bluuebunny/crossref_metadata_2025 huggingface dataset:
A High‐Performing Asymmetric Supercapacitor of Molybdenum Nitride and Vanadium Nitride Thin Films as Binder‐Free Electrode Grown through Reactive Sputtering
Authors: Adalati Ravikant , Kumar Ashwani , Kumar Yogesh , Chandra Ramesh
Published: July 2020

Transition‐metal nitride (TMN) thin‐film‐based electrodes are recognized for high‐performance, stable, flexible, and smart supercapacitors (SCs), as they exhibit extensive voltage range, good sustainability, and high electrical conductivity. Herein, using reactive DC magnetron sputtering, molybdenum nitride (Mo2N) and vanadium nitride (VN) thin films are deposited on 304 stainless steel substrate at 200 °C for asymmetric SC (ASC) applications. ASC is constructed using VN@SS as negative electrode and γ‐Mo2N@SS as positive electrode and examines the electrochemical behavior in aqueous solutions of 1 m Na2SO4 at several scan rates and current densities. To scrutinize the crystallographic details and electronic configuration of as‐deposited thin‐film electrodes, X‐ray diffraction and X‐ray photoelectron spectroscopy are used. To visualize the surface morphology, film thickness, and elemental composition, field‐emission scanning electron microscopy and energy dispersive X‐ray analysis is used. The results imply that TMN thin‐film‐based electrodes bestow super‐hydrophilic nature and give enhanced capacitance value along with excellent rate performance. This work demonstrates VN@SS and γ‐Mo2N@SS thin‐film‐based electrode for ASC, which show a high capacitance of ≈85.50 Fg−1 and a high specific power of ≈23.3 Wh kg−1 with a broadened voltage window of ≈1.4 V, and this is a potential candidate for energy storage devices.
The autism diagnostic observation schedule: Patterns in individuals with anorexia nervosa
Authors: Bentz Mette , Westwood Heather , Jepsen Jens Richardt Møllegaard , Plessen Kerstin Jessica , Tchanturia Kate
Published: July 2020

Objective

Studies have used the Autism Diagnostic Observation Schedule (the ADOS‐2) in individuals with anorexia nervosa (AN), but the patterns of scores have not been assessed. We examined which subset of the ADOS‐2 items best discriminate individuals with AN from healthy controls (HC), and assessed the potential clustering of AN participants based on different profiles of the ADOS‐2 item scores.

Method

We combined datasets from two previous studies, and (a) compared mean ranks between young AN participants (N = 118) and HC (N = 42), (ii) replicated the item selection procedure of the existing ADOS‐2 algorithm to assess sensitivity of items in the AN group, and (c) applied a two‐step clustering analysis in the AN group (N = 149).

Results

AN participants displayed significantly higher mean ranks than HC participants in five of 32 items. All five items are part of the existing ADOS‐2 algorithm. We found two clusters of AN participants; one representing normal social behaviour, comprising 68% of the individuals with AN, and one representing less efficient social behaviour, comprising 32% of individuals with AN.

Conclusions

The items comprising the social affective cluster of the existing ADOS‐2 algorithm are well suited to assess difficulties with social functioning in individuals with AN.
Stock‐induced Google trends and the predictability of sectoral stock returns
Authors: Salisu Afees A. , Ogbonna Ahamuefula E. , Adediran Idris
Published: July 2020

In this paper, we consider Google trends (G‐trends) as a measure of investors' attention in the predictability of stock returns across eleven major US sectors. The theoretical motivation for our paper is clear. In seeking information to guide investment decisions, investors' sentiments are shaped by news such as G‐trends that could induce changes in the prices of stocks. Thus, we construct a predictive model that incorporates G‐trends series as a predictor of stock returns and thereafter we account for evident asymmetry in G‐trends to analyze the signficance of positive‐ and negative‐worded news in the predictability of stock returns. We also compare single‐ and multi‐factor predictive models augmented with distinctive statistical effects against the baseline time series model. We highlight three key findings: (1) G‐trends record consistent negative correlations with stock returns across sectors. (2) The proposed predictive model with G‐trends outperforms the baseline (random walk) model. (3) The inclusion of asymmetry and macroeconomic variables improves the outperformance of G‐trends over the baseline model.
Evaluation of the efficacy of pimavanserin in the treatment of agitation and aggression in patients with Alzheimer's disease psychosis: A post hoc analysis
Authors: Ballard Clive G. , Coate Bruce , Abler Victor , Stankovic Srdjan , Foff Erin
Published: July 2020

Objectives

Patients with Alzheimer's disease psychosis (ADP) commonly experience concomitant agitation and aggression. We investigated whether a reduction in ADP following pimavanserin treatment conferred a reduction in associated agitation and aggression.

Methods

ACP‐103‐019 was a 12‐week, randomized, double‐blind, placebo‐controlled study that evaluated the efficacy of pimavanserin (34 mg) in reducing psychotic symptoms in patients with ADP. The primary endpoint was change from baseline in Neuropsychiatric Inventory‐Nursing Home Version‐Psychosis Score (NPI‐NH‐PS) at week six. A post hoc analysis examined whether there was a greater reduction in agitation and aggression (NPI‐NH domain C [agitation/aggression] and Cohen‐Mansfield Agitation Inventory‐Short Form [CMAI‐SF]) in pimavanserin‐treated patients who experienced a reduction of hallucinations and delusions (psychosis responders defined as ≥50% reduction from baseline in NPI‐NH‐PS, week six) when compared with those who did not (nonresponders).

