bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity of pemetrexed during renal impairment explained—Implications for safe treatment
Authors: Boosman René J. , Dorlo Thomas P. C. , de Rouw Nikki , Burgers Jacobus A. , Dingemans Anne‐Marie C. , van den Heuvel Michel M. , Hendriks Lizza E. L. , Biesma Bonne , Aerts Joachim G. J. V. , Croes Sander , Mathijssen Ron H. J. , Huitema Alwin D. R. , ter Heine Rob 
Published: June 2021

AbstractPemetrexed is an important component of first line treatment in patients with non‐squamous non‐small cell lung cancer. However, a limitation is the contraindication in patients with renal impairment due to hematological toxicity. Currently, it is unknown how to safely dose pemetrexed in these patients. The aim of our study was to elucidate the relationship between pemetrexed exposure and toxicity to support the development of a safe dosing regimen in patients with renal impairment. A population pharmacokinetic/pharmacodynamic analysis was performed based on phase II study results in three patients with renal dysfunction, supplemented with data from 106 patients in early clinical studies. Findings were externally validated with data of different pemetrexed dosing regimens. Alternative dosing regimens were evaluated using the developed model. We found that pemetrexed toxicity was driven by the time above a toxicity threshold concentration. The threshold for vitamin‐supplemented patients was 0.110 mg/mL (95% CI: 0.092‐0.146 mg/mL). It was observed that in patients with renal impairment (estimated glomerular filtration rate [eGFR]: <45 mL/min) the approved dose of 500 mg/m2 would yield a high probability of severe neutropenia in the range of 51.0% to 92.6%. A pemetrexed dose of 20 mg for patients (eGFR: 20 mL/min) is shown to be neutropenic‐equivalent to the approved dose in patients with adequate renal function (eGFR: 90 mL/min), but would result in an approximately 13‐fold lower area under the concentration‐time curve. The pemetrexed exposure‐toxicity relationship is explained by a toxicity threshold and substantially different from previously thought. Without prophylaxis for toxicity, it is unlikely that a therapeutic dose can be safely administered to patients with renal impairment.
BAG3 is a negative regulator of ciliogenesis in glioblastoma and triple‐negative breast cancer cells
Authors: Linder Benedikt , Klein Caterina , Hoffmann Marina E. , Bonn Florian , Dikic Ivan , Kögel Donat 
Published: June 2021

AbstractBy regulating several hallmarks of cancer, BAG3 exerts oncogenic functions in a wide variety of malignant diseases including glioblastoma (GBM) and triple‐negative breast cancer (TNBC). Here we performed global proteomic/phosphoproteomic analyses of CRISPR/Cas9‐mediated isogenic BAG3 knockouts of the two GBM lines U343 and U251 in comparison to parental controls. Depletion of BAG3 evoked major effects on proteins involved in ciliogenesis/ciliary function and the activity of the related kinases aurora‐kinase A and CDK1. Cilia formation was significantly enhanced in BAG3 KO cells, a finding that could be confirmed in BAG3‐deficient versus ‐proficient BT‐549 TNBC cells, thus identifying a completely novel function of BAG3 as a negative regulator of ciliogenesis. Furthermore, we demonstrate that enhanced ciliogenesis and reduced expression of SNAI1 and ZEB1, two key transcription factors regulating epithelial to mesenchymal transition (EMT) are correlated to decreased cell migration, both in the GBM and TNBC BAG3 knockout cells. Our data obtained in two different tumor entities identify suppression of EMT and ciliogenesis as putative synergizing mechanisms of BAG3‐driven tumor aggressiveness in therapy‐resistant cancers.
Synthesis and antimicrobial evaluation of new 2‐pyridinone and 2‐iminochromene derivatives containing morpholine moiety
Authors: Salem Mohamed A. , Abbas Samir Y. , Helal Mohamed H. , Alzahrani Abdullah Y. 
Published: June 2021

