bluuebunny/crossref_metadata_2025 huggingface dataset:
Ghost‐Mirror Approach for Accurate and Efficient Kinetic Monte Carlo Simulation of Seeded Emulsion Polymerization
Authors: Tripathi Amit K. , Tsavalas John G.
Published: June 2020

The kinetic Monte Carlo (kMC) method is well suited to the simulation of seeded emulsion polymerization reactions. Inadequate simulation volume results in an incorrect radical entry rate, and as such that inaccuracy propagates into the particle phase simulation. A novel kMC method is described here that has coined the Ghost‐Mirror approach (GM‐kMC) to guarantee sufficient aqueous phase simulation volume while minimizing the number of dispersed phase environments, and while maintaining accuracy and consistency with results produced by kMC simulations. To do so, a subset of a kMC method is replicated where only the aqueous phase reactions are treated in that extended volume; particle phases in those replicated volumes are untreated, as “ghosts”. In doing so, a critical condition for aqueous phase simulation volume is calculated to yield accurate results in the overall system. Important to emphasize though is that one does not require the equivalent number of simulated particles in the GM‐kMC approaches. The required number of particles to simulate accurate results can be even orders of magnitude smaller than the kMC approach; inherently offering significant gains in computational efficiency. This is extended further, reducing the required simulation time, by a hybrid extension to this GM‐kMC method.
A Prospective Validation of the Updated Movement Disorders Society Research Criteria for Prodromal Parkinson's Disease
Authors: Giagkou Nikolaos , Maraki Maria I. , Yannakoulia Mary , Kosmidis Mary H. , Dardiotis Efthimios , Hadjigeorgiou Georgios M. , Sakka Paraskevi , Ntanasi Eva , Anastasiou Costas A. , Xiromerisiou Georgia , Stefanis Leonidas , Scarmeas Nikolaos , Stamelou Maria
Published: June 2020

Objective

The objective of this study was to validate the recently updated research criteria for prodromal Parkinson's disease (pPD) proposed by the International Parkinson's Disease and Movement Disorders Society.

Methods

A total of 16 of 21 markers of pPD were ascertained in the Hellenic Longitudinal Investigation of Aging and Diet cohort composed of community‐dwelling individuals aged ≥65 years. The probability of pPD was calculated for 961 individuals without Parkinson's disease (PD) or dementia with Lewy bodies at baseline who were followed‐up for a median of 3 years. The ability of the criteria to predict conversion to PD/dementia with Lewy bodies was assessed by estimating their sensitivity and specificity, plotting receiver operating characteristics curves, and using logistic regression. These analyses were repeated using the original criteria.

Results

No incident PD/dementia with Lewy bodies case had probable pPD at baseline (ie, ≥80% pPD probability). At cut‐offs of 10%, 30%, and 50% probability of pPD, the sensitivity and specificity of the criteria ranged from 4.5% to 27.3%, and 85.7% to 98.3% respectively. The area under the receiver operating characteristics curve was 0.691 (95% confidence intervals, 0.605–0.777). In logistic regression models, the criteria‐derived posttest odds of pPD were a significant predictor of conversion at follow‐up. The updated criteria performed similarly to the original but showed a slight increase in sensitivity.

Conclusions

The new criteria demonstrated suboptimal sensitivity in our random sample of community‐dwelling individuals. The absence of specialized assessments with high likelihood ratios in our cohort could be hindering the demonstration of higher sensitivities. Such assessments should be a part of future validation attempts. © 2020 International Parkinson and Movement Disorder Society
The impact of high temperatures and extreme heat to delays on the London Underground rail network: An empirical study
Authors: Greenham Sarah , Ferranti Emma , Quinn Andrew , Drayson Katherine
Published: June 2020

Rail infrastructure is vulnerable to extreme weather events, resulting in damage and delays to networks. The impact of heat is a major concern for the London Underground (LU) by Transport for London (TfL) both now and in future, but existing studies are limited to passenger comfort on the deep tube and do not focus on infrastructure or the vast majority of the network, which is in fact above ground. For the first time, the present empirical study examines quantitatively the statistical relationship between LU delays (by synthesizing 2011–2016 industry data) with air temperature data (from Met Office archives). A range of testing shows strong statistical relationships between most delay variables and high temperatures, though not causality. Relationships were found between high temperatures and delays associated with different asset classes on different LU lines. Track‐related delays, often the focus of high‐temperature research (i.e. track buckling), show a relationship, although this is small relative to delays caused by other assets. Using UK Climate Projections 2009 (UKCP09) and assuming a similar future performance indicates that the share of annual delays owed to temperatures > 24°C may increase in frequency and length, depending on the emissions scenario. Recommendations include extending the analysis to the LU asset scale and considering the local environment to understand failure causality in order to mitigate future heat risk. A review of how TfL and other infrastructure operators capture delays for future analysis is necessary to facilitate climate resilience benchmarking between networks.
Recurrent de novo WFS1 pathogenic variants in Chinese sporadic patients with nonsyndromic sensorineural hearing loss
Authors: Guan Jing , Wang Hongyang , Lan Lan , Wu Yusen , Chen Guohui , Zhao Cui , Wang Dayong , Wang Qiuju
Published: June 2020

Background

Hereditary hearing loss (HL) is heterogeneous in terms of their phenotypic features, modes of inheritance, and causative gene mutations. The contribution of genetic variants to sporadic HL remains largely expanding. Either recessive or de novo dominant variants could result in an apparently sporadic occurrence of HL. In an attempt to find such variants we recruited 128 Chinese patients with sporadic nonsyndromic sensorineural HL (NSHL) and performed targeted deafness multigene sequencing in these unrelated trios‐families to elucidate the molecular basis.