Results

Pimavanserin‐treated patients with ≥50% response in psychotic symptoms (n = 44) showed a greater improvement in agitation and aggression symptoms on the NPI‐NH domain C (week six, least squares mean [LSM] difference = −3.64, t = −4.69, P < .0001) and the CMAI‐SF (week six, LSM difference = −3.71, t = −2.01, P = .0483) than nonresponders (n = 32). Differences between psychosis responders and nonresponders were also observed in patients with more severe agitation and aggression at baseline on the NPI‐NH domain C (responders, n = 26; nonresponders, n = 13; week six, LSM difference = −3.03, t = −2.44, P = .019).

Conclusions

Patients with ADP, who show improvement in psychotic symptoms after pimavanserin treatment, also experience an improvement in concomitant agitation and aggression.
Can we predict real‐time fMRI neurofeedback learning success from pretraining brain activity?
Authors: Haugg Amelie , Sladky Ronald , Skouras Stavros , McDonald Amalia , Craddock Cameron , Kirschner Matthias , Herdener Marcus , Koush Yury , Papoutsi Marina , Keynan Jackob N. , Hendler Talma , Cohen Kadosh Kathrin , Zich Catharina , MacInnes Jeff , Adcock R. Alison , Dickerson Kathryn , Chen Nan‐Kuei , Young Kymberly , Bodurka Jerzy , Yao Shuxia , Becker Benjamin , Auer Tibor , Schweizer Renate , Pamplona Gustavo , Emmert Kirsten , Haller Sven , Van De Ville Dimitri , Blefari Maria‐Laura , Kim Dong‐Youl , Lee Jong‐Hwan , Marins Theo , Fukuda Megumi , Sorger Bettina , Kamp Tabea , Liew Sook‐Lei , Veit Ralf , Spetter Maartje , Weiskopf Nikolaus , Scharnowski Frank
Published: July 2020

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real‐time fMRI neurofeedback studies report large inter‐individual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta‐analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pretraining functional localizer or no‐feedback runs (i.e., self‐regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pretraining activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain‐based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.
Do intrinsic brain functional networks predict working memory from childhood to adulthood?
Authors: Zhang Han , Hao Shuji , Lee Annie , Eickhoff Simon B. , Pecheva Diliana , Cai Shirong , Meaney Michael , Chong Yap‐Seng , Broekman Birit F. P. , Fortier Marielle V. , Qiu Anqi
Published: July 2020

Working memory (WM) is defined as the ability to maintain a representation online to guide goal‐directed behavior. Its capacity in early childhood predicts academic achievements in late childhood and its deficits are found in various neurodevelopmental disorders. We employed resting‐state fMRI (rs‐fMRI) of 468 participants aged from 4 to 55 years and connectome‐based predictive modeling (CPM) to explore the potential predictive power of intrinsic functional networks to WM in preschoolers, early and late school‐age children, adolescents, and adults. We defined intrinsic functional networks among brain regions identified by activation likelihood estimation (ALE) meta‐analysis on existing WM functional studies (ALE‐based intrinsic functional networks) and intrinsic functional networks generated based on the whole brain (whole‐brain intrinsic functional networks). We employed the CPM on these networks to predict WM in each age group. The CPM using the ALE‐based and whole‐brain intrinsic functional networks predicted WM of individual adults, while the prediction power of the ALE‐based intrinsic functional networks was superior to that of the whole‐brain intrinsic functional networks. Nevertheless, the CPM using the whole‐brain but not the ALE‐based intrinsic functional networks predicted WM in adolescents. And, the CPM using neither the ALE‐based nor whole‐brain networks predicted WM in any of the children groups. Our findings showed the trend of the prediction power of the intrinsic functional networks to cognition in individuals from early childhood to adulthood.
Multicomponent Alginate‐Derived Hydrogel Microspheres Presenting Hybrid Ionic‐Covalent Network and Drug Eluting Properties
Authors: Szabó Luca , Noverraz François , Gerber‐Lemaire Sandrine
Published: July 2020

The development of multifunctional encapsulation biomaterials could help the translation of cell‐based therapies into standard medical care. One of the major hurdles in the field of encapsulated cell transplantation is the current lack of materials presenting optimal properties, including long term stability, mechanical durability and non‐immunogenic character. Modification of sodium alginate (Na‐alg) with polyethylene glycol (PEG) derivatives, without restricting its gelling abilities, appeared as an efficient strategy to produce dual ionic‐covalent spherical hydrogels with enhanced mechanical performance as well as drug‐eluting microspheres (MS) for the mitigation of inflammatory response after transplantation. In this study, the combination of PEGylated alginates equipped with cross‐reactive functionalities and the anti‐inflammatory drug ketoprofen (KET) resulted in the assembly of multifunctional (MF) hybrid MS, merging the advantages of ionic‐covalent hydrogels with the ability for controlled drug delivery. Physical characterization confirmed their improved mechanical resistance, their higher shape recovery performance and increased stability toward non‐gelling ions, as compared to pure Ca‐alg hydrogels. In vitro release kinetics revealed the controlled and sustained delivery of KET for over two weeks.
Do Chinese listed corporations really tell the truth? Empirical evidence from semi‐parametric analysis
Authors: Wang Qiao , Nie Li
Published: July 2020

