bluuebunny/crossref_metadata_2025 huggingface dataset:
Siderophore‐Interacting Protein
Authors: Trindade Inês B , Moe Elin , Louro Ricardo O
Published: June 2020

Iron is an essential element for most organisms. Microorganisms have evolved small molecules with high affinity for Fe(III) named siderophores to obtain iron. SIPs (siderophore‐interacting proteins) are flavin‐based enzymes that catalyze the one‐electron reduction of Fe(III)‐siderophores. The reduction of Fe(III) to Fe(II) decreases the stability of the complex promoting ligand exchange and allowing time and site‐specific delivery of iron, making it available to the cells. SIPs described in this article contain stably attached flavins and use NADH and/or NADPH as reducing agents and these enzymes are widely conserved among bacteria. A superposition of the known structures show similar overall architecture, consisting of two domains (N‐terminal or NAD(P)H‐binding and C‐terminal or FAD‐binding) with the FAD buried in the interface in‐between.

In addition to NADH and NADPH, SfSIP can be directly reduced by ferredoxin to the hydroquinone state. Nonetheless, there is still much to learn regarding the mechanisms of Fe(III)‐siderophore reduction including the apparent functional redundancy of these enzymes in numerous microorganisms.
Psychodynamic psychotherapy: When it helps people in recovery
Authors: Knopf Alison
Published: June 2020

You have almost never read about psychoanalysis or its less intense relative, psychodynamic psychotherapy, in these pages. It's because it doesn't work to treat active substance use disorders (SUDs). But psychodynamic psychotherapy, with all of the psychoanalytic underpinnings, can be very helpful to patients in recovery, because in fact many of these patients are self‐medicating a past trauma.
Corrosion and Wear Study of Ni–W–B/WC Composite Coatings Electroplated by Pulse Plating
Authors: Ahmadiyeh Somayeh , Rasooli Ali , Hosseini Mir Ghasem
Published: June 2020

Herein, the effect of WC content (ranging from 0 to 12 g L−1 in the bath) is studied on the corrosion and wear properties of the Ni–W–B/WC pulse‐plated composite coatings. Results display that at the first step, increasing WC concentrations in the bath (up to 4 g L−1) increases WC content in the coating. However, further addition of WC particles decreases WC content in the coating because of the agglomeration of nanoparticles. Furthermore, the corrosion and wear resistance of the deposits improve considerably with raising the WC amount in the deposits. In other words, the coating electroplated at 4 g L−1 of nanoparticles in the bath displays the best electrochemical and wear behaviors. The uniform distribution of reinforced particles in the deposit is the main reason for achieving superior properties. A maximum corrosion resistance of about 65.8 kΩ cm2 is attained in the coating with 4 g L−1 WC in the bath. In addition, this coating displayed minimum values of wear weight loss (0.288 mg cm−2) and the friction coefficient (0.348). Higher WC contents in the bath negatively affect the properties of the coatings because of the existence of agglomerated particles and decreasing nanoparticle amounts in the coatings.
Die Totalsynthese des Antibiotikums Disciformycin B durch Ringschlussmetathese
Authors: Waser Philipp , Altmann Karl‐Heinz
Published: June 2020

Wir beschreiben die Totalsynthese des potenten neuen Antibiotikums Disciformycin B (2), das eine ausgeprägte Aktivität gegenüber Methicillin‐ und Vancomycin‐resistenten Stämmen von Staphylococcus aureus (MRSA/VRSA) aufweist. Der zentrale Syntheseschritt besteht in der Makrozyklisierung eines Tetraens zum 12‐gliedrigen Makrolactonring des Naturstoffs durch eine ringschließende Olefinmetathese. Zwar wurde neben dem Makrozyklus über einen alternativen Ringschlussmetatheseweg auch ein Cyclopentenderivat gebildet, es konnten jedoch Bedingungen gefunden werden, die das gewünschte Makrolacton als Hauptprodukt lieferten. Die Schlüsselschritte bei der Herstellung des Metathesesubstrats waren eine hocheffiziente Evans‐syn‐Aldolreaktion, die asymmetrische Brown‐Allylierung des Angelikaaldehyds, sowie die stereoselektive 1,2‐Reduktion eines Enons mittels Zn(BH4)2. Die Synthese wurde nach der Makrozyklisierung über eine dehydratative Glykosylierung zur Einführung des d‐Arabinofuranosylrests und schließlich eine chemoselektive Oxidation eines allylischen Alkohols zu Ende geführt.
Aromatic 19F–13C TROSY—[19F, 13C]‐Pyrimidine Labeling for NMR Spectroscopy of RNA
Authors: Nußbaumer Felix , Plangger Raphael , Roeck Manuel , Kreutz Christoph
Published: June 2020

We present the access to [5‐19F, 5‐13C]‐uridine and ‐cytidine phosphoramidites for the production of site‐specifically modified RNAs up to 65 nucleotides (nts). The amidites were used to introduce [5‐19F, 5‐13C]‐pyrimidine labels into five RNAs—the 30 nt human immunodeficiency virus trans activation response (HIV TAR) 2 RNA, the 61 nt human hepatitis B virus ϵ (hHBV ϵ) RNA, the 49 nt SAM VI riboswitch aptamer domain from B. angulatum, the 29 nt apical stem loop of the pre‐microRNA (miRNA) 21 and the 59 nt full length pre‐miRNA 21. The main stimulus to introduce the aromatic 19F–13C‐spin topology into RNA comes from a work of Boeszoermenyi et al., in which the dipole‐dipole interaction and the chemical shift anisotropy relaxation mechanisms cancel each other leading to advantageous TROSY properties shown for aromatic protein sidechains. This aromatic 13C–19F labeling scheme is now transferred to RNA. We provide a protocol for the resonance assignment by solid phase synthesis based on diluted [5‐19F, 5‐13C]/[5‐19F] pyrimidine labeling. For the 61 nt hHBV ϵ we find a beneficial 19F–13C TROSY enhancement, which should be even more pronounced in larger RNAs and will facilitate the NMR studies of larger RNAs. The [19F, 13C]‐labeling of the SAM VI aptamer domain and the pre‐miRNA 21 further opens the possibility to use the biorthogonal stable isotope reporter nuclei in in vivo NMR to observe ligand binding and microRNA processing in a biological relevant setting.
Four‐Dimensional Deoxyribonucleic Acid–Gold Nanoparticle Assemblies
Authors: Luo Ming , Xuan Mingjun , Huo Shuaidong , Fan Jilin , Chakraborty Gurudas , Wang Yixi , Zhao Hui , Herrmann Andreas , Zheng Lifei
Published: June 2020

