bluuebunny/crossref_metadata_2025 huggingface dataset:
Mild carotid stenosis creates gradual, progressive, lifelong brain, and eye damage: An experimental laboratory rat model
Authors: Tzameret Adi , Piontkewitz Yael , Nitzan Anat , Rudoler Nir , Bruzel Marina , Zilberstein Yael , Ziv Hana , Pri‐Chen Sarah , Solomon Arieh S.
Published: December 2019

In humans, carotid stenosis of 70% and above might be the cause of clinical symptoms such as transient ischemic attack and stroke. No clinical or animal studies have evaluated mild carotid occlusion, and few examined unilateral occlusion. Here, Westar rats underwent bilateral or unilateral carotid occlusion of 28–45%. Long‐term effects were evaluated 9–11 months later. We conducted cognitive evaluation using spatial learning in a water maze and exploration behavior in an open field. Morphology of the brain was examined by MRI using diffusion‐tensor imaging (DTI) and immunohistochemistry staining of the brain and eyes. Cognitive deficit was found in spatial memory and exploration behavior in both occluded groups. Brain and eyes histology presented severe damage in the bilateral group, compared to the unilateral one. DTI revealed an increase in mean diffusivity (MD) in the ventral thalamus and a decrease in fractional anisotropy in optic nerve and optic tract in bilateral rats, while unilateral rats showed only an increase in MD in the ventral pons. In those areas, a significant change in astrocytes, microglia, and number of apoptotic cells were found. Bilateral occlusion produced severe damage to both retinas, while unilateral occlusion produced damage mainly in the occluded side. We found that mild carotid stenosis, even in a unilateral occlusion, creates behavioral abnormalities presented by brain and eye histopathology. The results support our hypothesis that gradual formation of mild carotid stenosis along the life course leads to progressive damage that may create different degenerative diseases at a later age.
Evaluation of expanded gamut software solutions for spot color reproduction
Authors: Sharma Abhay , Seymour John
Published: December 2019

Expanded gamut printing is an approach in color reproduction that expands the color gamut of conventional CMYK printing processes via the use of additional colorants, such as Orange, Green, and Violet inks. This study evaluates the ability of commercial color management software to create an accurate solution for an expanded gamut printing system. In this study, two printing processes were used, an Epson SureColor P9000 inkjet printer/proofer and an HP Indigo 7900 digital production press, both with 7‐color expanded gamut ink sets. Software solutions from Alwan, CGS ORIS, ColorLogic, GMG Color, Heidelberg, and Kodak were evaluated. The systems were tested to see how well they could reproduce the colors in the entire PANTONE+ Solid Coated spot color library. It is shown that the solutions are able to reproduce 89% to 94% of the spot colors on the Epson P9000 inkjet printer and 77% to 87% of the library on the Indigo 7900, both to less than two CIEDE2000 (a typical tolerance in label and packaging work). The number of color patches in expanded gamut characterization test charts was noted, as this is still an area of proprietary, nonstandardized working practice. There are many different colorant combinations that can make the same color in expanded gamut printing. The ink build created by the different software solutions was studied, as it relates to press stability through appropriate choice of colorants. Pantone and Adobe provide everyday commercial tools for expanded color workflows. The study identified some issues with products from these companies that could confuse a less‐skilled user in a busy production environment. The conclusion of the study is that expanded gamut solutions for spot color printing produce totally acceptable results for digital printing processes; expanded gamut printing is ready, here and now. The findings show that expanded gamut printing can replace cumbersome conventional spot color workflows creating considerable savings and advantages, especially for label and packaging printers.
Single‐Dose Pharmacokinetics, Safety, and Tolerability of Avadomide (CC‐122) in Subjects With Mild, Moderate, or Severe Renal Impairment
Authors: Li Yan , MacGorman Kimberly , Liu Liangang , Chen Jian , Hoffmann Matthew , Palmisano Maria , Zhou Simon
Published: December 2019

CC‐122 (Avadomide) is a nonphthalimide analogue of thalidomide that has multiple pharmacological activities including immune modulation of several immune cell subsets, antigrowth activity, antiproliferative activity, and antiangiogenic activity. CC‐122 as monotherapy and in combination with other agents is being evaluated for multiple indications including hematologic malignancies and advanced solid tumors. Given that renal clearance is one of the major routes of elimination for CC‐122 and its clearance/exposure could be affected by renal impairment, a total of 50 subjects with various degrees of renal function were enrolled in an open‐label, single‐dose study to evaluate the impact of renal impairment on CC‐122 pharmacokinetic disposition. The study showed that following administration of a single oral dose of 3 mg CC‐122, renal impairment reduced both the apparent total plasma clearance and renal clearance of CC‐122, but it had less impact on CC‐122 absorption, as demonstrated by similar Tmax and Cmax among groups with various degrees of renal function. Compared with exposure in subjects with normal renal function, total plasma exposure to CC‐122 increased by ∼20%, ∼50%, and ∼120% in subjects with mild, moderate, and severe renal insufficiency, respectively. Results from this study combined with modeling/simulation suggest that dose adjustments are necessary in patients with moderate or severe but not with mild renal impairment. Finally, a single dose of 3 mg CC‐122 was safe and well tolerated by healthy subjects and subjects with mild, moderate, and severe renal impairment.
A Model‐Informed Drug Discovery and Development Strategy for the Novel Glucose‐Responsive Insulin MK‐2640 Enabled Rapid Decision Making
Authors: Visser Sandra A.G. , Kandala Bhargava , Fancourt Craig , Krug Alexander W. , Cho Carolyn R.
Published: December 2019

