bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering the anticancer mechanism of petroleum extracts of Farfarae Flos against Lewis lung cancer by metabolomics and network pharmacology analysis
Authors: Yu Shuting , Li Jing , Gao Wei , Wu Yongyan , Qin Xuemei , Li Zhenyu
Published: May 2020

Lung cancer shows the highest incidence rate in the world. Thus, it has become increasingly important to find therapeutic drugs to treat lung cancer. Farfarae Flos (FF) has been used in traditional Chinese medicine to treat pulmonary diseases such as cough, bronchitis and asthmatic disorders. In this study, the anti‐proliferation effects of petroleum extracts of FF (PEFF) on Lewis lung cancer cells and the corresponding mechanisms were studied using cell metabolomics. Fifteen differential metabolites in the cell extracts and the corresponding medium related to the anti‐proliferation effect of PEFF were identified, which were probably involved in pyruvate metabolism and glycine, serine and threonine metabolism. For the cellular uptake compounds in PEFF, six metabolites derived from two prototype compounds were also tentatively identified by UHPLC‐Q‐Orbitrap high‐resolution MS. Network pharmacology analysis demonstrated that the anti‐proliferation mechanism of PEFF was also probably related to the target genes, including, Aurora‐A, glutathione S‐transferase Mu 1 (GSTM1), glutathione S‐transferase P 1 (GSTP1), progesterone receptor and heme oxygenase‐1 (HO‐1), and further associated with the proteoglycans and PI3K/Akt signaling pathway. Cell metabolomics and network pharmacology analysis provided a holistic method to investigate the anti‐proliferation mechanisms of PEFF. However, further studies were still needed to validate the potential target genes, pathways and active compounds in PEFF.
Enantioselective LC–ESI–MS/MS method for quantitation of (−)‐lumefantrine and (+)‐lumefantrine in mice plasma and application to a pharmacokinetic study
Authors: Kiran Vinay , Balaji Narayanan , Gabani Bhavesh Babulal , Bajantri Manjuanth , Chandran Rajesh , Dixit Abhishek , Srinivas Nuggehally R. , Mullangi Ramesh
Published: May 2020

We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)‐LFN and (+)‐LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid‐phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA‐3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive‐ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra‐ and inter‐day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)‐LFN and (+)‐LFN, respectively. Both (−)‐LFN and (+)‐LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac‐LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.
Adherence with blood pressure monitoring wearable device among the elderly with hypertension: The case of rural China
Authors: Zhang Yuting , Fang Yuan , Xu Yi , Xiong Peng , Zhang Jingyi , Yang Jinru , Ran Li , Tan Xiaodong
Published: May 2020

Introduction

Wearable blood pressure (BP) monitor devices are increasingly adopted owing to the promotion of hypertension management program. However, little is known about the adherence and its associated factors in older adults (OAs) with hypertension.

Methods

The aim of this study was to determine factors associated with adherence to wearable BP monitor. In total, 212 OAs with hypertension in a remote rural area in China were asked to wear a BP monitor over 1‐month period. The following information on associated factors for adherence was collected, including demographic characteristics, cardiovascular health measurements, technology fluency, the Compliance of Hypertensive Patients' Scale, and the Health‐related Quality of Life Survey. As a result, the mean age of the 212 hypertension participants was 71.32 years (SD = 6.81).

Results

During the 30‐day survey, 50.94% of the participants with daily recoded BP wristband data were assigned as “BP device users.” The binary logistic regression model revealed that lower lifestyle compliance, lower medication compliance and higher total hypertension compliance were significant predictors for adherence. However, there were no differences concerning cardiovascular health factors, technology fluency, and health‐related quality of life between device users and nonusers.

Conclusion

Individuals reporting a higher level of total compliance in hypertension management were more likely to wear a BP monitor device among OAs with hypertension. In addition, further research is needed to determine how wearable mHealth technology can be used to develop better hypertension self‐management education programs for this population.
Are working memory and glutamate concentrations involved in early‐life stress and severity of psychosis?
Authors: Corcoran Mark , Hawkins Emma L. , O'Hora Denis , Whalley Heather C. , Hall Jeremy , Lawrie Stephen M. , Dauvermann Maria R.
Published: May 2020

Objective

Occurrences of early‐life stress (ELS) are associated with the severity of psychotic symptoms and working memory (WM) deficits in patients with psychosis (PSY). This study investigated potential mediation roles of WM behavioral performance and glutamate concentrations in prefrontal brain regions on the association between ELS and psychotic symptom severity in PSY.

Method

Forty‐seven patients with PSY (established schizophrenia, n = 30; bipolar disorder, n = 17) completed measures of psychotic symptom severity. In addition, data on ELS and WM performance were collected in both patients with PSY and healthy controls (HC; n = 41). Resting‐state glutamate concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) were also assessed with proton magnetic resonance spectroscopy for both PSY and HC groups. t tests, analyses of variance, and regression analyses were utilized.

Results

Participants with PSY reported significantly more ELS occurrences and showed poorer WM performance than HC. Furthermore, individuals with PSY displayed lower glutamate concentrations in the left DLPFC than HC. Neither ELS nor WM performance were predictive of severity of psychotic symptoms in participants with PSY. However, we found a significant negative correlation between glutamate concentrations in the left DLPFC and ELS occurrence in HC only.