Methods

We analyzed a total of 384 available members (probands and their two parents) from 128 unrelated Chinese families presenting with bilateral sensorineural HL, in which previous screening had found no mutations with the GJB2, SLC26A4, and MT‐RNR1 genes. We used a targeted genomic enrichment platform to simultaneously capture exons, splicing sites, and immediate flanking intron sequences of 127 known deafness genes. Sanger sequencing was used to identify probands and their two parents segregating causative variants in the candidate gene.

Results

We observed that two heterozygous de novo WFS1 mutations in exon 8: c.2051C>T (p.A684V) and c.2590G>A (p.E864K) in five families. The two de novo WFS1 mutations were found in 3.9% (5/128) of sporadic HL patients. We found that four of the five patients had the same de novo p.A684V mutation, and their audiograms showed symmetrical bilateral and profound sensorineural hearing impairments at all frequencies, but only the proband with de novo p.E864K mutation demonstrated significantly bilateral moderate low–mid frequency sensorineural HL. Our data suggest that this WFS1 p.A684V is likely to be a de novo mutational hot spot.

Conclusions

We found 3.9% (5/128) of sporadic NSHL is caused by de novo WFS1 mutations. Our data provide that the de novo p.E864K mutation is first identified and de novo p.A684V mutation is likely to be a mutational hot spot in WFS1. It is the first study to highlight that WFS1 gene with the two de novo mutations has been indicated to classify the distinct hearing impairment phenotypes. Furthermore, de novo p.A684V serves as a WFS1 mutational hot spot that was found in the Chinese population with sporadic childhood NSHL, and our study also provides pointers toward the necessity for sequencing of asymptomatic parents of a sporadic case with an apparent dominant pathogenic variant.
Turing vegetation patterns in a generalized hyperbolic Klausmeier model
Authors: Consolo Giancarlo , Currò Carmela , Valenti Giovanna
Published: June 2020

The formation of Turing vegetation patterns in flat arid environments is investigated in the framework of a generalized version of the hyperbolic Klausmeier model. The extensions here considered involve, on the one hand, the strength of the rate at which rainfall water enters into the soil and, on the other hand, the functional dependence of the inertial times on vegetation biomass and soil water. The study aims at elucidating how the inclusion of these generalized quantities affects the onset of bifurcation of supercritical Turing patterns as well as the transient dynamics observed from an uniformly vegetated state towards a patterned state. To achieve these goals, linear and multiple‐scales weakly nonlinear stability analysis are addressed, this latter being inspected in both large and small spatial domains. Analytical results are then corroborated by numerical simulations, which also serve to describe more deeply the spatio‐temporal evolution of the emerging patterns as well as to characterize the different timescales involved in vegetation dynamics.
Finite dimensional evolution algebras and (pseudo)digraphs
Authors: Ceballos M. , Núñez J. , Tenorio Á. F.
Published: June 2020

In this paper, we focus on the link between evolution algebras and (pseudo)digraphs. We study some theoretical properties about this association and determine the properties of the (pseudo)digraphs associated with each type of evolution algebras. We also analyze the isomorphism classes for each configuration associated with these algebras providing a new method to classify them, and we compare our results with the current classifications of two‐ and three‐dimensional evolution algebras. In order to complement the theoretical study, we have designed and performed the implementation of an algorithm, which constructs and draws the (pseudo)digraph associated with a given evolution algebra and another procedure to study the solvability of a given evolution algebra.
High/low‐volume center experience predicts outcome of AMS 800 in male stress incontinence: Results of a large middle European multicenter case series
Authors: Queissert Fabian , Hüsch Tanja , Kretschmer Alexander , Anding Ralf , Kirschner‐Hermanns Ruth , Pottek Tobias , Olianas Roberto , Friedl Alexander , Homberg Roland , Pfitzenmaier Jesco , Naumann Carsten M. , Nyarangi‐Dix Joanne , Hofmann Torben , Rose Achim , Schweiger Josef , Hübner Wilhelm , Loertzer Hagen , Bauer Ricarda M. , Haferkamp Axel , Schrader Andres J. ,   Debates On Male Incontinence (DOMINO)‐Project
Published: June 2020

Aim

To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study.

Methods

As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high‐volume centers.

Results

Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high‐volume centers. They implanted significantly more double cuffs (55% vs 12.1%;P < .001), used the perineal approach significantly more often (78% vs 67.7%;P = .003) and chose larger mean cuff sizes (4.63 cm vs 4.42 cm;P = .002). With a mean follow‐up of 18 months, the revision rate was significantly higher at low‐volume centers (38.5% vs 26.7%;P = .037), urethral erosion being the main reason for revision. Social continence (0‐1 pads/24 h) was achieved significantly more often in high‐volume centers (45.5% vs 24.2%;P = .002).

