bluuebunny/crossref_metadata_2025_split huggingface dataset:
Worse capecitabine treatment outcome in patients with a low skeletal muscle mass is not explained by altered pharmacokinetics
Authors: Molenaar‐Kuijsten Laura , Jacobs Bart Albertus Wilhelmus , Kurk Sophie Alberdine , May Anne Maria , Dorlo Thomas Petrus Catharina , Beijnen Jacob Hendrik , Steeghs Neeltje , Huitema Alwin Dagmar Redmar 
Published: June 2021

AbstractBackgroundA low skeletal muscle mass (SMM) has been associated with increased toxicity and shorter survival in cancer patients treated with capecitabine, an oral prodrug of 5‐fluorouracil (5‐FU). Capecitabine and its metabolites are highly water‐soluble and, therefore, more likely to distribute to lean tissues. The pharmacokinetics (PK) in patients with a low SMM could be changed, for example, by reaching higher maximum plasma concentrations. In this study, we aimed to examine whether the association between a low SMM and increased toxicity and shorter survival could be explained by altered PK of capecitabine and its metabolites.MethodsPreviously, a population PK model of capecitabine and metabolites in patients with solid tumors was developed. In our analysis, we included patients from this previous analysis for which evaluable abdominal computed tomography (CT)‐scans were available. SMM was measured on CT‐scans, by single slice evaluation at the third lumbar vertebra, using the Slice‐o‐Matic software. The previously developed population PK model was extended with SMM as a covariate, to assess the association between SMM and capecitabine and metabolite PK.ResultsPK and SMM data were available from 151 cancer patients with solid tumors. From the included patients, 55% had a low SMM. No relevant relationships were found between SMM and the PK parameters of capecitabine and, the active and toxic metabolite, 5‐FU. SMM only correlated with the PK of the, most hydrophilic, but inactive and non‐toxic, metabolite α‐fluoro‐β‐alanine (FBAL). Patients with a low SMM had a smaller apparent volume of distribution and lower apparent clearance of FBAL.ConclusionsNo alterations in PK of capecitabine and the active and toxic metabolite 5‐FU were observed in patients with a low SMM. Therefore, the previously identified increased toxicity and shorter survival in patients with a low SMM, could not be explained by changes in pharmacokinetic characteristics of capecitabine and metabolites.
Tricuspid clip implantation using the MitraClip system–A step‐by‐step guide
Authors: Kaple Ryan K. , Agarwal Vratika , Azarbal Amir , Sugeng Lissa , Tang Gilbert H. L. 
Published: June 2021

AbstractMany novel percutaneous interventions are being developed for application in the tricuspid valve position. At the present time, there are no commercially available devices for this application. There has been mounting evidence supporting the safety and efficacy of using the MitraClip system on the tricuspid valve. This review summarizes the peer reviewed data available to date supporting this procedure, outlines the step‐by‐step maneuvers using the MitraClip system for this application, and imaging techniques used prior to and during the procedure.
Random Packing Performance in Continuous Foam Fractionation
Authors: Gu Qianfeng , Xue Xiaochen , Darwesh Osama M. , Habimana Pascal , Liu Wei , Wu Zhaoliang , Li Zhiqiang 
Published: June 2021

AbstractThe #25 teller rosette (TR) random packing was used to enhance foam drainage in foam fractionation under continuous steady‐state conditions and tested using sodium dodecyl sulfate (SDS) as a model surfactant. A column without the #25 TR served as control. The results demonstrated that the #25 TR was capable of enhancing the foam drainage and enrichment ratio while reducing the liquid holdup. The experiment was set up with optimized feed flow rate, liquid pool height, air flow rate, and SDS feed concentration. The enrichment ratio obtained by the #25 TR column was 1.76 times higher compared with the control column. Based on the mass balances and equilibrium relationship, a new method for graphical illustration of theoretical stages is also presented.
Prediction of Thermal Behavior of Polycarbonate/Cerium Oxide Composite Films
Authors: Larosa Claudio , Saldābola Rūta , Zicāns Jānis , Merijs Meri Remo , Eggenhöffner Roberto , Converti Attilio 
Published: June 2021

