bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical solution to flow of Casson fluid via stretched permeable wedge with chemical reaction and mass transfer effects
Authors: Hussain Majid , Shoaib Muhammad , A. Ranjha Qasim , Shoaib Anwar Muhammad , Ahmad Zahoor , Inc Mustafa
Published: August 2023

The purpose of this research is to discuss a two-dimensional (2D), laminar, continuous flow of Casson liquid through a stretched porous wedge in the presence of chemical reaction and buoyancy effects over wedge. This research is aimed at analyzing chemically reacting flow of Casson model over a heated porous wedge in order to understand the features of dynamic wedge. The governing equations and involved parameters are nondimensionalized using transformations. Bvp4c, a numerical tool in Matlab is employed to assess the solution. Significant findings of the major dimensionless parameters on state profiles of velocity, temperature and concentration are drawn graphically. The principal results indicate the impacts of Casson parameter, Eckert and Prandtl number, R stretching parameter, [Formula: see text] chemical parameter, Sc Schmidt number, C mass transfer parameter, m wedge angle parameter on concentration, velocity and temperature field. The Sherwood, Nusselt number and skin friction numerical values are presented in tabular form. Major findings show that drag force at wedge declines for greater [Formula: see text]. Nusselt number shrinks for larger behavior for [Formula: see text]. Sherwood number upsurges for greater performance for chemical reaction parameter [Formula: see text]. Moreover, [Formula: see text] upsurges the temperature slowly but the impacts of [Formula: see text] on concentration show a decreasing behavior.
Bifurcation Analysis and Steady-State Patterns in Reaction–Diffusion Systems Augmented with Self- and Cross-Diffusion
Authors: Aymard Benjamin
Published: August 2023

In this article, a study of long-term behavior of reaction–diffusion systems augmented with self- and cross-diffusion is reported, using an augmented Gray–Scott system as a generic example. The methodology remains general, and is therefore applicable to some other systems. Simulations of the temporal model (nonlinear parabolic system) reveal the presence of steady states, often associated with energy dissipation. A Newton method based on a mixed finite element method is provided, in order to directly evaluate the steady states (nonlinear elliptic system) of the temporal system, and validated against its solutions. Linear stability analysis using Fourier analysis is carried out around homogeneous equilibrium, and using spectral analysis around nonhomogeneous ones. For the latter, the spectral problem is solved numerically. A multiparameter bifurcation is reported. Original steady-state patterns are unveiled, not observable with linear diffusion only. Two key observations are: a dependency of the pattern with the initial condition of the system, and a dependency on the geometry of the domain.
Uncovering the Correlation Between Spindle and Ripple Dynamics and Synaptic Connections in a Hippocampal-Thalamic-Cortical Model
Authors: Sriram Sridevi , Natiq Hayder , Rajagopal Karthikeyan , Parastesh Fatemeh , Jafari Sajad
Published: August 2023

Consolidation of new information in memory occurs through the simultaneous occurrence of sharp-wave ripples (SWR) in the hippocampus network, fast–slow spindles in the thalamus network, and up and down oscillations in the cortex network during sleep. Previous studies have investigated the influential and active role of spindles and sharp-wave ripples in memory consolidation. However, a detailed investigation of the effect of membrane voltage of neurons and synaptic connections between neurons in the cortex, hippocampus, and thalamus networks to create spindle and SWR is required. This paper studies the dynamic behaviors of a hippocampal-thalamic-cortical network as a function of synaptic connection between excitatory neurons, inhibitory neurons (in the hippocampus and cortex), reticular neurons, and thalamocortical neurons (in the thalamic network). The bifurcation diagrams of the hippocampus, cortex, and thalamus networks are obtained by varying the strengths of different synaptic connections. The power diagrams for SWR and sleep spindles are shown accordingly. The results show that variations in synaptic self-connection (and inhibitory synaptic connection) of excitatory neurons in the CA3 region, as well as synaptic connection between excitatory neurons from CA1 region to excitatory neurons (and inhibitory neurons) in the cortex network have the most significant influence on dynamical behavior of the network. Furthermore, comparing diagrams for different synaptic connections shows that SWR is formed by excitatory neurons in CA3 region of the hippocampal network, passes through CA1 region, and enters cortex network.
Stochastic Bifurcations and Multistage Order–Chaos Transitions in a 4D Eco-Epidemiological Model
Authors: Ryashko Lev , Perevalova Tatyana , Bashkirtseva Irina
Published: August 2023