Conclusion

In individuals with PSY, the current study found no evidence that the association between ELS and psychotic symptoms is mediated by WM performance or prefrontal glutamate concentrations. In HC, the association between ELS experience and glutamate concentrations may indicate a neurometabolite effect of ELS that is independent of an illness effect in psychosis.
The interplay between gamification and network structure in social learning environments: A case study
Authors: Sousa‐Vieira María E. , López‐Ardao Jose C. , Fernández‐Veiga Manuel , Ferreira‐Pires Orlando
Published: May 2020

Social learning environments (SLEs) are software suites that enable the application of both traditional and innovative teaching methodologies, blending activities tailored to the specific goals of the teaching style. In particular, SLEs have been used to introduce, on a medium and large scale, gamification strategies as a complement to traditional learning procedures. In this context, the existence of gamified activities can probably change the type and strength of the social relationships encouraged by the SLE among students. In this case study, we examine an SLE endowed with gamification capabilities and discuss the interplay between the designed gamified tasks and the resulting network of communications among the agents. Our findings reveal that the network structure reflects the interactions within the class in a nontrivial way and conversely that the network structure can be used to anticipate or predict the evolution of the student groups throughout the course. The results of this study support the claim that when the activities are designed around well‐conceived gamification and reward mechanisms, they quite easily capture the interest of the participants, whose engagement does not diminish with the progress of the academic term.
Computational thinking in programming with Scratch in primary schools: A systematic review
Authors: Fagerlund Janne , Häkkinen Päivi , Vesisenaho Mikko , Viiri Jouni
Published: May 2020

Computer programming is being introduced in educational curricula, even at the primary school level. One goal of this implementation is to teach computational thinking (CT), which is potentially applicable in various computational problem‐solving situations. However, the educational objective of CT in primary schools is somewhat unclear: curricula in various countries define learning objectives for topics, such as computer science, computing, programming or digital literacy but not for CT specifically. Additionally, there has been confusion in concretely and comprehensively defining and operationalising what to teach, learn and assess about CT in primary education even with popular programming akin to Scratch. In response to the growing demands of CT, by conducting a literature review on studies utilising Scratch in K–9, this study investigates what kind of CT has been assessed in Scratch at the primary education level. As a theoretical background for the review, we define a tangible educational objective for introducing CT comprehensively in primary education and concretise the fundamental skills and areas of understanding involved in CT as its “core educational principles”. The results of the review summarise Scratch programming contents that students can manipulate and activities in which they can engage that foster CT. Moreover, methods for formatively assessing CT via students' Scratch projects and programming processes are explored. The results underpin that the summarised “CT‐fostering” programming contents and activities in Scratch are vast and multidimensional. The next steps for this study are to refine pedagogically meaningful ways to assess CT in students' Scratch projects and programming processes.
Structural Characterization and α‐Glucosidase Inhibitory and Antioxidant Activities of Fucoidans Extracted from Saccharina japonica
Authors: Ke Songze , Wei Bin , Qiu Wenhui , Zhou Taoshun , Wang Sijia , Chen Jun , Chen Jianwei , Zhang Huawei , Jin Weihua , Wang Hong
Published: May 2020

Two sulfated fucoidan fractions (Lj3 and Lj5) were extracted from Saccharina japonica and then subjected to acid hydrolysis to obtain Lj3h and Lj5h. Lj3h and Lj5h were characterized using IR, methylation analysis, and mass spectrometry. It was found that Lj3h and Lj5h were homogeneous low molecular weight fucoidans. Specifically, Lj3h was composed of the main chain of 1,3‐linked α‐L‐fucopyranose residues with sulfate at C‐2 and/or C‐4 and three different monosaccharides (galactose, glucose, mannose) branched at C‐2 and/or C‐4 of fucose residue. Lj5h contained backbones of alternating galactopyranose residues and fucopyranose residues attached via a 1→3 linkage (galactofucan) and 1→6 linked galactan. The sulfation pattern was mainly located at C2/C4 fucose or galactose residues and more branches occupied at C‐4 of fucose residue and C‐2, C‐3 or/and C‐6 of galactose residue. In vitro assay indicated that, among the four fucoidans tested, only Lj5 showed potent α‐glucosidase inhibitory activity with IC50 of 153.27±22.89 μg/mL, and the two parent fucoidans, Lj3 and Lj5, showed better antioxidant activity than their derivatives. These findings highlight the structure and bioactivity diversity of Saccharina japonica‐derived fucoidans.
Penicimutanin C, a New Alkaloidal Compound, Isolated from a Neomycin‐Resistant Mutant 3‐f‐31of Penicillium purpurogenum G59
Authors: Wang Nan , Dong Yuan , Yang Yu , Xu Rui , Li Chang‐Wei , Cui Cheng‐Bin
Published: May 2020