A model‐informed drug discovery and development strategy played a key role in the novel glucose‐responsive insulin MK‐2640’s early clinical development strategy and supported a novel clinical trial paradigm to assess glucose responsiveness. The development and application of in silico modeling approaches by leveraging substantial published clinical insulin pharmacokinetic–pharmacodynamic (PKPD) data and emerging preclinical and clinical data enabled rapid quantitative decision making. Learnings can be applied to define PKPD properties of novel insulins that could become therapeutically meaningful for diabetic patients.
A novel mixed living high training low intervention and the hematological module of the athlete biological passport
Authors: Voss Sven Christian , Al‐Hamad Khalifa , Samsam Waseem , Cherif Anissa , Georgakopoulos Costas , Al Maadheed Mohammed , Balanos George , Lucas Sam , Sottas Pierre‐Edouard , Wilson Mathew , Townsend Nathan
Published: December 2019

Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well‐trained middle‐distance runners participated in a “live high, train low and high” (LHTLH) altitude training camp for 14 days. The participants spent ˜6 hr.d‐1 at 3000–5400 m during waking hours and ˜10 h.d‐1 overnight at 2400–3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF‐score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an “atypical passport finding” (ATPF) due to deviation of the OFF‐score. When this sample was evaluated by ABP experts it was considered “normal”. In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.
Predation of potential insect pests in oil palm plantations, rubber tree plantations, and fruit orchards
Authors: Denan Nuradilah , Wan Zaki Wan Mamat , Norhisham Ahmad R. , Sanusi Ruzana , Nasir Dzulhelmi Muhammad , Nobilly Frisco , Ashton‐Butt Adham , Lechner Alex M. , Azhar Badrul
Published: December 2019

In human‐modified landscapes, important ecological functions such as predation are negatively affected by anthropogenic activities, including the use of pesticides and habitat degradation. Predation of insect pests is an indicator of healthy ecosystem functioning, which provides important ecosystem services, especially for agricultural systems. In this study, we compare predation attempts from arthropods, mammals, and birds on artificial caterpillars in the understory, between three tropical agricultural land‐use types: oil palm plantations, rubber tree plantations, and fruit orchards. We collected a range of local and landscape‐scale data including undergrowth vegetation structure; elevation; proximity to forest; and canopy cover in order to understand how environmental variables can affect predation. In all three land‐use types, our results showed that arthropods and mammals were important predators of artificial caterpillars and there was little predation by birds. We did not find any effect of the environmental variables on predation. There was an interactive effect between land‐use type and predator type. Predation by mammals was considerably higher in fruit orchards and rubber tree than in oil palm plantations, likely due to their ability to support higher abundances of insectivorous mammals. In order to maintain or enhance natural pest control in these common tropical agricultural land‐use types, management practices that benefit insectivorous animals should be introduced, such as the reduction of pesticides, improvement of understory vegetation, and local and landscape heterogeneity.
Born globals from emerging economies: Reconciling early exporting with theories of internationalization
Authors: McCormick Marleen , Somaya Deepak
Published: December 2019

Research Summary

What explains born global firms who internationalize very early through exports, when theories of internationalization recommend they focus on domestic markets first? While prior research suggests a number of factors that enable exporting by new ventures, empirical tests of these theories have not evaluated if these factors uniquely explain new venture exporting. We propose and empirically test hypotheses that exporting by young (relative to established) emerging‐economy firms increases when they tap into the drivers of modern globalization (Internet technologies, global talent flows) and overcome home‐country institutional constraints (government inefficiencies, location), all of which have bigger impacts on exporting by young firms than established ones. Understanding these unique drivers of born global emerging‐economy firms is critical for reconciling this phenomenon with traditional theories of firm internationalization.

Managerial Summary

Our research finds that exporting by young firms are enabled to a greater extent (than established firms) when they use Internet technologies and tap into mobile talent (such as cross‐national entrepreneurs and leaders with international experience), which helps to overcome key constraints in tapping into international markets. We also found that young firms overcome home‐country institutional and infrastructure deficiencies in emerging economies, specifically, by receiving efficient government services and strategically locating in well‐resourced centers such as capital cities, which helps them more in exporting as compared to established firms. Our findings help to explain the modern phenomenon of “born global” firms, who have broken away from the traditional path of focusing first on domestic markets and then engaging in incremental international expansion.