Conclusions

Our study showed significantly better continence results and lower revision rates at high‐volume centers, confirming earlier results that are still true in this decade. We, therefore, recommend surgery for male incontinence at qualified centers.
A branch‐and‐cut approach and alternative formulations for the traveling salesman problem with drone
Authors: Schermer Daniel , Moeini Mahdi , Wendt Oliver
Published: June 2020

In this paper, we are interested in studying the traveling salesman problem with drone (TSP‐D). Given a set of customers and a truck that is equipped with a single drone, the TSP‐D asks that all customers are served exactly once and minimal delivery time is achieved. We provide two compact mixed integer linear programming formulations that can be used to address instances with up to 10 customer within a few seconds. Notably, we introduce a third formulation for the TSP‐D with an exponential number of constraints. The latter formulation is suitable to be solved by a branch‐and‐cut algorithm. Indeed, this approach can be used to find optimal solutions for several instances with up to 20 customers within 1 hour, thus challenging the current state‐of‐the‐art in solving the TSP‐D. A detailed numerical study provides an in‐depth comparison on the effectiveness of the proposed formulations. Moreover, we reveal further details on the operational characteristics of a drone‐assisted delivery system. By using three different sets of benchmark instances, consideration is given to various assumptions that affect, for example, technological drone parameters and the impact of distance metrics.
Adaptive large variable neighborhood search for a multiperiod vehicle and technician routing problem
Authors: Graf Benjamin
Published: June 2020

The VeRoLog Solver Challenge 2018–2019 of the EURO working group vehicle routing and logistics (VeRoLog) considers a multiperiod vehicle and technician routing and scheduling problem. This paper proposes a combination of large neighborhood and local search heuristics and a decomposition approach to efficiently generate competitive solutions under restricted computational resources. The interplay of the heuristics, the decomposition, and the way the search space is explored are orchestrated by an adaptive layer that explicitly considers the instance to be solved, a time limit and the performance of the computing environment. In a computational study it is shown that the method is efficient and effective, especially under tight time restrictions.
A local Fourier analysis of additive Vanka relaxation for the Stokes equations
Authors: Farrell Patrick E. , He Yunhui , MacLachlan Scott P.
Published: June 2020

Multigrid methods are popular solution algorithms for many discretized PDEs, either as standalone iterative solvers or as preconditioners, due to their high efficiency. However, the choice and optimization of multigrid components such as relaxation schemes and grid‐transfer operators is crucial to the design of optimally efficient algorithms. It is well known that local Fourier analysis (LFA) is a useful tool to predict and analyze the performance of these components. In this article, we develop a local Fourier analysis of monolithic multigrid methods based on additive Vanka relaxation schemes for mixed finite‐element discretizations of the Stokes equations. The analysis offers insight into the choice of “patches” for the Vanka relaxation, revealing that smaller patches offer more effective convergence per floating point operation. Parameters that minimize the two‐grid convergence factor are proposed and numerical experiments are presented to validate the LFA predictions.
Effects of Empagliflozin Treatment on Glycerol‐Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial
Authors: Neeland Ian J. , de Albuquerque Rocha Natalia , Hughes Connor , Ayers Colby R. , Malloy Craig R. , Jin Eunsook S.
Published: June 2020

Objective

The aim of this study was to determine the effects of empagliflozin on glycerol‐derived hepatic gluconeogenesis in adults with obesity without type 2 diabetes mellitus (T2DM) using oral carbon 13 (13C)‐labeled glycerol.

Methods

A randomized, double‐blind, placebo‐controlled trial was performed in participants with magnetic resonance imaging assessment of body fat and measurement of glycerol‐derived 13C enrichment in plasma glucose by nuclear magnetic resonance spectroscopy following ingestion of [U‐13C3]glycerol. Participants were randomized to oral empagliflozin 10 mg once daily or placebo for 3 months. Glycerol‐derived 13C enrichment studies were repeated, and treatment differences in the mean percentage of 13C glycerol enrichment in glucose were compared using mixed linear models.

Results

Thirty‐five participants completed the study. Empagliflozin increased glycerol‐derived 13C enrichment between baseline and follow‐up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). No difference was found with placebo. Glycerol‐derived 13C enrichment was lower in participants with high VAT compared with low VAT by 12.6% (P = 0.04), but there was no heterogeneity of the treatment effect by baseline VAT. Glycerol‐derived 13C enrichment was inversely correlated with VAT but was not correlated with weight loss.