Penicimutanin C, a new alkaloidal compound, was isolated from the neomycin‐resistant mutant strain 3‐f‐31 of the marine‐derived fungus, Penicillium purpurogenum G59, together with four known compounds. The structure of penicimutanin C, including the absolute configuration, was determined by spectroscopic and chemical methods. The absolute configuration of penicimutanin A was also re‐confirmed by Marfey's and chiral HPLC analyses of the hydrolyzed products. Penicimutanins C and A inhibited the proliferation of five human cancer cell lines to some extent. Penicimutanin C is the third dimer of diketopiperazine and penicimutanolone, which are only produced by mutants of P. purpurogenum G59 isolated to date, and it showed cytotoxic activity against human cancer cell lines. The neomycin‐resistant screening strategy has been previously successfully used to discover new compounds by activating silent metabolites in fungi, and the present results provide an additional example of the effectiveness of this method.
Impact of aortic angle on transcatheter aortic valve implantation outcome with Evolut‐R, Portico, and Acurate‐NEO
Authors: Gorla Riccardo , De Marco Federico , Garatti Andrea , Bianchi Giovanni , Popolo Rubbio Antonio , Acerbi Elena , Casenghi Matteo , Spagnolo Pietro , Brambilla Nedy , Testa Luca , Agnifili Mauro L. , Tusa Maurizio , Bedogni Francesco
Published: May 2020

Objectives

To investigate paravalvular leak (PVL) and devices success rates according to aortic angle (AA) in patients undergoing transcatheter aortic valve implantation (TAVI) with three new‐generation self‐expanding devices.

Background

The impact of aortic angle (AA) on TAVI device success and PVL rates is controversial.

Methods

This retrospective study included 392 patients submitted to TAVI for severe aortic stenosis with Portico, Evolut‐R and Acurate‐NEO, and available AA measurements at computed tomography (CT) angiography. AA was calculated from the implantation projection and was defined as the angle between the plane of aortic annulus and an ideal horizontal plane. Aorta was defined horizontal if AA>57° (75th percentile).

Results

In the horizontal group, the rates of moderate/severe PVL was higher in the Evolut‐R group (20.8%), which was also characterized by a lower implant compared to that of Acurate‐NEO, whereas device success was comparable among the three devices. AA was a significant predictor of moderate/severe PVLs (AUC 0.72, p = .002) only in the Evolut‐R population.

On multivariate analysis, calcium volume 850HU, bicuspid aortic valve, and implantation depth at the level of left coronary cusp were independent predictors of moderate/severe PVL. On univariate analysis in the horizontal aorta population, implantation depth was confirmed among the most significant predictors of moderate/severe PVL.

Conclusions

Despite comparable device success rates, horizontal aorta represented a technical challenge only in the Evolut‐R subgroup, which showed higher rates of moderate/severe PVL than Portico and Acurate‐NEO, and was associated with a low implant.
Seborrhoeic dermatitis and sebopsoriasis developing in patients on dupilumab: Two case reports
Authors: Al‐Janabi Ali , Marsland Alexander M.
Published: May 2020

Cutaneous adverse events to dupilumab can be varied; this necessitates keeping a broad differential diagnosis to identify seemingly paradoxical reactions. It may be possible to treat the adverse event concurrently without stopping dupilumab.
An Exploratory Investigation of Spinel LiMn1.5Ni0.5O4 as Cathode Material for Potassium‐Ion Battery
Authors: Bhatia Ankush , Pereira‐Ramos Jean‐Pierre , Emery Nicolas , Laïk Barbara , Smith Ronald I. , Baddour‐Hadjean Rita
Published: May 2020

The emerging interest in K‐ion batteries (KIBs) increases the importance of cathodes with high working voltage in this system. The LiMn1.5Ni0.5O4 spinel is a promising alternative for the next generation of high voltage Li‐ion positive electrodes and its delithiated structure could be of interest for KIBs. In this work, Li ions are extracted from LiMn1.5Ni0.5O4 by a first electrochemical oxidation. The electroformed λ‐Mn0.75Ni0.25O2 spinel phase is shown to convert into layered K0.5Mn0.75Ni0.25O2 (KMNO) at 20 °C along the first discharge in K cell. Then, 0.3 K+/KMNO (90 mAh g−1) are reversibly exchanged during the subsequent cycle. Superior electrochemical performance are reported for KMNO as compared to K0.5MnO2 (KMO): a higher working voltage vs. K+/K (3.10 V vs. 2.79 V), enhanced rate capability and better cycling stability (70 mAh g−1 after 60 cycles at C/20 for KMNO vs. 40 mAh g−1 for KMO). The contribution of the Ni redox system is revealed as a reason for these improved performances.
Numerical simulation of the mass transfer process of CO2 absorption by different solutions in a microchannel
Authors: Dong Rui , Chu Di , Sun Qiqi , Jin Zunlong
Published: May 2020

The flow and mass transfer characteristics of CO2 absorption in different liquid phases in a microchannel were studied by numerical simulation. The mixture gas phase contained 5 vol% CO2 and 95 vol% N2, and the different liquid phases were water, ethanol solution, 0.2 M monoethanolamine solution, and 0.2 M NaOH solution, respectively. Based on the permeation theory, the distribution of velocity and concentration in the slug flow was obtained by local simulation of flow and mass transfer coupling and was described in depth. The influence of contact time and bubble velocity on the mass transfer of the whole bubble was highlighted. The volumetric mass transfer coefficient on the bubble cap and liquid film, CO2 absorption rate, and enhancement factor were calculated and analyzed. The results showed that the volumetric mass transfer coefficients of chemical absorption were ~3 to 10 times that of physical absorption and the CO2 was absorbed more completely in chemical absorption. The new empirical correlations for predicting the mass transfer coefficient of the liquid phase were proposed respectively in physical absorption and chemical absorption, which were compared with the empirical formulas in the literature. The volumetric mass transfer coefficients obtained by predictive correlations are in good agreement with those obtained by simulation in this paper. This work made a basic prediction for CO2 absorption in microchannel and provides a foundation for later experimental research.
Frustrated Lewis Pairs: Discovery and Overviews in Catalysis
Authors: Li Nan , Zhang Wen‐Xiong
Published: May 2020

