bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of combined baseline and postprocedural troponin values on clinical outcome following the MitraClip procedure
Authors: Tabata Noriaki , Weber Marcel , Sugiura Atsushi , Ishii Masanobu , Öztürk Can , Tsujita Kenichi , Sinning Jan‐Malte , Werner Nikos , Nickenig Georg
Published: March 2020

Objectives

The purpose of this study was to investigate the impact of periprocedural troponin levels on clinical outcome following the MitraClip procedure.

Background

Cardiac troponin is known to be a predictive biomarker for various clinical outcomes; however, data about its predictive value in patients undergoing transcatheter mitral valve repair are limited.

Methods

Consecutive patients undergoing the MitraClip procedure were enrolled. Serum cardiac troponin I concentrations were measured before and after the procedure, and the maximal value recorded within 72 hr after the procedure was used for the postprocedural values. The clinical outcome was all‐cause mortality within a 1‐year follow‐up.

Results

Out of 354 patients, 29 patients (8.2%) were deceased within 1 year. Patients who died had significantly higher baseline (0.05 [0.01–0.08] vs. 0.01 [0.01–0.03] ng/ml; p < .001) and postprocedural troponin I values (0.51 [0.30–1.42] vs. 0.20 [0.33–0.55] ng/ml; p = .005). A Kaplan–Meier analysis showed that patients with higher baseline troponin I values had a significantly worse prognosis than those with lower values (log‐rank p < .001), and similarly, 1‐year mortality was significantly higher in patients with higher postprocedural troponin I than those with lower levels (log‐rank p = .021). Moreover, the highest mortality rate was observed in patients with both elevated baseline and postprocedural troponin I values (log‐rank p = .001), which was found to be an independent predictor of mortality by multivariable analyses.

Conclusions

The present study suggests that combined baseline and postprocedural troponin measurements are useful for risk stratification of 1‐year mortality following the MitraClip procedure.
Considerations for cardiac catheterization laboratory procedures during the COVID‐19 pandemic perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates
Authors: Szerlip Molly , Anwaruddin Saif , Aronow Herbert D. , Cohen Mauricio G. , Daniels Matthew J. , Dehghani Payam , Drachman Douglas E. , Elmariah Sammy , Feldman Dmitriy N. , Garcia Santiago , Giri Jay , Kaul Prashant , Kapur Navin K. , Kumbhani Dharam J. , Meraj Perwaiz M. , Morray Brian , Nayak Keshav R. , Parikh Sahil A. , Sakhuja Rahul , Schussler Jeffrey M. , Seto Arnold , Shah Binita , Swaminathan Rajesh V. , Zidar David A. , Naidu Srihari S.
Published: March 2020

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is highly infectious, carries significant morbidity and mortality, and has rapidly resulted in strained health care system and hospital resources. In addition to patient‐related care concerns in infected individuals, focus must also relate to diminishing community spread, protection of staff, case selection, and concentration of resources. The current document based on available data and consensus opinion addresses appropriate catheterization laboratory preparedness for treating these patients, including procedure‐room readiness to minimize external contamination, safe donning and doffing of personal protective equipment (PPE) to eliminate risk to staff, and staffing algorithms to minimize exposure and maximize team availability. Case selection and management of both emergent and urgent procedures are discussed in detail, including procedures that may be safely deferred or performed bedside.
In Situ Monitoring of Particle Formation with Spectroscopic and Analytical Techniques Under Solvothermal Conditions
Authors: Embrechts Heidemarie , Hartmann Martin , Peukert Wolfgang , Distaso Monica
Published: March 2020

The formation of multifunctional materials involves various simultaneous and closely entangled physicochemical processes including nucleation, growth, aggregation, and in some cases also growth by oriented aggregation. These elementary particle formation processes occur in broad size ranges from the molecular to micrometer level and time scales ranging from seconds to hours. This contribution demonstrates that the in situ monitoring of reaction mixtures and dispersions with several simultaneous analytical and spectroscopic techniques is an effective and widely applicable strategy to achieve an in‐depth understanding of the formation of complex particulate structures and to move towards the rational design of materials.
Effect of Catalyst Layer Hydrophobicity on Fe−N−C Proton Exchange Membrane Fuel Cells
Authors: Zhang Xinyue , Liu Qingtao , Shui Jianglan
Published: March 2020

The hydrophobicity of the cathode catalyst layer (CCL) affects the performance of the proton exchange membrane fuel cell (PEMFC) by adjusting the water management of the catalyst layer, which has been extensively studied in Pt‐based catalysts. Here, the effect of the hydrophobicity of Fe−N−C CCL on the performance of the PEMFC is investigated. The hydrophobicity of the Fe−N−C CCL is tuned by polytetrafluoroethylene (PTFE) by using three addition methods: 1) coat PTFE on Fe−N−C powder and heat‐treat; 2) mix PTFE emulsion with Fe−N−C ink and then brush the electrode; and 3) transfer a ground PTFE/Fe−N−C composite film onto the gas diffusion layer by the decal method. For each PTFE addition method, the optimized PTFE amount can increase the power density of Fe−C−N PEMFC by 15.1 %, 26.6 %, and 87.2 %, respectively. At the same time, it is found that enhanced hydrophobicity reduces the initial current decay rate of the Fe−N−C CCLs, but their residual current densities are close after a 50 h durability test at 0.5 V in a H2‐O2 PEMFC. It can be concluded that the hydrophobicity of the Fe−N−C CLL has a great influence on the power density of the fuel cell, but the influence on the long‐term durability of the fuel cell is negligible.
Chemometrics‐based vibrational spectroscopy for Juglandis semen extracts investigation
Authors: Radulescu Cristiana , Olteanu Radu Lucian , Stihi Claudia , Florescu Monica , Stirbescu Raluca Maria , Stanescu Sorina Geanina , Nicolescu Cristina Mihaela , Bumbac Marius
Published: March 2020