A video abstract is available at https://youtu.be/QPIR0CRazgw.
A novel region‐based multimodal image fusion technique using improved dictionary learning
Authors: Meher Bikash , Agrawal Sanjay , Panda Rutuparna , Dora Lingraj , Abraham Ajith
Published: December 2019

Recently, the sparse representation (SR) based algorithms have gained much attention from the researchers in the area of image fusion (IF). The building of a compact discriminative dictionary plays a vital role in the sparse‐based IF techniques. In this context, an efficient multimodal IF method based on improved dictionary learning is investigated. The key contributions of this paper are: (a) An improved KSVD algorithm is suggested for the dictionary learning process, (b) to reduce the computational time, only the informative patches are selected using energy feature, and (c) a novel region‐based fusion scheme is suggested for the first time for the problem on hand. The suggested technique is tested with a number of multimodal images from Harvard Medical School brain database. The results are compared with state‐of‐the‐art multiscale transform‐based methods and modified SR‐based methods. Unlike earlier methods, our proposed technique generates an adaptive dictionary through selection of informative patches only. This results in a compact dictionary with improved computational efficiency. The experimental results reveal that our approach outperforms other methods. The potential application of the suggested method could be in pathological images for follow‐up study and better treatment planning.
Chromogranin A in the early steps of the neurosecretory pathway
Authors: Laguerre Fanny , Anouar Youssef , Montero‐Hadjadje Maité
Published: December 2019

Chromogranin A (CgA) is a soluble glycoprotein stored with hormones and neuropeptides in secretory granules (SG) of most (neuro)endocrine cells and neurons. Since its discovery in 1967, many studies have reported its structural characteristics, biological roles, and mechanisms of action. Indeed, CgA is both a precursor of various biologically active peptides and a granulogenic protein regulating the storage and secretion of hormones and neuropeptides. This review emphasizes the findings and theoretical concepts around the CgA‐linked molecular machinery controlling hormone/neuropeptide aggregation and the interaction of CgA‐hormone/neuropeptide aggregates with the trans‐Golgi membrane to allow hormone/neuropeptide targeting and SG biogenesis. We will also discuss the intriguing alteration of CgA expression and secretion in various neurological disorders, which could provide insights to elucidate the molecular mechanisms underlying these pathophysiological conditions.
Domain‐based local pair natural orbital methods within the correlation consistent composite approach
Authors: Patel Prajay , Wilson Angela K.
Published: December 2019

Ab initio composite approaches have been utilized to model and predict main group thermochemistry within 1 kcal mol−1, on average, from well‐established reliable experiments, primarily for molecules with less than 30 atoms. For molecules of increasing size and complexity, such as biomolecular complexes, composite methodologies have been limited in their application. Therefore, the domain‐based local pair natural orbital (DLPNO) methods have been implemented within the correlation consistent composite approach (ccCA) framework, namely DLPNO‐ccCA, to reduce the computational cost (disk space, CPU (central processing unit) time, memory) and predict energetic properties such as enthalpies of formation, noncovalent interactions, and conformation energies for organic biomolecular complexes including one of the largest molecules examined via composite strategies, within 1 kcal mol−1, after calibration with 119 molecules and a set of linear alkanes. © 2019 Wiley Periodicals, Inc.
ZnO nanorods as efficient catalyst for the green synthesis of thiophene derivatives: Investigation of antioxidant and antimicrobial activity
Authors: Hamedani Naghmeh Faal , Ghazvini Maryam , Sheikholeslami‐Farahani Fatemeh , Bagherian‐Jamnani Mohammad Taghi
Published: December 2019

In this work, thiophene derivatives were synthesized in good yields via multicomponent reaction of isoquinoline, alkyl bromides, activated acetylenic compounds, isothiocyanates, and catalytic amounts of ZnO nanorods (NRs) at room temperature under solvent‐free conditions. This procedure for the synthesis of thiophene derivatives is green, easy, and simple with excellent yield. In addition, DPPH radical scavenging and ferric reduction power experiment has been studied for the evaluation of the antioxidant activity of some prepared thiophenes, for example, 5b, 5d, 5e, and 5f. As outcome, the compound 5d exhibited a noteworthy radical trapping activity and excellent reducing ability than synthetic antioxidants such as butylated hydroxytoluene (BHT) and 2‐tertbutylhydroquinone (TBHQ). Moreover, the antimicrobial activity of some synthesized thiophenes was confirmed by employing the disk diffusion test on Gram‐positive and Gram‐negative bacteria. The obtained results of disk diffusion test showed that compounds 5b, 5d, 5e, and 5f prevented bacterial growth.
Ligandless, deep eutectic solvent‐based ultrasound‐assisted dispersive liquid‐liquid microextraction with solidification of the aqueous phase for preconcentration of lead, cadmium, cobalt and nickel in water samples
Authors: Werner Justyna
Published: December 2019