AbstractAs trail to overcome on the antimicrobial drug‐resistance problems, new functionalized 2‐pyridinone and 2‐iminochromene derivatives bearing morpholine moiety were designed and synthesized. The 2‐pyridinone derivatives were obtained through the cyclization of cyanoacetohydrazone of 4‐morpholinylacetophenone with 1,3‐dicarbonyl compounds, α,β‐unsaturated nitriles or 2‐(arylidene)malononitriles. The 2‐iminochromene derivatives were synthesized through the ring closure of cyanoacetohydrazonewith salicylaldehyde derivatives. The antibacterial and antifungal activities for the synthesized 2‐pyridinone and 2‐iminochromene derivatives were investigated. Most of the tested compounds showed moderate activity against P. vulgaris. Compounds 4a,b and 5a,b showed moderate activity against G −ve bacteria. All iminochromene derivatives showed moderate activity against C. albicans. Compound 8c was the most active compound.
Performance analysis of modified sine cosine optimized multistage FOPD‐PI controller for load frequency control of an islanded microgrid system
Authors: Mishra Sonalika , Prusty Ramesh Chandra , Panda Sidhartha 
Published: June 2021

AbstractThis research work proposes a modified sine cosine algorithm (mSCA) to optimize the parameters of a multistage fractional‐order PD‐PI (MSFOPD‐PI) controller for load frequency control of an isolated AC microgrid. Microgrid considered here is a cluster of renewable energy sources like photovoltaic (PV), wind turbine generators (WTG) which diverges from their optimal operating point due to change in its environment. Initially, the performance of proposed mSCA algorithms is compared with the original sine cosine algorithm (CSA) well as other techniques like Crow search algorithm (CSA), Artificial bee colony (ABC), Cuckoo Search (CS), Gravitational search algorithm (GSA), Dragonfly (DA) and Genetic algorithm (GA) techniques using benchmark test functions reported in the literature. In the next stage, proposed mSCA is applied to optimize MS FOPD‐PI controller parameters under different fluctuating scenarios of source and load. To demonstrate the supremacy of the proposed MS FOPD‐PI controller the performances are compared with conventional PID, PI and I controllers. A sensitivity analysis is made by varying the system parameters to justify the controller's robustness.
Machine learning modeling of the effects of media formulated with various yeast extracts on heterologous protein production in Escherichia coli
Authors: Tachibana Seiga , Chiou Tai‐Ying , Konishi Masaaki 
Published: June 2021

AbstractIn microbial manufacturing, yeast extract is an important component of the growth media. The production of heterologous proteins often varies because of the yeast extract composition. To identify why this reduces protein production, the effects of yeast extract composition on the growth and green fluorescent protein (GFP) production of engineered Escherichia coli were investigated using a deep neural network (DNN)‐mediated metabolomics approach. We observed 205 peaks from the various yeast extracts using gas chromatography‐mass spectrometry. Principal component analyses of the peaks identified at least three different clusters. Using 20 different compositions of yeast extract in M9 media, the yields of cells and GFP in the yeast extract‐containing media were higher than those in the control without yeast extract by approximately 3.0‐ to 5.0‐fold and 1.5‐ to 2.0‐fold, respectively. We compared machine learning models and found that DNN best fit the data. To estimate the importance of each variable, we performed DNN with a mean increase error calculation based on a permutation algorithm. This method identified the significant components of yeast extract. DNN learning with varying numbers of input variables provided the number of significant components. The influence of specific components on cell growth and GFP production was confirmed with a validation cultivation.
Video Anthology of Movement Disorders Due to Infections in South Asia
Authors: Aggarwal Annu , Adukia Sachin , Bhatt Mohit 
Published: June 2021

AbstractSouth Asia, encompassing many populous countries including India, Pakistan, and Bangladesh, is home to a wide variety of infectious diseases several of which are disproportionately prevalent, endemic or distinctive to the region. These result in considerable morbidity and mortality, which can be greatly reduced through public‐health measures, timely diagnosis and treatment. Some of these infectious diseases have neurological manifestations including movement disorders either due to the pathogen being neuroinvasive or via an immune‐mediated response. For diseases such as Japanese encephalitis, movement disorders are the primary manifestation while for others, they can be a presenting feature. Thus, recognizing these movement disorders is often crucial to the diagnosis of the particular infection, and/or to exclude infection as a cause and arrive at the correct alternate diagnosis. Once diagnosed, the infection‐related movement disorders are treated by targeting the infectious agent, or symptomatically. In this article, we describe and illustrate a variety of movement disorders that are seen in patients infected by viruses, bacteria and parasites in South Asia. This would be of value to neurologists practicing in the region and, with the increasing ease in movement of people and pathogens, those practicing elsewhere.
Soliton‐mode proliferation induced by cross‐phase modulation of harmonic waves by a dark‐soliton crystal in optical media
Authors: Chenui Eugene Aban , Dikandé Alain Moïse 
Published: June 2021