A tritrophic “prey-intermediate predator-top predator” population system with disease in the intermediate predator is considered. For this 4D-model, the bifurcation analysis is performed. In this analysis, the rate of the disease transmission is used as a bifurcation parameter. A variety of mono-, bi- and tri-stable behaviors with regular and chaotic attractors are analyzed. It is shown how random disturbances of the bifurcation parameter cause multistage stochastic transformations, noise-induced excitement, and stochastic transitions from order to chaos and reversely. These noise-induced effects are studied in terms of stochastic P- and D-bifurcations.
Parametric Topological Entropy for Multivalued Maps and Differential Inclusions with Nonautonomous Impulses
Authors: Andres Jan , Ludvík Pavel
Published: August 2023

The main purpose of this paper is to investigate a parametric topological entropy for impulsive differential inclusions on tori. In this way, besides other matters, we would like to extend our recent results concerning impulsive differential equations as well as those on “nonparametric” topological entropy to impulsive differential inclusions. Parametric topological entropy, which is usually called a topological entropy for nonautonomous dynamical systems, is considered here via the compositions of associated multivalued Poincaré translation operators with the single-valued time-dependent impulsive maps. On compact polyhedra and, in particular on tori, parametric topological entropy for families of admissible multivalued maps can be estimated from below by means Ivanov-type inequality in terms of the asymptotic Nielsen and Lefschetz numbers which are, unlike the topological entropy, homotopy invariants. In the scalar case, an effective criterion for a positive parametric topological entropy can be given by topological degree arguments for equi-continuous impulsive maps. In a single-valued nonparametric case, a positive topological entropy usually signifies topological chaos. Some simple illustrative examples are provided.
An Extensible Modeling Method Supporting Ontology-Based Scenario Specification and Domain-Specific Extension
Authors: Baek Young-Min , Cho Esther , Shin Donghwan , Bae Doo-Hwan
Published: August 2023

Scenario-based techniques, also known as scenario methods, have been actively employed to resolve intricate problems for engineering complex software systems. Scenarios are powerful tools that allow engineers to analyze the dynamics and contexts of complex systems. Despite the widespread use, there is a lack of a well-established reference framework that systematically organizes key concepts and attributes of scenarios. This has left engineers without a systematic guidance at the method level, hindering their ability to utilize the scenario methods effectively. To address the challenges associated with scenario methods, this study aims to provide a reference framework and modeling method. By conducting a literature review and suggesting a Conceptual Scenario Framework (CSF), we establish a conceptual basis that systematically presents the core concepts and characteristics of scenarios. Additionally, we introduce the Extensible Scenario Modeling Method (ESMM) that empowers engineers to perform scenario modeling and domain-specific extensions using the framework. With the inclusion of the Extensible Scenario Modeling Language (ESML), which comprises domain-general model types and classes for scenario description and ontological analysis, ESMM facilitates flexible design of domain-specific scenario elements through language-level extensions. This study assesses the proposed method in comparison to existing scenario development methods in the automated driving system domain. Through an analysis of their ability to represent scenario data, it was established that the language constructs of ESML possess semantic expressiveness suitable for serving as a reference framework. Furthermore, the findings from the case study validate the extensibility of ESMM for specialization in creating a scenario modeling language tailored to specific domains, while also effectively supporting the ontological analysis of particular application domains.
Benchmarking Whole Knowledge Graph Embedding Techniques
Authors: Bonte Pieter , Hautte Sander Vanden , De Turck Filip , Van Hoecke Sofie , Ongenae Femke
Published: August 2023

Knowledge Graphs (KGs) are gaining popularity and are being widely used in a plethora of applications. They owe their popularity to the fact that KGs are an ideal form to integrate and retrieve data originating from various sources. Using KGs as input for Machine Learning (ML) tasks allows to perform predictions on these popular graph structures. However, KGs cannot directly be used as ML input in their graph representation, they first require to be transformed to a vector space representation through an embedding technique. As ML techniques are data-driven, they can generalize over unseen input data that deviates to some extent from the data they were trained upon. To fully exploit the generalization capabilities of ML algorithms when using embedded KGs as input, small changes in the KGs should also result in small changes in the embedding space. Various embedding techniques for graphs in general exist, however, they have not been tailored towards embedding whole KGs, while KGs can be considered a special kind of graph that adheres to a certain KG schema. This paper evaluates if these existing embedding techniques that embed the whole graphs can represent the similarity between KGs in their embedding space, allowing ML algorithms to generalize over their input. We compare the similarities between KGs in terms of changes in size, entity labels, and KG schema. We found that most techniques were able to represent the similarities in terms of size and entity labels in their embedding space, however, none of the techniques were able to capture the similarities in KG schema.
Left orderability and cyclic branched coverings of rational knots C(2p,2m,2n + 1)
Authors: Meyer Bradley , Tran Anh T.
Published: August 2023