We empirically analyse the authenticity of the information provided by Chinese listed corporations. First, we construct a signalling game among listed corporations and investors. We obtain the behaviours, which are positive strategic interactions on the amounts of stock issue and positive correlation between stock issuance and profit, of listed corporations when they provide untrue information. Second, by using the dataset of 2,408 listed corporations in 2016 from CCER China Economic and Financial Database, we prove that the optimal amounts of stock issue by maximizing the amounts of financing increase as the profits of listed corporations raise. And by applying single index estimation method, our parameter estimation results show that the strategic interactions among 2,408 Chinese listed corporations on the amounts of stock issue are positive. Therefore, there exists Chinese listed corporations who do not tell the truth in proving their information. Further analysis shows that 485 out of 2,408 Chinese listed corporations do not tell the truth in providing their profits. And most of the Chinese listed corporations with unauthentic declared profits report their profits lower than their true profits to reduce tax. And those who overstate their profits are large and medium enterprises from the first and second industries.
Large fluctuations of China's commodity prices: Main sources and heterogeneous effects
Authors: Xu Bin , Lin Boqiang
Published: July 2020

Assuming that the economic variables obey the normal distribution, existing studies often use traditional mean models to explore commodity prices. In fact, the distribution of economic data is often skewed. When the economic data is left‐biased or right‐biased, the quantile regression can more fully characterize the distribution of economic variables, and thus obtain a comprehensive analysis result. Moreover, the coefficient estimates of the quantile regression are more robust than those in the ordinary least squares regression. Therefore, this paper uses the quantile regression method to investigate commodity price fluctuations. The results show that the money supply has a greater impact on commodity prices in the lower 10th and 10th–25th quantile groups. Among all quantile groups, the impact of international oil prices on commodity prices in the upper 90th quantile group is the highest. The effect of the exchange rate in the 25th–50th quantile group is greater than those in other quantile groups. However, the real economy has a minimal impact on the 25th–50th quantile group. Thus, the heterogeneous effects of these influencing factors should be taken into consideration when stabilizing commodity prices.
Do investors herd? An examination of Pakistan stock exchange
Authors: Kashif Muhammad , Palwishah Rana , Ahmed Rizwan Raheem , Vveinhardt Jolita , Streimikiene Dalia
Published: July 2020

The study attempts to examine herding behaviour in Pakistan stock exchange and determine how herding behaviour responds to asymmetric market conditions. This study has employed CH model, CSSD & CSAD models, and State‐space model. We have used time series data for the period from 2000 to 2016, which include daily returns of KSE all share index and 890 firms listed on Pakistan stock exchange. The outcomes of the study not only reported significant evidence of herding behaviour in Pakistan stock market over the entire sample period but also found it to be more pronounced under extreme market conditions, market volatility and financial crisis. Further, it was found that herding behaviour increases before the crisis, whereas decreases at the time of crisis. Fund managers and investors need to take herding behaviour in to account to evaluate asset prices and require a large number of stocks for achieving a correlation of inferior degree in portfolios and same degree in diversification. In addition, funds herding can be used as a signal of managerial quality. Moreover, as herding implies that fund managers and investors react to regulatory changes in a similar way, which may prevent asset prices from reaching their fundamental values and further causes financial markets to become fragile and destabilize, thus policymakers should take measures to control herding.
Realized volatility forecasting and volatility spillovers: Evidence from Chinese non‐ferrous metals futures
Authors: Wang Donghua , Xin Yang , Chang Xiaohui , Su Xingze
Published: July 2020

We study the prediction of realized volatility of non‐ferrous metals futures traded on the Shanghai Futures Exchange from March 2011 to December 2017. A dynamic model averaging model is employed to combine multiple prediction models using time‐varying weights based on individual model performance. Empirical results also reveal that models incorporating volatility spillovers across metals are important for forecast combinations, and short‐term spillovers have a stronger impact than long‐term spillovers. This approach offers the best forecasting performance and allows users to identify the most dominant model at any given time and demonstrate when and how volatility transmission from another metal is valuable for forecasting. We also find evidence of distinct trading behaviours in emerging and developed markets.
Understanding Escherichia coli damages after chlorophyllin‐based photosensitization
Authors: Žudytė Bernadeta , Velička Martynas , Šablinskas Valdas , Lukšienė Živilė
Published: July 2020

