bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifocal breast cancers are more prevalent in BRCA2 versus BRCA1 mutation carriers
Authors: McCrorie Alan D , Ashfield Susannah , Begley Aislinn , Mcilmunn Colin , Morrison Patrick J , Boyd Clinton , Eccles Bryony , Greville‐Heygate Stephanie , Copson Ellen R , Cutress Ramsey I , Eccles Diana M , Savage Kienan I , McIntosh Stuart A
Published: February 2020

Multifocal (MF)/multicentric (MC) breast cancer is generally considered to be where two or more breast tumours are present within the same breast, and is seen in ~10% of breast cancer cases. This study investigates the prevalence of multifocality/multicentricity in a cohort of BRCA1/2 mutation carriers with breast cancer from Northern Ireland via cross‐sectional analysis. Data from 211 women with BRCA1/2 mutations (BRCA1‐91, BRCA2‐120) and breast cancer were collected including age, tumour focality, size, type, grade and receptor profile. The prevalence of multifocality/multicentricity within this group was 25% but, within subgroups, prevalence amongst BRCA2 carriers was more than double that of BRCA1 carriers (p = 0.001). Women affected by MF/MC tumours had proportionately higher oestrogen receptor positivity (p = 0.001) and lower triple negativity (p = 0.004). These observations are likely to be driven by the higher BRCA2 mutation prevalence observed within this cohort. The odds of a BRCA2 carrier developing MF/MC cancer were almost four‐fold higher than a BRCA1 carrier (odds ratio: 3.71, CI: 1.77–7.78, p = 0.001). These findings were subsequently validated in a second, large independent cohort of patients with BRCA‐associated breast cancers from a UK‐wide multicentre study. This confirmed a significantly higher prevalence of MF/MC tumours amongst BRCA2 mutation carriers compared with BRCA1 mutation carriers. This has important implications for clinicians involved in the treatment of BRCA2‐associated breast cancer, both in the diagnostic process, in ensuring that tumour focality is adequately assessed to facilitate treatment decision‐making, and for breast surgeons, particularly if breast conserving surgery is being considered as a treatment option for these patients.
A backward procedure for change‐point detection with applications to copy number variation detection
Authors: Jun Shin Seung , Wu Yichao , Hao Ning
Published: February 2020

Change‐point detection regains much attention recently for analyzing array or sequencing data for copy number variation (CNV) detection. In such applications, the true signals are typically very short and buried in the long data sequence, which makes it challenging to identify the variations efficiently and accurately. In this article, we propose a new change‐point detection method, a backward procedure, which is not only fast and simple enough to exploit high‐dimensional data but also performs very well for detecting short signals. Although motivated by CNV detection, the backward procedure is generally applicable to assorted change‐point problems that arise in a variety of scientific applications. It is illustrated by both simulated and real CNV data that the backward detection has clear advantages over other competing methods, especially when the true signal is short. The Canadian Journal of Statistics 48: 366–385; 2020 © 2020 Statistical Society of Canada
Preoperative paroxysmal atrial fibrillation predicts high cardiovascular mortality in patients undergoing surgical aortic valve replacement with a bioprosthesis: CAREAVR study
Authors: Nissinen Maunu , Lehto Joonas , Biancari Fausto , Nieminen Tuomo , Malmberg Markus , Yannopoulos Fredrik , Salmi Samuli , Airaksinen Juhani K. E. , Kiviniemi Tuomas , Hartikainen Juha E. K.
Published: February 2020

Background

Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive.

Purpose

We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis.

Methods

A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74).

Results

Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA2DS2‐VASc score (P = .333). At 12‐month follow‐up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P < .001). During follow‐up, incidence of fatal strokes in the paroxysmal AF group was higher compared to sinus rhythm group (1.9 vs 0.4 per 100 patient‐years, HR 4.4 95% Cl 1.8‐11.0, P = .001). Cardiovascular mortality was higher in the paroxysmal AF group than in the sinus rhythm group (5.0 vs 3.0 per 100 patient‐years, HR 1.70 95% CI 1.05‐2.76, P = .03) and equal to patients in the permanent AF (5.0 per 100 patient‐years).

Conclusion

Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life‐long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.
Diabetes induces differences in the F‐actin spatial organization of striated muscles
Authors: Romanelli Gerardo , Varela Rocío , Benech Juan C.
Published: February 2020