A green and efficient sample preparation method using a deep eutectic solvent‐based ultrasounds‐assisted dispersive liquid–liquid microextraction with solidification of the aqueous phase followed by high performance liquid chromatography analysis was developed for preconcentration and determination of heavy metals in environmental samples. In the proposed method, a novel, low density deep eutectic solvent was prepared by mixing trihexyl(tetradecyl)phosphonium chloride and thiosalicylic acid at a molar ratio of 1:2 and used both as an extractant and complexing agent. Ultrasound was used to disperse the extractant in the aqueous phase of the sample. Then, the phases were separated by centrifugation, after which the aqueous phase was frozen and the surface extractant phase was dissolved in a small volume of acetonitrile and subjected to liquid chromatographic analysis. The proposed method provided precisions (relative standard deviation, n = 5) in the range of 2.6–4.7%. The limit of detection were 0.05, 0.13, 0.06, and 0.11 µg/L for Pb(II), Cd(II), Co(II), Ni(II), respectively. The enhancement factors were equal to 154, 159, 162, and 158 for lead(II), cadmium(II), cobalt(II), and nickel(II), respectively. The accuracy of the proposed method was evaluated using certified reference materials (CA011b – hard drinking water, NIST 1643e – trace elements in water, TMRAIN‐04 – simulated rain sample).
Action research on neonatal nursing staff: Experiences caring for bubble continuous positive airway pressure patients
Authors: Lu Ming‐Huei , Li I‐Chuan
Published: December 2019

The objective of this study was to understand the experiences of special care nursery (SCN) nurses tending patients on bubble continuous positive airway pressure (bCPAP). The action research (AR) method with focus group interview was used, and five focus‐group interviews were conducted between November 2015 and January 2016. Twenty SCN nurses who had cared neonates on bCPAP for at least one shift were recruited and interviewed. Six themes were revealed in two stages. The first stage was “experience of change,” three themes evolved: “resistance to change,” “lack of confidence on new care model,” and “request administrative supports and resources from the hospital level.” The second stage was “willing to take challenge,” three themes evolved: “pursuit of proficiency in bCPAP care,” “mastering bPCAP: acquiring self‐efficacy, becoming competent, and collaborating as a team,” and “the development of creative care methods.” In the future when confronted with nurses resisting to new policies or changes, administrators should embrace their emotions, address their insecurity and fear, and provide adequate training to improve confidence through familiarity. Application of this model can help with policy implementation, thereby improving the overall caring quality.
The Brazilian bankruptcy law reform, corporate ownership concentration, and risk‐taking
Authors: Castro Martins Henrique
Published: December 2019

We investigate whether a bankruptcy reform, which increased creditors' protection, affected the risk taking of Brazilian firms. Collecting data from Brazilian (treatment group) and Argentinian, Chilean, Colombian, Mexican, and Peruvian firms (control group) and using a difference‐in‐difference technique, we show that Brazilian firms with concentrated ownership structure decreased risk taking after the reform. Our results suggest that these firms reduced risk in response to increasing creditors' protection, possibly because controlling shareholder fear losing control. Moreover, our results indicate that the reform probably provoked a wealth transfer from minorities to controlling shareholders.
Meta‐Analysis of Copper and Iron in Parkinson's Disease Brain and Biofluids
Authors: Genoud Sian , Senior Alistair M. , Hare Dominic J. , Double Kay L.
Published: December 2019

Background

Variations in study quality and design complicate interpretation of the clinical significance of consistently reported changes in copper and iron levels in human Parkinson's disease brain and biofluids.

Methods

We systematically searched literature databases for quantitative reports of biometal levels in the degenerating substantia nigra (SN), CSF, serum, and plasma in Parkinson's disease compared with healthy age‐matched controls and assessed the quality of these publications. The primary outcomes of our analysis confirmed SN copper and iron levels are decreased and increased, respectively, in the Parkinson's disease brain. We applied a novel Quality Assessment Scale for Human Tissue to categorize the quality of individual studies and investigated the effects of study quality on our outcomes. We undertook a random‐effects meta‐analysis and meta‐regression subgroup analysis.

Results

In the 18 eligible studies identified (211 Parkinson's disease, 215 control cases), SN copper levels were significantly lower (d, ‐2.00; 95% CI, ‐2.81 to ‐1.19; P < 0.001), and iron levels were significantly higher (d, 1.31; 95% CI, 0.38–2.24; P < 0.01) in Parkinson's disease. No changes were detected in CSF, serum, or plasma for any metals (29 studies; 2443 Parkinson's disease and 2183 control cases) except serum iron, which was lower in Parkinson's disease (14 studies; 1177 Parkinson's disease and 1447 control cases).

