bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidelines for Tuning the Excited State Hückel–Baird Hybrid Aromatic Character of Pro‐Aromatic Quinoidal Compounds**
Authors: Escayola Sílvia , Tonnelé Claire , Matito Eduard , Poater Albert , Ottosson Henrik , Solà Miquel , Casanova David
Published: February 2021

Pro‐aromatic molecules have higher‐energy diradicaloid states that are significantly influenced by resonance structures in which conjugated rings take on Hückel‐aromatic character. Recently, it has been argued that there are also pro‐aromatic molecules that adopt central units with 4nπ‐electron Baird‐aromatic character in the T1 state, although detailed analysis suggests that these compounds are better labelled as T1 Hückel–Baird hybrid molecules where Hückel‐aromaticity dominates. Herein, we consider a series of symmetrically substituted conjugated rings with potential Baird aromaticity in the lowest excited triplet and singlet states. Our computational results allow us to establish general guidelines for the rational design of molecules with excited state Hückel/Baird aromaticity in pro‐aromatic quinoidal compounds. We found two main strategies to promote high Baird aromatic character: 1) anionic and small conjugated rings with electron donating groups as substituents and small exocyclic groups with electron withdrawing substituents, or 2) electron deficient conjugated rings with exocyclic electron–donor substitution.
Synthesis, characterization, and biological activity of novel 3d metal coordination compounds with 2‐acetylpyridine N4‐allyl‐S‐methylisothiosemicarbazone
Authors: Graur Vasilii , Usataia Irina , Bourosh Pavlina , Kravtsov Victor , Garbuz Olga , Hureau Christelle , Gulea Aurelian
Published: February 2021

New zinc(II), copper(II), nickel(II), iron(III), and cobalt(III) coordination compounds, [Zn(HL)I2] (1), [Cu(HL)Cl2] (2), [Cu(HL)Br2] (3), {[Cu(HL)NO3]NO3}n (4), [Ni(HL)2](NO3)2 (5), [Fe(L)2]NO3(6), [Co(L)2]NO3 (7), and [Co(L)2]Cl·H2O (8), were obtained with 2‐acetylpyridine N4‐allyl‐S‐methylisothiosemicarbazone (HL). The isothiosemicarbazone proligand was characterized by nuclear magnetic resonance (NMR) (1H and 13C), infrared (IR) spectroscopy, and X‐ray diffraction. All the coordination compounds were characterized by elemental analysis, IR, UV–Vis spectroscopy, molar conductivity, and magnetic susceptibility measurements. Single‐crystal X‐ray diffraction analysis elucidated the structure of the cationic form of the proligand in the salt [H2L]I and compounds 1–4 and 8 and demonstrated an unusual way of coordination through methylated sulfur atom in 1 and 3. Nevertheless, the electron paramagnetic resonance (EPR) and UV–Vis investigations showed that this way of coordination quickly changes upon dissolution of coordination compounds in dimethyl sulfoxide (DMSO). The antiproliferative properties of these compounds towards human cervical epithelial HeLa, human epithelial pancreatic adenocarcinoma BxPC‐3, human muscle rhabdomyosarcoma spindle, large multinucleated RD cancer cell lines, and normal kidney epithelial MDCK cell line have been investigated. Copper coordination compounds (2–4) show promising anticancer activity with high selectivity (selectivity index [SI] = 10–18) towards BxPC‐3 cell line. They also possess significant antibacterial and antifungal activity, which is useful for cancer treatment.
Development of optimized triaxially electrospun titania nanofiber‐in‐nanotube core‐shell structure
Authors: Khan Muhammad Amir , Ahmad Adnan , Arshad Salman Noshear , Nazir Ahsan , Ahmad Sheraz , Khan Muhammad Qamar , Shahzad Amir , Satti Aamir Naseem , Qadir Muhammad Bilal , Khaliq Zubair
Published: February 2021

One dimensional (1D) nanostructures and its derivatives can be manipulated to serve special functions like hollow structure, and higher surface area. 1D TiO2 nanotube‐in‐nanofibers (NF@NT) are developed through triaxial electrospinning followed by a calcination process. A blended solution of polyvinyl pyrrolidone and tetra‐butyl titanate is used in outer and inner layers of nanofibers, respectively, while paraffin oil is used in the middle layer. The optimized triaxial nanofibers of 669.4 ± 52.43 nm are developed at 7.5 w/w% concentration, 28 kV applied voltage, and 24 cm spinning distance. TiO2 NF@NT structure is obtained through calcination of optimized triaxial nanofibers at 550°C. Subsequently, the morphology of TiO2 NF@NT and its uniform diameter distribution is confirmed through scanning electron microscopy. Fourier‐transform infrared spectroscopy results indicates the formation of TiO2 NF@NT. X‐Rays diffraction pattern peaks also reveals the presence of both anatase and rutile crystalline phases. The presence of only titanium (Ti) and oxygen (O) elements in the TiO2 NF@NT is confirmed through energy dispersive X‐ray spectroscopy. Brunauer–Emmett–Teller analysis indicates that TiO2 NF@NT has a higher specific surface area of ~141.68 m2/g compared with the solid TiO2 nanofiber (~75.31 m2/g). This study can be adopted to develop TiO2 NF@NT for wide range of application.
Polymermörtel‐Klebverbindungen für Holz‐Beton‐Verbundbrücken Teil 1
Authors: Kästner Martin , Rautenstrauch Karl
Published: February 2021