In this study, the chemical composition of Juglandis semen extracts obtained by different extraction solvents and methods were determined by Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy. The multivariate analyses, principal component analysis and hierarchical cluster analysis of the FTIR and Raman spectral datasets, were performed to determine the differences in the chemical composition according to the solvent (e.g., mixture of water with alcohol, glycerole, and propylene glycol) and the extraction method (i.e., ultrasound‐assisted extraction, rapid pressurized extraction, and subcritical fluid extraction). The obtained results reveal that the J. semen extracts with water‐alcohol solvent have equivalent chemical composition. A well‐defined differentiation based on extraction method could not be highlighted. Based on FTIR data compilation, it can be observed that a first classification can be made based on the solvent, acidic or basic, used for extraction methods (except subcritical fluid extraction ‐ SFE, clustering is clearly assigned by the solvent). Multivariate analysis on FTIR and Raman spectral data was able to differentiate SFE extract as a unique cluster, which means HFC134a solvent allowed a specific extraction (from organic constituents' point of view) due to the selected conditions of extraction method.
Gender differences in publication rates in oncology: Looking at the past, present, and future
Authors: Duma Narjust
Published: March 2020

Female physicians and scientists represent less than one third of first and senior authors in oncology journals. Equal opportunities and training in gender bias are necessary to level out the playing field for current and future female physicians and scientists.
An exercise oncology clinical pathway: Screening and referral for personalized interventions
Authors: Stout Nicole L. , Brown Justin C. , Schwartz Anna L. , Marshall Timothy F. , Campbell Anna M. , Nekhlyudov Larissa , Zucker David S. , Basen‐Engquist Karen M. , Campbell Grace , Meyerhardt Jeffrey , Cheville Andrea L. , Covington Kelley R. , Ligibel Jennifer A. , Sokolof Jonas M. , Schmitz Kathryn H. , Alfano Catherine M.
Published: March 2020

This article presents a clinical screening and referral framework to enable health care professionals to guide individuals with cancer to safe and effective exercise programs.
Majority of cerebrospinal fluid‐contacting neurons in the spinal cord of C57Bl/6N mice is present in ectopic position unlike in other studied experimental mice strains and mammalian species
Authors: Tonelli Gombalová Zuzana , Košuth Ján , Alexovič Matiašová Anna , Zrubáková Jarmila , Žežula Ivan , Giallongo Toniella , Di Giulio Anna Maria , Carelli Stephana , Tomašková Lenka , Daxnerová Zuzana , Ševc Juraj
Published: March 2020

Cerebrospinal fluid contacting neurons (CSF‐cNs) represent a specific class of neurons located in close vicinity of brain ventricles and central canal. In contrast with knowledge gained from other vertebrate species, we found that vast majority of CSF‐cNs in the spinal cord of C57Bl/6N mice is located in ectopic distal ventral position. However, we found that small number of ectopic CSF‐cNs is present also in spinal cord of other investigated experimental mice strains (C57Bl/6J, Balb/C) and mammalian species (Wistar rats, New Zealand White rabbits). Similarly, as the proximal populations, ectopic CSF‐cNs retain PKD2L1‐immunoreactivity and synaptic contacts with other neurons. On the other side, they show rather multipolar morphology lacking thick dendrite contacting central canal lumen. Ectopic CSF‐cNs in the spinal cord of C57Bl/6N mice emerge during whole period devoted to production of CSF‐cNs and reach their ventral destinations during first postnatal weeks. In order to identify major gene, whose impairment could trigger translocation of CSF‐cNs outside the central canal area, we took advantage of close consanguinity of C57Bl/6J substrain with normal CSF‐cN distribution and C57Bl/6N substrain with majority of CSF‐cNs in ectopic position. Employing in silico analyses, we ranked polymorphisms in C57Bl/6N substrain and selected genes Crb1, Cyfip2, Adamts12, Plk1, and Herpud2 as the most probable candidates, whose product dysfunction might be responsible for the ectopic distribution of CSF‐cNs. Furthermore, segregation analysis of F2 progeny of parental C57Bl/6N and Balb/C mice revealed that polymorphic loci of Crb1 and Cyfip2 underlie the ectopic position of CSF‐cNs in the spinal cord of C57Bl/6N mice.
Optimization of porous stents for endovascular repair of abdominal aortic aneurysms
Authors: Stockle Juan , Romero David A. , Amon Cristina H.
Published: March 2020