Frustrated Lewis Pairs (FLPs) are derived from simple combinations of Lewis acids (electron acceptors) and Lewis bases (electron donors), in which steric demands prevent from forming classical Lewis acid‐base adducts. Since 2006, FLP chemistry has emerged as a novel strategy for the design and application of main‐group chemistry and development of new metal‐free catalytic processes. This strategy has been applied to stoichiometric reactivity and then extended to catalysis. In this review, we briefly summarize the representative discoveries and developments of FLP chemistry in the field of catalysis, including hydrogenation, hydrosilylation, reduction of CO2, transformations of alkynes to organic derivatives, C—H bond borylation and polymerization.
Structural Consequences of the 1,2,3‐Triazole as an Amide Bioisostere in Analogues of the Cystic Fibrosis Drugs VX‐809 and VX‐770
Authors: Doiron Jake E. , Le Christina A. , Bacsa John , Breton Gary W. , Martin Kenneth L. , Aller Stephen G. , Turlington Mark
Published: May 2020

Although the 1,2,3‐triazole is a commonly used amide bioisostere in medicinal chemistry, the structural implications of this replacement have not been fully studied. Employing X‐ray crystallography and computational studies, we report the spatial and electronic consequences of replacing an amide with the triazole in analogues of cystic fibrosis drugs in the VX‐770 and VX‐809 series. Crystallographic analyses quantify subtle differences in the relative positions and conformational preferences of the R1 and R2 substituents attached to the amide and triazole bioisosteres. Computational studies derived from the X‐ray data highlight the improved hydrogen bonding donor and acceptor capabilities of the amide in comparison to the triazole. This analysis of the spatial and electronic differences between the amide and 1,2,3‐triazole will inform medicinal chemists as they consider using the triazole as an amide bioisostere.
Synthesis of Phospho‐Polypeptides via Phosphate‐Containing N‐Carboxyanhydride: Application in Enzyme‐Induced Self‐Assembly, and Calcium Carbonate Mineralization
Authors: Mondal Basudeb , Das Soumen , Panda Sidharth , Dutta Tahiti , Gupta Sayam Sen
Published: May 2020

An easy synthetic strategy was developed to synthesize the phosphate‐functionalized amino acid N‐carboxyanhydride (NCA), using simple primary amine initiators to obtain homo and block phospho‐polypeptides with controlled molecular weight and molecular weight distribution. The methodology was extended to the synthesis of the end‐functionalized homo polypeptides (15 to 50 repeat unit) and block co‐polypeptides with PEG (0.7 K, 2 K, and 5 K) and glycopolypeptide (15‐unit mannose glycopolypeptide) as one of the blocks. The deprotected fully water‐soluble anionic phosphate‐based polypeptides showed pH‐dependent helical conformation with a helical content of 20 %, which further changed to β‐sheets upon addition of the enzyme alkaline phosphatase (ALP) due to dephosphorylation. The block co‐polypeptide containing PEG as one of the blocks led to its self‐assembly into colloidal structures, such as vesicles with a hydrodynamic diameter of ∼250 nm, due to the formation of amphiphilic block co‐polymer upon dephosphorylation. The nature of the colloidal structures formed can be temporally controlled by the extent of dephosphorylation. Finally, the phospho‐polypeptides serve as a template for the mineralization of calcium carbonate with varying polymorphs and morphologies.
The Lymphoid Tissue Pharmacokinetics of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide in HIV‐Infected Persons
Authors: Fletcher Courtney V. , Podany Anthony T. , Thorkelson Ann , Winchester Lee C. , Mykris Timothy , Anderson Jodi , Jorstad Siri , Baker Jason V. , Schacker Timothy W.
Published: May 2020

The secondary lymphoid tissues (LT), lymph nodes (LN) and gut‐associated lymphoid tissue are the primary sites of HIV replication and where the latent pool of virus is maintained. We compared the pharmacokinetics of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in LT of 13 HIV‐infected persons receiving a TDF‐containing antiretroviral regimen who subsequently switched to a TAF‐containing regimen. Study participants were on stable antiretroviral therapy for ≥12 months with plasma HIV‐RNA < 48 copies/mL for 6 months before enrollment and entry CD4 cell counts > 300 cells/µL. Intracellular concentrations of tenofovir‐diphosphate (TFV‐DP) and emtricitabine‐triphosphate (FTC‐TP) were quantified in PBMCs and in mononuclear cells obtained from LN, ileum and rectal tissues. With TAF, the TFV‐DP concentrations in PBMCs and LN were 7.3‐fold and 6.4‐fold higher (ratios of geometric means of TAF to TDF), respectively, compared with TDF; ileal and rectal concentrations, however, were lower with geometric mean ratios of 0.14 and 0.18, respectively. A statistically significant relationship was observed between PBMC and LN concentrations of TFV‐DP. During TDF‐containing therapy, the expected effect of cobicistat to increase TFV plasma concentrations was observed, as were higher TFV‐DP concentrations in PBMCs and mononuclear cells from LN, ileum and rectal tissues. The higher TFV‐DP concentrations achieved with TAF in the LN provides the first human correlate of the observation in animals that TAF produced higher tenofovir LN concentrations. The ability to increase LN concentrations allows investigations of whether antiretroviral regimens with improved LN pharmacokinetics elicit a more complete virologic response in that compartment.
Proof of Concept: First Pediatric [14C]microtracer Study to Create Metabolite Profiles of Midazolam
Authors: van Groen Bianca D. , van Duijn Esther , de Vries Arjan , Mooij Miriam G. , Tibboel Dick , Vaes Wouter H. J. , de Wildt Saskia N.
Published: May 2020