Studies have shown the cytoskeleton disorganization produced by diabetes and quantified F‐actin fluorescence in the striated muscles of diabetic animals. However, at present, there are no studies that have quantified F‐actin spatial organization (F‐actin‐SO). Through our research, we analyzed the effect of diabetes on F‐actin‐SO in the cardiac and skeletal muscles of a mouse model. The muscle samples were labeled with phalloidin–rhodamine and analyzed with confocal microscopy. The analysis was done in two dimensions using four approaches: quantitation of (a) phalloidin‐occupied areas; (b) number of F‐actin‐unoccupied areas per muscular fiber; (c) F‐actin filament discontinuity; and (d) costamere periodicity. Our results showed that both the cardiac and skeletal muscles of the control mice had more phalloidin‐occupied areas than the diabetic mice. The skeletal muscles had a significantly higher number of F‐actin‐unoccupied areas per muscular fiber and more F‐actin discontinuities. Additionally, using western blot analyses, we showed that those differences were not due to α‐actin protein expression. Finally, we considered the importance of these findings in dysfunctional contraction, disassembly in cell–cell communication, conduction of muscle impulse, and changes in cell nanomechanics. Our results quantitatively demonstrated that diabetes severely affects F‐actin‐SO in striated muscles.
Pain in older survivors of hematologic malignancies after blood or marrow transplantation: A BMTSS report
Authors: Farrukh Naveed , Hageman Lindsey , Chen Yanjun , Wu Jessica , Ness Emily , Kung Michelle , Francisco Liton , Parman Mariel , Landier Wendy , Arora Mukta , Armenian Saro , Bhatia Smita , Williams Grant R.
Published: February 2020

Background

Blood or marrow transplantation (BMT) is increasingly offered to older adults with hematologic malignancies; however, their risk for severe pain is poorly understood. Using the Bone Marrow Transplant Survivor Study, the current study investigated the prevalence and predictors of pain after BMT (allogeneic or autologous) as well as its association with physical performance impairments and frailty.

Methods

The cohort included 736 patients with hematologic malignancies who underwent BMT at an age ≥ 60 years at 1 of 3 transplant centers between 1974 and 2014 and survived ≥2 years after BMT; 183 unaffected siblings also participated. Study participants reported on 4 pain domains (nonminor everyday pain, moderate to severe bodily pain, prolonged pain, and moderate to extreme pain interference), and the presence of 1 or more domains was indicative of a severe and/or life‐interfering pain composite variable.

Results

Overall, 39.4% of the BMT survivors reported severe pain with 2.6‐fold greater odds of reporting pain in comparison with sibling controls. Among BMT recipients, those with less education, lower incomes, and active chronic graft‐versus‐host disease had higher odds of reporting pain. In multivariable analyses, BMT survivors with pain were more likely to have impaired physical performance and were more likely to meet the frailty criteria. BMT survivors reported higher use of pain medications (17.8% vs 9.3%) and opioid pain medications (6.5% vs 2.2%) in comparison with sibling controls.

Conclusions

Nearly 40% of older BMT survivors who were followed for a median of 5 years after BMT reported pain, and BMT survivors had 2.6‐fold higher odds of reporting severe, nonminor or life‐interfering pain in comparison with siblings.
Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study
Authors: Takahama Takayuki , Azuma Koichi , Shimokawa Mototsugu , Takeda Masayuki , Ishii Hidenobu , Kato Terufumi , Saito Haruhiro , Daga Haruko , Tsuboguchi Yuko , Okamoto Isamu , Otsubo Kohei , Akamatsu Hiroaki , Teraoka Shunsuke , Takahashi Toshiaki , Ono Akira , Ohira Tatsuo , Yokoyama Toshihide , Sakai Kazuko , Yamamoto Nobuyuki , Nishio Kazuto , Nakagawa Kazuhiko
Published: February 2020

Background

Liquid biopsy allows the identification of patients whose tumors harbor specific mutations in a minimally invasive manner. No prospective data have been available for the efficacy of osimertinib in patients with non–small cell lung cancer (NSCLC) who develop resistance to first‐ or second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and who test positive for the TKI resistance–conferring T790M mutation of EGFR by liquid biopsy. Therefore, a phase 2 study was conducted to assess the efficacy and safety of osimertinib in such patients.

Methods

Eligible patients had advanced or recurrent NSCLC with known TKI‐sensitizing mutations of EGFR, had documented disease progression after treatment with at least 1 first‐ or second‐generation EGFR TKI, and were positive for the T790M mutation in plasma according to the Cobas EGFR Mutation Test v2 (Roche Diagnostics) or droplet digital polymerase chain reaction analysis. Patients were treated with osimertinib (80 mg/d) until disease progression. The primary endpoint was the overall response rate (ORR) in patients positive for T790M in plasma by the Cobas assay.

Results

Between June 2016 and November 2017, 276 patients were screened for their T790M status with a liquid biopsy. Seventy‐four patients were positive for T790M in plasma, and 53 of these individuals were enrolled in the study. The ORR for evaluable patients positive for T790M in plasma by the Cobas assay (n = 49) was 55.1% (95% confidence interval [CI], 40.2%‐69.3%). The median progression‐free survival for all evaluable patients (n = 52) was 8.3 months (95% CI, 6.9‐12.6 months).