This study presents a simulation‐based methodology to design porous stents to induce suitable hemodynamic environments inside abdominal aortic aneurysm (AAA) sacs. In the proposed methodology, an optimization algorithm iteratively modifies the porosity distribution of the stent and executes a computational fluid dynamics (CFD) simulation to determine the effect of these changes on the hemodynamic conditions inside the aneurysm sac. The optimization iterations proceed until relevant hemodynamic parameters are within ranges prescribed a priori by the user as desirable to control the progression of the AAA. The resulting porosity distribution uniquely describes the porous stent design that can control the hemodynamic environment (eg, shear stress at the aneurysm wall, pressure distribution, residence time), reducing AAA rupture risks and improving treatment efficacy. To demonstrate its potential, the proposed methodology is applied to idealized AAA geometry under steady‐state flow conditions, though it may be easily applied to more complex AAA geometries under transient, pulsatile flow conditions. The proposed methodology has the potential to enable the design of a new generation of porous stents tailored to patient‐specific geometries and flow conditions, to improve patient outcomes.
Topology hiding routing based on learning with errors
Authors: Wan Shaohua
Published: March 2020

The protocol of onion routing constitutes the underpinning of Onion Routing network for anonymous communication. However, since the main idea behind such protocol is to hierarchically peel the IP head and decode each crypted routing address, the topology with regards to path length or long‐term direction cannot be preserved. Owing to topology exposure, lots of attacks such as denial of service and differential flow analysis can be effectively conducted to violate the security of it. Moreover, considering that the path should be constructed by a sender in advance, onion routing is infeasible to be transplanted to ad hoc networks, let alone other defects such as heavy burden about computational complexity and package length. In this paper, a topology‐hiding routing protocol is proposed to address most of the aforementioned problems recurring to homomorphic learning with errors. Security analysis illustrated that nothing but only the IPs of adjacent hops will be revealed to any router. Also the computational complexity on sender side as well as the package length outperforms those of traditional onion routing algorithm in view of comparative simulation.
An Extensive Set of Accurate Fluoride Ion Affinities for p‐Block Element Lewis Acids and Basic Design Principles for Strong Fluoride Ion Acceptors
Authors: Erdmann Philipp , Leitner Jonas , Schwarz Julia , Greb Lutz
Published: March 2020

The computed fluoride ion affinity (FIA) is a valuable descriptor to assess the Lewis acidity of a compound. Despite its widespread use, the varying accuracy of applied computational models hampers the broad comparability of literature data. Herein, we evaluate the performance of selected methods (like DLPNO‐CCSD(T)) in FIA computations against CCSD(T)/CBS data and guide for the choice of suitable density functionals that allow the treatment of larger Lewis acids. Based on the benchmarked methods, we computed an extensive set of gas‐phase and solvation corrected FIA, that is covering group 13–16 elements featuring moderate to strong electron‐withdrawing substituents (190 entries). It permits an unbiased comparison of FIA over a significant fraction of the periodic table, serves as a source of reference for future synthetic or theoretical studies, and allows to derive some simple design principles for strong fluoride ion acceptors. Finally, the manuscript includes a tutorial section for the computation of FIA with and without the consideration of solvation.
Polydiacetylene–Perylenediimide Supercapacitors
Authors: De Adhikari Amrita , Morag Ahiud , Seo Joonsik , Kim Jong‐Man , Jelinek Raz
Published: March 2020

Organic supercapacitors have attracted interest as promising “green” and efficient components in energy storage applications. A polydiacetylene derivative coupled with reduced graphene oxide was employed, for the first time, to generate an organic pseudocapacitance‐based supercapacitor that exhibited excellent electrochemical properties. Specifically, diacetylene monomers were functionalized with perylenediimide (PDI), spontaneously forming elongated microfibers. Following polymerization through UV irradiation, the PDI–polydiacetylene microfibers were interspersed with reduced graphene oxide (rGO), generating a porous electrode material exhibiting a high surface area and facilitating efficient ion diffusion, both essential preconditions for supercapacitor applications. We show that PDI–polydiacetylene has an important role in enhancing the electrochemical properties as a supercapacitor electrode. Besides stabilizing the microporous electrode organization, the delocalized π electrons in both the PDI residues and conjugated network of the polydiacetylene contributed to a significantly higher capacitance (specific capacitance >600 F g−1 at 1 A g−1 current density), longer discharge time, and high power density. The PDI–polydiacetylene‐rGO electrodes were employed in a functional supercapacitor device.
High‐Loading Single‐Atom Copper Catalyst Supported on Coordinatively Unsaturated Al2O3 for Selective Synthesis of Homoallylboronates
Authors: Guo Tenglong , Tang Nanfang , Lin Feng , Shang Qinghao , Chen Shuai , Qi Haifeng , Pan Xiaoli , Wu Chuntian , Xu Guoliang , Zhang Jian , Xu Dezhu , Cong Yu
Published: March 2020

Single‐atom catalysts (SACs) as a bridge between hetero‐ and homogeneous catalysis have attracted much attention. However, it is still challenging to generate stable single atoms with high metal loadings, and the application of SACs in traditionally homogeneous catalytic reactions is highly desirable. Herein, a Cu SAC with a high Cu loading of 8.7 wt % supported on coordinatively unsaturated Al2O3 was prepared and used in the amine‐free synthesis of homoallylboranes. Up to 99 % conversion, 95 % 1,4‐selective boration of the enals, and 48–68 % isolated yields of homoallylboranes were achieved, equaling the results of reported homogenous catalysts, and the system was more efficient and stable than nano Cu/γ‐Al2O3. Mechanistic investigation indicated that Cu‐Bpin species are the active intermediates of selective boration. The superior catalytic and recycling performance of Cu SAC paves an efficient and green path toward selective synthesis of homoallyborane fine chemicals.
Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells
Authors: Nini Alessandro , Hoffmann Michèle Janine , Lampignano Rita , große Siemer Robert , van Dalum Guus , Szarvas Tibor , Cotarelo Cristina Lopez , Schulz Wolfgang Arthur , Niederacher Dieter , Neubauer Hans , Stoecklein Nikolas Hendrik , Niegisch Günter
Published: March 2020

Background

Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection.