AbstractThe generation of high‐intensity optical fields from harmonic‐wave photons, interacting with dark solitons via a cross‐phase modulation coupling, both propagating in a Kerr nonlinear medium, is examined. The focus is on a pump consisting of time‐entangled dark‐soliton patterns, forming a periodic waveguide along the path of the harmonic‐wave probe. It is shown that an increase of the strength of cross‐phase modulation coupling respective to the self‐phase modulation coupling, favors soliton‐mode proliferation in the bound‐state spectrum of the trapped harmonic‐wave probe. The induced soliton modes, which display structures of periodic soliton lattices, are not just rich in numbers, they also form a great diversity of population of soliton crystals with a high degree of degeneracy.
Local excitation universal parallel transmit pulses at 9.4T
Authors: Geldschläger Ole , Bosch Dario , Glaser Steffen , Henning Anke 
Published: June 2021

PurposeTo demonstrate that the concept of “universal pTx pulses” is applicable to local excitation applications.MethodsA database of B0/ maps from eight different subjects was acquired at 9.4T. Based on these maps, universal pulses that aim at local excitation of the visual cortex area in the human brain (with a flip angle of 90° or 7°) were calculated. The remaining brain regions should not experience any excitation. The pulses were designed with an extension of the “spatial domain method.” A 2D and a 3D target excitation pattern were tested, respectively. The pulse performance was examined on non‐database subjects by Bloch simulations and in vivo at 9.4T using a GRE anatomical MRI and a presaturated TurboFLASH mapping sequence.ResultsThe calculated universal pulses show excellent performance in simulations and in vivo on subjects that were not contained in the design database. The visual cortex region is excited, while the desired non‐excitation areas produce the only minimal signal. In simulations, the pulses with 3D target pattern show a lack of excitation uniformity in the visual cortex region; however, in vivo, this inhomogeneity can be deemed acceptable. A reduced field of view application of the universal pulse design concept was performed successfully.ConclusionsThe proposed design approach creates universal local excitation pulses for a flip angle of 7° and 90°, respectively. Providing universal pTx pulses for local excitation applications prospectively abandons the need for time‐consuming subject‐specific B0/ mapping and pTx‐pulse calculation during the scan session.
A novel and effective way to impose boundary conditions and to mitigate the surface effect in state‐based Peridynamics
Authors: Scabbia Francesco , Zaccariotto Mirco , Galvanetto Ugo 
Published: June 2021

AbstractPeridynamics is a nonlocal continuum theory capable of modeling effectively crack initiation and propagation in solid bodies. However, the nonlocal nature of this theory is the cause of two main problems near the boundary of the body: an undesired stiffness fluctuation, the so‐called surface effect, and the difficulty of defining a rational method to properly impose the boundary conditions. The surface effect is analyzed analytically and numerically in the present paper in a state‐based peridynamic model. The authors propose a modified fictitious node method based on an extrapolation with a truncated Taylor series expansion. Furthermore, a rational procedure to impose the boundary conditions is defined with the aid of the fictitious nodes. In particular, Neumann boundary conditions are implemented via the peridynamic concept of force flux. The accuracy of the proposed method is assessed by means of several numerical examples for a state‐based peridynamic model: with respect to the peridynamic model adopting no corrections, the results are significantly improved even if low values of the truncation order for the Taylor expansion are chosen.
Medications for attention‐deficit/hyperactivity disorder in Japan: A retrospective cohort study of label compliance
Authors: Fife Daniel , Voss Erica A. , Hardin Jill , Rofael Hany , Solomon Ira D. , Ryan Patrick B. , Stang Paul 
Published: June 2021

