fly’s eye fast radio burst survey
Authors: James C. W. , Bannister K. W. , Macquart J.-P. , Ekers R. D. , Oslowski S. , Shannon R. M. , Allison J. R. , Chippendale A. P. , Collier J. D. , Franzen T. , Hotan A. W. , Leach M. , McConnell D. , Pilawa M. A. , Voronkov M. A. , Whiting M. T.
Published: February 2019

The Commensal Real-time Australian Square Kilometre Array Pathfinder Fast Transients survey is the first extensive astronomical survey using phased array feeds. Since January 2017, it has been searching for fast radio bursts in fly’s eye mode. Here, we present a calculation of the sensitivity and total exposure of the survey that detected the first 20 of these bursts, using the pulsars B1641-45 and B0833-45 as calibrators. The beamshape, antenna-dependent system noise, and the effects of radio-frequency interference and fluctuations during commissioning are quantified. Effective survey exposures and sensitivities are calculated as a function of the source counts distribution. Statistical ‘stat’ and systematics ‘sys’ effects are treated separately. The implied fast radio burst rate is significantly lower than the 37 sky−1 day−1 calculated using nominal exposures and sensitivities for this same sample by Shannon et al. (2018). At the Euclidean (best-fit) power-law index of −1.5 (−2.2), the rate is

$12.7_{-2.2}^{+3.3}$

(sys) ± 3.6 (stat) sky−1 day−1 (

$20.7_{-1.7}^{+2.1}$

(sys) ± 2.8 (stat) sky−1 day−1) above a threshold of 56.6 ± 6.6(sys) Jy ms (40.4 ± 1.2(sys) Jy ms). This strongly suggests that these calculations be performed for other FRB-hunting experiments, allowing meaningful comparisons to be made between them.
Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia–reperfusion injury through depletion of glutathione
Authors: Skene Karen , Walsh Sarah K. , Okafor Oronne , Godsman Nadine , Barrows Charlotte , Meier Philip , Gordon Margaret J. , Beattie John H. , Wainwright Cherry L.
Published: February 2019

Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague–Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (<1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.
THE ETHICAL DISCUSSION OF PROTECTION (BOĒTHEIA) IN PLATO'SGORGIAS
Authors: Catana Leo
Published: February 2019

Over the last decades we have seen an increased interest in forensic rhetoric in Plato's dialogues, notably in relation to hisApology. However, little interest has been paid to this strain of rhetoric in relation to theGorgias. In this article I focus on one notion, βοήθεια, as it was discussed in Plato'sGorgias. This notion had a wide currency in forensic rhetoric in classical Athens.
Stance-taking and participation framework in museum commenting platforms: On subjects, objects, authors, and principals
Authors: Noy Chaim , Hamo Michal
Published: February 2019

The realization of subjectivity through language use is a key concern of sociolinguistic research. We argue for examining it by juxtaposing Goffman's participation framework and Du Bois’ stance triangle. We focus on museums’ commenting platforms as ‘stance-rich’ media (Du Bois 2007:151) by examining the communicative affordances of a visitor book at the Florida Holocaust Museum and analyzing museumgoers’ texts (3,064). These texts are homogeneous in their morally indignant evaluation of the Holocaust and their alignment with the museum, but heterogeneous in positioning and participation framework. Museumgoers’ texts are highly responsive to the setting and previous discourses of the museum and include patterns of shared authorship and principalship. These patterns allow museumgoers to construct shared, institutionally mandated, subjectivities while maintaining personal commitment. These findings contribute to our understanding of the construction of subjectivity as inherently dialogic, and as involving the purposeful use of a multiplicity of contextual resources. (Participation framework, stance triangle, repetitions, principalship, commitment, Holocaust, museums, visitor books)
A unificationist defence of revealed preferences
Authors: Vredenburgh Kate
Published: February 2019

Revealed preference approaches to modelling agents’ choices face two seemingly devastating explanatory objections. The no self-explanation objection imputes a problematic explanatory circularity to revealed preference approaches, while the causal explanation objection argues that, all things equal, a scientific theory should provide causal explanations, but revealed preference approaches decidedly do not. Both objections assume a view of explanation, the constraint-based view, that the revealed preference theorist ought to reject. Instead, the revealed preference theorist should adopt a unificationist account of explanation, allowing her to escape the two explanatory problems discussed in this paper.
QUANTILE-BASED STUDY OF (DYNAMIC) INACCURACY MEASURES
Authors: Kayal Suchandan , Moharana Rajesh , Sunoj S. M.
Published: February 2019