AbstractThermal effects in polycarbonate (PC) induced by lanthanide oxide nanoparticles (NPs) dispersed by blending were studied using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). DSC data proved the occurrence of solvent‐induced crystallization of polymer doped with cerium oxide (ceria). TGA was performed to predict PC flammability properties in composites with 5–15 wt % ceria NPs at various heating rates. Decomposition was represented by first‐order reactions and the Arrhenius equation. A model was formulated for thin samples subject to uniform heat irradiation, which is based on PC softening and decomposition into several products. This is an attempt to predict composite film burning behavior assuming constant heat transmission to samples.
In Situ Electrochemical Investigations of Inherently Chiral 2,2′‐Biindole Architectures with Oligothiophene Terminals
Authors: Malacrida Claudia , Scapinello Luca , Cirilli Roberto , Grecchi Sara , Penoni Andrea , Benincori Tiziana , Ludwigs Sabine 
Published: June 2021

AbstractThe synthesis and characterization of three new inherently chiral N,N′‐dipropyl‐3,3′‐diheteroaryl‐2,2′‐biindole monomers, nicknamed Ind2T4, Ind2T6 and Ind2Ph2T4, which differ in the number of thiophenes as terminals, are reported. In addition to a full monomer characterization, stable electroactive oligomeric films were obtained by electro‐oxidation upon cycling to potentials which activate the thiophene terminals. Cyclic voltammetry, UV‐Vis‐NIR spectroelectrochemistry and in situ conductance measurements show that oligomeric films of Ind2T6 present the best stability and electrochromic switching performance. Enantioselective tests with a chiral ferrocene amine clearly show the potential as chiral selectors for analytical and sensing purposes.
Pathways of the Extremely Reactive Iron(IV)‐oxido complexes with Tetradentate Bispidine Ligands
Authors: Abu‐Odeh Mahmud , Bleher Katharina , Johnee Britto Neethinathan , Comba Peter , Gast Michael , Jaccob Madhavan , Kerscher Marion , Krieg Saskia , Kurth Marius 
Published: June 2021

AbstractThe nonheme iron(IV)‐oxido complex trans‐N3‐[(L1)FeIV=O(Cl)]+, where L1 is a derivative of the tetradentate bispidine 2,4‐di(pyridine‐2‐yl)‐3,7‐diazabicyclo[3.3.1]nonane‐1‐one, is known to have an S=1 electronic ground state and to be an extremely reactive oxidant for oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) processes. Here we show that, in spite of this ferryl oxidant having the “wrong” spin ground state, it is the most reactive nonheme iron model system known so far and of a similar order of reactivity as nonheme iron enzymes (C−H abstraction of cyclohexane, −90 °C (propionitrile), t1/2=3.5 sec). Discussed are spectroscopic and kinetic data, supported by a DFT‐based theoretical analysis, which indicate that substrate oxidation is significantly faster than self‐decay processes due to an intramolecular demethylation pathway and formation of an oxido‐bridged diiron(III) intermediate. It is also shown that the iron(III)‐chlorido‐hydroxido/cyclohexyl radical intermediate, resulting from C−H abstraction, selectively produces chlorocyclohexane in a rebound process. However, the life‐time of the intermediate is so long that other reaction channels (known as cage escape) become important, and much of the C−H abstraction therefore is unproductive. In bulk reactions at ambient temperature and at longer time scales, there is formation of significant amounts of oxidation product – selectively of chlorocyclohexane – and it is shown that this originates from oxidation of the oxido‐bridged diiron(III) resting state.
Self‐Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery
Authors: Pottanam Chali Sharafudheen , Hüwel Sabine , Rentmeister Andrea , Ravoo Bart Jan 
Published: June 2021

AbstractSupramolecular nanogels are an emerging class of polymer nanocarriers for intracellular delivery, due to their straightforward preparation, biocompatibility, and capability to spontaneously encapsulate biologically active components such as DNA. A completely biodegradable three‐component cationic supramolecular nanogel was designed exploiting the multivalent host‐guest interaction of cyclodextrin and adamantane attached to a polypeptide backbone. While cyclodextrin was conjugated to linear poly‐L‐lysine, adamantane was grafted to linear as well as star shaped poly‐L‐lysine. Size control of nanogels was obtained with the increase in the length of the host and guest polymer. Moreover, smaller nanogels were obtained using the star shaped polymers because of the compact nature of star polymers compared to linear polymers. Nanogels were loaded with anionic model cargoes, pyranine and carboxyfluorescein, and their enzyme responsive release was studied using protease trypsin. Confocal microscopy revealed successful transfection of mammalian HeLa cells and intracellular release of pyranine and plasmid DNA, as quantified using a luciferase assay, showing that supramolecular polypeptide nanogels have significant potential in gene therapy applications.
Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib‐based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients
Authors: Kawaji‐Kanayama Yuka , Kobayashi Tsutomu , Muramatsu Ayako , Uchiyama Hitoji , Sasaki Nana , Uoshima Nobuhiko , Nakao Mitsushige , Takahashi Ryoichi , Shimura Kazuho , Kaneko Hiroto , Kiyota Miki , Wada Katsuya , Chinen Yoshiaki , Hirakawa Koichi , Fuchida Shin‐ichi , Shimazaki Chihiro , Matsumura‐Kimoto Yayoi , Mizutani Shinsuke , Tsukamoto Taku , Shimura Yuji , Horiike Shigeo , Taniwaki Masafumi , Kuroda Junya ,   Kyoto Clinical Hematology Study Group (KOTOSG) Investigators
Published: June 2021