Organization of gold nanoobjects by oligonucleotides has resulted in many three‐dimensional colloidal assemblies with diverse size, shape, and complexity; nonetheless, autonomous and temporal control during formation remains challenging. In contrast, living systems temporally and spatially self‐regulate formation of functional structures by internally orchestrating assembly and disassembly kinetics of dissipative biomacromolecular networks. We present a novel approach for fabricating four‐dimensional gold nanostructures by adding an additional dimension: time. The dissipative character of our system is achieved using exonuclease III digestion of deoxyribonucleic acid (DNA) fuel as an energy‐dissipating pathway. Temporal control over amorphous clusters composed of spherical gold nanoparticles (AuNPs) and well‐defined core–satellite structures from gold nanorods (AuNRs) and AuNPs is demonstrated. Furthermore, the high specificity of DNA hybridization allowed us to demonstrate selective activation of the evolution of multiple architectures of higher complexity in a single mixture containing small and larger spherical AuNPs and AuNRs.
Novel VO (IV) complexes derived from a macrochelates: Synthesis, characterization, molecular modeling and in vivo insulin‐mimic activity studies
Authors: El‐Gammal Ola A. , Gaber M. , Mandour Sh. A.
Published: June 2020

For the development of extensive investigations into a potential medicinal application of vanadium coordination compounds for the oral treatment of diabetes, new mono and bimetallic VO (IV) complexes with N,N′‐(2,2′‐(9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarbonyl) bis (hydrazine‐1‐carbonothioyl)) dibenzamide (H6EBT) and 2,2′‐((9S,10S,11R,12R)‐9,10‐dihydro‐9,10‐ethanoanthracene‐11, 12‐dicarbonyl) bis (N‐phenylhydrazine‐1‐carboxamide) (H6EPH) have been isolated and characterized. The FTIR and NMR spectral data revealed that H6EBT acts as neutral tridentate and dibasic hexadentate while H6EPH as dibasic tridentate and tetrabasic hexadentate. The electronic and ESR spectra indicated that complexes has octahedral geometry. ESR spectrum of [(VO)(H6EBT)(SO4)].5H2O gives a well resolved hyperfine eight‐line pattern typical spectrum for mononuclear vanadyl complexes with g˃ g⊥ = 1.9 suggesting that the ligand donor atoms ONS are coplanar with the two chelate rings forming octahedral geometry. Also, the high parallel hyperfine splitting value, A = 0.0108, than perpendicular one (A⊥ = 0.0087) indicated that the single d‐ electron is in a σ‐nonbonding orbital and aiming away from the equatorial ligands. On the other hand, the EPR spectra of the binuclear [(VO)2(H4EBT)(SO4)]3H2O and [(VO)2(H2EPH)(H2O)2].10H2O complexes gave a single broad line centered at g = 2.05 and 2.07, respectively, without resolved hyperfine structure paramagnetic triplet (S = 1) is consistent with the anomalous value of the magnetic moment value (μeff = 1.100 and 0.99 B.M.) supporting a binuclear nature. The TG analyses confirmed the existence of solvent molecules inside and/or outside the coordination sphere. The DFT molecular modeling of ligands and its VO (IV) complexes supported the suggested geometries. Also, all compounds were screened for in vivo insulin‐mimetic activity.
CeO2/Pd Nanoparticles Incorporated Fly Ash Zeolite: An Efficient and Recyclable Catalyst for Csp2‐Csp2Bond Formation Reactions
Authors: Sheeba Thavamani Seth , Sudharsan Murugesan , Santhana Mariya Anitha , Suresh Devarajan , Jose Amali Arlin , Rajeswari Sanniyasi , Peter Amaladhas Thomas
Published: June 2020

The catalytic activity of CeO2and palladium nanoparticles supported fly ash zeolite (CeO2/Pd@FAZ) for Csp2‐Csp2bond formation was studied. CeO2/Pd@FAZ was characterized by FTIR, XRD, EDAX and TEM studies. In the Suzuki‐Miyauracross‐coupling reaction, biphenyl derivatives with excellent yields were obtained, and the reaction conditions were optimized. The catalytic activity was explored using a wide variety of diversely substituted aryl bromides and chlorides with aryl boronic acid under optimized reaction conditions. The recyclability of the catalyst was established for three cycles, with the conversion rate from 99 to 40%, which gained the advantage of heterogeneous catalysis.
Catalytic steam reforming of toluene as model tar compound using Ni/coal fly ash catalyst
Authors: Lu Min , Xiong Zuhong , Li Jiqing , Li Xi , Fang Kejing , Li Tao
Published: June 2020