We consider cyclic branched coverings of a 3-parameter family of rational knots in [Formula: see text] and study the left orderability of their fundamental groups. We first compute the nonabelian [Formula: see text]-character varieties of the rational knots [Formula: see text] in the Conway notation, where [Formula: see text] are integers. We then study real points on these varieties and finally use them to determine the left orderability of the fundamental groups of cyclic branched coverings of [Formula: see text].
Tissue optical clearing enhances efficacy of vascular targeted photodynamic therapy of mouse dorsal skin
Authors: Liu Ying , Wang Qiushi , Liu Yidi , Wang Ying , Qiu Haixia , Zhu Dan , Gu Ying , Chen Defu
Published: August 2023

Vascular-targeted photodynamic therapy (V-PDT) is an effective treatment for port wine stains (PWS). However, repeated treatment is usually needed to achieve optimal treatment outcomes, possibly due to the limited treatment light penetration depth in the PWS lesion. The optical clearing technique can increase light penetration in depth by reducing light scattering. This study aimed to investigate the V-PDT in combination with an optical clearing agent (OCA) for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model. Vascular responses were closely monitored with laser speckle contrast imaging (LSCI), optical coherence tomography angiography, and stereo microscope before, during, and after the treatment. We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature. The combination of OCA and V-PDT resulted in significant vascular damage, including vasoconstriction and the reduction of blood flow. Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases, including PWS.
Spatial Structure of Places in Singapore from a Complexity Perspective of the Public Transport Network
Authors: Huynh Hoai Nguyen
Published: August 2023

As cities become increasingly developed, inclusive and equal provision of public services and affordable housing is essential in achieving sustainable growth and development. In Singapore, with much of the population living in public housing and taking public transport, there is a great need to understand their landscape across the country. In this study, using tools from Complexity Science, we elucidated the spatial organization of places in Singapore through public bus transport connectivity, and investigated the association between such pattern to the distribution of the population age groups and property price. From the spatial network of the public transport services, we probed the places’ scale using the continuum percolation approach to uncover their spatial pattern. After that, we employed an information-theoretic measure of complexity to quantify the spatial organization of the system. The results show that there is a critical distance embedded within the public transport system at which the structure of the places in Singapore emerges. In many areas, the connectivity between places map well, and are greatest within the official planning boundary, demonstrating the influence of upstream spatial planning in determining bus networks. Yet in mature towns (particularly those in the central region), bus connectivity spans beyond planning boundaries, suggesting a more organic pattern on the ground in places with a longer history of development. The complexity of the bus network maps remarkably well to residential areas, and was associated with the distribution of resident age groups, and to property prices. In particular, the well-connected areas in and around the central region of Singapore are associated with higher property price and an older population. In contrast, the peripheral less-connected areas tend to see a lower property price and a younger population. The findings can contribute to understanding the existing pattern of physical and social form within an urban system, highlighting the role of complexity science methods in uncovering ‘emergent’ patterns in bus transport networks, beyond initial spatial plans, as areas mature over time. It can also guide future planning by highlighting the areas where more attention is needed to enhance island wide public bus connectivity, and by doing so, enable the public transport system to contribute to reducing potential socio-economic polarization within the system.
Graph Learning Augmented Heterogeneous Graph Neural Network for Social Recommendation
Authors: Zhang Yiming , Wu Lingfei , Shen Qi , Pang Yitong , Wei Zhihua , Xu Fangli , Chang Ethan , Long Bo
Published: August 2023