Leistungsfähigkeit und Tragverhalten von Holz‐Beton‐Verbundkonstruktionen (HBV) sind entscheidend von der konstruktiven Ausbildung der Verbundfuge abhängig. Die meisten bislang für HBV‐Straßenbrücken entwickelten Verbundlösungen sind durch eine diskontinuierliche Schubübertragung gekennzeichnet, wobei die Schubtragfähigkeit des Holzes nicht optimal ausgenutzt wird. Ziel der im Beitrag vorgestellten Untersuchungen war die Entwicklung von Verbundfugenkonfigurationen mit kontinuierlichem Verbund zwischen Betonfahrbahnplatte und hölzernen Brückenhauptträgern. Zur Vergleichmäßigung der Schubbeanspruchung und zur Vermeidung tragfähigkeitsmindernder Spannungsspitzen im Bereich der Verbundelemente kommen mineralisch gefüllte, toleranzausgleichende Klebmörtel auf Epoxidharzbasis zum Einsatz. Die Beurteilung der Leistungsfähigkeit zweier weiterentwickelter Dübelleistenverbindungen mit Polymermörtelverguss sowie der direkten Polymermörtel‐Klebverbindung von Beton und Holz erfolgte anhand experimenteller und numerischer Untersuchungen. Der vorliegende erste Teil des Beitrags gibt einen Überblick über die entwickelten Verbundfugenkonfigurationen und geeignete Polymermörtel und fokussiert auf die Ergebnisse der Untersuchungen zum Schubtragverhalten. Auf Untersuchungen an Biegeträgern, Bemessungsansätze sowie Empfehlungen für die Ausführung wird im zweiten Teil eingegangen.
Socioeconomic status and concussion reporting: The distinct and mediating roles of gist processing, knowledge, and attitudes
Authors: Ajayi Peter T. , Garavito David M.N. , Reyna Valerie F.
Published: February 2021

Improving health outcomes for concussed athletes and others requires self‐reporting symptoms; not reporting risks second‐impact syndrome and death. However, concussions in adolescents and young adults are often underreported. We treat reporting as a risky decision, extending predictions of fuzzy‐trace theory (FTT). We hypothesize that low SES indirectly interferes with the development of cognitive skills that reduce unhealthy risky decision making. Specifically, we expect that SES may be related to intentions to report a concussion because low SES delays development of cognitive gist processing that reduces risk‐taking. Adolescents in high‐school and young adults in college (n = 1211) answered questions about concussion knowledge, concussion attitudes, and cognitive scales based on FTT: categorical thinking and endorsement of gist principles about risk. Overall, for each of the two age groups, and for athletes as well as nonathletes, SES was associated with reporting intentions, and this association was mediated by the three psychological predictors we tested: gist processing, concussion knowledge, and concussion attitudes. Results are consistent with lower SES reducing opportunities for normative cognitive development, the latter characterized by developmental increases in gist processing about risk. Hence, consistent with hypotheses, gist processing, concussion knowledge, and healthier attitudes about concussions were each associated with greater intentions to report concussions. Although educational initiatives currently focus on rote knowledge and healthy attitudes, future interventions to reduce concussion underreporting could benefit from explaining the gist of risk, especially to low SES youth, adapting successful FTT‐based risk‐reduction curricula from other domains.
Sensing and sensitive visualization of latent fingerprints on various surfaces using a versatile fluorescent aggregation‐induced emission‐based coumarin derivative
Authors: Kumar Naveen , Udayabhanu  , Ali Alghamdi Abdulaziz , Basavaraj R.B. , Mahadevan K.M. , Nagaraju G.
Published: February 2021

The marked rise in criminal activity in society has made a difficult task for forensic scientists who aim to track any crime scene effectively, therefore visualization of latent fingerprints (LFPs) plays an increasingly vital role in forensics. In the present report, a highly sensitive solvatochromism, aggregation‐induced emission‐based 2‐(4‐nitrophenyl)‐3H‐benzocoumarin fluorescent dye (CFD) was fabricated using an ultrasonication protocol. The fluorescence properties of the CFD were analyzed using fluorescence spectrophotometer. The CFD produced a greenish yellow emission in solid and fluid states. An in‐depth visualization of LFPs showed detailed ridge patterns under normal and ultraviolet light sources (254 and 365 nm) due to the excellent chemisorption of CFD onto the ridge patterns on the finger. All three types of ridge details were visualized without any background interference when using a simple and quick powder dusting method. Results revealed that, the present fluorescent dye can be used successfully for detection of latent fingerprints (LFPs) on various nonporous substrates surfaces, in organic light‐emitting diodes applications (OLEDs), and for electrochemical sensing.
How human serum albumin‐selective DNA aptamer binds to bovine and canine serum albumins
Authors: Kuntip Nattapon , Japrung Deanpen , Pongprayoon Prapasiri
Published: February 2021