In the present communication, we introduce quantile-based (dynamic) inaccuracy measures and study their properties. Such measures provide an alternative approach to evaluate inaccuracy contained in the assumed statistical models. There are several models for which quantile functions are available in tractable form, though their distribution functions are not available in explicit form. In such cases, the traditional distribution function approach fails to compute inaccuracy between two random variables. Various examples are provided for illustration purpose. Some bounds are obtained. Effect of monotone transformations and characterizations are provided.
Trends of hospitalisations rates in a cohort of HIV-infected persons followed in an Italian hospital from 1998 to 2016
Authors: Bellino S. , Borghetti A. , Lombardi F. , Camoni L. , Ciccullo A. , Baldin G. , Belmonti S. , Moschese D. , Lamonica S. , Cauda R. , Pezzotti P. , Di Giambenedetto S.
Published: February 2019

Here we evaluated hospitalisation rates and associated risk factors of human immunodeficiency virus (HIV)-infected individuals who were followed up in an Italian reference hospital from 1998 to 2016. Incidence rates (IR) of hospitalisations were calculated for five study periods from 1998 to 2016. The random-effects Poisson regression model was used to assess risk factors for hospitalisation including demographic and clinical characteristics. To consider that more events may occur for the same subject, multiple failure-time data analysis was also performed for selected causes using the Cox proportional hazards model. We evaluated 2031 patients. During 13 173 person-years (py) of follow-up, 3356 hospital admissions were carried out for 756 patients (IR: 255 per 1000 py). IR decreased significantly over the study period, from 634 in 1998–2000 to 126 per 1000 py in 2013–2016. Major declines were detected for AIDS-defining events, non-HIV/AIDS-related infections and neurological diseases. Older age, female sex, longer HIV duration and HCV coinfection were associated with a higher hospitalisation risk, whereas higher CD4 nadir and antiretroviral therapy were associated with a reduced risk. Influence of advanced HIV disease markers declined over time. Hospitalisation rates decreased during the study period in most causes. The relative weight of hospitalisations for non-AIDS-related tumours, cardiovascular, respiratory and kidney diseases increased during the study period, whereas those for AIDS-defining events declined.
Skin and soft tissue infections and current antimicrobial prescribing practices in Australian aged care residents
Authors: Bennett N. J. , Imam N. , Ingram R. J. , James R. S. , Buising K. L. , Bull A. L. , Chen C. S. , Thursky K. A. , Worth L. J.
Published: February 2019

To determine the burden of skin and soft tissue infections (SSTI), the nature of antimicrobial prescribing and factors contributing to inappropriate prescribing for SSTIs in Australian aged care facilities, SSTI and antimicrobial prescribing data were collected via a standardised national survey. The proportion of residents prescribed ⩾1 antimicrobial for presumed SSTI and the proportion whose infections met McGeer et al. surveillance definitions were determined. Antimicrobial choice was compared to national prescribing guidelines and prescription duration analysed using a negative binomial mixed-effects regression model. Of 12 319 surveyed residents, 452 (3.7%) were prescribed an antimicrobial for a SSTI and 29% of these residents had confirmed infection. Topical clotrimazole was most frequently prescribed, often for unspecified indications. Where an indication was documented, antimicrobial choice was generally aligned with recommendations. Duration of prescribing (in days) was associated with use of an agent for prophylaxis (rate ratio (RR) 1.63, 95% confidence interval (CI) 1.08–2.52), PRN orders (RR 2.10, 95% CI 1.42–3.11) and prescription of a topical agent (RR 1.47, 95% CI 1.08–2.02), while documentation of a review or stop date was associated with reduced duration of prescribing (RR 0.33, 95% CI 0.25–0.43). Antimicrobial prescribing for SSTI is frequent in aged care facilities in Australia. Methods to enhance appropriate prescribing, including clinician documentation, are required.
Social and economic influences on infant and child feeding practices in a Marshallese community
Authors: Ayers Britni L , Shreve Marilou D , Scott Allison L , Seaton Victoria A , Johnson Kelly V , Hawley Nicola L , Rowland Brett , Moore Ramey , McElfish Pearl A
Published: February 2019

Objective

The present study aimed to examine the key influences on infant and child feeding practices among a Marshallese community at each social ecological level. It is the first study to examine the key influences on infant and child feeding practices with Marshallese immigrant women in the USA and helps fill a gap in the previous literature that has included other immigrant women.