Social recommendation based on social network has achieved great success in improving the performance of the recommendation system. Since social network (user-user relations) and user-item interactions are both naturally represented as graph-structured data, Graph Neural Networks (GNNs) have thus been widely applied for social recommendation. Despite the superior performance of existing GNNs-based methods, there are still several severe limitations: (i) Few existing GNNs-based methods have considered a single heterogeneous global graph which takes into account user-user relations, user-item interactions, and item-item similarities simultaneously. That may lead to a lack of complex semantic information and rich topological information when encoding users and items based on GNN. (ii) Furthermore, previous methods tend to overlook the reliability of the original user-user relations which may be noisy and incomplete. (iii) More importantly, the item-item connections established by a few existing methods merely using initial rating attributes or extra attributes (such as category) of items, may be inaccurate or sub-optimal with respect to social recommendation. In order to address these issues, we propose an end-to-end heterogeneous global graph learning framework, namely
Graph Learning Augmented Heterogeneous Graph Neural Network
(GL-HGNN) for social recommendation. GL-HGNN aims to learn a heterogeneous global graph that makes full use of user-user relations, user-item interactions and item-item similarities in a unified perspective. To this end, we design a Graph Learner (GL) method to learn and optimize user-user and item-item connections separately. Moreover, we employ a Heterogeneous Graph Neural Network (HGNN) to capture the high-order complex semantic relations from our learned heterogeneous global graph. To scale up the computation of graph learning, we further present the Anchor-based Graph Learner (AGL) to reduce computational complexity. Extensive experiments on four real-world datasets demonstrate the effectiveness of our model.
Electrochemical Analysis of Sunset Yellow, Brilliant Blue, and Tartrazine Using Sensor Amplified with CuNiFe2O4 Hollow Spheres
Authors: Karami Maryam , Shabani-Nooshabadi Mehdi
Published: August 2023

One of the most important edible colours is used in various industries is Sunset Yellow, which is essential to measure according to its consumption. Therefore, a new electrochemical sensor is prepared to measure the food color additives in this work. In this study, CuNiFe2O4 nanospheres to prepare a potent modifier for carbon paste electrode (CPE). Due to environmental toxicity of food color additives, its sensitive, fast and, low-cost determination in workplace environments is of great interest. So, the modified CPE was applied as a sensitivity analysis approach for Sunset Yellow in present Brilliant Blue and Tartarzin in plasma samples. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used as techniques to optimize the analysis and measurement of Sunset Yellow. The calibration curve showed a linear range from 0.5 to 150 μM with a detection limit of 0.15 μM for Sunset Yellow. Simultaneous measurement of three colors, Sunset Yellow, Brilliant Blue and Tartrazine, is done on CPE/CuNiFe2O4 nanospheres surface and in simultaneous measurement received detection limits are 1.60 μM. The prepared sensor shows an outstanding ability to measure sunset in Sunich syrup and edible jelly as real samples.
Electrochemical Determination of Paraquat Using Ordered Mesoporous Carbon (CMK-3) Modified Glassy Carbon Electrode
Authors: Rajaram Rajendran , Kumar Sachin , Ramanujam Kothandaraman , Neelakantan Lakshman
Published: August 2023

Ordered mesoporous carbon namely, CMK-3 was synthesized by nano casting method, and characterized using various physicochemical and electroanalytical tools like HESEM, HRTEM, BET, etc. Using Cyclic voltammetric (CV) measurements on CMK-3 modified glassy carbon electrode (CMK-3/GCE) in the standard redox couple, [Fe(CN)6]3−/4−, the electrochemical surface area was deduced as 0.081 cm2. The modified electrode was used as an electrocatalyst for the determination of one of the herbicides, paraquat (PQ). The modified electrode shows enhanced sensitivity for the determination of PQ in phosphate buffer solution at pH 9.2 as compared to bare GCE. The concentration dependant CV studies showed a linear variation in sensitivity in the concentration range of 60 μM to 450 μM. The effect of the scan rate shows a linear variation in sensitivity as a function of the square root of scan rate suggesting a diffusion-controlled process during the detection of PQ. Anodic stripping square wave voltammetry (ASSWV) reveals the sensitivity and limit of detection as 9.51 μA μM−1 and 64 nM, respectively. The interfering ability of the other foreign molecules like metal ions, environmental samples, biomolecules, and pesticides was analyzed using CMK-3/GCE. The results revealed that the electrode is able to sense paraquat, with the retention in sensitivity ranges between 91% and 102%. The real-time applicability of the electrode was examined using vegetable and fruit extracts. The analysis revealed that the recovery values were between 102 % – 105 %.
Extending the Lifetime of pH Microelectrode with Stabilized Palladium Hydride
Authors: Li Yuanjiao , Perry Samuel C. , Mauzeroll Janine
Published: August 2023