Serum albumin (SA) is the most abundant carrier protein in blood. SA carries a diverse range of nutrients, drugs, and metal ions. It has wide clinical and biochemical applications. Human serum albumin (HSA) can be used as a biomarker for kidney and liver diseases. Aptasensor is one of potential HSA detection methods. HSA‐specific aptamer was selected for HSA detection. In animals, bovine serum albumin (BSA) and canine serum albumins (CSA) share high sequence similarities to HSA. Thus, it is interesting to explore the possibility of using HSA‐selective aptamer for BSA and CSA aptasensor. In this study, molecular dynamics (MD) simulations were initially employed to investigate the binding of aptamer to BSA and CSA in comparison to HSA. Like HSA, both BSA and CSA can bind aptamer, but different binding affinities are observed. BSA shows the tighter binding to aptamer than CSA. Domain III is found to be the aptamer‐binding domain although no specific aptamer conformation is captured. However, in all cases, the aptamer utilizes the 3′‐end to attach on an albumin surface. Both nucleobases and phosphate backbones on a DNA aptamer are important for albumin‐aptamer complexation. Our results imply the possibility of using HSA‐specific aptamer for BSA detection due to tighter binding observed, but may be less effective in CSA. However, the test in actual complicated condition must be further studied.
Varietal Differences of Prokupac, Evita and Čokot Zemun Based on Their Anthocyanins Content in Grape Skin Extract
Authors: Živković Jelena , Jadranin Milka , Pržić Zoran , Marković Nebojša , Sokolović Danijel , Šavikin Katarina , Menković Nebojša
Published: February 2021

In this study, we have analyzed the anthocyanin composition of skin extracts of three red grape varieties Prokupac, Evita and Čokot Zemun in order to distinguish these cultivars based on their anthocyanin profile. Also, mechanical analysis of grape bunches and berries was performed. According to our results, seventeen anthocyanins were identified using LC/MS technique and quantitative differences were recorded using HPLC‐DAD method. The highest content of total anthocyanins was obtained for Evita variety and the lowest one was recorded in Prokupac. Also, clear differences were observed in anthocyanins ratios. In comparison to Prokupac and Evita varieties, Čokot Zemun was characterized with a high content of coumaroyl derivatives of anthocyanin compounds, while high levels of acetylated derivatives were recorded in Prokupac. Data reported in this study represent a certain contribution to a database of mechanical properties and chemical composition of grape varieties originating from Balkan.
Effect of institutional transcatheter aortic valve replacement volume on mortality: A systematic review and meta‐analysis
Authors: Kir Devika , Shapero Kayle , Chatterjee Saurav , Grimshaw Alyssa , Oddleifson August , Spatz Erica S. , Goldsweig Andrew M. , Desai Nihar R.
Published: February 2021

Objective

We sought to conduct a systematic review and network meta‐analysis to examine the association between institutional transcatheter aortic valve replacement (TAVR) volume and all‐cause mortality.

Background

Since inception in 2011, there has been an exponential increase in the number of TAVR centers across the world. Multiple studies have questioned if a relationship exists between institutional TAVR volume and patient outcomes.

Methods

We performed a systematic literature search for relevant articles using a combination of free text terms in the title/abstract related to volume, TAVR, and patient outcomes. Two reviewers independently screened all titles/abstracts for eligibility based on pre‐specified criteria. All‐cause mortality data was pooled from eligible studies and centers were categorized as low‐(30–50 cases), intermediate‐, or high‐volume (75–130 cases) based on their annual TAVR volumes.

Results

Our search yielded an initial list of 11,153 citations, 120 full text studies were reviewed and 7 studies met all inclusion and exclusion criteria, yielding a total of 1,93,498 TAVRs. Categorized according to center's annual volume; 25,062 TAVRs were performed in low‐, 77,093 in intermediate‐ and 91,343 in high‐volume centers. Network meta‐analysis showed a relative reduction in mortality rates of 37%, 23% and 19%, for high volume versus low volume centers, high volume versus intermediate volume centers and intermediate versus low volume centers, respectively.

Conclusions

Existing research clearly shows an inverse relationship between annual TAVR procedural volume and all‐cause mortality. We need to focus on development of strong referral networks and consolidation rather than expansion of existing TAVR centers to improve patient outcomes, while ensuring adequate access‐to‐care.
Usability of Fantom Encore® scaffold in non‐complex bifurcations–Analysis in bench models
Authors: G. Toth Gabor , Ono Masafumi , Buschmann Eva , Wu Xinlei , Edl Dominik , Onuma Yoshinobu , Serruys Patrick WJC , Wijns William
Published: February 2021

Objective

Present bench study aimed to evaluate whether technical characteristics of Fantom Encore® bioresorbable scaffold (BRS) allow to perform proximal optimization/side branch dilation/proximal optimization (POT‐SB‐POT) technique, as an adequate solution for bifurcation percutaneous coronary intervention.

Methods

Two Fantom Encore® BRS platforms (small with 3.0 mm nominal diameter, n = 7; and large with 3.5 mm nominal diameter, n = 7) were evaluated in bench models, which were designed according to Finet‐law and fitted to nominal scaffold diameter in the distal main branch (MB) and fitted to indicated maximal expansion capacity in the proximal main branch (MB). Results were evaluated by (a) fluoroscopy, (b) optical coherence tomography (OCT) and (c) micro‐computed tomography (μCT).

Results

All procedures were performed according to the protocol. Careful review of the fluoroscopic loops by an independent operator did not reveal any strut fracture or major deformation. By OCT the overall rate of perfectly apposed struts in the bifurcation area was 15 ± 6% after SB opening, that increased significantly but remained low with 22 ± 9% after final POT (p = .001). Compared to SB ballooning alone, significant benefit of final POT was found in rate of perfect apposition in the proximal MB (15 ± 12% vs. 26 ± 15%, respectively; p = .017) and at the abostial side of polygon of confluence (7 ± 9% vs. 16 ± 13%, respectively; p = .005).