Conclusions

The results demonstrate the utility of liquid biopsy for the detection of T790M with the Cobas EGFR Mutation Test v2. Plasma genotyping with this assay is informative for treatment selection in clinical practice when tumor sampling is not feasible.
Using parametric model order reduction for inverse analysis of large nonlinear cardiac simulations
Authors: Pfaller M. R. , Cruz Varona M. , Lang J. , Bertoglio C. , Wall W. A.
Published: February 2020

Predictive high‐fidelity finite element simulations of human cardiac mechanics commonly require a large number of structural degrees of freedom. Additionally, these models are often coupled with lumped‐parameter models of hemodynamics. High computational demands, however, slow down model calibration and therefore limit the use of cardiac simulations in clinical practice. As cardiac models rely on several patient‐specific parameters, just one solution corresponding to one specific parameter set does not at all meet clinical demands. Moreover, while solving the nonlinear problem, 90% of the computation time is spent solving linear systems of equations. We propose to reduce the structural dimension of a monolithically coupled structure‐Windkessel system by projection onto a lower‐dimensional subspace. We obtain a good approximation of the displacement field as well as of key scalar cardiac outputs even with very few reduced degrees of freedom, while achieving considerable speedups. For subspace generation, we use proper orthogonal decomposition of displacement snapshots. Following a brief comparison of subspace interpolation methods, we demonstrate how projection‐based model order reduction can be easily integrated into a gradient‐based optimization. We demonstrate the performance of our method in a real‐world multivariate inverse analysis scenario. Using the presented projection‐based model order reduction approach can significantly speed up model personalization and could be used for many‐query tasks in a clinical setting.
Silicon Anodes for High‐Performance Storage Devices: Structural Design, Material Compounding, Advances in Electrolytes and Binders
Authors: Li Fangru , Xu Jie , Hou Zhiwei , Li Min , Yang Ru
Published: February 2020

Silicon has an extremely high theoretical capacity, a low voltage platform, and abundant natural reserves. It is considered to be one of the most promising anode materials for lithium‐ion batteries. However, there are still many problems with silicon as an anode material for lithium‐ion batteries. During the lithiation/delithiation of silicon, a huge volume expansion occurs, causing the silicon particles to pulverize and the capacity to drop sharply. Furthermore, the continuous increase in the silicon surface solid electrolyte interphase (SEI) films and the poor conductivity of silicon affect the specific capacity of the battery. Means to improve silicon‐based anodes with regard to electrode cycling performance and electrode capacity include structural design, composite preparation, or improvements in electrolytes and binders (for example, designing silicon nanomaterials of different dimensions from 0D to 3D, including silicon nanoparticles, nanowires, nanorods, thin films, porous silicon, and core‐shell structures). Silicon has been combined with different materials to buffer its own volume expansion, resulting in excellent performance. In addition, the design of a reasonable electrolyte solution, as well as the development of a self‐healing binder is one of the main methods to improve Si‐based anodes. In recent years, sodium/potassium ion batteries have been increasingly studied, and silicon and sodium/potassium can be alloyed. The corresponding theoretical capacity can reach 954 mAh g−1 and 955 mAh g−1, respectively. Advances in silicon‐based anodes for sodium/potassium ion storage are summarized herein.
Ultrafast Activating Strategy to Significantly Enhance the Electrocatalysis of Commercial Carbon Cloth for Oxygen Evolution Reaction and Overall Water Splitting
Authors: Huang Kun , Hu Aiping , Huang Cong , Li Yanhua , Zhou Haifeng , Xu Yali , Tang Qunli , Zhou Shengping , Chen Chuansheng , Chen Xiaohua
Published: February 2020

It is of desirability to prepare in situ self‐supporting electrocatalysts not only to meet application requirements but also to simplify the production process of working electrodes. In this work, oxygen‐containing free‐standing carbon cloth with abundant pores (e‐CC−H2) has been obtained through a facile two‐step electrochemical oxidation and hydrogen etching method. Compared to the previous activation strategies of carbon cloth (such as chemical activation), this method has the advantages of simplicity, time‐saving, low‐cost and energy‐saving. Benefiting from the abundance of defects and oxygen‐containing functional groups that are active sites for oxygen evolution reaction, the obtained e‐CC−H2 shows excellent electrocatalytic activity, with a low overpotential of 350 mV at a current density of 10 mA cm−2, a low Tafel slope (127 mV dec−1) and stable electrochemical activity. This strategy paves the way for the application of functionalized and flexible materials in the field of electrochemical energy storage.
In search of the lost polychromy of English medieval alabaster panels in the Southwest of France
Authors: Mounier Aurelie , Schlicht Markus , Mulliez Maud , Pacanowski Romain , Lucat Antoine , Mora Pascal
Published: February 2020