Methods

HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT‐PCR, western blot and fluorescence‐activated cell scanning (FACS) and compared to the strongly HER2‐expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike‐in experiments in the CellSearch system. Twenty‐one blood samples from 13 metastatic UC patients were analyzed for HER2‐positive CTCs with CellSearch.

Results

HER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10‐fold lower than in the HER‐2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike‐in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2.

Conclusions

Detection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial.
Flow cytometric analysis of fine needle aspirates is affected by tumor subtype, but not by anatomic location nor technique
Authors: Wake Laura M. , VandenBussche Christopher J. , Ali Syed Z. , Wagner‐Johnston Nina D. , Burns Kathleen H. , Gocke Christopher D. , Vuica‐Ross Milena , Borowitz Michael J. , Duffield Amy S.
Published: March 2020

Background

Current clinical practices are shifting towards utilizing less invasive biopsy techniques, including fine needle aspiration (FNA) and needle core biopsies. If a patient has a suspected hematologic malignancy, a portion of the FNA sample is typically submitted for flow cytometry (FC) analysis, providing valuable immunophenotypic data.

Methods

FNA specimens were identified via a pathology database search. All cases were morphologic evaluated and a subset of cases were analyzed by FC.

Results

245 hematologic FNA specimens were identified; 84% of these cases had an adequate number of cells for FC analysis, and an unequivocal morphologic diagnosis (benign or malignant) was rendered in 85%. The percentage of cases with an unequivocal diagnosis was statistically significantly higher in those with associated FC than with those without FC (90% vs 58%). Neither FNA technique nor anatomic site affected the likelihood of obtaining an adequate sample for FC analysis and/or rendering a definitive morphologic or unequivocal FC diagnosis. Likewise, tumor subtype did not affect the likelihood of acquiring enough cells for FC analysis, but occasionally resulted in equivocal FC diagnoses or discordant FNA and FC diagnoses. Aggressive B‐cell lymphomas and Hodgkin lymphomas were significantly less likely to be detected by FC as compared to low‐grade B‐cell lymphomas. Discrepancies between FNA and FC diagnoses occurred in 13% of cases. The majority of discrepancies (78%) included FC false negatives, while only 22% of cases had atypical or positive FC with negative FNA.

Conclusions

FNA with associated FC is a powerful diagnostic technique; however, lymphoma subtype may affect diagnostic sensitivity by FC, and therefore, discordant FNA and FC results should be interpreted with caution.
Canadian polar bear population structure using genome‐wide markers
Authors: Jensen Evelyn L. , Tschritter Christina , de Groot Peter V. C. , Hayward Kristen M. , Branigan Marsha , Dyck Markus , Clemente‐Carvalho Rute B. G. , Lougheed Stephen C.
Published: March 2020

Predicting the consequences of environmental changes, including human‐mediated climate change on species, requires that we quantify range‐wide patterns of genetic diversity and identify the ecological, environmental, and historical factors that have contributed to it. Here, we generate baseline data on polar bear population structure across most Canadian subpopulations (n = 358) using 13,488 genome‐wide single nucleotide polymorphisms (SNPs) identified with double‐digest restriction site‐associated DNA sequencing (ddRAD). Our ddRAD dataset showed three genetic clusters in the sampled Canadian range, congruent with previous studies based on microsatellites across the same regions; however, due to a lack of sampling in Norwegian Bay, we were unable to confirm the existence of a unique cluster in that subpopulation. These data on the genetic structure of polar bears using SNPs provide a detailed baseline against which future shifts in population structure can be assessed, and opportunities to develop new noninvasive tools for monitoring polar bears across their range.
High genetic diversity and stable Pleistocene distributional ranges in the widespread Mexican red oakQuercus castaneaNée (1801) (Fagaceae)
Authors: Peñaloza‐Ramírez Juan Manuel , Rodríguez‐Correa Hernando , González‐Rodríguez Antonio , Rocha‐Ramírez Víctor , Oyama Ken
Published: March 2020

The Mexican highlands are areas of high biological complexity where taxa of Nearctic and Neotropical origin and different population histories are found. To gain a more detailed view of the evolution of the biota in these regions, it is necessary to evaluate the effects of historical tectonic and climate events on species. Here, we analyzed the phylogeographic structure, historical demographic processes, and the contemporary period, Last Glacial Maximum (LGM) and Last Interglacial (LIG) ecological niche models ofQuercus castanea, to infer the historical population dynamics of this oak distributed in the Mexican highlands. A total of 36 populations ofQ. castaneawere genotyped with seven chloroplast microsatellite loci in four recognized biogeographic provinces of Mexico: the Sierra Madre Occidental (western mountain range), the Central Plateau, the Trans‐Mexican Volcanic Belt (TMVB, mountain range crossing central Mexico from west to east) and the Sierra Madre del Sur (SMS, southern mountain range). We obtained standard statistics of genetic diversity and structure and tested for signals of historical demographic expansions. A total of 90 haplotypes were identified, and 29 of these haplotypes were restricted to single populations. The within‐population genetic diversity was high (meanhS = 0.72), and among‐population genetic differentiation showed a strong phylogeographic structure (NST = 0.630 > GST = 0.266;p < .001). Signals of demographic expansion were identified in the TMVB and the SMS. The ecological niche models suggested a considerable percentage of stable distribution area for the species during the LGM and connectivity between the TMVB and the SMS. High genetic diversity, strong phylogeographic structure, and ecological niche models suggest in situ permanence ofQ. castaneapopulations with large effective population sizes. The complex geological and climatic histories of the TMVB help to explain the origin and maintenance of a large proportion of the genetic diversity in this oak species.
Friend or foe? A parasitic wasp shifts the cost/benefit ratio in a nursery pollination system impacting plant fitness
Authors: Villacañas de Castro Carmen , Hoffmeister Thomas S.
Published: March 2020