We report a new fabrication method to produce palladium hydride pH microelectrode using a chemical approach to synthesize the palladium hydride. In contrast to electrochemically generated palladium hydride microelectrodes, chemically generated palladium hydride microelectrodes are longer lasting and importantly have a good analytical performance under aerobic conditions. Chemically generated palladium hydride microelectrodes perform best in acid to neutral electrolytes devoid of Cl−. They can readily be produced on 10 μm diameter disk platinum microelectrodes, which makes them attractive candidates for future localized electrochemical studies.
Development of the General Methodology for Determining the Point of Zero Charge of Oxide Films by Contact Angle Titration
Authors: Chen Dihao , Dong Chaofang , Pan Jinshan , Engelhardt George R. , Macdonald Digby D.
Published: August 2023

The point of zero charge (pHpzc) is one of the most important properties in determining the nature of the surface charge on oxide films in contact with aqueous solutions. Contact angle titration is a simple, rapid and direct surface titration approach to determine the pHpzc of oxide films, compared with mass titration, potentiometric titration and batch equilibration method. Although contact angle titration has been an effective method to estimate the pHpzc in the past, there are some limitations in previous methodologies for the correlation between the contact angle and the surface charge density, due to the consideration of only the negative charged OH− at surface or the absence of a vital part of solution potential for the electrochemical potential of H+ in electrolyte. Based on the work of many previous contributors, two general thermodynamic methods for determining the pHpzc of oxide films by contact angle titration are developed here. The methods provide precise, fundamental understandings of the variation of the contact angle with surface charge density, which is of great significance for interfacial science.
Computational Identification of Most Deleterious Missense Mutations in Human PD-1 Gene
Authors: Ahmed Al-Madhagi Haitham
Published: August 2023

Traditional cancer treatment approaches are often hindered by the presence of toxic side effects and the high rate of relapse observed in treated organs. In contrast, novel immunotherapeutic strategies targeting immune checkpoint inhibitors, particularly PD-1, have demonstrated promising results with minimal adverse effects. However, the emergence of immunotherapeutic-resistant tumors, predominantly caused by intrinsic mutations, poses a significant obstacle to successful treatment outcomes. Consequently, the primary objective of this study was to screen for the most detrimental missense mutations in the PD-1 gene associated with immunotherapeutic resistance. To achieve this aim, a comprehensive screening process utilizing 20 web servers, incorporating both sequence- and structure-based methodologies, was undertaken. Through meticulous analysis and mutual disease association sorting, four specific missense mutations were successfully identified. These mutations, namely, R38C, D61V, R94C, and D117V, emerged as the leading contributors to genetic cancer progression and immunotherapeutic resistance against PD-1 blockers. The findings presented in this study are supported by multiple lines of evidence. A thorough examination of protein topology, structural alignment, docking interactions with PD-L1, and protein flexibility collectively confirmed the pathogenic nature of these sorted mutations. By considering these various aspects, we have gained a comprehensive understanding of the underlying mechanisms driving immunotherapeutic resistance. In conclusion, the comprehensive screening process undertaken in this study has successfully identified R38C, D61V, R94C, and D117V as the primary mutations contributing to genetic cancer progression and immunotherapeutic resistance against PD-1 blockers. The integration of protein topology analysis, structural alignment, docking studies with PD-L1, and assessment of protein flexibility have collectively provided robust evidence to support the pathogenic significance of these mutations.
The Seismic Design Process of RC Column Components in SDOF System considering the Earthquake Duration Effect
Authors: Wang Yukui , Zhang Dan , Liu Jing , Hu Zhangqi , Zhong Dou
Published: August 2023