Growth and development affect drug‐metabolizing enzyme activity thus could alter the metabolic profile of a drug. Traditional studies to create metabolite profiles and study the routes of excretion are unethical in children due to the high radioactive burden. To overcome this challenge, we aimed to show the feasibility of an absorption, distribution, metabolism, and excretion (ADME) study using a [14C]midazolam microtracer as proof of concept in children. Twelve stable, critically ill children received an oral [14C]midazolam microtracer (20 ng/kg; 60 Bq/kg) while receiving intravenous therapeutic midazolam. Blood was sampled up to 24 hours after dosing. A time‐averaged plasma pool per patient was prepared reflecting the mean area under the curve plasma level, and subsequently one pool for each age group (0–1 month, 1–6 months, 0.5–2 years, and 2–6 years). For each pool [14C]levels were quantified by accelerator mass spectrometry, and metabolites identified by high resolution mass spectrometry. Urine and feces (n = 4) were collected up to 72 hours. The approach resulted in sufficient sensitivity to quantify individual metabolites in chromatograms. [14C]1‐OH‐midazolam‐glucuronide was most abundant in all but one age group, followed by unchanged [14C]midazolam and [14C]1‐OH‐midazolam. The small proportion of unspecified metabolites most probably includes [14C]midazolam‐glucuronide and [14C]4‐OH‐midazolam. Excretion was mainly in urine; the total recovery in urine and feces was 77–94%. This first pediatric pilot study makes clear that using a [14C]midazolam microtracer is feasible and safe to generate metabolite profiles and study recovery in children. This approach is promising for first‐in‐child studies to delineate age‐related variation in drug metabolite profiles.
Searching for new long‐term urinary metabolites of metenolone and drostanolone using gas chromatography–mass spectrometry with a focus on non‐hydrolysed sulfates
Authors: Albertsdóttir Aðalheiður Dóra , Van Gansbeke Wim , Coppieters Gilles , Balgimbekova Kyzylkul , Van Eenoo Peter , Polet Michael
Published: May 2020

Sulfated metabolites have been shown to have potential as long‐term markers of anabolic–androgenic steroid (AAS) abuse. In 2019, the compatibility of gas chromatography–mass spectrometry (GC–MS) with non‐hydrolysed sulfated steroids was demonstrated, and this approach allowed the incorporation of these compounds in a broad GC–MS initial testing procedure at a later stage. However, research is needed to identify which are beneficial.

In this study, a search for new long‐term metabolites of two popular AAS, metenolone and drostanolone, was undertaken through two excretion studies each. The excretion samples were analysed using GC–chemical ionization–triple quadrupole MS (GC–CI–MS/MS) after the application of three separate sample preparation methodologies (i.e. hydrolysis with Escherichia coli–derived β‐glucuronidase, Helix pomatia–derived β‐glucuronidase/arylsulfatase and non‐hydrolysed sulfated steroids).

For metenolone, a non‐hydrolysed sulfated metabolite, 1β‐methyl‐5α‐androstan‐17‐one‐3ζ‐sulfate, was documented for the first time to provide the longest detection time of up to 17 days. This metabolite increased the detection time by nearly a factor of 2 in comparison with the currently monitored markers for metenolone in a routine doping control initial testing procedure. In the second excretion study, it prolonged the detection window by 25%.

In the case of drostanolone, the non‐hydrolysed sulfated metabolite with the longest detection time was the sulfated analogue of the main drostanolone metabolite (3α‐hydroxy‐2α‐methyl‐5α‐androstan‐17‐one) with a detection time of up to 24 days. However, the currently monitored main drostanolone metabolite in routine doping control, after hydrolysis of the glucuronide with E.coli, remained superior in detection time (i.e. up to 29 days).
IJED support for eating disorders research in the time of COVID‐19
Authors: Weissman Ruth S. , Klump Kelly L. , Wade Tracey , Thomas Jennifer J. , Frank Guido , Waller Glenn
Published: May 2020

This editorial reports on an anonymous survey question posed to eating disorders researchers about changes the International Journal of Eating Disorders (IJED) should implement to support the eating disorders research community affected by COVID‐19. The editorial accompanies an IJED article that details responses to the larger survey focusing more broadly on COVID‐19‐related research disruptions. Survey invitations were sent to editorial board members of eating disorders journals, members of eating disorder scientific organizations (e.g., Eating Disorders Research Society), and individuals who provided at least three IJED reviews in the prior 12 months. We reviewed the responses of 187 participants and identified three categories of changes that: (a) had already been implemented by the journal, (b) cannot be implemented because they fall outside the scope of IJED, or (c) will be implemented in coming weeks or months. The latter category includes publishing topical COVID‐19 papers, making some COVID‐19‐related content available open access, revising statistical guidelines, and issuing author guidance on reporting protocol changes caused by COVID‐19‐related disruptions. IJED recognizes the disruptive impacts that COVID‐19 has on all activities in our field, including clinical work, teaching, and advocacy, and is committed to supporting authors during this difficult time while striving to publish high‐quality research.
Authentication method using the variation of power generation time in energy harvester and its evaluation
Authors: Nozaki Yusuke , Yoshikawa Masaya
Published: May 2020