Conclusions

Reductions in copper levels and elevations in iron were confirmed as characteristic of the degenerating SN of Parkinson's disease. Iron in serum was also changed, but in the opposite direction to that in the SN and to a lesser extent. © 2019 International Parkinson and Movement Disorder Society
Intraclass correlations of seizure duration by wavelet transform, sample entropy, and visual determination in electroconvulsive therapy
Authors: Azuma Hideki , Ogawa Haruka , Suzuki Erina , Akechi Tatsuo
Published: December 2019

Although electroconvulsive therapy seizure duration has been shown to have limited relevance to efficacy, seizure duration remains important for clinically valid stimulus efficiency. There has been no report on seizure duration using sample entropy with Thymatron (Somatics, Inc), which is widely used in Japan. Furthermore, wavelet transform analysis is also suitable for a seizure because of the wide range of dominant frequencies. Therefore, in this study with Thymatron, the intraclass correlations of seizure duration determined by sample entropy, wavelet transform, and visual determination were investigated to determine whether these methods were applicable for clinical use. Wavelet transform, sample entropy, and the human rater had high intraclass correlations for seizure duration. The present results indicate that wavelet transform and sample entropy can be useful in the clinical electroconvulsive therapy setting, and they may also be suitable for clinical research into the mechanisms of the generalized tonic‐clonic seizures related to the efficacy of electroconvulsive therapy.
Differential Effects of Diet and Weight on Taste Responses in Diet‐Induced Obese Mice
Authors: Ahart Zachary C. , Martin Laura E. , Kemp Bailey R. , Dutta Banik Debarghya , Roberts Stefan G. E. , Torregrossa Ann‐Marie , Medler Kathryn F.
Published: December 2019

Objective

Previous studies have reported that individuals with obesity have reduced taste perception, but the relationship between obesity and taste is poorly understood. Earlier work has demonstrated that diet‐induced obesity directly impairs taste. Currently, it is not clear whether these changes to taste are due to obesity or to the high‐fat diet exposure. The goal of the current study was to determine whether diet or excess weight is responsible for the taste deficits induced by diet‐induced obesity.

Methods

C57BL/6 mice were placed on either high‐fat or standard chow in the presence or absence of captopril. Mice on captopril did not gain weight when exposed to a high‐fat diet. Changes in the responses to different taste stimuli were evaluated using live cell imaging, brief‐access licking, immunohistochemistry, and real‐time polymerase chain reaction.

Results

Diet and weight gain each affected taste responses, but their effects varied by stimulus. Two key signaling proteins, α‐gustducin and phospholipase Cβ2, were significantly reduced in the mice on the high‐fat diet with and without weight gain, identifying a potential mechanism for the reduced taste responsiveness to some stimuli.

Conclusions

Our data indicate that, for some stimuli, diet alone can cause taste deficits, even without the onset of obesity.
A structural equation modeling analysis of marital bullying scale
Authors: Arnout Boshra A. , Al‐Qadimi Fatma Y.
Published: December 2019

Bullying has received increasing research interest, whether bullying among students in schools and universities, or bullying among employees. There is still no accordance regarding to bullying between the couple. This study aimed to investigate the construct validity and psychometric properties of the marital bullying scale with advanced statistical procedure, structural equation modeling, and exploratory factor analysis. The researchers prepared the marriage bullying scale consisting of 25 self‐report items and applied it in a random sample consisting of (760) married individual, and then, the researchers extracted the psychometric characteristics of this scale. The finding indicated that the scale has psychometric properties with a high validity and reliability. In order to ensure the validity of the structure of this scale, the researchers developed a measurement model for marital bullying. The results of the exploratory factor analysis pointed to the saturation of the items of the scale (25) on five factors and accounted for 80.815% of the total variance of the scale. The first factor was verbal bullying that accounted for 37.658%, the second factor was physical bullying that accounted for 16. 249 %, the third factor was psychological bullying that accounted for 12.850 %, the fourth factor was social bullying that accounted for 8.584 %, and the fifth factor was family bullying that accounted for (5.475 %) of the total variance of marital bullying. And then by using confirmatory factor analysis, results showed that the structure of the proposed measurement model of marital bullying has good fitness with the data collected from the sample of the study, which enhances confidence in the ability of the scale to assess marital bullying. The findings shed new light on the underlying theory behind marital bullying and proved the usefulness of structural equation modeling framework in scale development.
Genetic syndromes associated with isolated fetal growth restriction
Authors: Meler Eva , Sisterna Silvina , Borrell Antoni
Published: December 2019

Early onset fetal growth restriction (FGR) may be due to impaired placentation, environmental or toxic exposure, congenital infections or genetic abnormalities.

Remarkable research, mainly based on retrospective series, has been published on the diverse genetic causes. Those have become more and more relevant with the improvement in the accuracy of the analysis techniques and the rising of breakthrough genomewide methods such as the whole genome sequencing.

However, no publication has presented an integrated view of management of those fetuses with an early and severe affection.

In this review, we explored to which extent genetic syndromes can cause FGR fetuses without structural defects. The most common chromosomal abnormalities (Triploidies and Trisomy 18), submicroscopic chromosomal anomalies (22q11.2 microduplication syndrome) and single gene disorders (often associated with mild ultrasound findings) related to early and severe FGR had been analysed. Finally, we addressed the impact of epigenetic marks on fetal growth, a matter of growing importance.