μCT analysis revealed a single strut fracture in one case with the small platform, while four cases showed single or multiple strut fractures with the large platform.

Conclusion

The mechanical characteristics of the device are not suitable for use of Conventional techniques for bifurcation PCI such as POT‐SB‐POT. The use of Fantom Encore® BRS for bifurcation PCI with relevant SB should not be encouraged.
Aortic stenosis in the time of COVID‐19: Development and outcomes of a rapid turnaround TAVI service
Authors: Adlam David , Chan Nathan , Baron Julia , Kovac Jan
Published: February 2021

The COVID‐19 pandemic has resulted in the cancellation of many elective surgical procedures. This has led to reports of an increase in mortality for patients with non‐Covid health conditions due to delayed definitive management. Patients with severe aortic stenosis have a high annual mortality if left untreated. These patients are at risk due to the reduced number of surgical aortic valve replacements and competition for intensive care facilities during the COVID‐19 pandemic. This case series suggests that the minimally invasive transcatheter aortic valve implantation is safe to continue during the COVID‐19 pandemic with adjustments to the patient pathway to minimize hospital stay and to reduce patient and staff exposure. This helps to reduce the delay of definitive treatment for patients with severe aortic stenosis.
NTRK2 Fusion driven pediatric glioblastoma: Identification of oncogenic Drivers via integrative Genome and transcriptome profiling
Authors: Britton Heidi M. , Levine Adrian B. , Shen Yaoqing , Mungall Karen , Serrano Jonathan , Snuderl Matija , Pleasance Erin , Jones Steven J. M. , Laskin Janessa , Marra Marco A. , Rassekh Shahrad R. , Deyell Rebecca , Yip Stephen , Cheng Sylvia , Dunham Chris
Published: February 2021

This is the first report of a NACC2‐NTRK2 fusion in a histological glioblastoma. Oncogenomic analysis revealed this actionable fusion oncogene in a pediatric cerebellar glioblastoma, which would not have been identified through routine diagnostics, demonstrating the value of clinical genome profiling in cancer care.
Ischemic colitis and atrial septal aneurysm as a potential cause of systemic thromboembolism
Authors: Subahi Eihab A. , Kumar Narinder , Hamid Abdulwahab M. , Elmahadi Mohamed S. , Yassin Mohamed A.
Published: February 2021

Atrial septal aneurysm is a rare cardiac abnormality with thromboembolic potential and should be considered in a patient with ischemic colitis with no obvious risk factors.
Use of the NobleStitch™ EL for the treatment of patients with residual right‐to‐left shunt following device closure of PFO
Authors: Chaudhry‐Waterman Nadia , Shapiro Stephen , Thompson James
Published: February 2021

The unique design of the NobleStitch™ EL allows it to be used to close residual defects following failed device PFO closure without impacting the integrity of previously placed double‐disk Gore occluders.
Giant Cerebral Hydatid Cyst: A Rare Case Report
Authors: Ganjeifar Babak , Ghafouri Majid , Shokri Azar , Rahbarian Yazdi Farhad , Hashemi Seyed Ahmad
Published: February 2021

The diagnosis of hydatid cyst should be considered in children with seizure in endemic regions.
Abdominal aortic thrombus formation in a neonate with an interrupted aortic arch
Authors: Yuhara Yuka , Kido Takahiro , Imagawa Kazuo , Yano Yusuke , Nozaki Yoshihiro , Ishiodori Takumi , Ishikawa Nobuyuki , Kato Hideyuki , Kato Yoshiaki , Takahashi‐Igari Miho , Murakami Takashi , Horigome Hitoshi , Takada Hidetoshi
Published: February 2021

We note the risk of paradoxical embolism in patients with congenital heart defects with a right‐to‐left shunt. These patients should be managed to ensure that abdominal aortic thrombi are not overlooked when their clinical conditions change.
A neonate born to an infected COVID‐19 mother was tested positive just 24 hours after its birth
Authors: Huseynova Roya Arif , A. Bin Mahmoud Latifa , Huseynov Oqtay , Almalkey Mishary , Amer Almotiri Ameen , Sumaily Haider Hussein , AbdelRahim Adli
Published: February 2021

Given the importance of possible vertical transmission, it is essential to study all neonates delivered from COVID‐19 positive mothers to analyze the route of transmission of infection that will optimize the universal testing for SARS‐CoV‐2 and minimize the risk of disease in neonates.
Modelling and validation of a gas‐solid fluidized bed using advanced measurement techniques
Authors: Uribe Sebastián , Taofeeq Haidar , Al‐Dahhan Muthanna
Published: February 2021

With a Euler‐two‐phase (E2P) approach, through computational fluid dynamics (CFD) techniques, a mathematical model for the prediction of the local hydrodynamic behaviour of a gas‐solid fluidized bed was implemented. Simulations are conducted for a fluidized bed of 0.14 m internal diameter packed with Gerdart B glass beads particles, with an average diameter of 365 μm, at dimensionless inlet velocities ranging from . The implemented model considers the multiphase and multiscale interactions through the inclusion of three sub‐models, which allows the model to have a broad range of applicability. Predictions were compared against experimental measurements reported on previous contributions for validation purposes. The experimental study was conducted by implementing advanced measurement techniques, such as a differential pressure transducer, and an optical fibre probe for simultaneous measurement of solids holdup and velocity, developed at the Multiphase Flow and Reactors Engineering and Applications Laboratory (mFReal). Local radial solids holdup, solids velocity, and pressure drop profiles were experimentally determined. Results show that the implemented model possesses a high predictive quality, predicting pressure drops with an average absolute relative error (AARE) between 8.6%–11.3%; solids holdup with a root mean squared deviation (RMSD) under 5%; and solids velocity with a RMSD under 22%.
Data‐driven hypotheses of reaction networks for thermochemical conversion of a physical mixture of levoglucosan and 2‐phenoxyethyl benzene
Authors: Sattari Fereshteh , Prasad Vinay
Published: February 2021