Although internet of things technology is widely used in various fields, internet of things has several issues such as energy efficiency and authentication for security. The energy harvesting technology, which harvests various energy (eg, sunlight, vibration, electromagnetic wave, and so on), and converts them to electric power, has attracted attention for the solving method for the first problem. Moreover, the physical unclonable function, which uses variances of semiconductor manufacturing variations for authentication, has attracted attention for the solving method for the other problem. This study proposes a new authentication method for energy harvester. The proposed method utilizes the difference in power generation time due to manufacturing variations for the device authentication. In addition, the proposed method can be realized in very low cost because it does not require a dedicated physical unclonable function circuit. Several experiments using an actual energy harvester verify the validity of the proposed method.
Arctic and boreal paleofire records reveal drivers of fire activity and departures from Holocene variability
Authors: Hoecker Tyler J. , Higuera Philip E. , Kelly Ryan , Hu Feng Sheng
Published: May 2020

Boreal forest and tundra biomes are key components of the Earth system because the mobilization of large carbon stocks and changes in energy balance could act as positive feedbacks to ongoing climate change. In Alaska, wildfire is a primary driver of ecosystem structure and function, and a key mechanism coupling high‐latitude ecosystems to global climate. Paleoecological records reveal sensitivity of fire regimes to climatic and vegetation change over centennial–millennial time scales, highlighting increased burning concurrent with warming or elevated landscape flammability. To quantify spatiotemporal patterns in fire‐regime variability, we synthesized 27 published sediment‐charcoal records from four Alaskan ecoregions, and compared patterns to paleoclimate and paleovegetation records. Biomass burning and fire frequency increased significantly in boreal forest ecoregions with the expansion of black spruce, ca. 6,000–4,000 years before present (yr BP). Biomass burning also increased during warm periods, particularly in the Yukon Flats ecoregion from ca. 1,000 to 500 yr BP. Increases in biomass burning concurrent with constant fire return intervals suggest increases in average fire severity (i.e., more biomass burning per fire) during warm periods. Results also indicate increases in biomass burning over the last century across much of Alaska that exceed Holocene maxima, providing important context for ongoing change. Our analysis documents the sensitivity of fire activity to broad‐scale environmental change, including climate warming and biome‐scale shifts in vegetation. The lack of widespread, prolonged fire synchrony suggests regional heterogeneity limited simultaneous fire‐regime change across our study areas during the Holocene. This finding implies broad‐scale resilience of the boreal forest to extensive fire activity, but does not preclude novel responses to 21st‐century changes. If projected increases in fire activity over the 21st century are realized, they would be unprecedented in the context of the last 8,000 yr or more.
Electrochemical Synthesis of 2,5‐Disubstituted 1,3,4‐Oxadiazoles from α‐Keto Acids and Acylhydrazines Under Mild Conditions
Authors: Lu Fangling , Gong Fengping , Li Liangsen , Zhang Kan , Li Zhen , Zhang Xinwei , Yin Ying , Wang Ying , Gao Ziwei , Zhang Heng , Lei Aiwen
Published: May 2020

1,3,4‐Oxadiazoles are a kind of useful heterocycles which can be frequently found in materials and bioactive molecules. In this study, intermolecular electrochemical cyclization between α‐keto acids and acylhydrazines has been developed for the synthesis of 2,5‐disubstituted 1,3,4‐oxadiazoles with the yield up to 91 %. This transformation can be run under mild reaction conditions in the absence of external oxidant, base and transition metal catalyst. Both symmetrical and unsymmetrical 2,5‐disubstituted 1,3,4‐oxadiazoles could be prepared according to the careful choice of the substrate combination. Gram scale synthesis also illustrates the potential application of this protocol in large preparation.
Substrate‐Controlled [5+1] Annulation of 5‐Amino‐1H‐phenylpyrazoles with Alkenes: Divergent Synthesis of Multisubstituted 4,5‐Dihydropyrazolo[1,5‐a]quinazolines
Authors: Jiang Xunyuan , Wei Xiaoyi , Lin Fei , Zhang Zhixiang , Yao Guangkai , Yang Shuai , Zhao Weijing , Zhao Chen , Xu Hanhong
Published: May 2020

A new and efficient [5+1] annulation reaction for the first synthesis of 5,5‐disubstituted 4,5‐dihydropyrazolo[1,5‐a]quinazolines is described. This transition‐metal‐free tandem cyclization was performed with 5‐amino‐1H‐phenylpyrazole and readily available electron‐deficient olefinic ester. The reaction proceeds via an aza‐Michael addition/Truce‐Smiles rearrangement/SNAr cyclization pathway, which was verified by DFT calculations. The participation of Truce‐Smiles rearrangement is substrate dependent and could prompt the process of cascade reactions. It is also the first report of alkenes acting as one‐carbon synthons for [5+1] hetero‐annulations.
Determination of acid dissociation constants of flavin analogues by capillary zone electrophoresis
Authors: Tanikami Yuki , Tagami Takuma , Sakamoto Mayu , Arakawa Yukihiro , Mizuguchi Hitoshi , Imada Yasushi , Takayanagi Toshio
Published: May 2020