Nursery pollination systems are species interactions where pollinators also act as fruit/seed herbivores of the plant partner. While the plants depend on associated insects for pollination, the insects depend on the plants’ reproductive structures for larval development. The outcome of these interactions is thus placed on a gradient between mutualism and antagonism. Less specialized interactions may fluctuate along this gradient with the ecological context, where natural enemies can play an important role. We studied whether a natural enemy may impact the level of seed consumption of a nursery pollinator and how this in turn may influence individual plant fitness. We used the plant Silene latifolia, its herbivore Hadena bicruris, and its ectoparasitoid Bracon variator as a model plant–herbivore–natural enemy system. We investigated seed output, germination, survival, and flower production as proxies for individual plant fitness. We show that B. variator decreases the level of seed consumption by H. bicruris larvae which in turn increased seed output in S. latifolia plants, suggesting that parasitism by B. variator may act as a regulator in the system. However, our results also show that plant survival and flower production decrease with higher seed densities, and therefore, an increase in seed output may be less beneficial for plant fitness than estimated from seed output alone. Our study should add another layer to the complex discussion of whether parasitoids contribute to plant fitness, as we show that taking simple proxies such as seed output is insufficient to determine the net effect of multitrophic interactions.
Exhaustive extraction of cyclopeptides from Amanita phalloides: Guidelines for working with complex mixtures of secondary metabolites
Authors: Scott Chialvo Clare H. , Griffin Logan H. , Reed Laura K. , Ciesla Lukasz
Published: March 2020

Understanding plant‐insect interactions is an active area of research in both ecology and evolution. Much attention has been focused on the impact of secondary metabolites in the host plant or fungi on these interactions. Plants and fungi contain a variety of biologically active compounds, and the secondary metabolite profile can vary significantly between individual samples. However, many experiments characterize the biological effects of only a single secondary metabolite or a subset of these compounds.

Here, we develop an exhaustive extraction protocol using an accelerated solvent extraction protocol to recover the complete suite of cyclopeptides and other secondary metabolites found in Amanita phalloides (death cap mushrooms) and compare its efficacy to the “Classic” extraction method used in earlier works.

We demonstrate that our extraction protocol recovers the full suite of cyclopeptides and other secondary metabolites in A. phalloides unlike the “Classic” method that favors polar cyclopeptides.

Based on these findings, we provide recommendations for how to optimize protocols to ensure exhaustive extracts and also the best practices when using natural extracts in ecological experiments.
Transcriptional analyses reveal the molecular mechanism governing shade tolerance in the invasive plant Solidago canadensis
Authors: Wu Miao , Li Zeyu , Wang Jianbo
Published: March 2020

Solidago canadensis is an invasive plant that is capable of adapting to variable light conditions. To elucidate the shade tolerance mechanism in S. canadensis at the molecular level, transcriptome analyses were performed for leaves growing under natural light and three shade level conditions. Many differentially expressed genes (DEGs) were found in the comparative analysis, including those involved in photosynthesis, antioxidant, and secondary metabolism of phenol‐ and flavonoid‐related pathways. Most genes encoding proteins involved in photosynthesis, such as photosystem I reaction center subunit (Psa), photosystem II core complex protein (Psb), and light‐harvesting chlorophyll protein (Lhca and Lhcb), and reactive oxygen species (ROS) scavenging‐related enzymes, such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), were upregulated with the shade levels. Furthermore, most of the DEGs related to secondary metabolite synthesis were also upregulated in the shade conditions. Our study indicates that S. canadensis can respond to shade stress by modulating the expression of several photosynthesis‐related, free radical scavenging‐related, and secondary metabolism‐related genes; thus, this species has the ability to adapt to different light conditions.
Changes in oxygen uptake kinetics after exercise caused by differences in loading pattern and exercise intensity
Authors: Ichikawa Yuri , Maeda Tomoko , Takahashi Tetsuya , Ashikaga Kohei , Tanaka Shiori , Sumi Yuki , Itoh Haruki
Published: March 2020

Aims

The kinetics of recovery‐period oxygen uptake (VO2) are affected by the O2 deficit generated during exercise. However, studies using ramp tests (RTs) and constant work rate tests (CT) have differently characterized VO2 responses to increased exercise intensity differently. We used these two types of loading patterns to investigate the effects of low‐intensity, medium‐intensity, and high‐intensity exercises on the half time (T1/2) of recovery‐period VO2 and the mechanism.