Conclusions

VAT is associated with endogenous glycerol–derived hepatic gluconeogenesis, and empagliflozin reduces endogenous glycerol gluconeogenesis in adults with obesity without T2DM. These findings suggest a mechanism by which sodium‐glucose cotransporter 2 inhibitors may prevent T2DM in obesity.
Mixed‐integer quadratic programming for automatic walking footstep placement, duration, and rotation
Authors: Maximo Marcos R. O. A. , Afonso Rubens J. M.
Published: June 2020

This paper presents a mixed‐integer model predictive controller for walking. In the proposed scheme, mixed‐integer quadratic programs (MIQP) are solved online to simultaneously decide center of mass jerks, footsteps positions, durations, and rotations while respecting actuation, geometry, and contact constraints. Most walking controllers require preplanned footstep rotations to avoid dealing with the nonlinearity introduced by foot rotation decision. The main contribution of this work is an optimization formulation where feet rotations are automatically planned to attain a reference speed rotation. Finally, simulation results are shown to present and discuss the capabilities of the proposed formulation.
Wilms tumors and their precursors: Radiological diagnosis versus histology
Authors: Dzhuma Kristina , Ducou Le Pointe Hubert , Coulomb Aurore , Tabone Marie‐Dominique , Bergeron Christophe , Audry Georges , Irtan Sabine
Published: June 2020

The radiological distinction of Wilms tumor (WT) nodules from nephrogenic rests (NR) in patients with multifocal unilateral WT or bilateral disease is challenging. The study aims to compare the radiology assessment of kidney nodules with their final histology in 48 patients. The final histology of 118 nodules corresponded to the initial radiological diagnosis while 40 (25%) nodules were misdiagnosed, 20 being initially diagnosed WT on imaging were proved to be NR at histology. The size of nodules at diagnosis might help to distinguish WT from NR before surgery. Homogeneity did not seem to be a key feature.
Impact of splenectomy on outcomes of hematopoietic stem cell transplantation in pediatric patients with transfusion‐dependent thalassemia
Authors: Sanpakit Kleebsabai , Narkbunnam Nattee , Buaboonnam Jassada , Takpradit Chayamon , Viprakasit Vip , Pongtanakul Bunchoo
Published: June 2020

Background

The role of splenectomy prior to hematopoietic stem cell transplantation (HSCT) is controversial. Only few studies compared the outcomes of splenectomized and nonsplenectomized children with transfusion‐dependent thalassemia (TDT) undergoing allogeneic HSCTs.

Methods

A retrospective analysis was undertaken on a transplantation cohort of TDT patients; August 1987‐December 2014 to compare transplant outcomes between splenectomized and nonsplenectomized groups.

Results

Ninety‐six transplants in 86 TDT patients were analyzed. Sixteen patients were splenectomized before HSCTs. The splenectomized patients were significantly older (8.0 ± 1.9 vs 4.7 ± 0.6 years; P = 0.001), had larger livers and spleens (P = 0.001), and had a significantly shorter neutrophil engraftment time (absolute neutrophil count > 500/mm3; 15.0 ± 2.3 vs 19.2 ± 1.3 days; P = 0.004). Graft rejection occurred in 13.8% of the nonsplenectomized group, but not among the splenectomized patients. Though the splenectomized group's mortality rate was higher (25.0% vs 8.8%), this was not statistically significant (P = 0.491). The main causes of death in both groups were severe infections. The five‐year overall survival (OS) rate was better for the nonsplenectomized group (91.78% vs 75.00%; P = 0.06).

Conclusions

Although splenectomies prior to HSCT for the TDT patients in our cohort were associated with faster neutrophil engraftments and lower rejection rates, they did not produce significantly better OS or affect the mortality. As the splenectomies did not provide any distinct advantages, this procedure should not be routinely performed as a pre‐HSCT regimen for TDT patients with splenomegaly. Better pre‐HSCT preparation for TDT patients, including early and adequate blood transfusions to avoid splenomegaly, is recommended.
Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy–induced vomiting in children: An open‐label, randomized phase 3 trial
Authors: Radhakrishnan Venkatraman , Pai Vishwajeeth , Rajaraman Swaminathan , Mehra Nikita , Ganesan Trivadi , Dhanushkodi Manikandan , Perumal Kalaiyarasi Jayachandran , Rajan Arun Kumar , Selvarajan Gangothri , Ranganathan Rama , Karunakaran Parathan , Sagar Tenali G.
Published: June 2020

Background

Breakthrough chemotherapy–induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open‐label, single‐center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV.

Procedure

Children aged 5‐18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms.

Results

Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm.

Conclusion

Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV.
Thermal conductivity of aligned CNT‐polyethylene nanocomposites and correlation with the interfacial thermal resistance
Authors: Liu Lanyu , Zhang Zhaoxia , Gou Xiaofan
Published: June 2020

Carbon nanotube (CNT) reinforced polymer composites have higher thermal conductivity than polymers themselves, so they have wide application prospects in many thermodynamic applications. It is of great significance to deeply understand the thermal conductivity of polymer nanocomposites and its creations, especially with the CNT‐polymer interface. In this article, for CNT‐polyethylene (PE) nanocomposites, the temperature distribution and thermal conductivity, and its correlation with the CNT volume fraction, the interfacial thermal resistance caused by interfacial defects in the CNT‐PE interface region, and mechanical strain were comprehensively studied through molecular dynamics simulation. The results show that the CNT volume fraction and mechanical stretches have remarkable effects on the thermal conductivity of the nanocomposite, and comparatively the influence of the interfacial defects is weak just in the range of the CNT volume fraction <0.3. The thermal conductivity rapidly increases when the volume fraction of CNTs changes from 0 to 0.20. Under tensile strain, the thermal conductivities κ∥ and κ⊥ (being parallel to and perpendicular to the stretching direction, also the direction of nanotubes) display quite different rules. The κ∥ increases linearly with the tensile strain, while the κ⊥ decreases linearly. After the CNT‐PE interfacial defect degree fd of assessing the defect extent was introduced, its dependence on the interfacial thermal resistance Ri was analytically given, and further the influence of the fd on the thermal conductivity was obtained through comparative studies of with/without interfacial defects. We found that the thermal conductivity has a sharply deduce when the fd is in the range of 30% to 60%.
Nanohydroxyapatite embedded blends of ethylene‐co‐vinyl acetate and millable polyurethane as piezoelectric materials: dielectric, viscoelastic and mechanical features
Authors: Shafeeq Valiyaveetil Haneefa , Subash Cherumannil Karumuthil , Varghese Soney , Unnikrishnan Gopalakrishna Panicker
Published: June 2020