At the end of this review, we should be able to provide an adequate counseling to parents in terms of diagnosis, prognosis and management of those pregnancies.
Taming the Internet Trolls With an Internet Ombudsperson: Ethical Social Media Regulation
Authors: Daskal Efrat , Wentrup Robert , Shefet Dan
Published: December 2019

Social media platforms have a powerful role as one of the main gatekeepers of the online sphere, alongside search engines and Internet service providers. Yet, given the variety of regulatory mechanisms, technological tools, and nonlegal ethical guidelines employed in regulating content on social media platforms, we argue that there is a need today for a consistent unified formal online content regulation structure. To address this issue, a number of European countries have suggested an old‐new policy instrument—the Internet ombudsperson. This article, therefore, develops the concept, firstly by framing it as part of the evolution of the institution of the media ombudsperson. We then describe the theoretical and conceptual framework of Internet ombudsperson and propose future implementations including a traditional national (mainly offline) model as well as an international blockchain model. We conclude by discussing the merits and drawbacks of our proposal as well as its possible theoretical implications.
Developing a revised definition of the Bobath concept: Phase three
Authors: Vaughan‐Graham Julie , Cheryl Cott , Holland Ann , Michielsen Marc , Magri Alba , Suzuki Mitsuo , Brooks Dina
Published: December 2019

Objective

To develop a revised definition of the Bobath concept that incorporates the perspectives of members of the International Bobath Instructors Training Association (IBITA).

Methods

A three‐phase consensus building design utilizing (i) focus groups; (ii) survey methods; and, (iii) real‐time Delphi. This paper presents the findings from the real‐time Delphi, an iterative process to collect and synthesize expert opinions anonymously, provide controlled feedback, with the overall goal of achieving consensus.

Results

One hundred and twenty‐one IBITA members participated in the real‐time Delphi. Over three Delphi Rounds, consensus was reached on six overarching conceptual statements and 11 statements representing unique aspects of Bobath clinical practice. One statement that aimed to describe the Bobath clinical term of “placing” was eliminated in Round One due to participant reservations that a text description was insufficient for this term. Seven statements underwent minor wording revisions in Round Two and Three to improve sentence clarity.

Conclusion

Using the real‐time Delphi, we were successful in gaining consensus in an expert group on a series of statements on which a revised definition of the Bobath concept could be based.
Modeling beta‐sheet peptide‐protein interactions: Rosetta FlexPepDock in CAPRI rounds 38‐45
Authors: Khramushin Alisa , Marcu Orly , Alam Nawsad , Shimony Orly , Padhorny Dzmitry , Brini Emiliano , Dill Ken A. , Vajda Sandor , Kozakov Dima , Schueler‐Furman Ora
Published: December 2019

Peptide‐protein docking is challenging due to the considerable conformational freedom of the peptide. CAPRI rounds 38‐45 included two peptide‐protein interactions, both characterized by a peptide forming an additional beta strand of a beta sheet in the receptor. Using the Rosetta FlexPepDock peptide docking protocol we generated top‐performing, high‐accuracy models for targets 134 and 135, involving an interaction between a peptide derived from L‐MAG with DLC8. In addition, we were able to generate the only medium‐accuracy models for a particularly challenging target, T121. In contrast to the classical peptide‐mediated interaction, in which receptor side chains contact both peptide backbone and side chains, beta‐sheet complementation involves a major contribution to binding by hydrogen bonds between main chain atoms. To establish how binding affinity and specificity are established in this special class of peptide‐protein interactions, we extracted PeptiDBeta, a benchmark of solved structures of different protein domains that are bound by peptides via beta‐sheet complementation, and tested our protocol for global peptide‐docking PIPER‐FlexPepDock on this dataset. We find that the beta‐strand part of the peptide is sufficient to generate approximate and even high resolution models of many interactions, but inclusion of adjacent motif residues often provides additional information necessary to achieve high resolution model quality.
Theoretical study on alkaloid encapsulating via cyclopentano‐cucurbit[n]uril (n = 8, 10)/graphene oxide heterojunction
Authors: Mehranfar Aliyeh , Izadyar Mohammad
Published: December 2019

Here, physical chemistry properties of the inclusion complexes of some alkaloids and cyclopentano‐cucurbit[8, 10]urils (Cy‐CB[8, 10]) were investigated via molecular dynamic (MD) simulations and density functional theory (DFT) calculations. The possibility of the heterojunction formation between cyclopentano‐cucurbit[8, 10]urils and graphene oxide was investigated via MD simulation. Based on the results, an effective role of graphene oxide on the encapsulation complex formation, especially in the presence of codeine and morphine was confirmed. DFT (M06‐2X) and DFT‐D3 (M06‐2X‐D3) functionals were applied for geometry optimization of the complexes. To have an insight into the atomic level, different analyses, such as natural bond orbital and quantum theory of atoms in molecule analyses were applied and discussed. DFT results confirm that Cy‐CB[8] makes a stronger interaction with alkaloids in comparison with Cy‐CB[10]. Thermodynamic studies show that the complexation process of codeine inside Cy‐CB[n] is more favorable than other complexes. Moreover, energy analysis showed that the van der Walls part plays an important role in alkaloid stabilization inside the Cy‐CB[n] cavity.
An unexpected new diploid Hieracium from Europe: Integrative taxonomic approach with a phylogeny of diploid Hieracium taxa
Authors: Mráz Patrik , Filipaş Liviu , Bărbos Marius Ioan , Kadlecová Jana , Paštová Ladislava , Belyayev Alexander , Fehrer Judith
Published: December 2019