Acid dissociation constants (pKa) of nine kinds of flavin analogues as molecular catalyst candidates were determined by CZE. Although some of the analogues are instable and degradable under the light exposure or in alkaline aqueous solutions, the effective electrophoretic mobility of the flavin analogue of interest has been measured with the residual substance. The pKa values of the flavin analogues were analyzed through the changes in the effective electrophoretic mobility with varying pH of the separation buffer. One or two steps pKa values were determined by the analysis. One of the degraded species from the flavin analogues, lumichrome, was also detected in the CZE analysis, and its pKa values were also determined. While coexisting impurities generated over the storage conditions were found in some analogues, the pKa values of the target analogues were successfully determined with the help of the CZE separations. A pressure‐assisted CZE was utilized for the determination or the estimation of the pKa values of such analogues as possessing carboxylic acid moiety.
Composition Engineering–Triggered Bifunctionality of Free‐Standing Coral‐Like 1T‐MoS2 for Highly Efficient Overall Water Splitting
Authors: Ding Xiaoqing , Li Xitao , Lv Xinding , Zheng Yan-Zhen , Wu Qibing , Ding Haiyang , Wu Jiaojiao , Li Ran , Tao Xia
Published: May 2020

Metallic‐phase 1T‐MoS2 with its good electronic conductivity and abundant active sites attracts more attention for energy conversion and storage. However, developing a high‐performance bifunctional 1T‐MoS2 for overall water splitting still is a challenge. Herein, a composition (Fe and Mn)‐engineering approach that is capable of triggering efficient hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) bifunctionality into coral‐like 1T‐MoS2 nanorods for overall water splitting is reported. The results demonstrate that composition engineering induces rich crystal defects and electronic structure variation of the freestanding coral‐like 1T‐MoS2, leading to outstanding HER (overpotential of 34.1 mV at 10 mA cm−2) and OER (overpotential of 220.0 mV at 50 mA cm−2) activity and excellent stability in alkaline media. The facile composition‐engineering activation strategy is also feasible to endow the other transition metal dichalcogenides with dual/multiple functionality.
Accuracy and spatial properties of distributed magnetic source imaging techniques in the investigation of focal epilepsy patients
Authors: Pellegrino Giovanni , Hedrich Tanguy , Porras‐Bettancourt Manuel , Lina Jean‐Marc , Aydin Ümit , Hall Jeffery , Grova Christophe , Kobayashi Eliane
Published: May 2020

Source localization of interictal epileptiform discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. We aimed to compare the performance of four different distributed magnetic source imaging (dMSI) approaches: Minimum norm estimate (MNE), dynamic statistical parametric mapping (dSPM), standardized low‐resolution electromagnetic tomography (sLORETA), and coherent maximum entropy on the mean (cMEM). We also evaluated whether a simple average of maps obtained from multiple inverse solutions (Ave) can improve localization accuracy. We analyzed dMSI of 206 IEDs derived from magnetoencephalography recordings in 28 focal epilepsy patients who had a well‐defined focus determined through intracranial EEG (iEEG), epileptogenic MRI lesions or surgical resection. dMSI accuracy and spatial properties were quantitatively estimated as: (a) distance from the epilepsy focus, (b) reproducibility, (c) spatial dispersion (SD), (d) map extension, and (e) effect of thresholding on map properties. Clinical performance was excellent for all methods (median distance from the focus MNE = 2.4 mm; sLORETA = 3.5 mm; cMEM = 3.5 mm; dSPM = 6.8 mm, Ave = 0 mm). Ave showed the lowest distance between the map maximum and epilepsy focus (Dmin lower than cMEM, MNE, and dSPM, p = .021, p = .008, p < .001, respectively). cMEM showed the best spatial features, with lowest SD outside the focus (SD lower than all other methods, p < .001 consistently) and high contrast between the generator and surrounding regions. The average map Ave provided the best localization accuracy, whereas cMEM exhibited the lowest amount of spurious distant activity. dMSI techniques have the potential to significantly improve identification of iEEG targets and to guide surgical planning, especially when multiple methods are combined.
A response‐locking protocol to boost sensitivity for fMRI‐based neurochronometry
Authors: Viswanathan Shivakumar , Abdollahi Rouhollah O. , Wang Bin A. , Grefkes Christian , Fink Gereon R. , Daun Silvia
Published: May 2020