We report the piezoelectric, dielectric and dynamic mechanical features of nanohydroxyapatite (nHA) embedded ethylene‐co‐vinyl acetate (EVA)/millable polyurethane (MPU) elastomer blends. The EVA/MPU/nHA systems were prepared by two‐roll milling followed by compression moulding. The piezoelectric features were probed by dynamic contact electrostatic force microscopy (EFM).The neat EVA/MPU blend was not found to exhibit ferroelectric properties. However, upon incorporation of nHA, butterfly loops of EFM amplitude signals as well as complementary hysteresis curves were obtained, confirming the introduction of ferro‐piezoelectric properties. The ferro‐piezoelectric features were found to be improved with an increase in nHA loading which recorded highest signals for 8 parts per hundred parts of rubber (phr) loaded composites. The fabricated devices generated a peak voltage of 4.02 V and 4.89 V respectively with 6 phr and 8 phr nHA loaded composites. Electrical properties such as dielectric constant, volume resistivity and loss factor as well as dynamic mechanical properties were examined. The viscoelastic features of the systems support the reinforcing feature with filler loading. TEM analysis of the composites indicated a uniform distribution of filler particles in the blend matrix, complementing the observed ferro‐piezoelectric, dielectric and dynamic mechanical properties. The simultaneous modulation of piezoelectric and viscoelastic properties is a preferred feature for fast‐responsive dielectric elastomers for their applications in various piezoelectric devices. © 2020 Society of Chemical Industry
Patients' communication preferences for receiving a cancer diagnosis: Differences depending on cancer stage
Authors: Kim Soo‐Hyun , Kim Jong‐Heun , Shim Eun‐Jung , Hahm Bong‐Jin , Yu Eun‐Seung
Published: June 2020

Objective

This study aimed to identify communication preferences for receiving a cancer diagnosis in South Korean patients and explore differences depending on cancer stage—with or without recurrence/metastasis.

Methods

A total of 312 patients from five cancer centers in South Korea completed the Korean version of the Measure of Patients' Preferences questionnaire, Mini‐Mental Adjustment to Cancer scale, Insomnia Severity Index, and Hospital Anxiety and Depression Scale.

Results

Among patients without recurrence/metastasis, four factors were indicated: “additional information,” “medical information,” “emotional support,” and “supportive environment.” Among patients with recurrence/metastasis, five factors were indicated: “medical information and explanation,” “emotional support,” “supportive environment,” “additional information,” and “informing family.” In the group without recurrence/metastasis, a positive attitude was a significant predictor of the preference for all four factors and a lower anxiety level was a predictor of the preference for additional information. Patients who reported a high level of anxious preoccupation preferred supportive environments. In the group with recurrence/metastasis, patients who showed a high level of cognitive avoidance preferred to receive medical and additional information and emotional support.

Conclusions

Cancer patients' preferences for communication when receiving bad news differ whether recurrence/metastasis or not in South Korea. Especially, patients with recurrence/metastasis preferred a clear explanation of medical information, and physicians informing patients' families about their diagnosis and prognosis. Thus, physicians should take patients' medical and psychological characteristics into consideration when delivering the news regarding their condition.
Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia
Authors: Monroe Madeline N. , Zhaorigetu Siqin , Gupta Vikas S. , Jin Di , Givan Katelyn D. , Curylo Alexander L. , Olson Scott D. , Cox Charles S. , Segura Ana , Buja Louis Maximilian , Grande‐Allen Kathryn Jane , Harting Matthew T.
Published: June 2020

Objective

Abnormal pulmonary vasculature directly affects the development and progression of congenital diaphragmatic hernia (CDH)‐associated pulmonary hypertension (PH). Though overarching structural and cellular changes in CDH‐affected pulmonary arteries have been documented, the precise role of the extracellular matrix (ECM) in the pulmonary artery (PA) pathophysiology remains undefined. Here, we quantify the structural, compositional, and mechanical CDH‐induced changes in the main and distal PA ECM and investigate the efficacy of mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) as a therapy to ameliorate pathological vascular ECM changes.

Methods

Pregnant Sprague‐Dawley rodents were administered nitrofen to induce CDH‐affected pulmonary vasculature in the offspring. A portion of CDH‐affected pups was treated with intravenous infusion of MSC‐EVs (1 × 1010/mL) upon birth. A suite of histological, mechanical, and transmission electron microscopic analyses were utilized to characterize the PA ECM.