Design

Community-based participatory research design with twenty-seven participants taking part in four qualitative focus groups.

Setting

The study took place within the Marshallese community in Arkansas, USA.

Participants

Participants included Marshallese women with children aged 1–3 years and/or caregivers. Caregivers were defined as someone other than the parent who cares for children. Caregivers were often older women in the Marshallese community.

Results

There were five primary themes within multiple levels of the Social Ecological Model. At the intrapersonal level, mothers’ and caregivers’ autonomy emerged. At the interpersonal level, child-led and familial influences emerged. At the organizational level, health-care provider influences emerged; and at the policy level, the Special Supplemental Nutrition Program for Women, Infants, and Children emerged as the most salient influence.

Conclusions

Marshallese immigrant women’s infant and child feeding practices are influenced at intrapersonal, interpersonal, organizational and policy levels. Understanding these multidimensional influences is necessary to inform the creation of culturally tailored interventions to reduce health disparities within the Marshallese community.
Revealing the Joint Mechanisms in Traditional Data Linked With Big	Data
Authors: de Schipper Niek C. , Van Deun Katrijn
Published: February 2019

Abstract. Recent technological advances have made it possible to study human behavior by linking novel types of data to more traditional types of psychological data, for example, linking psychological questionnaire data with genetic risk scores. Revealing the variables that are linked throughout these traditional and novel types of data gives crucial insight into the complex interplay between the multiple factors that determine human behavior, for example, the concerted action of genes and environment in the emergence of depression. Little or no theory is available on the link between such traditional and novel types of data, the latter usually consisting of a huge number of variables. The challenge is to select – in an automated way – those variables that are linked throughout the different blocks, and this eludes currently available methods for data analysis. To fill the methodological gap, we here present a novel data integration method.
Digital Footprints of Sensation Seeking
Authors: Schoedel Ramona , Au Quay , Völkel Sarah Theres , Lehmann Florian , Becker Daniela , Bühner Markus , Bischl Bernd , Hussmann Heinrich , Stachl Clemens
Published: February 2019

Abstract. The increasing usage of new technologies implies changes for personality research. First, human behavior becomes measurable by digital data, and second, digital manifestations to some extent replace conventional behavior in the analog world. This offers the opportunity to investigate personality traits by means of digital footprints. In this context, the investigation of the personality trait sensation seeking attracted our attention as objective behavioral correlates have been missing so far. By collecting behavioral markers (e.g., communication or app usage) via Android smartphones, we examined whether self-reported sensation seeking scores can be reliably predicted. Overall, 260 subjects participated in our 30-day real-life data logging study. Using a machine learning approach, we evaluated cross-validated model fit based on how accurate sensation seeking scores can be predicted in unseen samples. Our findings highlight the potential of mobile sensing techniques in personality research and show exemplarily how prediction approaches can help to foster an increased understanding of human behavior.
Integrating the Split/Analyze/Meta-Analyze (SAM) Approach and a Multilevel Framework to Advance Big Data Research in Psychology
Authors: Zhang Yucheng Eason , Liu Siqi , Xu Shan , Yang Miles M. , Zhang Jian
Published: February 2019

Abstract. Though big data research has undergone dramatic developments in recent decades, it has mainly been applied in disciplines such as computer science and business. Psychology research that applies big data to examine research issues in psychology is largely lacking. One of the major challenges regarding the use of big data in psychology is that many researchers in the field may not have sufficient knowledge of big data analytical techniques that are rooted in computer science. This paper integrates the split/analyze/meta-analyze (SAM) approach and a multilevel framework to illustrate how to use the SAM approach to address multilevel research questions with big data. Specifically, we first introduce the SAM approach and then illustrate how to implement this to integrate two big datasets at the firm level and country level. Finally, we discuss theoretical and practical implications, proposing future research directions for psychology scholars.
On Energy and Turbulent Mixing in the Thermocline
Authors: Dewar W. K. , McWilliams J. C.
Published: February 2019

A new method for computing the rate at which turbulent mixing builds potential energy in the ocean is described. The traditional approach has focused on the rate of change of the background potential energy associated with an adiabatically leveled state. We argue that when examining mixing events, so‐called “Thorpe” sorting yields a useful and local measure of diabatically generated potential energy and exhibits some advantages relative to adiabatic leveling. Among these, the open question about the leveling domain is avoided, the fate of kinetic energy during a mixing event is clearly defined, and the computational load associated with the leveling is relieved. The resultant kinetic energy equation leads to a natural definition of mixing efficiency and turbulent diffusivity in terms of sign definite viscous and diffusive contributions. Applications to 2‐D Kelvin Helmholtz instability demonstrate the utility of the procedure. We find an integrated efficiency of ≈ 0.15 for a Prandtl number of 1, and of ≈ 0.08 for a Prandtl number of 10. The larger is comparable to the classical value of 0.2 used frequently by the mixing community and smaller than that found in some recent simulations.
Downhill All The Way: Monitoring Landslides Using Geophysics
Authors: Whiteley James
Published: February 2019