Polychrome alabaster carvings, representing religious scenes, constitute England's major contribution to European mediaeval sculpture. During the period between 1350 and 1550, large number of alabaster carvings were produced in the Midlands. Despite their massive destruction during the English Reformation (ca.1534), more than 2500 of them still survive, either legally exported or sold clandestinely to the Continent. With more than 100 panels still existing, the Bordeaux region holds one of the largest concentrations of these reliefs. Most of them have unfortunately lost their medieval polychromy, but 20 can still provide valuable information. They are currently studied in our multidisciplinary research program “ALBATRES” (Polychromie, pigments, perception: les albâtres anglais de la fin du Moyen Âge conservés sur le territoire aquitain. Labex LaScArBx project [2018‐2020]). Focused on the panels' polychromy, the project links art history, archaeometry, optical and 3D engineering, and experimental archeology. The first aim is to obtain complete information on the materials and techniques used by medieval painters. The second consists in studying the functions of polychromy and its perception, by determining and interpreting the selection criteria and aesthetic uses of colors and gilding. The polychrome remains of the Aquitaine corpus are studied by means of visual examination, macrophotographic documentation, and noninvasive portable spectroscopic analyses (reflectance spectroscopy by fiber optics in visible and infrared ranges, fluorimetry, etc.). They reveal, among others, the presence of cinnabar, red lead, red ochre, copper green pigments, yellow ochre, gold, lead white, and others. The results allow the production of model samples to help understand the medieval color organization before proposing the coloring of a real copy of one of the studied panels (Virgin's Assumption, Musée d'Aquitaine, Bordeaux). The shape and the appearance of the color rendering could be improved thanks to a special device built at the IOGS to develop a shader that approximates as closely as possible the appearance of the panels. Finally, all information will be integrated on 3D model panels for better appreciation of the carvings and the artistic taste of medieval spectators.
Triarylisocyanurate‐Based Fluorescent Two‐Photon Absorbers
Authors: Gautier Yohan , Argouarch Gilles , Malvolti Floriane , Blondeau Benjamin , Richy Nicolas , Amar Anissa , Boucekkine Abdou , Nawara Krzysztof , Chlebowicz Katarzyna , Orzanowska Grażyna , Dudek Marta , Matczyszyn Katarzyna , Samoc Marek , Blanchard‐Desce Mireille , Mongin Olivier , Waluk Jacek , Paul Frédéric
Published: February 2020

The synthesis and characterization of six triarylisocyanurates, featuring 2,7‐fluorenyl or 9,10‐anthracenyl groups incorporated in their peripheral arms are reported. Photophysical studies reveal that these new octupolar derivatives are more fluorescent (ΦF≥0.60 for all new compounds except for 1,3,5‐tri(9H‐fluoren‐2‐yl)‐1,3,5‐triazinane‐2,4,6‐trione 3) and present a red‐shifted lowest absorption and emission compared to their known phenyl analogues of comparable size. Depending on the nature of the terminal substituent, fast intramolecular energy transfer among the three arms or localization of the excitation on a single branch occurs after population of their first singlet excited state. The latter effect was only observed in the presence of strongly electron‐releasing substituents in polar media. These new chromophores are also better two‐photon absorbers than the 1,4‐phenylene‐based isocyanurates reported so far, with cross sections σ2≥500 GM at 770 nm for 4‐NPh2 the fluorenyl group containing (13) and the anthracenyl group containing (14) chromophores. All these spectroscopic features, analyzed with the help of quantum chemical calculations, are crucial for the design of new biphotonic fluorescent dyes.
Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology
Authors: Janssen Julie M. , Dorlo Thomas P. C. , Steeghs Neeltje , Beijnen Jos H. , Hanff Lidwien M. , van Eijkelenburg Natasha K. A. , van der Lugt Jasper , Zwaan C. Michel , Huitema Alwin D. R.
Published: February 2020

In recent years new targeted small molecule kinase inhibitors have become available for pediatric patients with cancer. Relationships between drug exposure and treatment response have been established for several of these drugs in adults. Following these exposure–response relationships, pharmacokinetic (PK) target minimum plasma rug concentration at the end of a dosing interval (Cmin) values to guide therapeutic drug monitoring (TDM) in adults have been proposed. Despite the fact that variability in PK may be even larger in pediatric patients, TDM is only sparsely applied in pediatric oncology. Based on knowledge of the PK, mechanism of action, molecular driver, and pathophysiology of the disease, we bridge available data on the exposure–efficacy relationship from adults to children and propose target Cmin values to guide TDM for the pediatric population. Dose adjustments in individual pediatric patients can be based on these targets. Nevertheless, further research should be performed to validate these targets.
Photoisomerization‐Driven Photoluminescence Modulation in CdSeS Gradient Quantum Dot/Liquid Crystal Nanocomposites
Authors: Satapathy Pragnya , Navyashree V. , Santra Pralay K. , Prasad S. Krishna
Published: February 2020

We demonstrate that the photoluminescence in nanocomposites composed of gradient CdSeS quantum dots (QD) doped in a host nematic liquid crystal (LC) can be substantially modulated due to photoisomerisation of small amounts of an incorporated azobenzene‐based LC material. An attractive feature of this reversible second‐wavelength optical control is that it can be achieved with low magnitude (0.6 mW/cm2) actinic UV light, and thus has very little scope for undesirable photooxidation. The modulation magnitude is high (45 %) and lends itself to both spatial and temporal control. The dynamics of the process for the forward (UV‐on) process is much faster than the return to the equilibrium situation. However, by applying a DC bias field we show that this return can be accelerated by a factor of more than 6, which under ideal circumstances could even be 20. This low‐power second‐wavelength on‐demand optical technique for emission modulation is generic and holds promises for the development of light‐switchable QD‐based emissive displays and photonic devices.
Is the USDA core collection of common bean representative of genetic diversity of the species, as assessed by SNP diversity?
Authors: Kuzay Saarah , Hamilton‐Conaty Paige , Palkovic Antonia , Gepts Paul
Published: February 2020