Results

The CDH model main PA presented significantly altered characteristics—including greater vessel thickness, greater lysyl oxidase (LOX) expression, and a relatively lower ultimate tensile strength of 13.6 MPa compared to control tissue (25.1 MPa), suggesting that CDH incurs ECM structural disorganization. MSC‐EV treatment demonstrated the potential to reverse CDH‐related changes, particularly through rapid inhibition of ECM remodeling enzymes (LOX and MMP‐9). Additionally, MSC‐EV treatment bolstered structural aspects of the PA ECM and mitigated pathological disorganization as exhibited by increased medial wall thickness and stiffness that, while not significantly altered, trends away from CDH‐affected tissue.

Conclusions

These data demonstrate notable ECM remodeling in the CDH pulmonary vasculature, along with the capacity of MSC‐EVs to attenuate pathological ECM remodeling, identifying MSC‐EVs as a potentially efficacious therapeutic for CDH‐associated pulmonary hypertension.
Effects of CFTR modulators on pharmacokinetics of tobramycin during acute pulmonary exacerbations in the pediatric cystic fibrosis population
Authors: Albright Jared C. , Houck Andrew P. , Pettit Rebecca S.
Published: June 2020

Background

Individuals with cystic fibrosis (CF) require higher dosages of aminoglycosides due to an increased volume of distribution (Vd) and clearance. Optimal dosing of aminoglycosides in the CF population is essential as repeated exposure to aminoglycosides during acute pulmonary exacerbations increases risk of nephrotoxicity and ototoxicity. To date, no studies have evaluated whether chronic cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy affects pharmacokinetics of aminoglycoside antibiotics in patients with CF. The objective of this study was to determine if the addition of a CFTR modulator affects elimination rate (Ke) for intravenously administered tobramycin in the pediatric CF population.

Methods

This retrospective study included patients aged 2 to 18 years with CF receiving chronic therapy with a CFTR modulator. Patients included had an admission both pre‐ and post‐chronic CFTR modulator therapy during which they received therapy with IV tobramycin.

Results

Thirty‐four patients were included in the study. The median time between pre‐ and post‐modulator admissions was 16.5 (13.8) months. Duration of CFTR modulator therapy before post‐modulator admission was a median of 8 (10.3) months. There was no significant difference in Ke (hr−1) between pre‐ and post‐modulator therapy, 0.41 (0.21) pre and 0.39 (0.09) post (P = .5). Vd and peak concentration were similar between both groups. There was no difference in nephrotoxicity as defined by the pRIFLE criteria (P = .25).

Conclusions

The pharmacokinetic parameters of intravenously administered tobramycin during admission for acute pulmonary exacerbation do not appear to change significantly after initiating chronic therapy with a CFTR modulator. Empiric dose adjustments for patients on CFTR modulators are not recommended.
Progress toward Alzheimer's disease treatment: Leveraging the Achilles' heel of Aβ oligomers?
Authors: Fantini Jacques , Chahinian Henri , Yahi Nouara
Published: June 2020

After three decades of false hopes and failures, a pipeline of therapeutic drugs that target the actual root cause of Alzheimer's disease (AD) is now available. Challenging the old paradigm that focused on β‐amyloid peptide (Aβ) aggregation in amyloid plaques, these compounds are designed to prevent the neurotoxicity of Aβ oligomers that form Ca2+permeable pores in the membranes of brain cells. By triggering an intracellular Ca2+overdose, Aβ oligomers induce a cascade of neurotoxic events including oxidative stress, tau hyperphosphorylation, and neuronal loss. Targeting any post‐Ca2+entry steps (e.g., tau) will not address the root cause of the disease. Thus, preventing Aβ oligomers formation and/or blocking their toxicity is by essence the best approach to stop any progression of AD. Three categories of anti‐oligomer compounds are already available: antibodies, synthetic peptides, and small drugs. Independent in silico‐based designs of a peptide (AmyP53) and a monoclonal antibody (PMN310) converged to identify a histidine motif (H13/H14) that is critical for oligomer neutralization. This “histidine trick” can be viewed as the Achilles' heel of Aβ in the fight against AD. Moreover, lipid rafts and especially gangliosides play a critical role in the formation and toxicity of Aβ oligomers. Recognizing AD as a membrane disorder and gangliosides as the key anti‐oligomer targets will provide innovative opportunities to find an efficient cure. A “full efficient” solution would also need to be affordable to anyone, as the number of patients has been following an exponential increase, affecting every part of the globe.
Adjuvant radiation therapy for a subtotally resected, low‐grade hemangiopericytoma of the cerebellum
Authors: Crisostomo Benedict Mihangel P. , Fragrante Edilberto Joaquin V. , Chavez Lorelei L.
Published: June 2020

Intracranial hemangiopericytoma of the posterior fossa represents an infrequent location for a tumor. Reported herein is a case of subtotally resected, cerebellar hemangiopericytoma, diagnosed as a grade I subtype histopathologically according to the World Health Organization classification. Controversy exists regarding whether adjuvant radiation therapy is indicated in such low‐grade, partially‐excised tumors, where treatment is typically reserved for advanced histological grades. Accounting for the biological behavior and propensity for local recurrence of this tumor histology, radiation therapy is often offered. A total dose of 5400 cGy in 30 daily fractions is administered to the residual tumor and postoperative site through 3‐D conformal techniques. Treatment is delivered with 6‐MV photons using a linear accelerator, and set‐up verification is carried out using kV imaging. In the reported case, adequate tumor coverage was achieved with respect to the pertinent organs‐at‐risk. This patient's treatment course was unremarkable, and surveillance imaging at 6 months follow up showed no evidence of residual disease. Longer follow up is recommended to adequately assess local control benefit and survival outcomes for the treatment plan given.
The effect of pirfenidone on rat chronic prostatitis/chronic pelvic pain syndrome and its mechanisms
Authors: Peng Xufeng , Guo Hailin , Chen Jun , Wang Jihong , Huang Jianwen
Published: June 2020