Methods and results

Ten healthy men aged 21.2 ± 0.9 years underwent symptom‐limited cardiopulmonary exercise tests with the ramp protocol to determine their anaerobic threshold. All subjects subsequently underwent three submaximal RT and CT at low, moderate, and high intensities. In all RTs, subjects began exercise by warming up (20 W). In CT, T1/2 was significantly lengthened as exercise intensity increased (CT‐low: 34.0 ± 3.9 s, CT‐moderate: 39.5 ± 3.5 s, CT‐high:44.6 ± 4.2 s; P < 0.01, ANOVA), whereas no significant change was observed in RT, which began with the same work rate (RT‐low: 46.0 ± 5.7 s, RT‐moderate: 45.7 ± 4.8 s, RT‐high: 44.6 ± 3.5 s, RT‐max: 44.8 ± 3.2 s; P = 0.868, ANOVA). Only high‐intensity exercise resulted in two components (the fast and slow components) of VO2 decay, reflecting the increased O2 deficit by anaerobic metabolism.

Conclusions

The exercise intensity at the beginning of an exercise affects early recovery‐period VO2, which is a fast component. The T1/2 of recovery‐period VO2 occurs during the fast component, and an increase in O2 deficit affects both the fast and slow components, lengthening the T1/2. The T1/2 of recovery‐period VO2 in CT at moderate or high intensities, even if not symptom limited, can be used to evaluate exercise intolerance and early occurrence of anaerobic metabolism. Submaximal exercise tests may be considered as convenient methods for evaluating exercise tolerance in patients with cardiac failure.
Pseudopericyclic Dearomative 1,6‐Cyclization of 1‐(2‐Pyridyl)‐2‐azabuta‐1,3‐dienes: Synthesis and Ring–Chain Valence Equilibria of 4H‐Pyrido[1,2‐a]pyrazines
Authors: Filippov Ilya P. , Novikov Mikhail S. , Khlebnikov Alexander F. , Rostovskii Nikolai V.
Published: March 2020

The 1,6‐electrocyclization of 1‐(2‐pyridyl)‐2‐azabuta‐1,3‐dienes obtained by RhII‐catalyzed reaction of pyridotriazoles with 2H‐azirines affords stable non‐aromatic 4H‐pyrido[1,2‐a]pyrazines despite the fact that the reaction proceeds with irreversible dearomatization of the pyridine aromatic system. This pseudopericyclic cyclization occurs when the 2‐azabutadiene contains H, alkyl, or Ph at the C4 atom and an electron‐withdrawing substituent at the C1 atom. A number of stable 4H‐pyrido[1,2‐a]pyrazines as well as 1H‐pyrazino[1,2‐a]quinoline and 4H‐benzo[4,5]oxazolo[3,2‐a]pyrazine derivatives were synthesized. Whereas 4‐alkyl‐substituted pyridopyrazines are stable at room temperature, 4‐phenyl‐substituted pyridopyrazines exist in ring–chain valence equilibrium with 1‐(2‐pyridyl)‐2‐azabutadienes. Thermodynamic stability of the 4H‐pyrido[1,2‐a]pyrazine decreases with increasing size of the substituent at the C6 atom.
A triple‐band circularly polarized annular ring antenna with asymmetric ground plane for wireless applications
Authors: Dhara Reshmi , Mitra Monojit
Published: March 2020

Herein a compact triple‐band circularly polarized (CP) microstrip patch antenna, loaded with a single annular ring patch with eight symmetrical slots along its periphery and a series of octagonal closed ring resonators (CRRs) on the opposite side of the substrate, is proposed. Evolution process of the antenna geometry reveals that the eight symmetrical slots and the CRRs are responsible for increased impedance bandwidth (IBW), while simulated (high‐frequency structure simulator (HFSS) and computer simulation tool) triple CP bands obtained due to the uses of crossshaped slit resonating at 7.5 GHz (152.2 MHz); asymmetric ground plane at 10.2 GHz (161 MHz); and square open‐loop at 12.2 GHz (112.5 MHz). Series of parasitic strips improved CP radiation and remove ripple in the radiation pattern. The antenna presented here, is compact, fabricated with an optimized dimension of 35 × 30 × 1.6 mm3, on low cost FR‐4 substrate with copper cladding. The measured <10‐dB IBW ranges from 4.08‐5.05 GHz and 5.98 GHz up to 13.6 GHz. Simulated maximum peak gain found to be 4.45 dBi at 13 GHz. The antenna proposed herein is appropriate for wireless applications.
Boosting oxygen evolution reaction by activation of lattice‐oxygen sites in layered Ruddlesden‐Popper oxide
Authors: Zhu Yinlong , Tahini Hassan A. , Hu Zhiwei , Yin Yichun , Lin Qian , Sun Hainan , Zhong Yijun , Chen Yubo , Zhang Feifei , Lin Hong‐Ji , Chen Chien‐Te , Zhou Wei , Zhang Xiwang , Smith Sean C. , Shao Zongping , Wang Huanting
Published: March 2020

Emerging anionic redox chemistry presents new opportunities for enhancing oxygen evolution reaction (OER) activity considering that lattice‐oxygen oxidation mechanism (LOM) could bypass thermodynamic limitation of conventional metal‐ion participation mechanism. Thus, finding an effective method to activate lattice‐oxygen in metal oxides is highly attractive for designing efficient OER electrocatalysts. Here, we discover that the lattice‐oxygen sites in Ruddlesden‐Popper (RP) crystal structure can be activated, leading to a new class of extremely active OER catalyst. As a proof‐of‐concept, the RP Sr3(Co0.8Fe0.1Nb0.1)2O7‐δ (RP‐SCFN) oxide exhibits outstanding OER activity (eg, 334 mV at 10 mA cm−2 in 0.1 M KOH), which is significantly higher than that of the simple SrCo0.8Fe0.1Nb0.1O3‐δ perovskite and benchmark RuO2. Combined density functional theory and X‐ray absorption spectroscopy studies demonstrate that RP‐SCFN follows the LOM under OER condition, and the activated lattice oxygen sites triggered by high covalency of metal‐oxygen bonds are the origin of the high catalytic activity.