Core collections are envisioned to be a representative subset of larger germplasm collections. They were introduced to facilitate the characterization and use of these germplasm collections. The common bean (Phaseolus vulgaris L.) core collection of the USDA Western Regional Plant Introduction Station was one of the first collections to be established in the early 1990s. Here, we evaluate the representativity of this common bean collection in light of the availability of a single nucleotide polymorphism (SNP) platform and new information about genetic diversity of the species, including phaseolin and seed type data. The SNP diversity was studied with a combination of STRUCTURE, principal coordinate analysis (PCoA), and neighbor‐joining analysis (NJA). STRUCTURE analyses were conducted for K (number of subpopulations) = 3 and K = 7, based on the ad hoc statistic ΔK. The K = 3 analysis recognized the split between Andean and Mesoamerican domesticates and the subdivision of the Mesoamerican domesticates into high‐ (Durango/Jalisco) and low‐altitude (Mesoamerica) ecogeographic races. The K = 7 analysis further subdivided the Andean group identified for K = 3, as well as the high‐altitude group from the Mesoamerican gene pool. It also identified smaller groups consisting of Mesoamerican wild beans. The PCoA and NJA confirmed the STRUCTURE results and highlighted the existence of presumed hybridization among groups. Our results suggest that this core collection should be updated by adding domesticated categories, developing a separate wild common bean core collection, and developing cores for specific purposes.
Resistance to wheat rusts identified in wheat/Amblyopyrum muticum chromosome introgressions
Authors: Fellers John P. , Matthews Angie , Fritz Allan K. , Rouse Matthew N. , Grewal Surbhi , Hubbart‐Edwards Stella , King Ian P. , King Julie
Published: February 2020

Wheat (Triticum aestivum L.) rusts are a worldwide production problem. Plant breeders have used genetic resistance to combat these fungi. However, single‐gene resistance is rapidly overcome as a result of frequent occurrence of new virulent fungal strains. Thus, a supply of new resistance sources is continually needed, and new resistance sources are limited within hexaploid wheat genetic stocks. Wild relatives are able to be a resource for new resistance genes but are hindered because of chromosome incapability with domesticated wheats. Twenty‐eight double‐haploid hexaploid wheat/Amblyopyrum muticum (Boiss.) Eig introgression lines, with introgressions covering the majority of the T genome, were evaluated for resistance to Puccinia triticina Erikss., P. graminis Pers.:Pers. f.sp. tritici Erikss. & E. Henning, and P. striiformis Westend. f.sp. tritici Erikss.. At the seedling level, four lines were resistant to races of P. triticina, six lines were resistant to P. graminis, and 15 lines were resistant to P. striiformis. At the adult stage, 16 lines were resistant to P. triticina. Line 355 had resistance to all three rusts and line 161 had resistance to all tested races of P. triticina. Some of these lines will require further work to reduce the size of the introgressed segment; however, lines 92 and 355 have very small fragments and can be used directly as new resistance donors.
Catalytic Semi‐Water–Gas Shift Reaction: A Simple Green Path to Formic Acid Fuel
Authors: Qadir Muhammad I. , Castegnaro Marcus V. , Selau Felipe F. , Samperi Mario , Fernandes Jesum Alves , Morais Jonder , Dupont Jairton
Published: February 2020

Formic acid (FA) is a promising CO and hydrogen energy carrier, and currently its generation is mainly centered on the hydrogenation of CO2. However, it can also be obtained by the hydrothermal conversion of CO with H2O at very high pressures (>100 bar) and temperatures (>200 °C), which requires days to complete. Herein, it is demonstrated that by using a nano‐Ru/Fe alloy embedded in an ionic liquid (IL)‐hybrid silica in the presence of the appropriate IL in water, CO can be catalytically converted into free FA (0.73 m) under very mild reactions conditions (10 bar at 80 °C) with a turnover number of up to 1269. The catalyst was prepared by simple reduction/decomposition of Ru and Fe complexes in the IL, and it was then embedded into an IL‐hybrid silica {1‐n‐butyl‐3‐(3‐trimethoxysilylpropyl)‐imidazolium cations associated with hydrophilic (acetate, SILP‐OAc) and hydrophobic [bis((trifluoromethyl)sulfonyl)amide, SILP‐NTf2] anions}. The location of the alloy nanoparticles on the support is strongly related to the nature of the anion, that is, in the case of hydrophilic SILP‐OAc, RuFe nanoparticles are more exposed to the support surface than in the case of the hydrophobic SILP‐NTf2, as determined by Rutherford backscattering spectrometry. This catalytic membrane in the presence of H2O/CO and an appropriate IL, namely, 1,2‐dimethyl‐3‐n‐butylimidazolium 2‐methyl imidazolate (BMMIm⋅MeIm), is stable and recyclable for at least five runs, yielding a total of 4.34 mof free FA.
Modeling and analysis of LC filter integrated quasi‐Z source indirect matrix converter
Authors: Guo Mingzhu , Liu Yushan , Ge Baoming , Liu Shuo , Li Xiao , Ferreira Fernando J.T.E. , de Almeida Anibal T.
Published: February 2020