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable problem of the urogenital system. The aetiopathogenesis and effective treatments for CP/CPPS are needed to be untangled. Pirfenidone is a molecule that exhibits anti‐inflammatory, antifibrotic, and antioxidative stress capacities in a variety of animal experiments and clinical trials. This study was aimed to investigate the therapeutic effect of pirfenidone on CP/CPPS and to identify the mechanism responsible for it.

Methods

A CP/CPPS model was induced in rats by intraprostatic injection of complete Freund's adjuvant (CFA). Blood and prostatic tissues were harvested for assessment after the administration of pirfenidone or vehicle for 4 weeks.

Results

The findings revealed that pirfenidone significantly ameliorated chronic pelvic pain and inhibited prostatic inflammation and fibrosis. Further study found that pirfenidone suppressed the expression of proinflammatory mediators, including tumor necrosis factor‐α, interleukin‐1β (IL‐1β), IL‐6, IL‐8. Pirfenidone exhibited a potent antioxidant capacity through improving the activities of glutathione, catalase, total superoxide dismutase, and reducing the production of malondialdehyde. Furthermore, pirfenidone also facilitated the polarization of M2 macrophages and suppressed the activation of the nuclear factor‐κB (NF‐κB) signaling pathway.

Conclusions

Pirfenidone can exert a beneficial effect against CFA‐induced CP/CPPS by anti‐inflammatory, antioxidative, antifibrotic properties, and the function is mediated at least partly through the M2 polarization of macrophages and the inhibition of NF‐κB signaling pathway. These findings suggest that pirfenidone holds promise as a potential therapeutic for the treatment of CP/CPPS.
Mutations at sterol 14α‐demethylases (CYP51A&B) confer the DMI resistance in Colletotrichum gloeosporioides from grape
Authors: Wang Jin , Shi Dongya , Wei Lingling , Chen Wenchan , Ma Weiwei , Chen Changjun , Wang Kai
Published: June 2020

BACKGROUND

Grape anthracnose caused by the ascomycete fungus Colletotrichum gloeosporioides has been widely controlled by demethylation inhibitors (DMIs) for decades in China. The resistance status and mechanism of C. gloeosporioides against DMIs is not well understood.

RESULTS

All difenoconazole‐resistant (DfnR) isolates from vineyards exhibited decreased fitness. Positive cross‐resistance was detected between DMI triazoles. Sequence alignment results from the DfnR and DfnS isolates revealed that multiple mutations are distributed at CgCYP51A, concomitant with mutations at CgCYP51B. The half maximal effective concentration (EC50) values of single deleted and complemented mutants of CgCYP51A and CgCYP51B showed that ΔCgCYP51A became more sensitive to difenoconazole, but not ΔCgCYP51B. Furthermore, all single complemented mutants had a stronger biological fitness than the progenitor strain. All the defectives of ΔCgCYP51A and ΔCgCYP51B could be restored by complementation of the whole corresponding gene from the resistant strains. Relative gene expression of CgCYP51A and CgCYP51B in most of the mutants was greatly upregulated relative to the progenitor isolate when treated with difenoconazole at the same concentration. Moreover, the extension of five amino acids (GNETI) caused by mutation at the stop codon of CgCYP51A, concurrent with other seven amino acid substitutions and the synonymous mutation P10P (CCG → CCT), significantly enhanced DMI resistance.

CONCLUSION

The DMI resistance of C. gloeosporioides selected in vineyards is conferred by mutations at CgCYP51s, and validated by a genetics method. The roles of CgCYP51A and CgCYP51B overlap, and are counter‐balanced, but cannot be replaced reciprocally. © 2020 Society of Chemical Industry
Inhibitory and anti‐inflammatory effects of two antimicrobial peptides moronecidin and temporin‐1Dra against Propionibacterium acnes in vitro and in vivo
Authors: Wu Yun , Zhang Guangxian , Zhou Maojun
Published: June 2020