Pathogenic strains of bacteria are causing various illnesses all around the world and have a major socio‐economic impact. Thus, fast‐ and low‐cost methods for the microbial control of foods are needed. One of them might be photosensitization. This study looks deeper into the mechanism of Escherichia coli damage by chlorophyllin‐based photosensitization. Fluorimetric data indicate that after 15 minute incubation with chlorophyllin (Chl) (1.5 × 10−5 M Chl) 0.73 ± 0.03 μM of this compound was associated with E. coli cell surface. After photoactivation (405 nm, 6–30 J/cm2) significant reduction (88.2%) of bacterial viability was observed. Higher concentration of Chl (5 × 10−4 M Chl) reduced viability of bacteria more than by 98%. Results indicated that reactive oxygen species (ROS) took place in this inactivation. Colloidal surface enhanced Raman scattering (SERS) spectroscopy was employed to detect the molecular changes in the treated bacteria. It was found that Chl‐based based photosensitization triggers multiple surface structure changes in E. coli what induce lethal unrepairable damages and inactivation of pathogen.
Investigation of genomic DNA methylation by ultraviolet resonant Raman spectroscopy
Authors: D'Amico Francesco , Zucchiatti Paolo , Latella Katia , Pachetti Maria , Gessini Alessandro , Masciovecchio Claudio , Vaccari Lisa , Pascolo Lorella
Published: July 2020

Cytosine plays a preeminent role in DNA methylation, an epigenetic mechanism that regulates gene expression, the misregulation of which can lead to severe diseases. Several methods are nowadays employed for assessing the global DNA methylation levels, but none of them combines simplicity, high sensitivity, and low operating costs to be translated into clinical applications. Ultraviolet (UV) resonant Raman measurements at excitation wavelengths of 272 nm, 260 nm, 250 nm, and 228 nm have been carried out on isolated deoxynucleoside triphosphates (dNTPs), on a dNTP mixture as well as on genomic DNA (gDNA) samples, commercial from salmon sperm and non‐commercial from B16 murine melanoma cell line. The 228 nm excitation wavelength was identified as the most suitable energy for enhancing cytosine signals over the other DNA bases. The UV Raman measurements performed at this excitation wavelength on hyper‐methylated and hypo‐methylated DNA from Jurkat leukemic T‐cell line have revealed significant spectral differences with respect to gDNA isolated from salmon sperm and mouse melanoma B16 cells. This demonstrates how the proper choice of the excitation wavelength, combined with optimized extraction protocols, makes UV Raman spectroscopy a suitable technique for highlighting the chemical modifications undergone by cytosine nucleotides in gDNA upon hyper‐ and hypo‐methylation events.
Lactate Dehydrogenase Inhibition With Oxamate Exerts Bone Anabolic Effect
Authors: Hollenberg Alex M , Smith Charles O , Shum Laura C , Awad Hani , Eliseev Roman A
Published: July 2020

Cellular bioenergetics is a promising new therapeutic target in aging, cancer, and diabetes because these pathologies are characterized by a shift from oxidative to glycolytic metabolism. We have previously reported such glycolytic shift in aged bone as a major contributor to bone loss in mice. We and others also showed the importance of oxidative phosphorylation (OxPhos) for osteoblast differentiation. It is therefore reasonable to propose that stimulation of OxPhos will have bone anabolic effect. One strategy widely used in cancer research to stimulate OxPhos is inhibition of glycolysis. In this work, we aimed to evaluate the safety and efficacy of pharmacological inhibition of glycolysis to stimulate OxPhos and promote osteoblast bone-forming function and bone anabolism. We tested a range of glycolytic inhibitors including 2-deoxyglucose, dichloroacetate, 3-bromopyruvate, and oxamate. Of all the studied inhibitors, only a lactate dehydrogenase (LDH) inhibitor, oxamate, did not show any toxicity in either undifferentiated osteoprogenitors or osteoinduced cells in vitro. Oxamate stimulated both OxPhos and osteoblast differentiation in osteoprogenitors. In vivo, oxamate improved bone mineral density, cortical bone architecture, and bone biomechanical strength in both young and aged C57BL/6J male mice. Oxamate also increased bone formation by osteoblasts without affecting bone resorption. In sum, our work provided a proof of concept for the use of anti-glycolytic strategies in bone and identified a small molecule LDH inhibitor, oxamate, as a safe and efficient bone anabolic agent. © 2020 American Society for Bone and Mineral Research (ASBMR).
Optimal Designs for Model‐Based Assessment of Insulin Sensitivity and Glucose Effectiveness
Authors: Ibrahim Moustafa M. A. , Redestad Erik , Kjellsson Maria C.
Published: July 2020

The integrated minimal model allows assessment of clinical diagnosis indices, for example, insulin sensitivity (SI) and glucose effectiveness (SG), from data of the insulin‐modified intravenous glucose tolerance test (IVGTT), which is laborious with an intense sampling schedule, up to 32 samples. The aim of this study was to propose a more informative, although less laborious, IVGTT design to be used for model‐based assessment of SI and SG. The IVGTT design was optimized simultaneously for all design variables: glucose and insulin infusion doses, time of glucose dose and start of insulin infusion, insulin infusion duration, sampling times, and number of samples. Design efficiency was used to compare among different designs. The simultaneously optimized designs showed a profound higher efficiency than both standard rich (32 samples) and sparse (10 samples) designs. The optimized designs, after removing replicate sample times, were 1.9 and 7.1 times more efficient than the standard rich and sparse designs, respectively. After including practical aspects of the designs, for example, sufficient duration between samples and avoidance of prolonged hypoglycemia, we propose 2 practical designs with fewer sampling times and lower input of glucose and insulin than standard designs, constrained to prevent hypoglycemia. The optimized practical rich design is equally efficient in assessing SI and SG as the rich standard design, but with half the number of the samples, while the optimized practical sparse design has 1 less sample and requires 4.6 times fewer individuals for equal certainty when assessing SI and SG than the sparse standard design.
Effects of reward magnitude frames on measures of delay discounting in a hypothetical money scenario
Authors: Harman Michael , Kodak Tiffany , McKerchar Todd
Published: July 2020