Hieracium s.str. (Asteraceae) is one of the largest angiosperm genera notorious for its taxonomic complexity caused by widespread interspecific hybridization. This process is tightly coupled with polyploidization and apomixis – asexual reproduction by seeds, which has ensured the persistence of otherwise sterile interspecific hybrids. As a result, apomictic polyploid taxa dominate the taxonomic diversity of the genus whilst sexual diploid species are extremely rare and mostly confined to southern Europe. As diploid taxa are assumed to be the parents of apomictic lineages, the discovery of any new diploid species is important for understanding evolutionary processes and diversity patterns in the genus. Here, we describe a new diploid species, Hieracium vranceae, a narrow endemic to the Munţii Vrancei (Vrancea Mountains, Eastern Carpathians, Romania). This taxon with a distinctive morphology and a strong affinity to relic rocky habitats was first collected in 2013. This means that, even in Europe, some regions, like the Eastern Carpathians, are botanically underexplored and might still preserve an undiscovered diversity of plants. Phylogenetic analyses with multiple molecular markers (low‐copy nuclear genes gsh1 and sqs, nuclear ribosomal ETS, four cpDNA loci) applied to all diploid Hieracium species support specific rank for H. vranceae. In contrast, molecular data suggest conspecifity of two pairs of species, H. lucidum/H. cophanense from Sicily and H. naegelianum/H. renatae from the Balkans, which are moreover only weakly differentiated morphologically. Molecular (cpDNA) and cytogenetic (GISH, FISH) analyses furthermore revealed that H. vranceae has been involved as a maternal parent in the origin of an allotriploid apomictic species, H. telekianum, to which H. vranceae contributed one haplome. The other putative parents of H. telekianum are the diploid narrow endemic H. pojoritense and probably H. sparsum s.l. Our data thus stress the importance of interspecific hybridization for an evolutionary shift from sexuality to apomixis in Hieracium. Our findings furthermore highlight the significance of that part of the Carpathians as one of the most important evolutionary/refugial centres of Hieracium and suggest dynamic species ranges at a regional scale allowing physical contact of taxa whose distributional ranges are nowadays completely allopatric.
Information‐theoretic approach in density functional theory and its recent applications to chemical problems
Authors: Rong Chunying , Wang Bin , Zhao Dongbo , Liu Shubin
Published: December 2019

Using simple functionals of the electron density to appreciate and quantify molecular structure and chemical reactivity properties is a recent endeavor in density functional theory (DFT) toward the development of a new chemical reactivity theory. According to the first Hohenberg–Kohn theorem in DFT, the electron density alone should be able to determine any property in the ground state. Exchange and correlation energies are such properties, so are molecular structure and chemical reactivity, and hence they all should accurately be determined by electron density functionals. Quantities such as Shannon entropy, Fisher information, Ghosh–Berkowitz–Parr entropy, information gain, Onicescu information energy, etc., from the information‐theoretic approach are simple electron density functionals, whose analytical forms are exactly known. In this article, we demonstrate their usefulness and validity to quantify regioselectivity, stereoselectivity, and other structure and reactivity properties. We will outline the current understanding of its theoretical framework at first, and then highlight recent applications to chemical problems including isomeric and conformational stability, electrophilicity and nucleophilicity, strong covalent and weak noncovalent interactions, acidity and basicity, aromaticity and antiaromaticity, and numerous other properties. The effort of employing electron density functionals to quantify chemical concepts should open up a new door for us to ultimately develop a chemical reactivity theory using the DFT language.

This article is characterized under:

Structure and Mechanism > Reaction Mechanisms and Catalysis

Electronic Structure Theory > Density Functional Theory

Structure and Mechanism > Molecular Structures

Molecular and Statistical Mechanics > Molecular Interactions
A Novel d‐f Heterometallic CdII‐EuIII Metal‐organic Framework as a Sensitive Luminescent Sensor for the Dual Detection of Ronidazole and 4‐Nitrophenol
Authors: Jiang Meng‐Yue , Yu Li , Zhou Yi‐Cheng , Jia Jing , Si Xue‐Jian , Dong Wen‐Wen , Tian Zheng‐Fang , Zhao Jun , Li Dong‐Sheng
Published: December 2019

A novel three‐dimensional (3D) d‐f heterometallic metal‐organic framework (MOF) formulated as [EuCd1.5L2(H2O)3]·2H2O (1) [H3L = 5‐(4‐(tetrazol‐5‐yl)phenyl)isophthalic acid] was successfully synthesized and characterized. Structural analysis displays that 1 features a 3D (3, 12)‐connected framework constructed by [Eu2Cd3(tetrazole)4(COO)8] units. The powder X‐ray diffraction measurement of 1 immersed in different solvents reveals that 1 possess good solvent stability. It is worth noting that 1 displays highly selective detection for ronidazole (RDZ) and 4‐nitrophenol (4‐NP) through luminescence quenching. The possible mechanism of luminescent sensing is also well discussed.
The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective
Authors: Mammadzada Parviz , Corredoira Pablo M. , André Helder
Published: December 2019