Coal fly ash (CFA), a solid waste from power plants, was selected as the support of Ni‐based catalysts used for steam reforming of toluene in a fixed‐bed reactor. The CFA support was thermally pretreatment first, followed by chemical activation with different treatment time (6 h to 4 days) in 2‐mol/L HNO3 solution. Then, series low‐cost catalysts were prepared by wet impregnation. The prepared catalysts were characterized suitably by X‐ray diffraction (XRD), Brunauere–Emmette–Teller (BET), temperature programmed reduction (TPR), temperature programmed desorption (TPD), and Raman techniques. According to the catalyst characterization, the chemical pretreatment could improve the support property by adjusting the chemical composition. The Fe‐rich Fe‐Ni and Ni‐Co alloy was formed by H2 reduction on the Ni/CFA‐6h and Co‐Ni/CFA‐6h catalysts, respectively. In the catalytic steam reforming of toluene, the Ni/CFA‐6h had the best catalytic active among all monometallic catalysts, which could be attributed to the existence of Fe0.94Ni0.06 particles, and its performance could be further improved after partly replacing Ni by Co. The Co‐Ni/CFA‐6h catalyst exhibited the best ability of carbon deposit resistance, implying that its catalytic performance slightly lower than Ni/SiO2 was due to the too large SBET surface area gap.
A hybrid system of hydrogel/frog egg‐like microspheres accelerates wound healing via sustained delivery ofRCSPs
Authors: Ji Xuan , Liu Guomin , Cui Yutao , Jia Wenyuan , Luo Yungang , Cheng Zhiqiang
Published: June 2020

In this article, a hybrid system of hydrogel/frog egg‐like microspheres (H‐FMS) formed by the combination of coaxial electrostatic spraying and freeze‐drying was introduced for enhancing wound healing efficiency through the sustained release ofRana chensinensisskin peptides (RCSPs). The porous PVA/gelatin hydrogel were obtained and frog egg‐like microspheres (FMS) of sodium alginate (SA), shaping uniform and smooth, were embedded into hydrogel. Based on PVA/gelatin hydrogel, the FMS addition increased the water absorption of hydrogel to 1,105%. RCSPs were more effectively encapsulated into FMS than solid microspheres (MS). Not only does the H‐FMS act as good “depots” for sustained release of RCSPs over 9 days, without exhibiting obvious burst release, but also show good biocompatibility in vitro. In vivo studies on wound healing as well as the histology of fibroblasts, re‐epithelialization, inflammation, and hair follicles indicated that the structure of H‐FMS released RCSPs continuously and promoted wound healing in rats significantly.
Polypropylene/phosphazene nanotube nanocomposites: Thermal, mechanical, and flame retardation studies
Authors: Rangaraj Vengatesan M. , Singh Swati , Devaraju Subramani , Wadi Vijay S. , Alhassan Saeed , Anjum Dalaver H. , Mittal Vikas
Published: June 2020

In this study, flame retardant polypropylene (PP) nanocomposites with superior mechanical performance have been developed using amine‐functionalized phosphazene nanotubes (APZS, 1–10 wt%) through melt‐blending method. Polypropylene‐graft‐maleic anhydride was used as the compatibilizer to attain effective interaction between the nanofiller and the PP matrix. The characterization of amine‐functionalized phosphazene nanotubes (APZS) using solid‐state nuclear magnetic resonance (NMR), X‐ray photoelectron spectroscopy, X‐ray diffraction, fourier‐transform infrared (FTIR), and transmission electron microscopy indicated successful amine functionalization, though structural changes were observed as compared to the unfunctionalized nanotubes. Owing to the covalent polymer‐filler interfacial interactions and resulting in uniform filler dispersion, the nanocomposites exhibited significant enhancement in the tensile modulus up to 5 wt% APZS content (98% increment at 5 wt% content as compared to pure polymer). The addition of a small fraction of APZS (1 wt%) improved the impact strength of the nanocomposite by more than 180%. APZS acted as a weak nucleating agent for PP, thereby leading to enhanced degree of crystallinity (up to 5 wt% APZS content). The thermal stability of the nanocomposites was also enhanced with APZS content. The nanocomposites with 5 and 10 wt% APZS loading exhibited a V0 rating in UL‐94 test, indicating that APZS introduced a robust flame retardancy behavior in the PP nanocomposites. The limiting oxygen index values also confirmed the findings from the UL‐94 analysis. The developed nanocomposites exhibit high potential of use in a wide range of high temperature applications.
Osteological description of casque ontogeny in the southern cassowary (Casuarius casuarius) using micro‐CT imaging
Authors: Green Todd L. , Gignac Paul M.
Published: June 2020

Extant cassowaries (Casuarius) are unique flightless birds found in the tropics of Indo‐Australia. They have garnered substantial attention from anatomists with focus centered on the bony makeup and function of their conspicuous cranial casques, located dorsally above the orbits and neurocranium. The osteological patterning of the casque has been formally described previously; however, there are differing interpretations between authors. These variable descriptions suggest that an anatomical understanding of casque anatomy and its constituent elements may be enhanced by developmental studies aimed at further elucidating this bizarre structure. In the present study, we clarify casque osteology of the southern cassowary (C. casuarius) by detailing casque anatomy across an extensive growth series for the first time. We used micro‐computed tomography (μCT) imaging to visualize embryonic development and post‐hatching ontogeny through adulthood. We also sampled closely related emus (Dromaius novaehollandiae) and ostriches (Struthio camelus) to provide valuable comparative context. We found that southern cassowary casques are comprised of three paired (i.e., nasals, lacrimals, frontals) and two unpaired elements (i.e., mesethmoid, median casque element). Although lacrimals have rarely been considered as casque elements, the contribution to the casque structure was evident in μCT images. The median casque element has often been cited as a portion of the mesethmoid. However, through comparisons between immature C. casuarius and D. novaehollandiae, we document the median casque element as a distinct unit from the mesethmoid.
Expanding the Chinese hamster ovary cell long noncoding RNA transcriptome using RNASeq
Authors: Motheramgari Krishna , Valdés‐Bango Curell Ricardo , Tzani Ioanna , Gallagher Clair , Castro‐Rivadeneyra Marina , Zhang Lin , Barron Niall , Clarke Colin
Published: June 2020