Developments in geophysical methods used to monitor surface and subsurface changes prior to landslides can lead to improved prediction and early warning.
Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts
Authors: Chen Chun-Hau , Bhasin Swati , Khanna Prateek , Joshi Mukta , Joslin Patrick MN. , Saxena Ruchi , Amin Seema , Liu Suhu , Sindhu Shreya , Walker Sarah R. , Catalano Paul , Frank David A. , Alper Seth L. , Bhasin Manoj , Bhatt Rupal S.
Published: February 2019

Several therapeutic options are available for metastatic RCC, but responses are almost never complete, and resistance to therapy develops in the vast majority of patients. Consequently, novel treatments are needed to combat resistance to current therapies and to improve patient outcomes. We have applied integrated transcriptome and proteome analyses to identify cathepsin B (CTSB), a cysteine proteinase of the papain family, as one of the most highly upregulated gene products in established human RCC xenograft models of resistance to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). We used established RCC models to test the significance of CTSB in the progression of renal cancer. Our evaluation of CTSB showed that stable CTSB knockdown suppressed RCC growth in vitro and in vivo. Stable over-overexpression of wild-type CTSB (CTSBwt/hi), but not of an CTSB active site mutant (CTSBN298A), rescued cell growth in CTSB knockdown cells and abolished the efficacy of VEGFR TKI treatment. Genome-wide transcriptome profiling of CTSB knockdown cells demonstrated significant effects on multiple metabolic and stem cell-related pathways, with ALDHA1A (ALDH1) as one of the most significantly downregulated genes. Importantly, survival analysis across 16 major TCGA cancers revealed that CTSB overexpression is associated with low rates of three and five year patient survival rates (P = 2.5e–08, HR = 1.4). These data strongly support a contribution of CTSB activity to RCC cell growth and tumorigenicity. They further highlight the promise of CTSB inhibition in development of novel combination therapies designed to improve efficacy of current TKI treatments of metastatic RCC.
Author Correction: Prioritizing phylogenetic diversity captures functional diversity unreliably
Authors: Mazel Florent , Pennell Matthew W. , Cadotte Marc W. , Diaz Sandra , Riva Giulio Valentino Dalla , Grenyer Richard , Leprieur Fabien , Mooers Arne O. , Mouillot David , Tucker Caroline M. , Pearse William D.
Published: February 2019

The original version of this Article contained a plotting error in Figure 3g. The Serranidae and Siganidae families were misplaced in the plotted phylogeny. This error has now been corrected in the PDF and HTML versions of the Article. For comparison, the original, incorrect version of Figure 3g is presented in the associated Author Correction.
Nanoparticle-based hollow microstructures formed by two-stage nematic nucleation and phase separation
Authors: Riahinasab Sheida T. , Keshavarz Amir , Melton Charles N. , Elbaradei Ahmed , Warren Gabrielle I. , Selinger Robin L. B. , Stokes Benjamin J. , Hirst Linda S.
Published: February 2019

Rapid bulk assembly of nanoparticles into microstructures is challenging, but highly desirable for applications in controlled release, catalysis, and sensing. We report a method to form hollow microstructures via a two-stage nematic nucleation process, generating size-tunable closed-cell foams, spherical shells, and tubular networks composed of closely packed nanoparticles. Mesogen-modified nanoparticles are dispersed in liquid crystal above the nematic-isotropic transition temperature (TNI). On cooling through TNI, nanoparticles first segregate into shrinking isotropic domains where they locally depress the transition temperature. On further cooling, nematic domains nucleate inside the nanoparticle-rich isotropic domains, driving formation of hollow nanoparticle assemblies. Structural differentiation is controlled by nanoparticle density and cooling rate. Cahn-Hilliard simulations of phase separation in liquid crystal demonstrate qualitatively that partitioning of nanoparticles into isolated domains is strongly affected by cooling rate, supporting experimental observations that cooling rate controls aggregate size. Microscopy suggests the number and size of internal voids is controlled by second-stage nucleation.
Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions
Authors: Le Phuong , Lim Sung Jun , Baculis Brian C. , Chung Hee Jung , Kilian Kristopher A. , Smith Andrew M.
Published: February 2019