Proliferation of Propionibacterium acnes (P. acnes) is one of the main pathogenetic mechanisms of acne. Antimicrobial peptides with low‐drug resistance and nonresidual are potential anti‐acne agents. In this study, two antimicrobial peptides named temporin‐1Dra and moronecidin were synthesized and tested their antimicrobial activity against P. acnes in vitro and in vivo. These two peptides inhibited the growth of Escherichia coli, Staphylococcus aureus, Candida albicans, and P. acnes. The minimal inhibitory concentrations (MICs) of temporin‐1Dra and moronecidin to P. acnes were 30 and 10 μM, respectively. Both peptides exhibited strong resistance to heat and pH, but no obvious cytotoxicity to HaCaT cells. They also displayed persistent antimicrobial activities in the microbial challenge test. In the P. acnes‐induced inflammation mouse model, moronecidin significantly decreased the ear swelling thickness in a concentration‐dependent manner. At the 14th day after injection, 20 μg/day moronecidin reduced the ear swelling thickness to 46.15 ± 5.23% compared with the normal cream group. Tissue staining showed that moronecidin effectively reduced abscess and thickness of the dermis layer. Our results indicate that the antimicrobial peptide moronecidin could be developed as a potential natural anti‐acne agent in the cosmetics or pharmaceutical industries.
Radio Frequency Mixer Based on Magnetic Skyrmion
Authors: Song Chengkun , Ma Yunxu , Jin Chendong , Xia Haiyan , Wang Jianing , Zeng Zhaozhuo , Wang Jianbo , Liu Qingfang
Published: June 2020

A radio frequency (RF) mixer constructed by skyrmion‐based spin transfer nano‐oscillator (STNO) is proposed. The skyrmion oscillator is treated as an information carrier and one of the input signals, and a perpendicular microwave field acts as another input signal. It is demonstrated that skyrmion‐based RF mixer can transmit two input signals to an output signal with multiple new frequencies, which are equal to the sum and difference of input frequencies. Through micromagnetic simulations, it is found that the frequency of output signals is modulated by the amplitude of input microwave field as well as the current density applied in skyrmion oscillator and by other magnetic parameters of oscillator (such as magnetic anisotropy). Compared with conventional RF mixer with nonlinear element, such as diode, the skyrmion‐based RF mixer integrates both input signals and output signal functionality with nanometer size, which is more efficient and shows significant potential application in the RF multiplication devices, integrated electronics, and microwave generators.
Fully Printed Inverters using Metal‐Oxide Semiconductor and Graphene Passives on Flexible Substrates
Authors: Singaraju Surya Abhishek , Marques Gabriel Cadilha , Gruber Patric , Kruk Robert , Hahn Horst , Breitung Ben , Aghassi-Hagmann Jasmin
Published: June 2020

Printed and flexible metal‐oxide transistor technology has recently demonstrated great promise due to its high performance and robust mechanical stability. Herein, fully printed inverter structures using electrolyte‐gated oxide transistors on a flexible polyimide (PI) substrate are discussed in detail. Conductive graphene ink is printed as the passive structures and interconnects. The additive printed transistors on PI substrates show an ratio of and show mobilities similar to the state‐of‐the‐art printed transistors on rigid substrates. Printed meander structures of graphene are used as pull‐up resistances in a transistor–resistor logic to create fully printed inverters. The printed and flexible inverters show a signal gain of 3.5 and a propagation delay of 30 ms. These printed inverters are able to withstand a tensile strain of 1.5% following more than 200 cycles of mechanical bending. The stability of the electrical direct current (DC) properties has been observed over a period of 5 weeks. These oxide transistor‐based fully printed inverters are relevant for digital printing methods which could be implemented into roll‐to‐roll processes.
Preparation and characterisation of IAEA‐603, a new primary reference material aimed at the VPDB scale realisation for δ13C and δ18O determination
Authors: Assonov Sergey , Groening Manfred , Fajgelj Ales , Hélie Jean‐Francois , Hillaire‐Marcel Claude
Published: June 2020

Rationale

NBS19 carbonate, a primary reference material (RM) for the Vienna Pee Dee Belemnite (VPDB) scale realisation introduced in 1987, was exhausted in 2009, and no primary RM was available for several years. This study describes the preparation and characterisation of a new RM, IAEA‐603 (Ca‐carbonate, calcite of marble origin), which shall serve as a new primary RM (replacement for NBS19) or primary calibrator aimed at the highest realisation of the VPDB scale for δ13C and δ18O values, including the VPDB‐CO2 δ18O scale.

Methods

IAEA‐603 preparation and characterisation (value transfer) against NBS19 were performed by addressing the major modern technical requirements for the production and characterisation of RMs (ISO Guide 35). IAEA‐603 was produced in a large quantity, and the first batch was sealed into ampoules (0.5 g) to ensure RM integrity during storage; four other batches were sealed for long‐term storage. The most accurate method of CO2 preparation for isotope mass spectrometry was used, namely carbonate–H3PO4 reaction under controlled conditions.

Results

The assigned values of δ13C = +2.460 ± 0.010‰ and δ18O = −2.370 ± 0.040‰ (k = 1) are based on a large number of analyses (~10 mg aliquots) performed at IAEA and address all the known uncertainty components. For aliquots down to 120 μg, the δ18O uncertainty remains unchanged but shall be doubled for δ13C. The uncertainty components considered are as follows: (a) material homogeneity (within and between the 5200 ampoules produced), (b) value assignment against NBS19, (c) storage effects and (d) effect of the 17O correction.

Conclusions

The new primary RM IAEA‐603 replaces NBS19 in its use as the highest calibrator for the VPDB δ13C and δ18O scale, including the VPDB‐CO2 δ18O scale. The use of IAEA‐603 will allow laboratories worldwide to establish consistent realisation of the scales for δ13C and δ18O values and metrological comparability of measurement results for decades. The VPDB scale definition based on NBS19 stays valid.