In order to study seismic design process of RC (reinforced concrete) column components considering the effect of earthquake duration, the degradation law of capacity under random amplitude hysteresis history was conducted by the research group, and the estimation method for the energy dissipation capacity of RC column components was suggested. Furthermore, the correlation between the stiffness decay index and energy dissipation capacity, hysteresis histories, and structural parameters was proposed, and the performance classification criteria based on the stiffness decay index was established. On this basis, the connection between the stiffness decay index and structural parameters and seismic parameters was established, and the seismic design process of RC column components in SDOF (single degree of freedom) system was proposed. The research indicated that the proposed seismic design process based on stiffness decay index can effectively consider the effect of earthquake duration. The stiffness decay index is more suitable for defining structural damage than deformation index and Park-Ang index. The stiffness decay index establishes quantitative relationships with seismic parameters and structural parameters, facilitating performance-based design in engineering practice. The increase in earthquake duration exacerbates the damage of RC column components, and this effect is more pronounced at the beginning of the earthquake and gradually decreases over time.
Modelling Method on Dynamic Optimal Setting and Associated Control for Intermittent Bus Lane
Authors: Xie Xiaolan , Dong Luxi , Feng Liangyuan , Zhang Lieping , Li Hailing
Published: August 2023

A new type of dynamic bus lane not only ensures the strategy of bus priority but also significantly improves the spatiotemporal utilization of road resources and reduces the conflicting demands of buses and social vehicles on road resources. Firstly, the heterogeneity of bus arrival time is analysed according to the process of aggregation and dissipation of vehicle queues at intersections. Considering the correlation between the operating states of social vehicles and buses, a dynamic control strategy for bus lane based on the insertable interval of social vehicles is established. Secondly, combining the setting conditions of the intermittent bus lane control area with the correlation scenario of signal control at intersections and then according to the HCM 2010 vehicle delay equation and the BPR function, the associated optimized control model with the minimum total travel time consumption of the road section as the objective function is constructed. The global optimal control of the intermittent bus lane is realized through the computational experiment. Finally, the setting conditions and benefits of three lane organization schemes (including intersect (i.e., no bus priority), parallel, and intermittent bus lanes) are compared and analysed through case study. The results indicate that the intermittent priority bus lanes have opening hours, which can not only ensure bus priority but also expand the right way for social vehicles and make full use of road space resources, thus improving the overall traffic efficiency.
Supp Figure S1 from Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5–13/TESARO PR-30–50–10-C BRAVO Study
Authors: Turner Nicholas C. , Balmaña Judith , Poncet Coralie , Goulioti Theodora , Tryfonidis Konstantinos , Honkoop Aafke H. , Zoppoli Gabriele , Razis Evangelia , Johannsson Oskar T. , Colleoni Marco , Tutt Andrew N. , Audeh William , Ignatiadis Michail , Mailliez Audrey , Trédan Olivier , Musolino Antonino , Vuylsteke Peter , Juan-Fita Maria Jose , Macpherson Iain R.J. , Kaufman Bella , Manso Luis , Goldstein Lori J. , Ellard Susan L. , Láng István , Jen Kai Yu , Adam Virginie , Litière Saskia , Erban John , Cameron David A.
Published: August 2023

local assessments of progression free survival
Data from Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5–13/TESARO PR-30–50–10-C BRAVO Study
Authors: Turner Nicholas C. , Balmaña Judith , Poncet Coralie , Goulioti Theodora , Tryfonidis Konstantinos , Honkoop Aafke H. , Zoppoli Gabriele , Razis Evangelia , Johannsson Oskar T. , Colleoni Marco , Tutt Andrew N. , Audeh William , Ignatiadis Michail , Mailliez Audrey , Trédan Olivier , Musolino Antonino , Vuylsteke Peter , Juan-Fita Maria Jose , Macpherson Iain R.J. , Kaufman Bella , Manso Luis , Goldstein Lori J. , Ellard Susan L. , Láng István , Jen Kai Yu , Adam Virginie , Litière Saskia , Erban John , Cameron David A.
Published: August 2023

AbstractPurpose:
To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer.
Patients and Methods:
BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician's choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor–positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety.
Results:
After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n = 141) versus 3.1 months in the PC arm [n = 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65–1.44; P = 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63–1.42) and 0.65 (95% CI, 0.46–0.93), respectively. ORR was 35% (95% CI, 26–45) with niraparib and 31% (95% CI, 19–46) in the PC arm.
Conclusions:
Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.
Supplementary Table S3 from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Gene specific methylation results
Supplementary Table S1 from Development and validation of a 15-gene expression signature with superior prognostic ability in stage II colorectal cancer
Authors: Rokavec Matjaž , Özcan Elif , Neumann Jens , Hermeking Heiko
Published: August 2023