Our ability to study Chinese hamster ovary (CHO) cell biology has been revolutionised over the last decade following the development of next generation sequencing technology and publication of reference DNA sequences for CHO cells and the Chinese hamster. RNA sequencing has not only enabled the association of transcript expression with bioreactor conditions and desirable bioprocess phenotypes but played a key role in the characterisation of protein coding and small noncoding RNAs. The annotation of long noncoding RNAs, and therefore our understanding of their role in CHO cell biology, has been limited to date. In this manuscript, we use high‐resolution RNASeq data to more than double the number of annotated lncRNA transcripts for the CHO K1 genome. In addition, the utilisation of strand‐specific sequencing enabled the identification of more than 1,000 new antisense and divergent lncRNAs. The utility of monitoring lncRNA expression is demonstrated through an analysis of the transcriptomic response to a reduction of cell culture temperature and identification of simultaneous sense/antisense differential expression for the first time in CHO cells. To enable further studies of lncRNAs, the transcripts annotated in this study have been made available for the CHO cell biology community.
Potential utilization of bulgur bran as a source of dietary fiber in cookies
Authors: Saka İrem , Özkaya Hazım , Özkaya Berrin
Published: June 2020

Background and objectives

In this study, the utilization of bulgur bran as a fiber source in cookies was investigated. Different levels of bulgur bran (0%, 5%, 10%, 15%, 20%) with different particle sizes (200 µm, 400 µm, 850 µm) were blended with flour, and the blends were evaluated for dietary fiber and phytic acid content. Also, the effect of bulgur bran on the rheological properties of dough and the physical, structural, and sensory properties of cookies were investigated.

Findings

Bulgur bran increased the amounts of dietary fiber in cookies significantly, depending on the addition rate. The addition of bulgur bran increased the phytic acid content of cookies. The water absorption, dough development time, and stability of the farinograms increased as the rate of incorporation and particle size of bulgur bran increased. As the particle size and bran levels increased in mixtures, cookie thickness increased, but the spread ratio decreased, and cookies became darker in color. The addition of bulgur bran increased the breaking strength of cookies. Sensory evaluation showed that as the particle size of the participating bran increased, consumer acceptability was reduced. It was concluded that acceptable cookies could be obtained by incorporating bulgur bran at rates lower than 10% in the formulation.

Conclusion

As a result, it was determined that bulgur bran contained high amount of dietary fiber, whereas it contained low amount of phytic acid. Therefore, it can be used as an alternative to other cereal brans, both in terms of functionality and human health.

Significance and novelty

Findings of this study revealed useful information on chemical composition of bulgur bran and utilization in cookies. These results showed that bulgur bran could be used as a good source of fiber for different products in the bakery industry.
PhotoMetrix and colorimetric image analysis using smartphones
Authors: Böck Fernanda Carla , Helfer Gilson Augusto , da Costa Adilson Ben , Dessuy Morgana Bazzan , Ferrão Marco Flôres
Published: June 2020

The steady advances in technology employed in smartphones, coupled with the high availability and the ease access to these devices, increased the interest in applying it to analytical purposes. The main goal is to develop simple, fast, and low‐cost analytical methods, generating immediate results. Different analytical strategies using smartphones have been proposed to identify or determine different analytes in a wide range of matrices. Some of them use the smartphone to capture the images, to process them, and to provide the analytical results. Others use this device just for image acquisition. In this context, this review aimed to relate previous works that used smartphones to acquire images for analytical purposes, with a special focus on PhotoMetrix application, which is a tool for chemical analysis. This application allows the decomposition of digital images acquired by smartphone cameras and to process them within the same device, allowing in situ chemical analysis.
An analysis of vascular properties using pulse wave analysis in patients with vasovagal syncope
Authors: Jang Ji‐Hun , Park Jin‐Hee , Ko Kyu‐Yong , Baek Yong‐Soo , Kwon Sung‐Woo , Park Sang‐Don , Shin Sung‐Hee , Woo Seong‐Ill , Kwan Jun , Kim Dae‐Hyeok
Published: June 2020

Background

Vasovagal syncope (VVS) is a common cause of recurrent syncope. Nevertheless, the exact hemodynamic mechanism has not been elucidated. Pulse wave analysis (PWA) is widely used to evaluate vascular properties, as it reflects the condition of the entire arterial system.

Hypothesis

Cardiovascular autonomic modulation may influence the hemodynamic mechanism and result in different vascular properties between VVS patients and healthy individuals.

Methods

We enrolled consecutive patients diagnosed with VVS on head‐up tilt testing from January 2014 to August 2019. Healthy subjects were enrolled as the control group. We performed PWA on all participants. Using propensity score matching, we assembled a study population with similar baseline characteristics and compared hemodynamic parameters.

Results

A total of 111 VVS patients (43 ± 18 years, 72 females) and 475 healthy control subjects (48 ± 13 years, 192 females) were enrolled. Compared to the healthy control subjects, the VVS patients had a higher augmentation index (AIx) adjusted to a heart rate of 75 beats per minute (AIx@HR75, 20.5 ± 13.1% vs 16.7 ± 11.9%, P = .003). After 1:1 matched comparison (111 matched control), VVS patients consistently showed higher AIx@HR75 (20.5 ± 13.1% vs 16.7 ± 12.9%, P = .02) than the matched control group. According to age distribution, VVS patients showed significantly higher AIx@HR75 (10.6 ± 11.7% vs 2.5 ± 11.1%, P = .01) in a young age (15‐33 years) group.