The current study analyzed the effects of three frames of reward magnitude—quantity, volume, and duration—on the rate at which college students discounted hypothetical, delayed monetary rewards. Hypothetical scenarios were presented using the fill‐in‐the‐blank discounting questionnaire and participants made choices between immediate and delayed hypothetical monetary rewards. Scenarios framed the monetary choices as (a) quantity of dollar bills, (b) height (inches) of a stack of dollar bills, and (c) duration of time spent in a hypothetical cash machine to collect dollar bills. For each scenario, participants' subjective values were used to calculate the area under the curve (AuC). Framing resulted in a moderate effect size: The duration frame yielded significantly smaller AuC values compared to the quantity and volume frames. Thus, the framing of reward magnitude was a significant variable in controlling discounting rates for hypothetical, delayed monetary rewards. Subsequent investigations should be aware of the independent effects of the reward magnitude frames on delay discounting rates.
Linking gene expression and phenotypic changes in the developmental and evolutionary origins of osteosclerosis in the ribs of bowhead whales (Balaena mysticetus)
Authors: Cooper Lisa N. , Ball Hope C. , Vinyard Christopher J. , Safadi Fayez F. , George John C. , Thewissen Johannes G. M.
Published: July 2020

Bowhead whales are among the longest‐lived mammals with an extreme lifespan of about 211 years. During the first 25 years of their lives, rib bones increase in mineral density and the medulla transitions from compact to trabecular bone. Molecular drivers associated with these phenotypic changes in bone remain unknown. This study assessed expression levels of osteogenic genes from samples of rib bones of bowheads. Samples were harvested from prenatal to 86‐year‐old whales, representing the first third of the bowhead lifespan. Fetal to 2‐year‐old bowheads showed expression levels consistent with the rapid deposition of the bone extracellular matrix. Sexually mature animals showed expression levels associated with low rates of osteogenesis and increased osteoclastogenesis. After the first 25 years of life, declines in osteogenesis corresponded with increased expression of EZH2, an epigenetic regulator of osteogenesis. These findings suggest EZH2 may be at least one epigenetic modifier that contributes to the age‐related changes in the rib bone phenotype along with the transition from compact to trabecular bone. Ancient cetaceans and their fossil relatives also display these phenotypes, suggesting EZH2 may have shaped the skeleton of whales in evolutionary history.
Use of skimmed breast milk for an infant with a long‐chain fatty acid oxidation disorder: A novel therapeutic intervention
Authors: Kritzer Amy , Tarrant Stacey , Sussman‐Karten Karen , Barbas Kimberly
Published: July 2020

The focus of dietary therapy for long chain fatty acid oxidation disorders (LC‐FAODs) is to minimize fatty acid oxidation by avoiding fasting and providing sufficient calories. Dietary therapy involves restriction of long‐chain triglycerides (LCT), and provision of medium‐chain triglycerides as an alternate energy source. It is well established that the use of breast milk through the first year of a newborn's life has significant health benefits. While very few medical contraindications to breastfeeding exist, feeding an infant with a severe carnitine acylcarnitine translocase (CACT) deficiency typically requires cessation of breastfeeding as approximately 50% of the calories in human milk come from LCT. In this case report, we present the innovative and successful use of skimmed breast milk incorporated into the dietary management of an infant with severe CACT deficiency. Given the poor prognosis for individuals with severe CACT deficiency on standard dietary therapy, the use of skimmed breast milk represents an important measure to try to improve short‐term and long‐term outcomes. Given the many proven benefits of breast milk, this case illustrates that skimmed breast milk can be combined with appropriate fat sources to provide complete nutrition for children with severe CACT deficiency. After over 12 months on this regimen, this patient has experienced normal growth and development and has had no acute decompensations.
Lithium influences whole‐organism metabolic rate in Drosophila subobscura
Authors: Kurbalija Novičić Zorana , Bodén Robert , Kozarski Ksenija , Jelić Mihailo , Jovanović Vladimir M. , Cunningham Janet L.
Published: July 2020

Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito‐nuclear introgression lines of Drosophila subobscura to disentangle the independent effects of mitochondrial DNA (mtDNA) against a common nuclear DNA background. The study addressed three issues: (a) whether lithium has a dose‐dependent effect on whole‐organism metabolic rate, (b) whether mtDNA haplotypes show divergent metabolic efficiency measured by metabolic rate to lithium exposure and (c) whether lithium influences the whole‐organism metabolic rate across sexes. The results confirm that lithium influenced the whole‐organism metabolic rate, showing a subtle balance between efficacy and adverse effects within a narrow dose range. In addition, lithium exposure was found to influence metabolism differently based on mtDNA haplotypes and sex. This preliminary research may have a range of biological implications for the role of mitochondrial variability in psychiatric disease and treatment by contributing to the understanding and predicting of the lithium treatment response and risk for toxic side effects.
Product personalization and firm performance: An empirical analysis of the pharmaceutical industry
Authors: Ben‐Jebara Marouen , Modi Sachin B.
Published: July 2020