The distribution of single-cell properties across a population of cells can be measured using diverse tools, but no technology directly quantifies the biochemical stimulation events regulating these properties. Here we report digital counting of growth factors in single cells using fluorescent quantum dots and calibrated three-dimensional deconvolution microscopy (QDC-3DM) to reveal physiologically relevant cell stimulation distributions. We calibrate the fluorescence intensities of individual compact quantum dots labeled with epidermal growth factor (EGF) and demonstrate the necessity of near-infrared emission to overcome intrinsic cellular autofluoresence at the single-molecule level. When applied to human triple-negative breast cancer cells, we observe proportionality between stimulation and both receptor internalization and inhibitor response, reflecting stimulation heterogeneity contributions to intrinsic variability. We anticipate that QDC-3DM can be applied to analyze any peptidic ligand to reveal single-cell correlations between external stimulation and phenotypic variability, cell fate, and drug response.
3D ink-extrusion additive manufacturing of CoCrFeNi high-entropy alloy micro-lattices
Authors: Kenel Christoph , Casati Nicola P. M. , Dunand David C.
Published: February 2019

Additive manufacturing of high-entropy alloys combines the mechanical properties of this novel family of alloys with the geometrical freedom and complexity required by modern designs. Here, a non-beam approach to additive manufacturing of high-entropy alloys is developed based on 3D extrusion of inks containing a blend of oxide nanopowders (Co3O4 + Cr2O3 + Fe2O3 + NiO), followed by co-reduction to metals, inter-diffusion and sintering to near-full density CoCrFeNi in H2. A complex phase evolution path is observed by in-situ X-ray diffraction in extruded filaments when the oxide phases undergo reduction and the resulting metals inter-diffuse, ultimately forming face-centered-cubic equiatomic CoCrFeNi alloy. Linked to the phase evolution is a complex structural evolution, from loosely packed oxide particles in the green body to fully-annealed, metallic CoCrFeNi with 99.6 ± 0.1% relative density. CoCrFeNi micro-lattices are created with strut diameters as low as 100 μm and excellent mechanical properties at ambient and cryogenic temperatures.
Lithium anode stable in air for low-cost fabrication of a dendrite-free lithium battery
Authors: Shen Xiaowei , Li Yutao , Qian Tao , Liu Jie , Zhou Jinqiu , Yan Chenglin , Goodenough John B.
Published: February 2019

Lithium metal, the ideal anode material for rechargeable batteries, suffers from the inherent limitations of sensitivity to the humid atmosphere and dendrite growth. Herein, low-cost fabrication of a metallic-lithium anode that is stable in air and plated dendrite-free from an organic-liquid electrolyte solves four key problems that have plagued the development of large-scale Li-ion batteries for storage of electric power. Replacing the low-capacity carbon anode with a safe, dendrite-free lithium anode provides a fast charge while reducing the cost of fabrication of a lithium battery, and increasing the cycle life of a rechargeable cell by eliminating the liquid-electrolyte ethylene-carbonate additive used to form a solid-electrolyte interphase passivation layer on the anode that is unstable during cycling. This solution is accomplished by formation of a hydrophobic solid-electrolyte interphase on a metallic-lithium anode that allows for handling of the treated lithium anode membrane in a standard dry room during cell fabrication.
Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer
Authors: Zhao Jun , Wen Xiaofei , Tian Li , Li Tingting , Xu Chunyu , Wen Xiaoxia , Melancon Marites P. , Gupta Sanjay , Shen Baozhong , Peng Weiyi , Li Chun
Published: February 2019

Immunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) due to the presence of an immunosuppressive tumor-associated stroma. Here, we demonstrate an effective modulation of that stroma by irreversible electroporation (IRE), a local ablation technique that has received regulatory approval in the United States. IRE induces immunogenic cell death, activates dendritic cells, and alleviates stroma-induced immunosuppression without depleting tumor-restraining collagen. The combination of IRE and anti-programmed cell death protein 1 (anti-PD1) immune checkpoint blockade promotes selective tumor infiltration by CD8+ T cells and significantly prolongs survival in a murine orthotopic PDAC model with a long-term memory immune response. Our results suggest that IRE is a promising approach to potentiate the efficacy of immune checkpoint blockade in PDAC.
Photosynthetic apparatus of Rhodobacter sphaeroides exhibits prolonged charge storage
Authors: Ravi Sai Kishore , Rawding Piper , Elshahawy Abdelnaby M. , Huang Kevin , Sun Wanxin , Zhao Fangfang , Wang John , Jones Michael R. , Tan Swee Ching
Published: February 2019