In this work, we analyze the hydrous pyrolysis of a physical mixture of the model components representing cellulose (levoglucosan) and lignin (2‐phenoxyethyl benzene). Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1H‐NMR) spectroscopy was used to characterize the products of the reaction. The main objective of the work was to use data‐driven methods to develop a reaction network for this system based on the spectroscopic data. This was achieved using Bayesian hierarchical clustering to identify pseudocomponents and Bayesian networks to develop a reaction network between these pseudocomponents. The data‐driven reaction network was shown to be consistent with the known chemistry of the pyrolysis of cellulose and lignin, and the chemistry of the physical mixture incorporated/combined elements of the reaction mechanisms of cellulose and lignin.
Obtaining Kinetics From Continuous Processes: Sampling Multiple Time Points Concurrently With a Single Valve Rotation
Authors: Morin Mathieu A. , Mallik Debasis , Zhang Wenyao , Pietro William , Manthorpe Jeffrey M. , Organ Michael G.
Published: February 2021

The manufacturers of fine chemicals and pharmaceuticals are beginning to accept flow chemistry as a production alternative following the lead of commodity chemical manufacturers, who have been producing goods in continuous format for decades. The ability to trace time backwards by retracting the spatial length of a flow reactor is perhaps one of the biggest advantages of flowed synthesis. However, in the absence of an appropriate tool that would allow scientists to sample throughout the entire space of a production line, the theory is not possible to put into practice. A step in this direction has been taken with the invention of a unique, multi‐port valve/flow reactor that allows the chemist to simultaneously sample multiple timepoints of a chemical transformation with one single valve actuation, thereby capturing instantaneously the entire reaction course of the flowed chemical process.
Forage accumulation and radiation use of alfalfa under deficit irrigation
Authors: Liu Minguo , Mu Le , Lu Yixiao , Yang Huimin
Published: February 2021

The supply of high‐quality forage is fundamental to the development of ruminant animal production in drought areas where irrigation provides strong support to the forage production. The objective was to explore the response of alfalfa (Medicago sativa L.) growth and radiation use to deficit irrigation in a 2‐yr field study. Two deficit‐irrigation treatments and a full‐irrigation control (CK) were established under flood irrigation. Growth‐related indicators and radiation use were measured regularly. Results showed that deficit irrigation reduced forage accumulation, leaf area index (LAI), plant relative water content (RWC), and radiation use efficiency (RUE) of alfalfa. Compared with CK, slight deficit irrigation (SD) and moderate deficit irrigation (MD) decreased forage accumulation rate by 20 and 30%, respectively. Logistic model as a function of growing degree days (GDD) fitted well LAI change (R2 > .9). Deficit irrigation reduced the average rate of quick growth of LAI from 5 to 36%. Water deficit did not significantly change the GDD corresponding to the rapid growth phase but reduced the growth rate. Under deficit irrigation, decreased LAI did not always lead to significant cumulative intercepted photosynthetically active radiation (CIPAR) decrease, but resulted in significantly lowered RUE. In conclusion, the decrease of forage accumulation of alfalfa under deficit irrigation would be caused mainly by weakened photosynthetic ability (representing RUE).
Identification of Hypoxia‐inducible factor (HIF) stabilizer roxadustat and its possible metabolites in thoroughbred horses for doping control
Authors: Mathew Binoy , Philip Moses , Perwad Zubair , Karatt Tajudheen K. , Caveney Marina Rodriguez , Subhahar Michael Benedict , Karakka Kal Abdul Khader
Published: February 2021

Hypoxia‐inducible factor (HIF) stabilizer belongs to a novel class of pharmacologically active substances, which are capable of inducing the endogenous erythropoietic system. The transcriptional activator HIF has been shown to significantly increase blood hemoglobin and is well set for the treatment of anemia resulting from chronic kidney disease. This research work reports a comprehensive study of the most popular HIF stabilizer roxadustat and its metabolites in thoroughbred horse urine after oral administration. The plausible structures of the detected metabolites were postulated using liquid chromatography‐high‐resolution mass spectrometry. Under the experimental condition 13 metabolites (7 phase I, 1 phase II, and 5 conjugates of phase I metabolism) were positively detected (M1–M13). The major phase I metabolites identified were formed by hydroxylation. Dealkylated and hydrolyzed phase I metabolites were also observed in this study. In phase II, a glucuronic acid conjugate of roxadustat was detected as the major metabolite. The sulfonic acid conjugates were observed to be formed from phase I metabolites. The characterized in vivo metabolites can potentially serve as target analytes for doping control analysis; hence, the result is an important tool for assessing its use and abuse in competitive sport.
Retinol binding protein 1 affects Xenopus anterior neural development via all‐trans retinoic acid signaling
Authors: Flach Hannah , Basten Thomas , Schreiner Corinna , Dietmann Petra , Greco Sara , Nies Lea , Roßmanith Nathalie , Walter Svenja , Kühl Michael , Kühl Susanne J.
Published: February 2021

Background

Retinol binding protein 1 (Rbp1) acts as an intracellular regulator of vitamin A metabolism and retinoid transport. In mice, Rbp1 deficiency decreases the capacity of hepatic stellate cells to take up all‐trans retinol and sustain retinyl ester stores. Furthermore, Rbp1 is crucial for visual capacity. Although the function of Rbp1 has been studied in the mature eye, its role during early anterior neural development has not yet been investigated in detail.