AbstractBackgroundCombinatory strategies with carfilzomib (CFZ), a second‐generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting.AimsTo evaluate the real‐world efficacy and safety of CFZ‐based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group.Methods and ResultsAll 50 patients with RRMM enrolled in this study were treated with CFZ‐based treatments between 2017 and 2019. KRD and KD were administered to 31 and 19 patients, respectively. The overall response rates (ORRs) were 80.6% with KRD and 73.7% with KD. Two‐year progression‐free survival (PFS) and overall survival (OS) were 58.5% and 79.7% with KRD, and 23.1% and 52.6% with KD. By multivariate analysis, refractoriness to BTZ and to LEN were identified as independent unfavorable factors for both PFS and OS. The common non‐hematologic AEs included hypertension (42.0%), fever (24.0%), fatigue (24.0%), and infection (16.0%). No serious heart failure was observed. This study is registered as UMIN000025108.ConclusionThis study suggests the need of the development of novel CFZ‐containing strategy which can overcome the refractoriness to BTZ and/or LEN, while both KRD and KD were shown to be mostly feasible in Asian patients in a daily practice setting.
Ship‐iceberg discrimination from Sentinel‐1 synthetic aperture radar data using parallel convolutional neural network
Authors: Song Lan , Peters Dennis K. , Huang Weimin , Power Desmond 
Published: June 2021

SummaryShips and icebergs are similar in size and intensity in SAR images, so it is difficult to distinguish them in remote sensing images. Deep learning is a technique based on neural networks, which has played an important role in image information processing. In order to address the challenge of ship and iceberg classification, we present a convolutional neural network (CNN) based classification method for iceberg and ship discrimination from Sentinel‐1 SAR images with different polarizations and incidence angles. The method is based on the fixed constant false alarm rate (CFAR) detector and the CNN model has three input channels, then the model was trained using parallel algorithm. The CNN is trained using 1443 images and tested using 161 images. The CNN model is also compared with support vector machine (SVM) and k nearest neighbors (kNN) using the same dataset. Comparison shows the CNN‐based method performs the best, and it achieved a validation accuracy of 96%.
Accelerated Reaction Engineering of Photo(bio)catalytic Reactions through Parallelization with an Open‐Source Photoreactor
Authors: Winkler Christoph K. , Simić Stefan , Jurkaš Valentina , Bierbaumer Sarah , Schmermund Luca , Poschenrieder Silvan , Berger Sarah A. , Kulterer Elisa , Kourist Robert , Kroutil Wolfgang 
Published: June 2021

AbstractPhotobiocatalysis is an alternative approach in synthesis that has received much attention in the recent years. Due to the youth of the topic, only few reactor systems are commercially available. To allow a parallel parameter‐screening approach as often used in the optimization of biocatalytic processes, a photoreactor was developed that can illuminate up to 24 samples at well‐defined reaction conditions. The device‘s optical features and temperature regulation have been thoroughly characterized and its application was demonstrated in four examples, specifically three photobiocatalytic and one photocatalytic process: (i) Light‐dependent decarboxylation using a photodecarboxylase; (ii) Reduction of protochlorophyllide using a protochlorophyllide oxidoreductase; (iii) Photosynthetic oxygen production performed by cyanobacteria; and (iv) (−)‐Riboflavin‐catalyzed (E/Z)‐isomerization of cinnamic acid derivatives.
Long‐term effects of father involvement in childhood on their son's physiological stress regulation system in adulthood
Authors: Choi Jieun , Kim Hyoun K. , Capaldi Deborah M. , Snodgrass James Josh 
Published: June 2021