AbstractAimTo assess label compliance in prescription of medications approved for treatment of attention‐deficit/hyperactivity disorder (ADHD) in Japan at the time of this study: methylphenidate (MPH), atomoxetine, and guanfacine.MethodsRetrospective descriptive study was conducted in prevalent‐user cohorts from the Japan Medical Data Center database. Patients who were prescribed a study drug between January 1, 2013 and September 30, 2018 and were in the database for ≥30 days were included. A prescription was considered compliant if all 4 criteria were satisfied: appropriate age, daily dose not exceeding the approved maximum, no contraindicated concurrent medications, and no contraindicated conditions.ResultsAmong 17 418 patients who were prescribed a study drug during 2013‐2018, 73% were male and 53% were children (aged <18 years). Fewer than 2% of prescriptions were for patients outside the approved age, 10%‐13% of patients in the atomoxetine and MPH cohorts received ≥1 prescription exceeding maximum approved dose, no patients were co‐prescribed a contraindicated medication, and 16%–18% of patients in the MPH cohorts had ≥1 contraindicated condition. During their first 500 days of use, for approximately 73%‐86% of patients, all prescriptions were compliant with all label requirements.ConclusionsAmong patients exposed to ADHD medications in Japan during 2013‐2018, nearly all prescriptions for these medications were label‐compliant for age. For >85% of patients, all prescriptions were label‐compliant for dose, and for approximately 80%, all prescriptions were label‐compliant for contraindicated conditions. We did not find evidence of widespread abuse or noncompliant use of prescribed ADHD medications.
Sex differences in the outcomes of adults admitted to inpatient rehabilitation after stroke
Authors: MacDonald Shannon L. , Hall Ruth E. , Bell Chaim M. , Cronin Shawna , Jaglal Susan B. 
Published: June 2021

AbstractIntroductionSeveral differences have been reported between male and female patients with stroke in clinical and sociodemographic features, treatment, and outcomes. Potential effects in the inpatient rehabilitation population are unclear.ObjectiveTo evaluate the differences between male and female patients in discharge functional status, length of stay, and discharge home after inpatient rehabilitation for stroke.DesignRetrospective, population‐based cohort study.SettingInpatient rehabilitation centers in Ontario, Canada.ParticipantsMale (N = 10,684) and female (N = 9459) patients discharged from acute care between September 1, 2012 and August 31, 2017, with a diagnosis of stroke and subsequently admitted to inpatient rehabilitation.Exposure VariableFemale sex.Main Outcome MeasuresDischarge Functional Independence Measure (FIM) score, length of stay, and discharge home.ResultsFemale patients had a lower functional status at discharge (mean FIM score 94.1 vs. 97.8, p < .001) and a lower proportion were discharged home (81.1% vs. 82.9%, p = .001). Female and male patients had similar rehabilitation length of stay (mean 31.8 vs. 31.7 days, p = .90). In the adjusted analyses, there was no difference in discharge functional status between male and female patients (FIM score β −.20 [95% confidence interval [CI] −0.64 to 0.25]). Female patients had a mean length of stay 2% shorter (0.98 [95% CI 0.96–0.99]) and a higher odds of discharge home (odds ratio [OR] 1.14 [95% CI 1.05–1.24]).ConclusionsThere were no clinically significant sex differences in outcomes after inpatient rehabilitation for stroke. Observed sex disparities in the general stroke population may not be directly applicable to individuals undergoing inpatient rehabilitation.
The assimilation of microwave humidity sounder observations in all‐sky conditions
Authors: Candy Brett , Migliorini Stefano 
Published: June 2021