Results

We showed that rbp1 is expressed in the eye, anterior neural crest cells (NCCs) and prosencephalon of the South African clawed frog Xenopus laevis. Rbp1 knockdown led to defects in eye formation, including microphthalmia and disorganized retinal lamination, and to disturbed induction and differentiation of the eye field, as shown by decreased rax and pax6 expression. Furthermore, it resulted in reduced rax expression in the prosencephalon and affected cranial cartilage. Rbp1 inhibition also interfered with neural crest induction and migration, as shown by twist and slug. Moreover, it led to a significant reduction of the all‐trans retinoic acid target gene pitx2 in NCC‐derived periocular mesenchyme. The Rbp1 knockdown phenotypes were rescued by pitx2 RNA co‐injection.

Conclusion

Rbp1 is crucial for the development of the anterior neural tissue.
Does CBM maze assess reading comprehension in 8–9‐year olds at‐risk for dyslexia?
Authors: Pollitt Shelby , Harrison Gina
Published: February 2021

Recent research has reported the word‐level, code‐related focus of curriculum‐based measures (CBM) of reading comprehension such as Maze (Muijselaar et al., 2017) with typically developing readers, but research has yet to examine whether this finding also applies to children at‐risk for dyslexia. We administered a collection of cognitive, linguistic, CBM, and norm‐referenced measures to children whose word reading and decoding fluency fell below the 25th percentile and were, therefore, considered at‐risk readers. We found that language comprehension contributed additional variance beyond decoding (fluency and accuracy measures) to reading comprehension as assessed by the WIAT‐III, but that decoding explained the most variance in children's performance on the CBM Maze task (vis à vis the simple view of reading). The findings have practical implications to the use of CBM Maze as a formative assessment with children at‐risk for dyslexia and elucidate the need for additional or alternative assessments to capture the reading comprehension construct.
Optimization and validation of a cost‐effective protocol for biosurveillance of invasive alien species
Authors: Milián‐García Yoamel , Young Robert , Madden Mary , Bullas‐Appleton Erin , Hanner Robert H.
Published: February 2021

Environmental DNA (eDNA) metabarcoding has revolutionized biodiversity monitoring and invasive pest biosurveillance programs. The introduction of insect pests considered invasive alien species (IAS) into a non‐native range poses a threat to native plant health. The early detection of IAS can allow for prompt actions by regulating authorities, thereby mitigating their impacts. In the present study, we optimized and validated a fast and cost‐effective eDNA metabarcoding protocol for biosurveillance of IAS and characterization of insect and microorganism diversity. Forty‐eight traps were placed, following the CFIA's annual forest insect trapping survey, at four locations in southern Ontario that are high risk for forest IAS. We collected insects and eDNA samples using Lindgren funnel traps that contained a saturated salt (NaCl) solution in the collection jar. Using cytochrome c oxidase I (COI) as a molecular marker, a modified Illumina protocol effectively identified 2,535 Barcode Index Numbers (BINs). BINs were distributed among 57 Orders and 304 Families, with the vast majority being arthropods. Two IAS (Agrilus planipennis and Lymantria dispar) are regulated by the Canadian Food Inspection Agency (CFIA) as plant health pests, are known to occur in the study area, and were identified through eDNA in collected traps. Similarly, using 16S ribosomal RNA and nuclear ribosomal internal transcribed spacer (ITS), five bacterial and three fungal genera, which contain species of regulatory concern across several Canadian jurisdictions, were recovered from all sampling locations. Our study results reaffirm the effectiveness and importance of integrating eDNA metabarcoding as part of identification protocols in biosurveillance programs.
Plant species with the trait of continuous flowering do not hold core roles in a Neotropical lowland plant‐pollinating insect network
Authors: Hinton Chelsea R. , Peters Valerie E.
Published: February 2021

Plant–animal interaction science repeatedly finds that plant species differ by orders of magnitude in the number of interactions they support. The identification of plant species that play key structural roles in plant–animal networks is a global conservation priority; however, in hyperdiverse systems such as tropical forests, empirical datasets are scarce. Plant species with longer reproductive seasons are posited to support more interactions compared to plant species with shorter reproductive seasons but this hypothesis has not been evaluated for plant species with the longest reproductive season possible at the individual plant level, the continuous reproductive phenology. Resource predictability is also associated with promoting specialization, and therefore, continuous reproduction may instead favor specialist interactions. Here, we use quantitative pollinating insect–plant networks constructed from countryside habitat of the Tropical Wet forest Life Zone and modularity analysis to test whether plant species that share the trait of continuous flowering hold core roles in mutualistic networks. With a few exceptions, most plant species sampled within our network were assigned to the role of peripheral. All but one network had significantly high modularity scores and each continuous flowering plant species was in a different module. Our work reveals that the continuous flowering plant species differed in some networks in their topological role, and that more evidence was found for the phenology to support specialized subsets of interactions. Our findings suggest that the conservation of Neotropical pollinating insect communities may require planting species from each module rather than identifying and conserving network hubs.
RAD sequencing of common whelk, Buccinum undatum, reveals fine‐scale population structuring in Europe and cryptic speciation within the North Atlantic
Authors: Goodall Jake , Westfall Kristen Marie , Magnúsdóttir Hildur , Pálsson Snæbjörn , Örnólfsdóttir Erla Björk , Jónsson Zophonías O.
Published: February 2021