Recent advances in manufacturing and communication technology have made it possible for firms to offer products that are personalized to individual customers’ specifications. While personalizing products leads to benefits for firms, it also requires significant resources, calling into question the financial efficacy of this practice. This situation is especially salient in the pharmaceutical industry, where drugs are personalized to individuals. This type of medicine is expected to account for approximately 50% of drug spending in the U.S. market by 2022; however, the rising costs of producing and delivering such medications make their viability uncertain. In this study, we present a framework that conceptualizes a nonlinear inverted U‐shaped relationship between product personalization and financial performance. We further investigate the role of supply‐chain disintermediation in enhancing the benefits of personalization. Analysis of data from the pharmaceutical industry confirms that product personalization improves financial performance only up to a point, beyond which firms experience negative performance effects. Furthermore, supply‐chain disintermediation moderates this relationship such that the inverted U‐shape is steeper with increasing disintermediation levels. Together, these findings provide important guidelines for managers formulating their firms’ product personalization strategies.
Estimation of direct medical costs of warfarin, dabigatran and rivaroxaban treatments in non‐valvular atrial fibrillation patients in a tertiary public hospital, Malaysia
Authors: Tan Swee Kee , Looi Wan Lin , Yeo Hui Yee
Published: July 2020

Background

Non‐vitamin K antagonist oral anticoagulants (NOACs) are effective alternatives to warfarin for stroke prevention in non‐valvular atrial fibrillation (NVAF) patients. However, concerns have arisen due to their higher costs than warfarin.

Aim

To estimate and compare the total direct medical costs of warfarin, dabigatran and rivaroxaban treatments in NVAF patients in Penang general hospital.

Methods

This was a retrospective study capturing one year of data from January to December 2015. The data were extracted from hospital records. The total direct medical costs, including any costs associated with treatment‐related complications, were calculated as the sum of drug acquisition cost, INR point‐of‐care testing cost, personnel cost and treatment‐related complications cost. Descriptive statistical analysis was performed to describe the results.

Results

A total of 224 patients (warfarin, n = 122; dabigatran, n = 63; rivaroxaban, n = 39) were recruited. The total direct medical costs including cost of any treatment‐related complications for warfarin ranged from MYR1269.77 to MYR2383.35. The total direct medical costs with treatment‐related complications for dabigatran and rivaroxaban were MYR3469.18 and MYR2883.35, respectively. During the study period, one ischaemic stroke (0.82%) and three major bleeding events (2.46%) were observed in the warfarin group, whereas only one patient (1.59%) in the dabigatran group experienced minor bleeding. Drug acquisition costs for NOACs were high, which accounted for 80% of the total direct medical costs in the dabigatran group. However, the direct medical costs for warfarin increased by 4‐fold when treatment‐related complications costs were included.

Conclusion

The direct medical costs of NOACs were relatively higher than warfarin, however, the incidence of major bleeding was higher in the warfarin group.
Interactive Web‐based Data Visualization and Analysis Tool for Synthetizing on‐farm Research Networks Data
Authors: Laurent Anabelle , Lyu Xiaodan , Kyveryga Peter , Makowski David , Hofmann Heike , Miguez Fernando
Published: July 2020

The on‐farm research network concept enables a group of farmers to test new agricultural management practices under local conditions with support from local researchers or agronomists. Different on‐farm trials based on the same experimental design are conducted over several years and sites to test the effectiveness of different innovative management practices aimed at increasing crop productivity and profitability. As a larger amount of historical trial data are being accumulated, data of all the trials require analyses and summarization. Summaries of on‐farm trials are usually presented to farmers as individual field reports, which are not optimal for the dissemination of results and decision making. A more practical communication method is needed to enhance result communication and decision making. R Shiny is a new rapidly developing technology for turning R data analyses into interactive web applications. For the first time for on‐farm research networks, we developed and launched an interactive web tool called ISOFAST using R Shiny. ISOFAST simultaneously reports all trial results about the same management practice to simplify interpretation of multi‐site and multi‐year summaries. We used a random‐effects model to synthetize treatment differences at both the individual trial and network levels and generate new knowledge for farmers and agronomists. The friendly interface enables users to explore trial summaries, access model outputs, and perform economic analysis at their fingertips. This paper describes a case‐study to illustrate how to use the tool and make agronomic management decisions based on the on‐farm trial data. We also provided technical details and guidance for developing a similar interactive visualization tool customized for on‐farm research network. ISOFAST is currently available at https://analytics.iasoybeans.com/cool-apps/ISOFAST/.
Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus
Authors: Fearing Bailey V. , Speer Julie E. , Jing Liufang , Kalathil Aravind , P. Kelly Michael , M. Buchowski Jacob , P. Zebala Lukas , Luhmann Scott , C. Gupta Munish , A. Setton Lori
Published: July 2020