Supplementary Table S1 shows a list of 394 genes that were significantly associated with survival in CRC patient cohorts.
Supplementary Fig 3 from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Comparison of locations of positive versus negative cis-eQTMs that overlap with DMRs for: IMU vs HPV(-) (1st row), IMU vs KRT (2nd row), and KRT vs HPV(-) (3rd row) of each panel. (A) CpG island annotations; (B) genic annotations. 1st and 2nd columns are hypermethylated in the first comparison group; 3rd and 4th columns are hypomethylated in the first comparison group. Negative eQTMs are in the 1st and 3rd columns, while positive eQTMs are in the 2nd and 4th columns.
Supplementary Fig 1 from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Companion figure showing significance results for main Figure 1D-F and Figure 2A.
Supplementary Table 5 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Patient markers distinguishing the eight different patient classes
Supplementary Table 4 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Percentages of cancer in model simulations
Supplementary Table 3 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Parameter values of eight patient groups
Supplementary Table 1 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

List of model assumptions
Supplementary Figure 4 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Pairwise combinations of the most sensitive model parameters
Supplementary Figure 2 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Comparison of cancer and non-cancer simulations
FIGURE 5 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Comparison between model simulations and histology images (tufting and bridging). A, Pathology slice of a prostate cancer patient (H&E staining, 400x magnification) showing a “tufted” pattern of growths on the luminal cell layer. B, Model simulation depicting the tufting growth pattern. C, Pathology slice of a prostate cancer patient (H&E staining, 400x magnification) showing bridging; growth of cells from one side of the acinus toward the other side. D, Simulated prostate cancer development showing the bridging growth pattern.
Development and Validation of a 15-gene Expression Signature with Superior Prognostic Ability in Stage II Colorectal Cancer
Authors: Rokavec Matjaz , Özcan Elif , Neumann Jens , Hermeking Heiko
Published: August 2023

Currently, there is no consensus about the use of adjuvant chemotherapy for patients with stage II colorectal cancer. Here, we aimed to identify and validate a prognostic mRNA expression signature for the stratification of patients with stage II colorectal cancer according to their risk for relapse. First, publicly available mRNA expression profiling datasets from 792 primary, stage II colorectal cancers from six different training cohorts were analyzed to identify genes that are consistently associated with patient relapse-free survival (RFS). Second, the identified gene expression signature was experimentally validated using NanoString technology and computationally refined on primary colorectal cancer samples from 205 patients with stage II colorectal cancer. Third, the refined signature was validated in two independent publicly available cohorts of 166 patients with stage II colorectal cancer. Bioinformatics analysis of training cohorts identified a 61-gene signature that was highly significantly associated with RFS (HR = 37.08, P = 2.68*10−106, sensitivity = 89.29%, specificity = 89.61%, and AUC = 0.937). The experimental validation and refinement revealed a 15-gene signature that robustly predicted relapse in three independent cohorts: an in-house cohort (HR = 20.4, P = 8.73*10−23, sensitivity = 90.32%, specificity = 80.99%, AUC = 0.812), GSE161158 (HR = 5.81, P = 3.57*10−4, sensitivity = 64.29%, specificity = 81.67%, AUC = 0.796), and GSE26906 (HR = 7.698, P = 7.26*10−8, sensitivity = 61.54%, specificity = 78.33%, AUC = 0.752). In the pooled training cohort, the 15-gene signature (HR = 4.72, P = 7.76*10−25, sensitivity = 75%, specificity = 67.44%, AUC = 0.784) was superior to the Oncotype DX colon 7-gene signature (HR = 2.698, P = 6.3*10−8, sensitivity = 62.16%, specificity = 55.5%, AUC = 0.633). We report the identification and validation of a novel mRNA expression signature for robust prognostication and stratification of patients with stage II colorectal cancer, with superior performance in the analyzed validation cohorts when compared with clinicopathologic biomarkers and signatures currently used for stage II colorectal cancer prognostication.