Photosynthetic proteins have been extensively researched for solar energy harvesting. Though the light-harvesting and charge-separation functions of these proteins have been studied in depth, their potential as charge storage systems has not been investigated to the best of our knowledge. Here, we report prolonged storage of electrical charge in multilayers of photoproteins isolated from Rhodobacter sphaeroides. Direct evidence for charge build-up within protein multilayers upon photoexcitation and external injection is obtained by Kelvin-probe and scanning-capacitance microscopies. Use of these proteins is key to realizing a ‘self-charging biophotonic device’ that not only harvests light and photo-generates charges but also stores them. In strong correlation with the microscopic evidence, the phenomenon of prolonged charge storage is also observed in primitive power cells constructed from the purple bacterial photoproteins. The proof-of-concept power cells generated a photovoltage as high as 0.45 V, and stored charge effectively for tens of minutes with a capacitance ranging from 0.1 to 0.2 F m−2.
Ediacaran biozones identified with network analysis provide evidence for pulsed extinctions of early complex life
Authors: Muscente A. D. , Bykova Natalia , Boag Thomas H. , Buatois Luis A. , Mángano M. Gabriela , Eleish Ahmed , Prabhu Anirudh , Pan Feifei , Meyer Michael B. , Schiffbauer James D. , Fox Peter , Hazen Robert M. , Knoll Andrew H.
Published: February 2019

Rocks of Ediacaran age (~635–541 Ma) contain the oldest fossils of large, complex organisms and their behaviors. These fossils document developmental and ecological innovations, and suggest that extinctions helped to shape the trajectory of early animal evolution. Conventional methods divide Ediacaran macrofossil localities into taxonomically distinct clusters, which may represent evolutionary, environmental, or preservational variation. Here, we investigate these possibilities with network analysis of body and trace fossil occurrences. By partitioning multipartite networks of taxa, paleoenvironments, and geologic formations into community units, we distinguish between biostratigraphic zones and paleoenvironmentally restricted biotopes, and provide empirically robust and statistically significant evidence for a global, cosmopolitan assemblage unique to terminal Ediacaran strata. The assemblage is taxonomically depauperate but includes fossils of recognizable eumetazoans, which lived between two episodes of biotic turnover. These turnover events were the first major extinctions of complex life and paved the way for the Cambrian radiation of animals.
Metal–peptide rings form highly entangled topologically inequivalent frameworks with the same ring- and crossing-numbers
Authors: Sawada Tomohisa , Saito Ami , Tamiya Kenki , Shimokawa Koya , Hisada Yutaro , Fujita Makoto
Published: February 2019

With increasing ring-crossing number (c), knot theory predicts an exponential increase in the number of topologically different links of these interlocking structures, even for structures with the same ring number (n) and c. Here, we report the selective construction of two topologies of 12-crossing peptide [4]catenanes (n = 4, c = 12) from metal ions and pyridine-appended tripeptide ligands. Two of the 100 possible topologies for this structure are selectively created from related ligands in which only the tripeptide sequence is changed: one catenane has a T2-tetrahedral link and the other a three-crossed tetrahedral link. Crystallographic studies illustrate that a conformational difference in only one of the three peptide residues in the ligand causes the change in the structure of the final tetrahedral link. Our results thus reveal that peptide-based folding and assembly can be used for the facile bottom-up construction of 3D molecular objects containing polyhedral links.
Supercluster-coupled crystal growth in metallic glass forming liquids
Authors: Xie Yujun , Sohn Sungwoo , Wang Minglei , Xin Huolin , Jung Yeonwoong , Shattuck Mark D. , O’Hern Corey S. , Schroers Jan , Cha Judy J.
Published: February 2019