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A gas outburst prevention and control strategy for single thick coal seams with high outburst risk: A case study of Hudi Coal Mine in Qinshui Basin
Authors: Li Hong , Ma Jinkui , Wang Zhiquan , Wang Wei , Liu Yanwei
Published: March 2020

Coal and gas outburst is one of the most harmful natural disaster in coal mine production. The frequency and scope of outburst are closely related to the metamorphic degree of coal seam, the depth of coal seam, and the complexity of geological structure. In general, the use of traditional along‐seam borehole or cross‐seam borehole can meet the needs of gas control. However, for the coal seams with high outburst risk, these methods fail to meet the demands of high‐yield and high‐efficiency coal recovery as well as safe, green, and economical coal mining. Although pressure‐relief gas extraction in the protective seam and coalbed methane (CBM) pre‐extraction can eliminate outburst risk in coal seams, these methods can hardly help realize the green development trend of coal and CBM co‐extraction because they cannot guarantee the current situation of highly mechanized mining. In this study, a three‐dimensional coal and CBM co‐extraction strategy was proposed. The strategy includes three levels of three‐dimensional gas prevention and control methods. The first level is the combination of ground and underground gas extraction methods, to achieve joint extraction of ground and underground gas. The second level is the full‐coverage extraction of the coal resources to be mined, to achieve joint extraction through upper and lower cross‐seam borehole and along‐seam borehole. The third level is the optimization of ground and underground extraction and utilization systems, to realize the full utilization of CBM and to achieve the goal of coal and CBM co‐extraction. The three‐dimensional gas prevention and control method constructs a new gas control model for single thick coal seams with high gas outburst risk and realizes the all‐round coordination and unity of different gas control methods spatially and temporally. The gas control strategy completely eliminates the high gas outburst risk of a single thick coal seam and has been successfully applied in Hudi Coal Mine. The application results verify that the method can effectively guarantee the operation safety during highly mechanized mining, realize extraction and full utilization of separate‐source gas, and provide guidance and direction for coal and CBM co‐extraction with similar extraction conditions.
Rapid and sensitive detection of mycotoxins by advanced and emerging analytical methods: A review
Authors: Singh Jyoti , Mehta Alka
Published: March 2020

Quantification of mycotoxins in foodstuffs is extremely difficult as a limited amount of toxins are known to be presented in the food samples. Mycotoxins are secondary toxic metabolites, made primarily by fungal species, contaminating feeds and foods. Due to the presence in globally used grains, it is an unpreventable problem that causes various acute and chronic impacts on human and animal health. Over the previous few years, however, progress has been made in mycotoxin analysis studies. Easier techniques of sample cleanup and advanced chromatographic approaches have been developed, primarily high‐performance liquid chromatography. Few extremely sophisticated and adaptable tools such as high‐resolution mass spectrometry and gas chromatography–tandem MS/MS have become more important. In addition, Immunoassay, Advanced quantitative techniques are now globally accepted for mycotoxin analysis. Thus, this review summarizes these traditional and highly advance methods and their characteristics for evaluating mycotoxins.
Immuno‐oncology gene expression profiling of formalin‐fixed and paraffin‐embedded clear cell renal cell carcinoma: Performance comparison of theNanoString nCountertechnology with targetedRNAsequencing
Authors: Talla Suranand B. , Rempel Eugen , Endris Volker , Jenzer Maximilian , Allgäuer Michael , Schwab Constantin , Kazdal Daniel , Stögbauer Fabian , Volckmar Anna‐Lena , Kocsmar Ildiko , Neumann Olaf , Schirmacher Peter , Zschäbitz Stefanie , Duensing Stefan , Budczies Jan , Stenzinger Albrecht , Kirchner Martina
Published: March 2020

Inflammatory gene signatures are currently being explored as predictive biomarkers for immune checkpoint blockade, and particularly for the treatment of renal cell cancers. From a diagnostic point of view, the nCounter analysis platform and targeted RNA sequencing are emerging alternatives to microarrays and comprehensive transcriptome sequencing in assessing formalin‐fixed and paraffin‐embedded (FFPE) cancer samples. So far, no systematic study has analyzed and compared the technical performance metrics of these two approaches. Filling this gap, we performed a head‐to‐head comparison of two commercially available immune gene expression assays, using clear cell renal cell cancer FFPE specimens. We compared the nCounter system that utilizes a direct hybridization technology without amplification with an NGS assay that is based on targeted RNA‐sequencing with preamplification. We found that both platforms displayed high technical reproducibility and accuracy (Pearson coefficient: ≥0.96, concordance correlation coefficient [CCC]: ≥0.93). A density plot for normalized expression of shared genes on both platforms showed a comparable bi‐modal distribution and dynamic range. RNA‐Seq demonstrated relatively larger signaling intensity whereas the nCounter system displayed higher inter‐sample variability. Estimated fold changes for all shared genes showed high correlation (Spearman coefficient: 0.73). This agreement is even better when only significantly differentially expressed genes were compared. Composite gene expression profiles, such as an interferon gamma (IFNg) signature, can be reliably inferred by both assays. In summary, our study demonstrates that focused transcript read‐outs can reliably be achieved by both technologies and that both approaches achieve comparable results despite their intrinsic technical differences.
The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2‐deficient leukoencephalopathy
Authors: Hamilton Noémie , Rutherford Holly A. , Petts Jessica J. , Isles Hannah M. , Weber Thomas , Henneke Marco , Gärtner Jutta , Dunning Mark J. , Renshaw Stephen A.
Published: March 2020