AbstractUsing a long‐term prospective longitudinal study of U.S. men and their fathers, the present study examined the extent to which the quantity (i.e., shared activities between fathers and sons) and the quality (i.e., assessors’ ratings of fathers’ positive behaviors toward sons and the relationship quality between fathers and sons) of father involvement during childhood influenced sons’ diurnal patterns of salivary cortisol in adulthood (late 30s) directly and indirectly through substance use across the 20s. Findings indicated that the quantity of father involvement during childhood was directly associated with sons’ diurnal cortisol patterns assessed almost 30 years later. Specifically, the quantity of father involvement in childhood significantly increased the intercept (i.e., upon awakening) and also led to a greater reduction in cortisol across the day, suggesting a well‐regulated diurnal cortisol pattern. The quantity of father involvement significantly reduced the amount of sons’ illicit drug and tobacco use across the 20s. Tobacco use across the 20s was associated with a lower cortisol intercept level (upon awakening), although the mediating path was not significant. The present study provided empirical evidence demonstrating long‐term physiological and behavioral consequences of father involvement in childhood and its potency as a crucial early caregiving environment for sons.
An N‐terminal fusion allele to study melanin concentrating hormone receptor 1
Authors: Jasso Kalene R. , Kamba Tisianna K. , Zimmerman Arthur D. , Bansal Ruchi , Engle Staci E. , Everett Thomas , Wu Chang‐Hung , Kulaga Heather , Reed Randal R. , Berbari Nicolas F. , McIntyre Jeremy C. 
Published: June 2021

AbstractCilia on neurons play critical roles in both the development and function of the central nervous system (CNS). While it remains challenging to elucidate the precise roles for neuronal cilia, it is clear that a subset of G‐protein‐coupled receptors (GPCRs) preferentially localize to the cilia membrane. Further, ciliary GPCR signaling has been implicated in regulating a variety of behaviors. Melanin concentrating hormone receptor 1 (MCHR1), is a GPCR expressed centrally in rodents known to be enriched in cilia. Here we have used MCHR1 as a model ciliary GPCR to develop a strategy to fluorescently tag receptors expressed from the endogenous locus in vivo. Using CRISPR/Cas9, we inserted the coding sequence of the fluorescent protein mCherry into the N‐terminus of Mchr1. Analysis of the fusion protein (mCherryMCHR1) revealed its localization to neuronal cilia in the CNS, across multiple developmental time points and in various regions of the adult brain. Our approach simultaneously produced fortuitous in/dels altering the Mchr1 start codon resulting in a new MCHR1 knockout line. Functional studies using electrophysiology show a significant alteration of synaptic strength in MCHR1 knockout mice. A reduction in strength is also detected in mice homozygous for the mCherry insertion, suggesting that while the strategy is useful for monitoring the receptor, activity could be altered. However, both lines should aid in studies of MCHR1 function and contribute to our understanding of MCHR1 signaling in the brain. Additionally, this approach could be expanded to aid in the study of other ciliary GPCRs.
Antipredator phenotype in crucian carp altered by a psychoactive drug
Authors: Vinterstare Jerker , Brönmark Christer , Nilsson P. Anders , Langerhans R. Brian , Berglund Olof , Örjes Jennie , Brodin Tomas , Fick Jerker , Hulthén Kaj 
Published: June 2021

AbstractPredator‐inducible defenses constitute a widespread form of adaptive phenotypic plasticity, and such defenses have recently been suggested linked with the neuroendocrine system. The neuroendocrine system is a target of endocrine disruptors, such as psychoactive pharmaceuticals, which are common aquatic contaminants. We hypothesized that exposure to an antidepressant pollutant, fluoxetine, influences the physiological stress response in our model species, crucian carp, affecting its behavioral and morphological responses to predation threat. We examined short‐ and long‐term effects of fluoxetine and predator exposure on behavior and morphology in crucian carp. Seventeen days of exposure to a high dose of fluoxetine (100 µg/L) resulted in a shyer phenotype, regardless of the presence/absence of a pike predator, but this effect disappeared after long‐term exposure. Fluoxetine effects on morphological plasticity were context‐dependent as a low dose (1 µg/L) only influenced crucian carp body shape in pike presence. A high dose of fluoxetine strongly influenced body shape regardless of predator treatment. Our results highlight that environmental pollution by pharmaceuticals could disrupt physiological regulation of ecologically important inducible defenses.
A guide to state–space modeling of ecological time series
Authors: Auger‐Méthé Marie , Newman Ken , Cole Diana , Empacher Fanny , Gryba Rowenna , King Aaron A. , Leos‐Barajas Vianey , Mills Flemming Joanna , Nielsen Anders , Petris Giovanni , Thomas Len 
Published: June 2021