Cells of the nucleus pulposus (NP) are essential contributors to extracellular matrix synthesis and function of the intervertebral disc. With age and degeneration, the NP becomes stiffer and more dehydrated, which is associated with a loss of phenotype and biosynthetic function for its resident NP cells. Also, with aging, the NP cell undergoes substantial morphological changes from a rounded shape with pronounced vacuoles in the neonate and juvenile, to one that is more flattened and spread with a loss of vacuoles. Here, we make use of the clinically relevant pharmacological treatment verteporfin (VP), previously identified as a disruptor of yes‐associated protein‐TEA domain family member‐binding domain (TEAD) signaling, to promote morphological changes in adult human NP cells in order to study variations in gene expression related to differences in cell shape. Treatment of adult, degenerative human NP cells with VP caused a shift in morphology from a spread, fibroblastic‐like shape to a rounded, clustered morphology with decreased transcriptional activity of TEAD and serum‐response factor. These changes were accompanied by an increased expression of vacuoles, NP‐specific gene markers, and biosynthetic activity. The contemporaneous observation of VP‐induced changes in cell shape and prominent, time‐dependent changes within the transcriptome of NP cells occurred over all timepoints in culture. Enriched gene sets with the transition to VP‐induced cell rounding suggest a major role for cell adhesion, cytoskeletal remodeling, vacuolar lumen, and MAPK activity in the NP phenotypic and functional response to changes in cell shape.
Retention mechanism of pH‐peak‐focusing in countercurrent chromatographic separation of baicalin and wogonoside from Scutellaria baicalensis Georgi
Authors: Wang Chaoyue , Zuo Guanglei , Wang Xiang , Kim Hyun Yong , Zhao Shanshan , Sun Wenyu , Tong Shengqiang , Lim Soon Sung
Published: July 2020

An efficient and target‐oriented pH‐peak‐focusing countercurrent chromatographic method was established for large‐scale separation of baicalin and wogonoside from the crude exact of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. An optimized two‐phase solvent system composed of n‐butanol–ethyl acetate–methanol–water (1:4:0.5:5, v/v) was selected. Trifluoroacetic acid (10 mmol/L) was added to the upper organic phase, used as the stationary phase. One liter of the aqueous lower phase was used as the mobile phase for 0–350 min, and then 10 mmol/L ammonia was added to remaining 1 L of the aqueous lower phase and used as the mobile phase for 350–600 min. In total, 493.2 mg of baicalin with 98.6% purity and 88.6 mg of wogonoside with 98.9% purity were obtained from 1.0 g of crude exact of S. baicalensis by countercurrent chromatography in a single run. The acid dissociation constant (pKa) and oil–water partition coefficient values of two components were measured to better understand the mechanism of separation. Results showed that pH‐peak‐focusing countercurrent chromatography with a polar solvent system added with trifluoroacetic acid could be an efficient method for large‐scale isolation of organic acids, which are difficult to separate with conventional countercurrent chromatography due to their poor solubility in non‐polar solvents.
Tephra deposits and carbon dynamics in peatlands of a volcanic region: Lessons from the Hekla 4 eruption
Authors: Möckel Susanne C. , Erlendsson Egill , Prater Isabel , Gísladóttir Guðrún
Published: July 2020

Interactions between tephra deposits from volcanic eruptions and peatland carbon (C) dynamics are poorly understood despite the significant extent of peatlands influenced by tephra worldwide. Tephra falls can affect peat accumulation within a radius of at least 1,000 km. In Iceland, volcanic activity is amongst the highest in the world and it might even increase due to pressure release on subglacial volcanoes. A potent combination of sparse vegetation, low cohesion of Andosols, and frequent strong winds, facilitates the regular input of mineral aeolian material from eroded areas into peatlands in Iceland, in addition to tephra deposits. We present results of a study on the impact of a major tephra deposit, the Hekla 4 tephra, on C dynamics in Icelandic peatlands. We investigated three sites at differing distances from the active volcanic zones and major erosion areas in the interior of the country. A combination of variables was applied, including laboratory C mineralization at 5, 15 and 25°C and C structure obtained by solid‐state 13C NMR spectroscopy. Tephra deposits seem to affect C dynamics. Differences in C mineralization can only be partially explained by C structure. The C mineralization from soils with conspicuously similar C structure differs by a factor of up to 2.7. Temperature sensitivity of decomposition after the tephra deposition increases by a factor of up to 2.2. Changes in inorganic matter and the ratio of soil organic matter to soil organic carbon by a factor of up to 1.3 and 1.4, respectively, were also observed.
Experimental Demonstration of 11‐Dimensional 10‐Party Quantum Secret Sharing
Authors: Pinnell Jonathan , Nape Isaac , de Oliveira Michael , TabeBordbar Najmeh , Forbes Andrew
Published: July 2020

Quantum secret sharing is the art of securely sharing information between more than two people in such a way that its reconstruction requires the collaboration of a certain number of parties. Here, by taking advantage of the high‐dimensional Hilbert space for orbital angular momentum and using Perfect Vortex beams as their carriers, a proof‐of‐principle implementation of a high‐dimensional quantum secret sharing scheme is presented. This scheme is experimentally implemented with a fidelity of 93.4%, for 10 participants in dimensions—the highest number of participants and dimensions to date. The implementation can easily be scaled to higher dimensions and any number of participants, opening the way for securely distributing information across a network of nodes.
Anticholinergics May Carry Significant Cognitive and Gait Burden in Parkinson's Disease
Authors: Rajan Roopa , Saini Arti , Verma Bhawna , Choudhary Nishu , Gupta Anu , Vishnu Venugopalan Y. , Bhatia Rohit , Singh Mamta B. , Srivastava Achal K. , Srivastava Madakasira Vasantha Padma
Published: July 2020

Background

Anticholinergic drugs are associated with significant cognitive and other adverse events in older adults, including those with Parkinson's disease (PD). Anticholinergic effects are considered lesser in younger individuals and the burden and outcomes in younger patients with PD are unknown.