Conclusions

VVS patients had greater arterial stiffness than healthy subjects. This is one of the plausible mechanisms of the pathophysiology of VVS.
Using SPAdes De Novo Assembler
Authors: Prjibelski Andrey , Antipov Dmitry , Meleshko Dmitry , Lapidus Alla , Korobeynikov Anton
Published: June 2020

SPAdes—St. Petersburg genome Assembler—was originally developed for de novo assembly of genome sequencing data produced for cultivated microbial isolates and for single‐cell genomic DNA sequencing. With time, the functionality of SPAdes was extended to enable assembly of IonTorrent data, as well as hybrid assembly from short and long reads (PacBio and Oxford Nanopore). In this article we present protocols for five different assembly pipelines that comprise the SPAdes package and that are used for assembly of metagenomes and transcriptomes as well as assembly of putative plasmids and biosynthetic gene clusters from whole‐genome sequencing and metagenomic datasets. In addition, we present guidelines for understanding results with use cases for each pipeline, and several additional support protocols that help in using SPAdes properly. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Assembling isolate bacterial datasets

Basic Protocol 2: Assembling metagenomic datasets

Basic Protocol 3: Assembling sets of putative plasmids

Basic Protocol 4: Assembling transcriptomes

Basic Protocol 5: Assembling putative biosynthetic gene clusters

Support Protocol 1: Installing SPAdes

Support Protocol 2: Providing input via command line

Support Protocol 3: Providing input data via YAML format

Support Protocol 4: Restarting previous run

Support Protocol 5: Determining strand‐specificity of RNA‐seq data
Artificial Intelligence and Mechanistic Modeling for Clinical Decision Making in Oncology
Authors: Benzekry Sebastien
Published: June 2020

The amount of “big” data generated in clinical oncology, whether from molecular, imaging, pharmacological, or biological origin, brings novel challenges. To mine efficiently this source of information, mathematical models able to produce predictive algorithms and simulations are required, with applications for diagnosis, prognosis, drug development, or prediction of the response to therapy. Such mathematical and computational constructs can be subdivided into two broad classes: biologically agnostic, statistical models using artificial intelligence techniques, and physiologically based, mechanistic models. In this review, recent advances in the applications of such methods in clinical oncology are outlined. These include machine learning applied to big data (omics, imaging, or electronic health records), pharmacometrics and quantitative systems pharmacology, as well as tumor kinetics and metastasis modeling. Focus is set on studies with high potential of clinical translation, and particular attention is given to cancer immunotherapy. Perspectives are given in terms of combinations of the two approaches: “mechanistic learning.”
MTXPK.org: A Clinical Decision Support Tool Evaluating High‐Dose Methotrexate Pharmacokinetics to Inform Post‐Infusion Care and Use of Glucarpidase
Authors: Taylor Zachary L. , Mizuno Tomoyuki , Punt Nieko C. , Baskaran Balaji , Navarro Sainz Adriana , Shuman William , Felicelli Nicholas , Vinks Alexander A. , Heldrup Jesper , Ramsey Laura B.
Published: June 2020

Methotrexate (MTX), an antifolate, is administered at high doses to treat malignancies in children and adults. However, there is considerable interpatient variability in clearance of high‐dose (HD) MTX. Patients with delayed clearance are at an increased risk for severe nephrotoxicity and life‐threatening systemic MTX exposure. Glucarpidase is a rescue agent for severe MTX toxicity that reduces plasma MTX levels via hydrolysis of MTX into inactive metabolites, but is only indicated when MTX concentrations are > 2 SDs above the mean excretion curve specific for the given dose together with a significant creatinine increase (> 50%). Appropriate administration of glucarpidase is challenging due to the ambiguity in the labeled indication. A recent consensus guideline was published with an algorithm to provide clarity in when to administer glucarpidase, yet clinical interpretation of laboratory results that do not directly correspond to the algorithm prove to be a limitation of its use. The goal of our study was to develop a clinical decision support tool to optimize the administration of glucarpidase for patients receiving HD MTX. Here, we describe the development of a novel 3‐compartment MTX population pharmacokinetic (PK) model using 31,672 MTX plasma concentrations from 772 pediatric patients receiving HD MTX for the treatment of acute lymphoblastic leukemia and its integration into the online clinical decision support tool, MTXPK.org. This web‐based tool has the functionality to utilize individualized demographics, serum creatinine, and real‐time drug concentrations to predict the elimination profile and facilitate model‐informed administration of glucarpidase.
Photomanipulation of the Mechanical Properties in a Liquid Crystal with Azo‐Containing Bent‐Core Mesogens
Authors: Kurachkina Marharyta , Nádasi Hajnalka , Alaasar Mohamed , Tschierske Carsten , Eremin Alexey
Published: June 2020

We demonstrate the reversible photomanipulation of the bulk mechanical properties in the azobenzene‐containing bent‐core liquid crystal. The azobenzene groups in the mesogens exhibit reversible cis‐trans photoisomerization abilities. An unprecedentedly large reduction by the factor of more than 5 of the splay elastic constant in a cybotactic‐type nematic phase was found under exposure to the UV. This opens up the possibility to manipulate the mechanical properties of liquid crystals using light. The liquid crystal material is also distinguished by the sign inversion of low‐frequency temperature‐dependent dielectric anisotropy. Such behavior can be related to the presence of smectic‐like nanoclusters both in the isotropic phase near the clearing point and in the cybotactic nematic phase.
Transcriptional profiling and immunophenotyping show sustained activation of blood monocytes in subpatent Plasmodium falciparum infection
Authors: Loughland Jessica R , Woodberry Tonia , Field Matt , Andrew Dean W , SheelaNair Arya , Dooley Nicholas L , Piera Kim A , Amante Fiona H , Kenangalem Enny , Price Ric N , Engwerda Christian R , Anstey Nicholas M , McCarthy James S , Boyle Michelle J , Minigo Gabriela
Published: June 2020

Objectives

Malaria, caused by Plasmodium infection, remains a major global health problem. Monocytes are integral to the immune response, yet their transcriptional and functional responses in primary Plasmodium falciparum infection and in clinical malaria are poorly understood.