Buccinum undatum is a subtidal gastropod that exhibits clear spatial variation in several phenotypic shell traits (color, shape, and thickness) across its North Atlantic distribution. Studies of spatial phenotypic variation exist for the species; however, population genetic studies have thus far relied on a limited set of mitochondrial and microsatellite markers. Here, we greatly expand on previous work by characterizing population genetic structure in B. undatum across the North Atlantic from SNP variation obtained by RAD sequencing. There was a high degree of genetic differentiation between Canadian and European populations (Iceland, Faroe Islands, and England) consistent with the divergence of populations in allopatry (FST > 0.57 for all pairwise comparisons). In addition, B. undatum populations within Iceland, the Faroe Islands, and England are typified by weak but significant genetic structuring following an isolation‐by‐distance model. Finally, we established a significant correlation between genetic structuring in Iceland and two phenotypic traits: shell shape and color frequency. The works detailed here enhance our understanding of genetic structuring in B. undatum and establish the species as an intriguing model for future genome‐wide association studies.
Orientation behavior of riparian long‐jawed orb weavers (Tetragnatha elongata) after displacement over water
Authors: Goedeker Sidney J. , Wrynn Theresa E. , Gall Brian G.
Published: February 2021

Many organisms possess remarkable abilities to orient and navigate within their environment to achieve goals. We examined the orientation behavior of a riparian spider, the Long‐Jawed Orb Weaver (Tetragnatha elongata), when displaced onto the surface of the water. When displaced, spiders move with alternating movements of the first three leg pairs while dragging the most posterior pair of legs behind them. In addition, spiders often perform a series of orientation behaviors consisting of concentric circles before ultimately choosing a path of travel directly toward the nearest point to land. While the number of orientation behaviors increased with increasing distance from shore, distance from shore had no effect on the direction of travel, which was significantly oriented toward the closest shoreline. These results indicate a complex ability to orient toward land when displaced onto water, possibly to decrease the amount of time on the surface of the water and thus decrease predation risk.
State‐wide population characteristics and long‐term trends for eastern box turtles in North Carolina
Authors: Roe John H. , Graeter Gabrielle J. , LaVere Ashley A. , Somers Ann B.
Published: February 2021

Turtles are in decline worldwide, and the magnitude and recent acceleration of population declines requires immediate action to inform conservation and management plans. Long‐term studies of population trends and characteristics covering multiple populations across a range of environmental contexts are needed to guide the most effective management decisions, yet such studies are uncommon. Eastern box turtle (Terrapene carolina carolina) populations have declined and require conservation action throughout much of their range. We assessed sources of variation and temporal trends inT. c. carolinapopulation characteristics from 39 sites spanning four ecoregions in North Carolina using capture–mark–recapture. Surprisingly, there was no evidence of population decline at any site over a ten‐year period (2008–2017). Population densities ranged from 0.2 to 6.0 turtles per hectare, decreasing with more urban development and increasing with more wetland habitats in the surrounding landscape. Populations varied in demographic structure but had similar sex ratios and more adults than immature turtles in each ecoregion even after adjusting for variation in encounter probability among groups and body sizes. Survivorship was similar among life stages and sexes and only weakly related to body size. After adjusting for emigration, annual survival probability ranged from 90.7% to 96.8% for the various demographic groups and body sizes. Growth rates decreased with increasing body size, with rates ranging from approximately 15‐mm carapace length per year in the smallest individuals to near zero in the largest individuals. No aspect of population demographic structure or vital rates was related to surrounding landscape context. Population trends and characteristics were consistent among ecoregions, suggesting no need for region‐specific conservation or management with respect to the population characteristics examined. However, given the high site‐specific variability in nearly all estimated parameters, managers would benefit from targeting local threats such as urban land development and wetland destruction to ensure local population viability. The population characteristics reported here can serve as a useful baseline to compare population trends at these sites as monitoring continues. Our approach could be a useful model for other regions to follow in developing monitoring programs for this and other imperiled turtles.
Overarching policy framework for product life extension in a circular economy—A bottom‐up business perspective
Authors: Milios Leonidas
Published: February 2021