The existing model of LC filter integrated quasi‐Z source indirect matrix converter (QZS‐IMC) was derived using the DC circuit modeling method, which is mainly effective in DC circuit. As an ac circuit, the existing voltage boost ratio model of LC filter integrated QZS‐IMC exhibits a big error from the real boost ratio. Moreover, current amplitude and phase angle of QZS network were not considered in the existing model. This paper proposes a new comprehensive model of LC filter integrated QZS‐IMC taking into account the circuit's ac characteristics. The new model shows that voltage boost ratio is strongly related to QZS network inductance, capacitance, and frequency of input power supply. It can be concluded from the new model that the boost ratio is higher than 1/(1 − 2D), which is the boost ratio of existing model. Moreover, the new model shows that power factor affects voltage gain of QZS‐IMC system. The new model is compared with the existing model, circuit simulation, and experimental test. The results verify the new model and analysis.
Malignant effusions from extranodal NK/T‐cell lymphomas are frequently of anaplastic morphology with azurophilic granules and of T‐cell lineage
Authors: Liu Chih‐Yi , Chen Bo‐Jung , Chuang Shih‐Sung ,   Taiwan Hematopathology Study Group
Published: February 2020

Background

Extranodal natural killer/T‐cell lymphoma (ENKTL) nasal type is an extranodal lymphoma, with most cases arising from the prototypic nasal/upper aerodigestive tract and the cell of origin (COO) is frequently of NK cells. Effusion involvement by ENKTL is rare. The cytomorphological and immunophenotypical features and COO of effusion ENKTL are elusive.

Design

We report four new cases of effusion ENKTL, reviewing the cytomorphological features and investigating their COO by immunohistochemistry for T‐cell receptor (TCR) protein expression and clonality assay for TCR gene rearrangement. We also reviewed 12 additional cases of effusion ENKTL from the literature.

Results

All our four cases showed anaplastic tumor cells with fine to coarse azurophilic granules, with the primary tumor organs from the prototypic sites (2), small intestine (1), or indeterminate (1). The COO was either T‐cell (3) or NK‐cell (1). Compiling our four cases with that from the literature, all 16 effusion ENKTL cases were Epstein‐Barr virus‐associated and the majority (83%; 10/12) originated from the nonprototypic sites. Five of six (83%) effusion ENKTL cases were of T‐cell lineage. Prognosis was poor with a median survival time of only 2.4 months.

Conclusions

Our study revealed that ENKTL in the effusion might be characterized by anaplastic large cell morphology, cytoplasmic azurophilic granules, and a higher proportion of T‐cell lineage as compared to de novo tumors arising from the prototypic sites. ENKTL rarely presented in effusion, which is associated with dismal outcome. Large international studies are warranted to validate these findings.
Gray plumage color is more cryptic than brown in snowy landscapes in a resident color polymorphic bird
Authors: Koskenpato Katja , Lehikoinen Aleksi , Lindstedt Carita , Karell Patrik
Published: February 2020

Camouflage may promote fitness of given phenotypes in different environments. The tawny owl (Strix aluco) is a color polymorphic species with a gray and brown morph resident in the Western Palearctic. A strong selection pressure against the brown morph during snowy and cold winters has been documented earlier, but the selection mechanisms remain unresolved. Here, we hypothesize that selection favors the gray morph because it is better camouflaged against predators and mobbers in snowy conditions compared to the brown one. We conducted an online citizen science experiment where volunteers were asked to locate a gray or a brown tawny owl specimen from pictures taken in snowy and snowless landscapes. Our results show that the gray morph in snowy landscapes is the hardest to detect whereas the brown morph in snowy landscapes is the easiest to detect. With an avian vision model, we show that, similar to human perceivers, the brown morph is more conspicuous than the gray against coniferous tree trunks for a mobbing passerine. We suggest that with better camouflage, the gray morph may avoid mobbers and predators more efficiently than the brown morph and thus survive better in snowy environments. As winters are getting milder and shorter in the species range, the selection periods against brown coloration may eventually disappear or shift poleward.
Steep topography buffers threatened gymnosperm species against anthropogenic pressures in China
Authors: Jensen Ditte Arp , Ma Keping , Svenning Jens‐Christian
Published: February 2020

China is one of the most species‐rich countries in the world, harboring many rare gymnosperms. Following recent human‐led loss of forests, China is now experiencing increases in forest cover resulting from efforts of reforestation schemes. As anthropogenic activities have previously been found to interact with topography in shaping forest cover in China and considering the large human population and the ongoing population increase of the country, it is important to understand the role of anthropogenic pressures relative to environmental drivers for shaping species distributions here. Based on the well‐established relationship between human population density and topography, we propose a hypothesis for explaining species distributions in a country dominated by human activities, predicting that species are more likely to occur in areas of steep topography under medium human population densities compared to low and high human population densities. Using species occurrence data from the Chinese Vascular Plant Distribution Database along with a common SDM method (maximum entropy modeling), we tested this hypothesis. Our results show that steep topography has the highest importance for predicting Chinese gymnosperm species occurrences in general, and threatened species specifically, in areas of medium human population densities. Consequently, these species are more often found in areas of steep terrain, supporting the proposed hypothesis. Results from this study highlight the need to include topographically heterogeneous habitats when planning new protected areas for species conservation.
Sex‐specific floral attraction traits in a sequentially hermaphroditic species
Authors: Peach Kristen , Liu Jasen W. , Klitgaard Kristen N. , Mazer Susan J.
Published: February 2020