Methods

The transcriptional and functional profiles of monocytes were examined in controlled human malaria infection with P. falciparum blood stages and in children and adults with acute malaria. Monocyte gene expression and functional phenotypes were examined by RNA sequencing and flow cytometry at peak infection and compared to pre‐infection or at convalescence in acute malaria.

Results

In subpatent primary infection, the monocyte transcriptional profile was dominated by an interferon (IFN) molecular signature. Pathways enriched included type I IFN signalling, innate immune response and cytokine‐mediated signalling. Monocytes increased TNF and IL‐12 production upon in vitro toll‐like receptor stimulation and increased IL‐10 production upon in vitro parasite restimulation. Longitudinal phenotypic analyses revealed sustained significant changes in the composition of monocytes following infection, with increased CD14+CD16− and decreased CD14−CD16+ subsets. In acute malaria, monocyte CD64/FcγRI expression was significantly increased in children and adults, while HLA‐DR remained stable. Although children and adults showed a similar pattern of differentially expressed genes, the number and magnitude of gene expression change were greater in children.

Conclusions

Monocyte activation during subpatent malaria is driven by an IFN molecular signature with robust activation of genes enriched in pathogen detection, phagocytosis, antimicrobial activity and antigen presentation. The greater magnitude of transcriptional changes in children with acute malaria suggests monocyte phenotypes may change with age or exposure.
Adamantinoma‐like Ewing sarcoma of the thyroid
Authors: Jones Robert , Maleki Zahra
Published: June 2020

Adamantinoma‐like Ewing sarcoma (ALES) is a rare variant of Ewing sarcoma family of tumors (ESFTs). ALES is characterized by translocations of the EWSR1 (Ewing sarcoma breakpoint region 1) gene on chromosome 22, morphologic features of small round blue cell tumors with focal squamous differentiation, and a unique immunoprofile. Herein, we report a 21‐year‐old patient who presented with severe, acute onset back pain. Imaging revealed a large, exophytic, heterogeneously enhancing mass in the left thyroid and numerous lytic bone lesions. Fine‐needle aspiration of the thyroid, revealed a cellular smear with “small round blue cell” morphology. The unique immunoprofile of positive ESFT markers (NKX2.2 and CD99), along with positive markers of squamous epithelial differentiation (AE1/AE3 and p40), led to a diagnosis of ALES. This was confirmed by fluorescence in situ hybridization, which demonstrated EWSR1 rearrangement in 74% of nuclei.
Fine‐needle aspiration findings of fibroadenoma with pseudolactational changes in the vulva: A case report
Authors: Mohammadnia Avval Maryam , Vijayananda Kumar Perikala , Momtahan Mozhdeh
Published: June 2020

Fibroadenoma is a common benign neoplasm of the breast and ectopic breast tissue, associated with possible lactational changes in pregnant or lactating women. Uncommon pseudolactational changes are possible in this neoplasm among nulliparous women. Fibroadenoma and lactating adenoma are rarely seen in the vulvar region. Theoretically, pseudolactational changes can occur in fibroadenomas of the vulva in young nulliparous women although there have been no reports so far. In this case report, we describe the fine‐needle aspiration (FNA) cytology of a vulvar fibroadenoma with pseudolactational changes in a young nulliparous woman. This type of neoplasm has not been reported so far, and it may be misdiagnosed as a malignancy because of its cytological features, such as isolated cells with large nuclei and distinct nucleoli.
Cytomorphological spectrum of hand, wrist, and foot lesions at tertiary care center in central India
Authors: Panwar Hemlata , Tandon Ashwani , Joshi Deepti , Goel Garima , Mahabharti Kodavali , Kapoor Neelkamal
Published: June 2020

Background

Fine‐needle aspiration cytology (FNAC) being a fast technique is used as a primary investigation to diagnose wide spectrum of hand, wrist, and foot lesions. These sites are prone to trauma, reparative, and infectious process, which forms mass lesions mimicking neoplasia. Our study highlighted the importance of FNAC with the chance of reduction in biopsy or excision.

Aims and objectives

To report the prevalence and cytomorphological spectrum of hand and foot lesions with the aim of consolidating the diagnostic potential and also correlate the cytological evaluation with histopathology.

Materials and methods

This retrospective observational study was done in central India for the period of 5.5 years. The archive cytology slides of patients with palpable lesions at these sites are reviewed and analyzed.

Results

Of the total 6512 FNAC cases, 115 cases presented as swelling in the hand, wrist, and foot are reviewed. Age ranged from 4 months to 80 years with M:F = 1.25:1. Of the 111 satisfactory smears (96.7%), 21 cases (18.9%) diagnosed as inflammatory lesion, including synovitis, tuberculosis, gout, and fat necrosis. Sixty cases as benign non‐neoplastic (tumor‐like) lesions with the most common being ganglion (29). Of the 30 neoplastic lesions, 26 were benign tumor with the most common being mesenchymal neoplasms (19), followed by giant cell tumor of tendon sheath. Malignant tumors included malignant melanoma, small round cell tumor, and squamous‐cell carcinoma.