The contribution of microglia in neurological disorders is emerging as a leading disease driver rather than a consequence of pathology. RNAseT2‐deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimicking a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to a viral infection suggest an inflammatory and embryonic origin of the pathology. There are no treatments available for this disease as our understanding of the cellular drivers of the pathology are still unknown. In this study, using a zebrafish mutant for the orthologousrnaset2gene, we have identified an inflammatory signature in early development and an antiviral immune response in mature adult brains. Using the optical transparency and the ex utero development of the zebrafish larvae we studied immune cell behavior during brain development and identified abnormal microglia as an early marker of pathology. Live imaging and electron microscopy identified that mutant microglia displayed an engorged morphology and were filled with undigested apoptotic cells and undigested substrate. Using microglia‐specific depletion and rescue experiments, we identified microglia as drivers of this embryonic phenotype and potential key cellular player in the pathology of RNAseT2‐deficient leukoencephalopathy. Our zebrafish model also presented with reduced survival and locomotor defects, therefore recapitulating many aspects of the human disease. Our study therefore placed ourrnaset2mutant at the forefront of leukodystrophy preclinical models and highlighted tissue‐specific approaches as future therapeutic avenues.
Biological tumor markers (maspin, CD105, nm23‐H1) and disease relapse in laryngeal cancer: cluster analysis
Authors: Franz Leonardo , Tealdo Giulia , Contro Giacomo , Bandolin Luigia , Carraro Valentina , Giacomelli Luciano , Alessandrini Lara , Blandamura Stella , Marioni Gino
Published: March 2020

Background

The aim of this investigation was to see if a panel of biomarkers (maspin, CD105, and nm23‐H1) could be used to stratify patients with laryngeal squamous cell carcinoma (LSCC) in homogeneous disease recurrence risk clusters.

Methods

Cluster analysis was used to classify 89 patients based on their immunohistochemical expression of nm23‐H1, CD105, and maspin.

Results

Our analysis identified seven homogeneous clusters: the LSCC recurrence rate was lowest in cluster 6 (non‐nuclear maspin pattern, nuclear nm23‐H1 expression ≥10%, endothelial CD105 expression <6%; P = .009), and highest in cluster 3 (non‐nuclear maspin pattern, nuclear nm23‐H1 expression <10%, endothelial CD105 expression ≥6%; P <.001).

Conclusions

Similar panels of biological variables identified by cluster analysis should be tested in prospective clinical trials to establish whether treating patients identified as being at higher risk of LSCC recurrence more aggressively could significantly improve their recurrence rate and/or disease‐specific survival.
A Randomized Double-Blind Placebo-Controlled First-In-Human Phase 1 Trial of TransCon PTH in Healthy Adults
Authors: Karpf David B , Pihl Susanne , Mourya Sanchita , Mortensen Eva , Kovoor Eshwari , Markova Denka , Leff Jonathan A
Published: March 2020

TransCon PTH is a sustained-release, essentially inactive prodrug transiently bound to an inert carrier, designed to release PTH(1-34), and in development for hypoparathyroidism (HP). This phase 1, randomized, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) trial evaluated safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of TransCon PTH in healthy adults. SAD and MAD cohorts consisted of 10 subjects (eight active, two placebo) who received up to seven single or six multiple ascending doses of TransCon PTH, respectively. TransCon PTH doses ranged from 3.5 to 124 μg PTH(1-34) for the SAD cohorts and 3.5 to 24 μg PTH(1-34)/day for the MAD cohorts. The primary PK endpoint was Free PTH. The PD endpoints included albumin adjusted serum calcium (sCa), fractional excretion of calcium (FECa), intact endogenous PTH(1-84), bone turnover markers, renal tubular maximum reabsorption of phosphate/glomerular filtration rate (TMP/GFR), serum phosphate (sP) and magnesium, and 1,25 dihydroxyvitamin D. TransCon PTH was generally well tolerated; there were no drug-related serious adverse events (SAEs), and all AEs were transient in nature. Free PTH demonstrated an effective half-life of approximately 60 hours and a dose-dependent, sustained exposure with an infusion-like profile within the calculated physiologic range for active PTH at steady-state. Albumin-adjusted sCa demonstrated a dose-dependent, sustained response with complete control of FECa despite modest hypercalcemia at higher doses. Renal tubular maximum reabsorption of phosphate/glomerular filtration rate (TMP/GFR) showed a dose-dependent decrease, resulting in a dose-dependent decrease in sP. TransCon PTH administered daily for 10 days showed no increase in the osteoblastic bone formation markers, serum bone-specific alkaline phosphatase (BSAP) or P1NP, or the osteoclastic bone resorption marker, urine NTx, but modestly and transiently increased the osteoclast marker, serum CTx. These phase 1 data support TransCon PTH as a daily replacement therapy for HP providing physiological levels of PTH 24 hours per day and advancement into phase 2 clinical development. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.