Many angiosperms are hermaphroditic and produce bisexual flowers in which male (pollen export) and female (stigma receptivity) functions are separated temporally. This sequential hermaphroditism may be associated with variation in flower size, color, or pattern, all of which may influence pollinator attraction. In this study, we describe variation in these traits across discrete functional sex stages within and between 225 greenhouse‐grown individuals of Clarkia unguiculata (Onagraceae). In addition, to identify the effects of floral phenotype on pollinator attraction in this species, we examine the effects of these floral traits on pollen receipt in ~180 individuals in an experimental field array.

Petal area, ultraviolet (UV)‐absorbing nectar guide area, and blue and green mean petal reflectance differ significantly across the functional sex stages of C. unguiculata. Male‐ and female‐phase flowers display significantly different pollinator attraction traits. Petal and UV nectar guide area increase as flowers progress from male phase to female phase, while blue reflectance and green reflectance peak during anther maturation.

In field arrays of C. unguiculata, female‐phase flowers with large UV nectar guides receive more pollen than those with small nectar guides, and female‐phase flowers with high mean blue reflectance values are more likely to receive pollen than those with low blue reflectance. Female‐phase flowers with green mean reflectance values that differ most from background foliage also receive more pollen than those that are more similar to foliage. These findings indicate that components of flower color and pattern influence pollen receipt, independent of other plant attributes that may covary with floral traits. We discuss these results in the context of hypotheses that have been proposed to explain sex‐specific floral attraction traits, and we suggest future research that could improve our understanding of sexual dimorphism in sequentially hermaphroditic species and the evolution of features that promote outcrossing.
Specialization of plant–pollinator interactions increases with temperature at Mt. Kilimanjaro
Authors: Classen Alice , Eardley Connal D. , Hemp Andreas , Peters Marcell K. , Peters Ralph S. , Ssymank Axel , Steffan‐Dewenter Ingolf
Published: February 2020

Aim

Species differ in their degree of specialization when interacting with other species, with significant consequences for the function and robustness of ecosystems. In order to better estimate such consequences, we need to improve our understanding of the spatial patterns and drivers of specialization in interaction networks.

Methods

Here, we used the extensive environmental gradient of Mt. Kilimanjaro (Tanzania, East Africa) to study patterns and drivers of specialization, and robustness of plant–pollinator interactions against simulated species extinction with standardized sampling methods. We studied specialization, network robustness and other network indices of 67 quantitative plant–pollinator networks consisting of 268 observational hours and 4,380 plant–pollinator interactions along a 3.4 km elevational gradient. Using path analysis, we tested whether resource availability, pollinator richness, visitation rates, temperature, and/or area explain average specialization in pollinator communities. We further linked pollinator specialization to different pollinator taxa, and species traits, that is, proboscis length, body size, and species elevational ranges.

Results

We found that specialization decreased with increasing elevation at different levels of biological organization. Among all variables, mean annual temperature was the best predictor of average specialization in pollinator communities. Specialization differed between pollinator taxa, but was not related to pollinator traits. Network robustness against simulated species extinctions of both plants and pollinators was lowest in the most specialized interaction networks, that is, in the lowlands.

Conclusions

Our study uncovers patterns in plant–pollinator specialization along elevational gradients. Mean annual temperature was closely linked to pollinator specialization. Energetic constraints, caused by short activity timeframes in cold highlands, may force ectothermic species to broaden their dietary spectrum. Alternatively or in addition, accelerated evolutionary rates might facilitate the establishment of specialization under warm climates. Despite the mechanisms behind the patterns have yet to be fully resolved, our data suggest that temperature shifts in the course of climate change may destabilize pollination networks by affecting network architecture.
Simplified Compact Perovskite Solar Cells with Efficiency of 19.6% via Interface Engineering
Authors: Li Dedi , Liu Changwen , Chen Shi , Kong Weiguang , Zhang Haichao , Wang Deng , Li Yan , Chang Jianhui , Cheng Chun
Published: February 2020