While common growth models assume a structure-less liquid composed of atomic flow units, structural ordering has been shown in liquid metals. Here, we conduct in situ transmission electron microscopy crystallization experiments on metallic glass nanorods, and show that structural ordering strongly affects crystal growth and is controlled by nanorod thermal history. Direct visualization reveals structural ordering as densely populated small clusters in a nanorod heated from the glass state, and similar behavior is found in molecular dynamics simulations of model metallic glasses. At the same growth temperature, the asymmetry in growth rate for rods that are heated versus cooled decreases with nanorod diameter and vanishes for very small rods. We hypothesize that structural ordering enhances crystal growth, in contrast to assumptions from common growth models. The asymmetric growth rate is attributed to the difference in the degree of the structural ordering, which is pronounced in the heated glass but sparse in the cooled liquid.
Publisher Correction: Negative differential resistance as a critical indicator for the discharge capacity of lithium-oxygen batteries
Authors: Hase Yoko , Komori Yasuhiro , Kusumoto Takayoshi , Harada Takashi , Seki Juntaro , Shiga Tohru , Kamiya Kazuhide , Nakanishi Shuji
Published: February 2019

The original version of this Article contained an error in the title, which was previously incorrectly given as ‘Negative differential resistance as a critical indicator for the discharge capacity of lithium-oxygene batteries’. The correct version states ‘lithium-oxygen’ in place of ‘lithium-oxygene’. This has been corrected in both the PDF and HTML versions of the Article.
Somatic mutations of PREX2 gene in patients with hepatocellular carcinoma
Authors: Yang Ming-Hui , Yen Chia-Hung , Chen Yen-Fu , Fang Cheng-Chieh , Li Chung-Hsien , Lee Kuo-Jui , Lin Yi-Hsiung , Weng Chien-Hui , Liu Tze-Tze , Huang Shiu-Feng , Teh Bin Tean , Chen Yi-Ming Arthur
Published: February 2019

Characterized with a high recurrence rate and low detection rate, prevention is the best approach to reduce mortality in hepatocellular carcinoma (HCC). The overexpression of Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2 (PREX2) is observed in various tumors, including HCC; and the frequent PREX2 mutations in melanoma are associated with invasiveness. We sought to identify somatic mutations and the functional changes in mutational signatures of PREX2. Genomic DNA sequencing was performed in 68 HCC samples with three types of hepatitis viral infection status: HBs Ag-positive, anti-HCV Ab-positive, and negative for any hepatitis B or C markers. Stabilities and interactions of proteins as well as cell proliferation and migration were evaluated. Fourteen non-silent point mutations in PREX2 were detected, with 16 of 68 HCC patients harboring at least one non-silent mutation. All mutant forms of PREX2, except for K400f, had an extended half-life compared with wild-type PREX2. Moreover, only the half-life of S1113R was twice that of the wild-type. PREX2 mutant-S1113R also promoted migration and activated the AKT pathway as well as impaired HectH9-mediated ubiquitination. Our study identified a gain-of-function mutation of PREX2 – S1113R in HCC. Such mutation enhanced PREX2 protein stability, promoted cell proliferation, and was associated with aggressiveness of HCC.
Human-attacks by an urban raptor are tied to human subsidies and religious practices
Authors: Kumar Nishant , Jhala Yadvendradev V. , Qureshi Qamar , Gosler Andrew G. , Sergio Fabrizio
Published: February 2019

Growing urbanization is increasing human-wildlife interactions, including attacks towards humans by vertebrate predators, an aspect that has received extremely scarce investigation. Here, we examined the ecological, landscape and human factors that may promote human-aggression by raptorial Black kitesMilvus migransin the 16-millions inhabitants megacity of Delhi (India). Physical attacks depended on human activities such as unhygienic waste management, ritual-feeding of kites (mainly operated by Muslims), human density, and presence of a balcony near the nest, suggesting an association between aggression and frequent-close exposure to humans and derived food-rewards. Surprisingly, while more than 100,000 people could be at risk of attack in any given moment, attitudes by local inhabitants were strikingly sympathetic towards the birds, even by injured persons, likely as a result of religious empathy. These results highlight the importance of socio-cultural factors for urban biota and how these may radically differentiate the under-studied cities of developing countries from those of western nations, thus broadening our picture of human-wildlife interactions in urban environments. The rapid sprawling of urban and suburban areas with their associated food-subsidies is likely to increase proximity and exposure of large predators to humans, and vice versa, leading to heightened worldwide conflicts.
Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting
Authors: Lee Jong Geol , Ha Chang Hoon , Yoon Bohyun , Cheong Seung-A. , Kim Globinna , Lee Doo Jae , Woo Dong-Cheol , Kim Young-Hak , Nam Sang-Yoon , Lee Sang-wook , Sung Young Hoon , Baek In-Jeoung
Published: February 2019