Understanding the mechanisms that underlie age-related macular degeneration (AMD) has led to the identification of key molecules. Hypoxia-inducible transcription factors (HIFs) have been associated with choroidal neovascularization and the progression of AMD into the neovascular clinical phenotype (nAMD). HIFs regulate the expression of multiple growth factors and cytokines involved in angiogenesis and inflammation, hallmarks of nAMD. This knowledge has propelled the development of a new group of therapeutic strategies focused on gene therapy. The present review provides an update on current gene therapies in ocular angiogenesis, particularly nAMD, from both basic and clinical perspectives.
Structural genome analysis in cultivated potato taxa
Authors: Kyriakidou Maria , Achakkagari Sai Reddy , Gálvez López José Héctor , Zhu Xinyi , Tang Chen Yu , Tai Helen H. , Anglin Noelle L. , Ellis David , Strömvik Martina V.
Published: December 2019

Key message

Twelve potato accessions were selected to represent two principal views on potato taxonomy. The genomes were sequenced and analyzed for structural variation (copy number variation) against three published potato genomes.

The common potato (Solanum tuberosumL.) is an important staple crop with a highly heterozygous and complex tetraploid genome. The other taxa of cultivated potato contain varying ploidy levels (2X–5X), and structural variations are common in the genomes of these species, likely contributing to the diversification or agronomic traits during domestication. Increased understanding of the genomes and genomic variation will aid in the exploration of novel agronomic traits. Thus, sequencing data from twelve potato landraces, representing the four ploidy levels, were used to identify structural genomic variation compared to the two currently available reference genomes, a double monoploid potato genome and a diploid inbred clone ofS. chacoense. The results of a copy number variation analysis showed that in the majority of the genomes, while the number of deletions is greater than the number of duplications, the number of duplicated genes is greater than the number of deleted ones. Specific regions in the twelve potato genomes have a high density of CNV events. Further, the auxin-induced SAUR genes (involved in abiotic stress), disease resistance genes and the 2-oxoglutarate/Fe(II)-dependent oxygenase superfamily proteins, among others, had increased copy numbers in these sequenced genomes relative to the references.
Electro-fluidic timer for event control in paper-based devices
Authors: Llorella Anna , Navarro-Segarra Marina , Merino-Jiménez Irene , Esquivel Juan Pablo , Sabaté Neus
Published: December 2019

In this paper, we present a simple yet smart electro-fluidic platform that enables automatic time control in a very affordable and simple manner. The system is based on the electric detection of a fluid front when it crosses a particular area of a paper strip. The detection can be used to trigger the sequential activation or deactivation of different electronic modules (heating of molecular diagnostics, time interval detection, or readout of test results) with an accuracy within the range of minutes. The whole system is implemented with a few number of discrete electronic components such as transistors, resistors and capacitors that, if required, can be totally fabricated using printed electronics technology. This platform opens new possible applications for paper-based point-of care (POC) diagnostic devices and enables the possibility of these devices to introduce time control functions without the need for any external instrumentation and human action.
How much does the rainfall temporal resolution affect rainfall thresholds for landslide triggering?
Authors: Gariano Stefano Luigi , Melillo Massimo , Peruccacci Silvia , Brunetti Maria Teresa
Published: December 2019

In many areas of the world, the prediction of rainfall-induced landslides is usually carried out by means of empirical rainfall thresholds. Their definition is complicated by several issues, among which are the evaluation and quantification of diverse uncertainties resulting from data and methods. Threshold effectiveness and reliability strongly depend on the quality and quantity of rainfall measurements and landslide information used as input. In this work, the influence of the temporal resolution of rainfall measurements on the calculation of landslide-triggering rainfall thresholds is evaluated and discussed. For the purpose, hourly rainfall measurements collected by 172 rain gauges and geographical and temporal information on the occurrence of 561 rainfall-induced landslides in Liguria region (northern Italy) in the period 2004–2014 are used. To assess the impact of different temporal resolutions on the thresholds, rainfall measurements are clustered in increasing bins of 1, 3, 6, 12 and 24 h. A comprehensive tool is applied to each dataset to automatically reconstruct the rainfall conditions responsible for the failures and to calculate frequentist cumulated event rainfall–rainfall duration (ED) thresholds. Then, using a quantitative procedure, the calculated ED thresholds are validated. The main finding of the work is that the use of rainfall measurements with different temporal resolutions results in considerable variations of the shape and the validity range of the thresholds. Decreasing the rainfall temporal resolution, thresholds with smaller intercepts, higher slopes, shorter ranges of validity and higher uncertainties are obtained. On the other hand, it seems that the rainfall temporal resolution does not influence the validation procedure and the threshold performance indicators. Overall, the use of rainfall data with coarse temporal resolution causes a systematic underestimation of thresholds at short durations, resulting in relevant drawbacks (e.g. false alarms) if the thresholds are implemented in operational systems for landslide prediction.