For the commercialization of perovskite solar cells (PSCs), it is more appealing to develop high‐performance simplified PSCs where perovskite films are just sandwiched between the back and front electrodes, in order to simplify the fabrication process and to reduce the cost. However, to date, this kind of devices shows rather low performance, and there are few researches on this subject. Herein, we report on a kind of compact PSCs (CPSCs) that are free of independent charge transport layers (CTLs). The devices are realized by the use of organic monolayer‐modified effective electrodes, along with the use of [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM)‐assisted anti‐solvent technique to obtain ultra‐thin (~10 nm) PCBM‐embedded perovskite films. Compared to control devices, CPSCs achieve a promising champion power conversion efficiency of 19.6% with largely reduced hysteresis. Moreover, the unencapsulated CPSC shows good stability under ambient atmosphere, with only 10% efficiency loss after 60 days’ storage. This work indicates that, by delicate design, CPSCs with smaller materials consumption in device architecture can perform competitively as conventional PSCs. Further reduction in the actual usage of costly CTL materials can be expected upon our CPSCs by developing more facile and economic methods to prepare ultra‐thin CTLs.
Effectiveness of sacubitril–valsartan in cancer patients with heart failure
Authors: Martín‐Garcia Ana , López‐Fernández Teresa , Mitroi Cristina , Chaparro‐Muñoz Marinela , Moliner Pedro , Martin‐Garcia Agustin C. , Martinez‐Monzonis Amparo , Castro Antonio , Lopez‐Sendon Jose L. , Sanchez Pedro L.
Published: February 2020

Aims

Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy‐related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD.

Methods and results

We performed a retrospective multicentre registry (HF‐COH) in six Spanish hospitals with cardio‐oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow‐up was 4.6 [1; 11] months. Sixty‐seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti‐cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty‐nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty‐five per cent were on beta‐blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N‐terminal pro‐B‐type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow‐up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril–valsartan dose (low or medium/high doses).

Conclusions

Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N‐terminal pro‐B‐type natriuretic peptide levels, and symptomatic status in patients with CTRCD.
Ischaemic cardiomyopathy. Pathophysiological insights, diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology
Authors: Cabac‐Pogorevici Irina , Muk Balazs , Rustamova Yasmin , Kalogeropoulos Andreas , Tzeis Stylianos , Vardas Panos
Published: February 2020

Ischaemic cardiomyopathy (ICM) represents an important cardiovascular condition associated with substantially increased morbidity and mortality. It is characterised from a broad spectrum of clinical manifestations and pathophysiological substrates and its diagnosis is based on the demonstration of significant left ventricular dysfunction in the context of significant epicardial coronary artery disease. Contemporary management aims at improving prognosis through evidence‐based pharmacotherapy and device therapy, where indicated. Whilst the beneficial role of revascularisation remains clear in patients with strong indications such as those with symptoms and/or acute coronary syndromes, for those patients that are asymptomatic and suffer from stable ischaemic heart disease the impact of revascularisation on hard outcomes remains less well defined and currently its adoption is hampered by the lack of robust randomised data. The aim of this review is therefore to provide a constructive appraisal on the pathophysiology of ICM, the role of the various non‐invasive imaging techniques in the diagnosis of ICM and the differentiation between viable and non‐viable myocardium and finally discourse the potential role of revascularisation and contemporary device therapy in the management of patients with ICM.
A Gold‐Catalyzed Acid‐Assisted Regioselective Cyclization for the Synthesis of Polysubstituted Oxazoles
Authors: Wang Qian , Hoffmann Stephanie , Schießl Jasmin , Rudolph Matthias , Rominger Frank , Hashmi A. Stephen K.
Published: February 2020

Polysubstituted oxazole derivatives are obtained through a regioselective gold‐catalyzed reaction of α‐alkynylamides and alkynoates in the presence of nitriles. The intermediary obtained gold carbenes are generated by alkyne oxidation with a pyridine N‐oxide. Acidic conditions ensure that only one of the two carbonyl oxygen atoms in these intermediates selectively cyclizes to the products in excellent yields.
Calix[6]arene Derivatives with Differently Modified Bridges
Authors: Shalev Ori , Biali Silvio E.
Published: February 2020

A calix[6]arene derivative where all methylene bridges have been formally replaced by two different types of groups (carbonyl and bromomethylene, 7), was prepared via bromination (NBS, CH2Cl2, irradiation) of a diketocalix[6]arene. Reaction of all‐trans 7 with MeOH afforded the all‐trans decamethoxy ether calix[6]arene derivative.
Scale‐down simulators for mammalian cell culture as tools to access the impact of inhomogeneities occurring in large‐scale bioreactors
Authors: Paul Katrin , Herwig Christoph
Published: February 2020

During the scale‐up of a bioprocess, not all characteristics of the process can be kept constant throughout the different scales. This typically results in increased mixing times with increasing reactor volumes. The poor mixing leads in turn to the formation of concentration gradients throughout the reactor and exposes cells to varying external conditions based on their location in the bioreactor. This can affect process performance and complicate process scale‐up. Scale‐down simulators, which aim at replicating the large‐scale environment, expose the cells to changing environmental conditions. This has the potential to reveal adaptation mechanisms, which cells are using to adjust to rapidly fluctuating environmental conditions and can identify possible root causes for difficulties maintaining similar process performance at different scales. This understanding is of utmost importance in process validation. Additionally, these simulators also have the potential to be used for selecting cells, which are most robust when encountering changing extracellular conditions. The aim of this review is to summarize recent work in this interesting and promising area with the focus on mammalian bioprocesses, since microbial processes have been extensively reviewed.