Objectives

To determine the cumulative anticholinergic burden in a cohort of younger of patients with PD and to correlate the same with cognitive impairment and freezing of gait (FOG).

Methods

We conducted a cross‐sectional study to identify the cumulative anticholinergic burden from medications prescribed to patients with PD. Two standard scales, the Anticholinergic Cognitive Burden (ACB) scale and the ACB score, were used to calculate the anticholinergic burden from prescriptions. We identified commonly prescribed drugs contributing to anticholinergic effects and correlated the cumulative ACB score with cognitive impairment (Movement Disorder Society–Unified Parkinson's Disease Rating Scale item 1.1) and FOG (Movement Disorder Society–Unified Parkinson's Disease Rating Scale items 2.13 and 3.11).

Results

We recruited 287 patients with PD (68.9% male) with a mean age of 56.9 ± 11.8 years and a duration of symptoms 6.3 ± 6.9 years. Median ACB score was 4 (range 0–12). A total of 164 (58.4%) patients had total ACB score > 3. ACB score > 3 was independently associated with cognitive impairment (Odds Ratio, 2.55; 95% confidence interval, 1.43–4.53; P < 0.001) and FOG using patient‐reported measures (Odds Ratio, 3.192; 95% Confidence Interval, 1.68–6.07; P < 0.001) and objective measures (odds ratio, 2.41; 95% confidence interval, 1.27–4.6, P = 0.007).

Conclusion

Patients with PD are exposed to significant anticholinergic burden from drugs prescribed for PD and non‐PD indications. Higher anticholinergic burden is associated with cognitive impairment and FOG even in younger patients with PD.
GTPase Regulator Associated with Focal Adhesion Kinase 1 (GRAF1) Immunoglobulin‐Associated Ataxia and Neuropathy
Authors: Pittock Sean J. , Alfugham Nora , O'Connor Kevin , Hinson Shannon , Kunchok Amy , Lennon Vanda A. , Komorowski Lars , Probst Christian , McKeon Andrew
Published: July 2020

Background

To date, 10 patients with GTPase Regulator Associated with Focal Adhesion Kinase 1/Rho GTPase Activating Protein 26‐Immunoglobulin (GRAF1/ARHGAP26‐IgG) associated neurological disorders have been described, most with ataxia.

Objective

To report the clinical, oncological, and radiological associations of GRAF1 autoantibodies.

Methods

We identified 17 patients whose serum and/or cerebrospinal fluid IgG was confirmed to target GRAF1/ARHGAP26‐IgG by both tissue‐based immunofluorescence and transfected cell‐based assay. Clinical information was available on 14 patients.

Results

The median age at neurological symptom onset was 51 years, and 8 (47%) were men. The predominant clinical features were subacute progressive cerebellar ataxia (13) or peripheral neuropathy (2). Magnetic resonance imaging brain (7 available) showed cerebellar atrophy (4, 1 also cerebrum and brainstem atrophy). Of 7 cerebrospinal fluids available for testing, 5 showed pleocytosis with oligoclonal bands in 3. Squamous cell carcinoma was observed in 3 patients (head and neck [2], lung [1]).

Conclusion

GTPase Regulator Associated with Focal Adhesion Kinase 1 autoimmunity manifests commonly with subacute ataxia and cerebellar degeneration with a potential association with squamous cell carcinoma. Peripheral neuropathy may also be encountered. Cases in this series responded poorly to immunotherapy.
APP‐Related Corticobasal Syndrome: Expanding the List of Corticobasal Degeneration Look Alikes
Authors: Abate Filomena , Dati Giovanna , Ginevrino Monia , Valente Enza M. , Barone Paolo , Picillo Marina
Published: July 2020

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Choice of Lipid Emulsion Determines Inflammation of the Gut‐Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition
Authors: Lou Phing‐How , Lucchinetti Eliana , Wawrzyniak Paulina , Morsy Yasser , Wawrzyniak Marcin , Scharl Michael , Krämer Stefanie D. , Rogler Gerhard , Hersberger Martin , Zaugg Michael
Published: July 2020

Scope

The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n‐3 fatty acid‐based Omegaven versus n‐6 fatty acid‐based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance.

Methods and results

Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL‐TPN, no chow), an Omegaven group (OV‐TPN, no chow), or a chow only group (without JVC). Both TPN elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL‐TPN increases interleukin‐6 and interferon‐γ, while OV‐TPN reduces interleukin‐4, monocyte chemoattractant protein‐1, and interleukin‐1α. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon‐like peptide‐1 (GLP‐1) were higher in IL‐TPN. Gluconeogenesis is increased in IL‐TPN and the nuclear profile of key metabolic transcription factors shows a liver‐protective phenotype in OV‐TPN. OV‐TPN increases insulin sensitivity in the liver and skeletal muscle.

Conclusion

OV‐TPN as opposed to IL‐TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by “re‐sensitizing” the liver and skeletal muscle to insulin.