AbstractState–space models (SSMs) are an important modeling framework for analyzing ecological time series. These hierarchical models are commonly used to model population dynamics, animal movement, and capture–recapture data, and are now increasingly being used to model other ecological processes. SSMs are popular because they are flexible and they model the natural variation in ecological processes separately from observation error. Their flexibility allows ecologists to model continuous, count, binary, and categorical data with linear or nonlinear processes that evolve in discrete or continuous time. Modeling the two sources of stochasticity separately allows researchers to differentiate between biological variation and imprecision in the sampling methodology, and generally provides better estimates of the ecological quantities of interest than if only one source of stochasticity is directly modeled. Since the introduction of SSMs, a broad range of fitting procedures have been proposed. However, the variety and complexity of these procedures can limit the ability of ecologists to formulate and fit their own SSMs. We provide the knowledge for ecologists to create SSMs that are robust to common, and often hidden, estimation problems, and the model selection and validation tools that can help them assess how well their models fit their data. We present a review of SSMs that will provide a strong foundation to ecologists interested in learning about SSMs, introduce new tools to veteran SSM users, and highlight promising research directions for statisticians interested in ecological applications. The review is accompanied by an in‐depth tutorial that demonstrates how SSMs can be fitted and validated in R. Together, the review and tutorial present an introduction to SSMs that will help ecologists to formulate, fit, and validate their models.
Large‐scale patterns of green turtle trophic ecology in the eastern Pacific Ocean
Authors: Seminoff Jeffrey A. , Komoroske Lisa M. , Amorocho Diego , Arauz Randall , Chacón‐Chaverrí Didiher , de Paz Nelly , Dutton Peter H. , Donoso Miguel , Heidemeyer Maike , Hoeffer Gabriel , Todd Jones T. , Kelez Shaleyla , Lemons Garrett E. , Rguez‐Baron Juan M. , Sampson Laura , Santos Baca Lucía , Steiner Todd , Vejar Rubio Maria , Zárate Patricia , Zavala‐Norzagaray Alan , Popp Brian N. 
Published: June 2021

AbstractTrophic position and niche width are fundamental components of a species’ ecology, reflecting resource use, and influencing key demographic parameters such as somatic growth, maturation, and survival. Concepts about a species’ trophic niche space have important implications for local management and habitat protection, and can shed light about resilience to changing climate for species occurring over broad spatial scales. For elusive marine animals such as sea turtles, trophic niche is challenging to study, and researchers often rely on other metrics, such as isotopic niche, as a proxy. Here, stable isotope analysis (δ13C and δ15N values) was conducted on bulk skin tissue of 718 green turtles (Chelonia mydas) distributed among 16 foraging areas in the eastern Pacific from the USA to Chile, a range spanning ~10,000 km. Compound‐specific nitrogen isotope analysis of amino acids (CSIA‐AA) was applied to 21 turtles among seven sites. Isotopic niche space was determined via Bayesian ellipse area (BEA) and convex hull area (CHA) analyses of bulk isotope values, which were also used along with amino acid δ15N values to determine trophic position (TP). Substantial variability in bulk tissue δ13C and δ15N values was found within and among sites, and amino acid δ15N values confirmed this was largely due to spatial differences in baseline nitrogen isotopic compositions, but also to a lesser extent from TP differences among the green turtle foraging populations. Isotope niche space varied among sites, influenced by the diversity of prey types and relative input of terrestrial‐ vs. marine‐derived nutrients; BEAs were the most suitable measurement of isotopic niche space due to the larger influence of outlying values with the CHA approach. Amino acid isotope‐derived TP estimates that accounted for local habitat conditions (e.g., mixed seagrass/macroalgae diet) performed the best among several approaches; TP ranged from 2.3 to 3.6, which indicates an omnivorous diet for most populations. In addition to providing additional spatial resolution for δ13C and δ15N isoscapes in the eastern Pacific, especially in coastal habitats, this study further establishes CSIA‐AA as an effective tool to study the trophic ecology of sea turtles across a variety of food webs and habitats.