AbstractNumerical weather prediction (NWP) schemes use a wide variety of satellite observations to help constrain atmospheric analyses. Passive microwave humidity data from channels operating in the water vapour band at 183 GHz, such as those on the Microwave Humidity Sounder (MHS), are an important component of the satellite observing network. At this frequency the observations are very sensitive to scattering from ice crystals and, until recently, quality‐control tests were used at the Met Office to exclude assimilation of these data in regions of strong scattering such as thick cirrus clouds. In the work described here we report on improvements to the pre‐processing and assimilation of MHS data within the global NWP scheme at the Met Office, with the goal of utilising the data in scenes where liquid and ice cloud strongly affect the radiances. These improvements include the introduction of an observation operator that models the effects of ice scattering, and a scene‐dependent observation error model. The error model is based on the estimated cloud ice and cloud liquid in the field of view. The new scheme has increased observation usage of MHS data over ocean by up to 40%. Trials have shown benefits to forecasts in both boreal summer and winter seasons. In the boreal summer period, for example, low‐level wind forecast errors have improved in the Northern Hemisphere extratropics by up to 0.6%. Also, our experiments show evidence of significant improvements to the fit between observations and short‐range forecasts for humidity‐sensitive channels operating in both the microwave and infrared regions of the electromagnetic spectrum.
Retaining problems or solutions? The post‐acquisition performance implications of director retention
Authors: Campbell Robert J. , Busenbark John R. , Graffin Scott D. , Boivie Steven 
Published: June 2021

AbstractResearch SummaryDirector retention is a common practice during acquisitions, whereby the acquiring firm adds at least one director from the target onto its board. Despite the regularity of the phenomenon, little is understood about the post‐acquisition financial implications of director retention. In this exploratory study, we investigate the financial impact (via long‐term investor value appropriation) of director retention in a sample of acquisitions among publicly traded firms. Our empirical analyses consistently illustrate negative financial ramifications of director retention for the acquiring firm across multiple analytic models, time horizons of performance, and samples. We delineate implications for research on boards of directors and acquisitions, and we offer preliminary theoretical logic and empirical analyses for future scholarship to elucidate the mechanisms driving antecedents and outcomes of director retention.Managerial SummaryDespite the prevalence of director retention—a practice where an acquirer adds at least one director from the target onto the board of the ongoing firm—research on the topic is equivocal about the financial implications of this practice. We argue this is a crucial oversight because new directors can have an incredible influence on the trajectory of the firm and its subsequent performance, a fact that is particularly true in the turbulent post‐acquisition period. In our study, we empirically examine the impact of director retention on post‐acquisition performance. Across multiple analyses and time intervals of performance, we consistently find that director retention is negatively associated with the performance of the acquiring firm. Accordingly, our findings suggest that acquirers should generally approach direction retention with caution.
Genotyping‐by‐sequencing resolves relationships in Polygonaceae tribe Eriogoneae
Authors: Pearman Peter B. , Alioto Tyler S. , Trotta Jean‐Remi P. , Columbus J. Travis 
Published: June 2021

AbstractThe resolution of cryptic diversity is essential for understanding the evolutionary diversification of lineages and establishing conservation priorities. We examine relationships in Eriogoneae (Polygonaceae), a diverse lineage in western North America. We ask whether Eriogonum umbellatum, a morphologically and ecologically diverse species, is monophyletic and whether its varieties represent evolutionary lineages. We use genotyping‐by‐sequencing to assemble a SNP dataset for 51 species in the genera Chorizanthe, Eriogonum and Sidotheca. We report a hierarchical phylogenetic analysis using maximum likelihood to estimate the evolutionary history of Eriogoneae. We illustrate admixture components for 21 populations of E. umbellatum, representing four varieties, and test for lineage structure using TreeMix. We identify strongly supported clades within Eriogoneae. Many relationships in the Eucycla + Oregonium and Latifolia clades are supported, while most relationships within the Eriogonum subg. Oligogonum clade and a clade with most Chorizanthe remain unresolved. Eriogonum congdonii resolves within the main E. umbellatum clade, while populations of three varieties of E. umbellatum are closely related to E. ursinum and are associated with serpentine soils. ADmixture and TreeMix analyses suggest E. umbellatum varieties represent evolutionary lineages. These results from SNP data are largely consistent with previous phylogenetic studies of Eriogoneae based on sequence variation. Structure within Oligogonum suggests consistent environmental association and radiation after initial colonization of serpentine. Morphology is unreliable for the infraspecific taxonomy of E. umbellatum. Additional molecular studies are needed to resolve the evolutionary relationships and ecological diversification within this species, in Oligogonum, and in Eriogoneae.