The timeline of brain‐wide neural activity relative to a behavioral event is crucial when decoding the neural implementation of a cognitive process. Yet, fMRI assesses neural processes indirectly via delayed and regionally variable hemodynamics. This method‐inherent temporal distortion impacts the interpretation of behavior‐linked neural timing. Here we describe a novel behavioral protocol that aims at disentangling the BOLD dynamics of the pre‐ and post‐response periods in response time tasks. We tested this response‐locking protocol in a perceptual decision‐making (random dot) task. Increasing perceptual difficulty produced expected activity increases over a broad network involving the lateral/medial prefrontal cortex and the anterior insula. However, response‐locking revealed a previously unreported functional dissociation within this network. preSMA and anterior premotor cortex (prePMV) showed post‐response activity modulations while anterior insula and anterior cingulate cortex did not. Furthermore, post‐response BOLD activity at preSMA showed a modulation in timing but not amplitude while this pattern was reversed at prePMV. These timeline dissociations with response‐locking thus revealed three functionally distinct sub‐networks in what was seemingly one shared distributed network modulated by perceptual difficulty. These findings suggest that our novel response‐locked protocol could boost the timing‐related sensitivity of fMRI.
Effect of gauze placement soaked with adrenaline at suprabullar recess on hemostasis during endoscopic sinus surgery: A randomized controlled trial
Authors: Omura Kazuhiro , Hosokawa Yu , Nomura Kazuhiro , Aoki Satoshi , Tochigi Kosuke , Miyashita Keisuke , Tanaka Yasuhiro , Otori Nobuyoshi , Kojima Hiromi
Published: May 2020

Background

Topical application of vasoconstrictors is necessary for endoscopic sinus surgery (ESS) for a bloodless surgical view and reduced intraoperative bleeding. We aimed to verify the effectiveness of gauze placement soaked with adrenaline at suprabullar recess, where the anterior ethmoidal artery exists, on hemostasis during ESS.

Methods

A randomized, double‐blinded trial was carried out for 26 patients receiving ESS. At the beginning of the surgery, gauze soaked with 2% lidocaine with or without 1:10 000 adrenaline was placed at the suprabullar recess for 8 minutes. Estimated blood loss, surgical field score, and operation time were compared between the two groups.

Results

Estimated blood loss and surgical field score were significantly smaller in the adrenaline group than in the no adrenaline group. Operation time was not significantly different between the two groups.

Conclusion

Gauze placement soaked with adrenaline at suprabullar recess reduces estimated blood loss and clears the surgical field during ESS.
Effect of COVID‐19 in selecting otolaryngology as a specialty
Authors: Go Beatrice , Rajasekaran Karthik
Published: May 2020

Coronavirus disease 2019 has undoubtedly impacted the health care system while causing lasting and profound implications for medical education. Senior medical students seeking exposure to the field of otolaryngology now find themselves in the challenging position of obtaining the experiences to make an informed decision on a future specialty. Virtual electives using comprehensive online material, discussion, and videos as well as the advent of telemedicine may be potential solutions to increase exposure to otolaryngology. While incorporating opportunities for authentic patient interactions is still a challenge, it is crucial that the academic otolaryngology community prioritize seeking solutions for interested medical students.
Differential propagation of ripples along the proximodistal and septotemporal axes of dorsal CA1 of rats
Authors: Kumar Mekhala , Deshmukh Sachin S.
Published: May 2020

The functional connectivity of the hippocampus with its primary cortical input, the entorhinal cortex, is organized topographically. In area CA1 of the hippocampus, this leads to different functional gradients along the proximodistal and septotemporal axes of spatial/sensory responsivity and spatial resolution respectively. CA1 ripples, a network phenomenon, allow us to test whether the hippocampal neural network shows corresponding gradients in functional connectivity along the two axes. We studied the occurrence and propagation of ripples across the entire proximodistal axis along with a comparable spatial range of the septotemporal axis of dorsal CA1. We observed that ripples could occur at any location, and their amplitudes were independent of the tetrode location along the proximodistal and septotemporal axes. When a ripple was detected on a particular tetrode (“reference tetrode”), however, the probability of cooccurrence of ripples and ripple amplitude observed on the other tetrodes decreased as a function of distance from the reference tetrode. This reduction was greater along the proximodistal axis than the septotemporal axis. Furthermore, we found that ripples propagate primarily along the proximodistal axis. Thus, over a spatial scale of ∼1.5 mm, the network is anisotropic along the two axes, complementing the topographically organized cortico‐hippocampal connections.
Evaluation and determination of subsurface drainage spacing in two steady and unsteady flow conditions with closure of the impermeable layer to the ground surface. case study: Markazi province, Iran*
Authors: Moshayedi Behzad , Najarchi Mohsen , Najafizadeh Mohammad Mahdi , Khaghani Shahab
Published: May 2020

In this paper unsteady methods which are a function of time and steady conditions that are independent of time are used to evaluate the subsurface drainage system established in the upstream lands of the Senejan plain located in the centre of Iran. In order to determine the drain spacing, the steady Hooghoudt model and the unsteady Glover–Dumm, modified Glover and van Schilfgaarde models in rainy periods of 2, 3, 4 and 5 days were used, and the distance between computational drains at two depths install drains (180 and 200 cm) was compared with the results of the subsurface drainage project. To compare the results, the mean absolute error (MAE) and standard error (σ) were used. The results showed that MAE and σ values in the 3‐, 4‐ and 5‐day rainfall in the Glover–Dumm model are 9.75 and 0.196% for the depth of 180 cm and 7.944 and 0.15% for the depth of 200 cm, respectively. The above coefficients obtained in the van Schilfgarde model were 8.098 and 0.162% and 6.685 and 0.134% for 2 days precipitation respectively. The results show that the steady method is not in good agreement with the values of the drain spacing. © 2020 John Wiley & Sons, Ltd.