Conclusion

FNAC is useful investigation for early diagnosis of hand and foot lesions. These lesions are benign mostly with less malignancy occurrence (<2%), compared with other soft tissue lesions.
Periodontal risk markers in children and adolescents with type 1 diabetes: A systematic review and meta‐analysis
Authors: Jensen Emilija , Allen Gabrielle , Bednarz Jana , Couper Jennifer , Peña Alexia
Published: June 2020

Background

Periodontal disease is a frequent complication of diabetes in adults, and both conditions are associated with systemic inflammatory states. This systematic review and meta‐analysis was conducted to establish the relative severity of periodontal disease risk markers in children and adolescents with type 1 diabetes (T1D).

Methods

A systematic search strategy using PubMed and EMBASE databases was performed to identify relevant studies assessing periodontal risk markers in children and adolescents and T1D through to February 2019. Eligible studies were assessed for quality and heterogeneity, and a random effects model was used to estimate differences in selected periodontal risk markers in children with T1D relative to healthy controls.

Results

The search identified 551 studies from which 23 were found to meet the inclusion criteria. Random effects meta‐analyses demonstrated that relative to healthy controls, children and adolescents with T1D had higher mean values for plaque index, gingival index, bleeding on probing, pocket depth and clinical attachment loss (all P < .001).

Conclusions

Risk markers for periodontal disease were found to be more pronounced among children and adolescents with T1D compared to healthy controls. Early referral of these at risk individuals for dental examination is recommended to allow for early intervention.
Associations between haemoglobin A1c and mortality rate in the KORA S4 and the Heinz Nixdorf Recall population‐based cohort studies
Authors: Kowall Bernd , Rathmann Wolfgang , Kuß Oliver , Herder Christian , Roden Michael , Stang Andreas , Erbel Raimund , Huth Cornelia , Thorand Barbara , Meisinger Christa , Jöckel Karl‐Heinz , Peters Annette
Published: June 2020

Background

There is limited knowledge about mortality risk in persons with increased haemoglobin A1c (HbA1c) levels below the diabetes threshold. Moreover, little is known about how associations between increased HbA1c and mortality depend on the length of follow‐up. Therefore, we studied associations between HbA1c and mortality over long‐term follow‐up in persons with and without known diabetes.

Methods

We used data from two German population‐based cohort studies: KORA S4 Study (Southern Germany, n = 1458, baseline visits in 1999 to 2001, baseline age 55 to 74 years, mortality follow‐up 16.8 years) and Heinz Nixdorf Recall (HNR) Study (Ruhr area, n = 4613, baseline visits in 2000 to 2003, baseline age 45 to 75 years, mortality follow‐up 17.8 years). Adjusted log‐linear models were fitted to estimate relative risks (RRs) with 95% confidence intervals (CI).

Results

In both cohorts, participants with HbA1c 39 to 41 mmol/mol (5.7%‐5.9%) and HbA1c 42 to 46 mmol/mol (6.0% to 6.4%) did not have a larger overall mortality risk than participants with HbA1c < 39 mmol/mol (5.7%): the corresponding adjusted RRs were 1.00 (95% CI: 0.83‐1.21) and 1.01 (0.80‐1.27) in KORA and 0.99 (0.82‐1.21) and 0.83 (0.65‐1.07) in the HNR Study. For the pooled cohorts, the RR for HbA1c 39 to 46 mmol/mol (5.7%‐6.4%) was 0.96 (0.85‐1.07). Associations between newly detected diabetes (HbA1c ≥ 6.5%) and mortality were weak after 4 and 8 years of follow‐up, but were stronger after 12 years of follow‐up, whereas associations between previously known diabetes (baseline) and mortality decreased.

Conclusions

HbA1c‐defined pre‐diabetes is not associated with overall mortality. For newly detected and previously known diabetes, mortality risks vary with length of follow‐up.
Detection of bioactive peptides including gonadotrophin‐releasing factors (GnRHs) in horse urine using ultra‐high performance liquid chromatography–high resolution mass spectrometry (UHPLC/HRMS)
Authors: Kwok Karen Y. , Choi Timmy L. S. , Kwok Wai Him , Lau Ming Yip , Leung Elvis M. K. , Leung Gary N. W. , Wong Jenny K. Y. , Wan Terence S. M. , Adrian Farrington F. , Prabhu Anil , Ho Emmie N. M.
Published: June 2020

The use of bioactive peptides as a doping agent in both human and animal sports has become increasingly popular in recent years. As such, methods to control the misuse of bioactive peptides in equine sports have received attention. This paper describes a sensitive accurate mass method for the detection of 40 bioactive peptides and two non‐peptide growth hormone secretagogues (< 2 kDa) at low pg/mL levels in horse urine using ultra‐high performance liquid chromatography‐high resolution mass spectrometry (UHPLC/HRMS). A simple mixed‐mode cation exchange solid‐phase extraction (SPE) cartridge was employed for the extraction of 42 targets and/or their in vitro metabolites from horse urine. The final extract was analyzed using UHPLC/HRMS in positive electrospray ionization (ESI) mode under both full scan and data independent acquisition (DIA, for MS2). The estimated limits of detection (LoD) for most of the targets could reach down to 10 pg/mL in horse urine. This method was validated for qualitative detection purposes. The validation data, including method specificity, method sensitivity, extraction recovery, method precision, and matrix effect were reported. A thorough in vitro study was also performed on four gonadotrophin‐releasing factors (GnRHs), namely leuprorelin, buserelin, goserelin, and nafarelin, using the S9 fraction isolated from horse liver. The identified in vitro metabolites have been incorporated into the method for controlling the misuse of GnRHs. The applicability of this method was demonstrated by the identification of leuprorelin and one of its metabolites, Leu M4, in urine obtained after intramuscular administration of leuprorelin to a thoroughbred gelding (castrated horse).
Intraspecific genetic variation of a Fagus sylvatica population in a temperate forest derived from airborne imaging spectroscopy time series
Authors: Czyż Ewa A. , Guillén Escribà Carla , Wulf Hendrik , Tedder Andrew , Schuman Meredith C. , Schneider Fabian D. , Schaepman Michael E.
Published: June 2020