The rat is a time-honored traditional experimental model animal, but its use is limited due to the difficulty of genetic modification. Although engineered endonucleases enable us to manipulate the rat genome, it is not known whether the newly identified endonuclease Cpf1 system is applicable to rats. Here we report the first application of CRISPR-Cpf1 in rats and investigate whether Apoe knockout rat can be used as an atherosclerosis model. We generated Apoe- and/or Ldlr-deficient rats via CRISPR-Cpf1 system, characterized by high efficiency, successful germline transmission, multiple gene targeting capacity, and minimal off-target effect. The resulting Apoe knockout rats displayed hyperlipidemia and aortic lesions. In partially ligated carotid arteries of rats and mice fed with high-fat diet, in contrast to Apoe knockout mice showing atherosclerotic lesions, Apoe knockout rats showed only adventitial immune infiltrates comprising T lymphocytes and mainly macrophages with no plaque. In addition, adventitial macrophage progenitor cells (AMPCs) were more abundant in Apoe knockout rats than in mice. Our data suggest that the Cpf1 system can target single or multiple genes efficiently and specifically in rats with genetic heritability and that Apoe knockout rats may help understand initial-stage atherosclerosis.
Functional expression of a peritrophin A-like SfPER protein is required for larval development in Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Rodríguez-de la Noval Claudia , Rodríguez-Cabrera Lianet , Izquierdo Laurent , Espinosa Luis A. , Hernandez Daily , Ponce Milagro , Moran-Bertot Ivis , Tellez-Rodríguez Pilar , Borras-Hidalgo Orlando , Huang Siliang , Kan Yunchao , Wright Denis J. , Ayra-Pardo Camilo
Published: February 2019

Peritrophins are associated with structural and functional integrity of peritrophic membranes (PM), structures composed of chitin and proteins. PM lines the insect midgut and has roles in digestion and protection from toxins. We report the full-length cDNA cloning, molecular characterization and functional analysis of SfPER, a novel PM peritrophin A protein, in Spodoptera frugiperda. The predicted amino acid sequence indicated SfPER’s domain structure as a CMCMC-type, consisting of a signal peptide and three chitin-binding (C) domains with two intervening mucin-like (M) domains. Phylogenetic analysis determined a close relationship between SfPER and another S. frugiperda PM peritrophin partial sequence. SfPER transcripts were found in larvae and adults but were absent from eggs and pupae. Chitin affinity studies with a recombinant SfPER-C1 peritrophin A-type domain fused to SUMO/His-tag confirmed that SfPER binds to chitin. Western blots of S. frugiperda larval proteins detected different sized variants of SfPER along the PM, with larger variants found towards the posterior PM. In vivo suppression of SfPER expression did not affect susceptibility of larvae to Bacillus thuringiensis toxin, but significantly decreased pupal weight and adult emergence, possibly due to PM structural alterations impairing digestion. Our results suggest SfPER could be a novel target for insect control.
Vitamin D Receptor Polymorphism and DHCR7 Contribute to the Abnormal Interplay Between Vitamin D and Lipid Profile in Rheumatoid Arthritis
Authors: Rodríguez-Carrio Javier , Alperi-López Mercedes , Naves-Díaz Manuel , Dusso Adriana , López Patricia , Ballina-García Francisco Javier , Cannata-Andía Jorge B. , Suárez Ana
Published: February 2019

Emerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7 levels and vitamin D-related polymorphisms (VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878) were analyzed in 211 RA patients,94 controls and in a prospective cohort of 13 RA patients undergoing TNFα-blockade. Vitamin D was decreased in RA (p < 0.001), correlated to HDL-cholesterol (r = 0.217, p < 0.001) and total-/HDL-cholesterol ratio (r = −0.227, p = 0.004). These correlations were restricted to the VDR-rs2228570 status. Vitamin D deficiency was associated with lower HDL-cholesterol (p = 0.028), higher tender (p = 0.005) and swollen (p = 0.002) joint counts, higher DAS28 (p = 0.018) and HAQ (p = 0.024) in AG/AA-patients but not in their GG-counterparts. The associations among DHCR7, vitamin D and lipid profile followed a seasonal pattern, decreased DHCR7 (p = 0.008) and vitamin D (p < 0.001) and increased total-cholesterol (p = 0.025) being found in winter/spring. Increasing vitamin D upon TNFα-blockade paralleled RA clinical improvement (r = −0.610, p = 0.027) and DHCR7 elevation (r = 0.766, p = 0.002). In conclusion, vitamin D-related polymorphisms and DHCR7 are pivotal to understand the complex, seasonal associations between vitamin D and lipid profile in RA.