Public policy has a critical role to play in supporting business actors towards their transition to more sustainable and less resource‐intensive practices within the context of a Circular Economy (CE). The European Union (EU) CE Action Plan sets a special focus on the role of business in adopting and promoting circular economic principles in their operations, and thus leading the transition towards CE. Companies need to design and adopt innovative business models that enable the capture of residual value in products. Product life extension strategies, such as re‐use, hold the highest potential to retain the materials and energy embedded in products. However, companies that adopt such business practices face multiple barriers deriving from the present socio‐economic conditions and find themselves in need of direct policy interventions to be able to compete with incumbent firms. This contribution identifies supporting interventions that could enable companies engaging in product life extension to scale up and lead the transition to a CE. Empirical evidence was gathered from such companies in five economic sectors in Sweden through questionnaires. Based on the results, an overarching policy framework is proposed, including wide cross‐sectoral policy measures, such as (1) public procurement, (2) increased provision and access to information and (3) government leadership, setting mandatory re‐use targets.
The diagnostic and prognostic value of galectin‐3 in patients at risk for heart failure with preserved ejection fraction: results from the DIAST‐CHF study
Authors: Trippel Tobias Daniel , Mende Meinhard , Düngen Hans‐Dirk , Hashemi Djawid , Petutschnigg Johannes , Nolte Kathleen , Herrmann‐Lingen Christoph , Binder Lutz , Hasenfuss Gerd , Pieske Burkert , Wachter Rolf , Edelmann Frank
Published: February 2021

Aims

Galectin‐3 (Gal‐3) predicts long‐term outcome among patients with heart failure (HF) with preserved ejection fraction (HFpEF). The ability of Gal‐3 to diagnose and predict incident HFpEF in a cohort at risk for HFpEF is of particular interest. We aimed to determine the association between Gal‐3 and clinical manifestations of HFpEF, the relationship between Gal‐3 and all‐cause mortality, or the composite of cardiovascular hospitalization and death.

Methods and results

The observational Diast‐CHF study included patients aged 50 to 85 years with ≥1 risk factor for HF (e.g. hypertension, diabetes mellitus, and atherosclerotic disease) or previously suspected HF. Patients were followed for 10 years. The association between Gal‐3, evidence of diastolic dysfunction, and Framingham criteria for HF was examined. All deaths and hospitalizations were adjudicated as cardiovascular or non‐cardiovascular. The analysis population was composed of 1386 subjects (67 years old, 50.9% female). The area under the receiver operating characteristic curve to diagnose HFpEF was 0.71. At a cut‐off value of 13.57 ng/mL, sensitivity was 0.61 and specificity was 0.73 for Gal‐3, and the diagnostic power to detect HFpEF was superior to N‐terminal pro‐brain natriuretic peptide (area under the receiver operating characteristic curve 0.59, P > 0.001). Baseline Gal‐3 was associated with risk factors for HF (P < 0.001). Higher levels of Gal‐3 predicted incident HFpEF (P < 0.05), adjusted all‐cause mortality (P < 0.001), and the adjusted composite of cardiovascular hospitalization and death (P < 0.001), both independent from N‐terminal pro‐brain natriuretic peptide.

Conclusions

Gal‐3 differentiated patients with HFpEF from an overall cohort of well‐characterized patients with risk factors for HFpEF. Independent of other factors, baseline Gal‐3 levels were associated with a higher risk for incident HFpEF, mortality, or the composite of cardiovascular hospitalization and death over 10 year follow‐up. In conjunction with clinical parameters, Gal‐3 adds a statistically significant value for the diagnosis of HFpEF within this study, yet the clinical relevance remains debatable.
Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)
Authors: Caslavska Jitka , Thormann Wolfgang
Published: February 2021

The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis‐ based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field‐amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.
A time averaged steady state method for the Navier–Stokes equations
Authors: Zhao Mengjie , Zorrilla Rubén , Rossi Riccardo , Wüchner Roland
Published: February 2021

This work derives an incompressible variational multiscales time‐averaged Navier–Stokes (NS) formulation that aims at obtaining accurate steady state solutions. Rather than using the standard time instantaneous velocity and pressure, the new formulation devises a time averaging procedure based on rewriting and solving the NS equations in terms of the newly defined time‐averaged velocity and pressure. Hence, the method could be understood as a convenient change of variable so that the problem is rewritten directly in terms of the steady state quantities. The important advantage of such a point of view is that it can in principle be applied to any other formulation. Such time averaging procedure is complemented by two time step modification strategies in order to accelerate the convergence to the steady state. The guidelines of an integrated framework are presented in the article, starting with the description of the proposed numerical technique applied to general incompressible flows. The explanation is enhanced with a one‐dimensional (1D) nonlinear oscillator example. Several results are presented concerning analytical benchmarks, simulation of flows in laminar, transitional and turbulent regimes with and without an inherently steady solution.
Formation of the node of Ranvier by Schwann cells is under control of transcription factor Sox10
Authors: Saur Anna‐Lena , Fröb Franziska , Weider Matthias , Wegner Michael
Published: February 2021

The transcription factor Sox10 is an essential regulator of genes that code for structural components of the myelin sheath and for lipid metabolic enzymes in both types of myelinating glia in the central and peripheral nervous systems. In an attempt to characterize additional Sox10 target genes in Schwann cells, we identified in this study a strong influence of Sox10 on the expression of genes associated with adhesion in the MSC80 Schwann cell line. These included the genes for Gliomedin, Neuronal cell adhesion molecule and Neurofascin that together constitute essential Schwann cell contributions to paranode and node of Ranvier. Using bioinformatics and molecular biology techniques we provide evidence that Sox10 directly activates these genes by binding to conserved regulatory regions. For activation, Sox10 cooperates with Krox20, a transcription factor previously identified as the central regulator of Schwann cell myelination. Both the activating function of Sox10 as well as its cooperation with Krox20 were confirmed in vivo. We conclude that the employment of Sox10 and Krox20 as regulators of structural myelin sheath components and genes associated with the node of Ranvier is one way of ensuring a biologically meaningful coordinated formation of both structures during peripheral myelination.