The growing pace of environmental change has increased the need for large‐scale monitoring of biodiversity. Declining intraspecific genetic variation is likely a critical factor in biodiversity loss, but is especially difficult to monitor: assessments of genetic variation are commonly based on measuring allele pools, which requires sampling of individuals and extensive sample processing, limiting spatial coverage. Alternatively, imaging spectroscopy data from remote platforms may hold the potential to reveal genetic structure of populations. In this study, we investigated how differences detected in an airborne imaging spectroscopy time series correspond to genetic variation within a population of Fagus sylvatica under natural conditions.

We used multi‐annual APEX (Airborne Prism Experiment) imaging spectrometer data from a temperate forest located in the Swiss midlands (Laegern, 47°28'N, 8°21'E), along with microsatellite data from F. sylvatica individuals collected at the site. We identified variation in foliar reflectance independent of annual and seasonal changes which we hypothesize is more likely to correspond to stable genetic differences. We established a direct connection between the spectroscopy and genetics data by using partial least squares (PLS) regression to predict the probability of belonging to a genetic cluster from spectral data.

We achieved the best genetic structure prediction by using derivatives of reflectance and a subset of wavebands rather than full‐analyzed spectra. Our model indicates that spectral regions related to leaf water content, phenols, pigments, and wax composition contribute most to the ability of this approach to predict genetic structure of F. sylvatica population in natural conditions.

This study advances the use of airborne imaging spectroscopy to assess tree genetic diversity at canopy level under natural conditions, which could overcome current spatiotemporal limitations on monitoring, understanding, and preventing genetic biodiversity loss imposed by requirements for extensive in situ sampling.
B‐type natriuretic peptide is associated with post‐discharge stroke in hospitalized patients with heart failure
Authors: Hotsuki Yu , Sato Yu , Yoshihisa Akiomi , Watanabe Koichiro , Kimishima Yusuke , Kiko Takatoyo , Yokokawa Tetsuro , Abe Satoshi , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Takeishi Yasuchika
Published: June 2020

Aims

Recently, B‐type natriuretic peptide (BNP) has been attracting attention as a predictor of stroke in patients with atrial fibrillation or those with prior stroke experience. However, the association between BNP and stroke has not been examined in patients with chronic heart failure (CHF). In the current study, we assessed whether BNP is associated with future occurrence of stroke in patients with CHF.

Methods and results

We prospectively studied 1803 consecutive patients who were admitted for decompensated HF and assessed the predictive value of circulating BNP levels for occurrence of post‐discharge stroke.

A total of 69 (3.8%) patients experienced a stroke (the stroke group) during the post‐discharge follow‐up period of a median of 1150 days. The stroke group showed a higher CHADS2 score. With respect to past medical history, the stroke group had a higher prevalence of arterial hypertension, atrial fibrillation, prior stroke, and chronic kidney disease. Echocardiographic parameters showed no significant differences between the two groups. In contrast, BNP levels were significantly higher in the stroke group than in the non‐stroke group (452.1 vs. 222.7 pg/mL, P < 0.001). Multivariate Cox proportional hazard analysis indicated that BNP levels were independently associated with post‐discharge stroke (hazard ratio 2.636, 95% confidence interval 1.595–4.357, P < 0.001). The survival classification and regression tree analysis revealed that the accurate cut‐off point of BNP in predicting post‐discharge stroke was 187.7 pg/mL. We added high BNP level (BNP ≥ 180 pg/mL) as one point to CHADS2 score. The BNP‐added CHADS2 score was compared with CHADS2 score alone by using c‐statistics. The areas under the curve of CHADS2 score, BNP, and BNP‐added CHADS2 score were 0.698, 0.616, and 0.723, respectively. The predictive value of BNP‐added CHADS2 score was higher compared with those of CHADS2 score (P = 0.026).

Conclusions

The assessment of BNP may predict the occurrence of stroke in CHF patients used alone or in combination with established CHADS2 score.
Low Molecular Weight Di‐ to Tetrapeptide Transmembrane Cation Transporters
Authors: Benke Bahiru P. , Behera Harekrushna , Madhavan Nandita
Published: June 2020

Low molecular weight di‐, tri‐ and tetrapeptide transmembrane ion transporters containing aminobenzoic acid and l/d alanine are reported. These short peptides transport alkali metal cations in preference to halides across the lipid bilayer most likely through a carrier mechanism. Easy access to these peptides and the ability to install diverse functional groups into the peptidic scaffold make them attractive scaffolds for therapeutic use.
Can Heteroarenes/Arenes Be Hydrogenated Over Catalytic Pd/C Under Ambient Conditions?
Authors: Tanaka Nao , Usuki Toyonobu
Published: June 2020

Hydrogenation of over a dozen aromatic compounds, including both heteroarenes and arenes, over palladium on carbon (Pd/C, 1–100 mol%) with H2‐balloon pressure at room temperature is reported. Analyses using pyridine as a model substrate revealed that acetic acid was the best solvent, as using only 1 mol% Pd/C provided piperidine quantitatively. Substrate scope analysis and density functional theory calculations indicated that reaction rates are highly dependent on frontier molecular orbital characteristics and the steric bulkiness of substituents. Moreover, the established method was used for the concise synthesis of the anti‐Alzheimer drug donepezil (Aricept®).