Significance:

We identified and validated a 15-gene expression signature for robust prognostication and stratification of patients with stage II colorectal cancer, with superior performance when compared with currently used biomarkers. Therefore, the 15-gene expression signature has the potential to improve the prognostication and treatment decisions for patients with stage II colorectal cancer.
Effect of Benralizumab on Mucus Plugs in Severe Eosinophilic Asthma
Authors: Sakai Natsumi , Koya Toshiyuki , Murai Yui , Tsubokawa Fumito , Tanaka Kentaro , Naramoto Shun , Aoki Ami , Shima Kenjiro , Kimura Yosuke , Watanabe Satoshi , Hasegawa Takashi , Kikuchi Toshiaki
Published: August 2023

Introduction: Mucus plugs are associated with airway obstruction in severe asthma and are involved in the formation of activated eosinophils. Benralizumab, an anti-interleukin-5 receptor antibody, markedly reduces not only peripheral blood eosinophils but also airway eosinophils; however, its effects on mucus plugs have not been clarified. In this study, we examined the efficacy of benralizumab on mucus plugs using computed tomography (CT) imaging. Methods: Twelve patients who were administered benralizumab and underwent CT before and approximately 4 months after the introduction of benralizumab were included in this study, and the number of mucus plugs before and after benralizumab administration was compared. The correlation between the clinical background and treatment effect was also examined. Results: The number of mucus plugs significantly decreased after the introduction of benralizumab. The number of mucus plugs was correlated with sputum eosinophil percentage and eosinophil cationic protein in the sputum supernatants and inversely correlated with forced expiratory volume in 1 s (FEV1). Benralizumab induction resulted in a marked decrease in blood and sputum eosinophil levels and a significant improvement in asthma symptoms, quality of life scores, FEV1, and exacerbation frequency. Furthermore, there was a significant correlation between the reduction in mucus plugs and changes in the symptom score or FEV1. Discussion/Conclusion: These data suggest that benralizumab may have the potential to improve symptoms and respiratory function in patients with severe eosinophilic asthma by reducing mucus plugs.
Comparing Ultrasound with Magnetic Resonance Imaging in the Evaluation of Subungual Glomus Tumors and Subungual Myxoid Cysts
Authors: Dhami Alysha , Vale S. Max , Richardson Michael L , Schachtel April K. , Fleckman Philip
Published: August 2023

Introduction: Subungual myxoid cysts and subungual glomus tumors demonstrate characteristic features on magnetic resonance imaging (MRI) and ultrasound (US). It is not yet well-established whether US is congruent to MRI in diagnostic evaluation of these subungual lesions. Methods: Participants with clinical suspicion for subungual glomus tumors or subungual myxoid cysts were recruited. After clinical evaluation, participants underwent radiography, MRI, and US plus biopsy, aspiration, or excision where possible. Differential diagnoses were revised after review of imaging, and imaging findings were compared to definitive diagnosis by pathology, aspiration, or clinical course. Results: All lesions were visible on both US and MRI and size estimates agreed between the two modalities. US and MRI findings of subungual glomus tumors and subungual myxoid cysts agreed with their known respective imaging characteristics. Conclusions: Diagnosis of subungual myxoid cysts and subungual glomus tumors agreed between US and MRI. We provide sample MRI and US imaging parameters for optimal evaluation of subungual myxoid cysts and glomus tumors. We demonstrate that subungual MRI evaluation can be performed without special equipment, allowing for evaluation by most radiology departments. Lastly, US is user-dependent and may be non-inferior for a sonographer familiar with subungual US.
Perioperative Outcome of Thulium Laser Enucleation of the Prostate versus Robot-Assisted Simple Prostatectomy: A Propensity Score-Matched Analysis
Authors: Hartung Friedrich Otto , Kowalewski Karl-Friedrich , Morina Fehmi , Egen Luisa , Neuberger Manuel , Gruene Britta , Wenk Maren , Kriegmair Maximilian Christian , Nuhn Philipp , Patroi Paul , Westhoff Niklas , Honeck Patrick , Rassweiler-Seyfried Marie-Claire , Michel Maurice Stephan , Herrmann Jonas
Published: August 2023

Introduction: The aim of this study was to investigate and compare clinical safety and efficiency of Thulium laser enucleation of the prostate (ThuLEP) and robot-assisted simple prostatectomy (RASP) for the treatment of large gland benign prostatic hyperplasia in a tertiary care center. Methods: Perioperative data of 39 patients who underwent RASP in our institution from 2015 to 2021 was collected. Propensity score matching using prostate volume, patient age, and body mass index (BMI) was performed from a database of 1,100 Patients treated by ThuLEP from 2009 to 2021. A total of 76 patients were matched. Preoperative parameters such as BMI, age, and prostate volume, as well as intra- and postoperative parameters such as operation time, resection weight, transfusion rate, postoperative catheterization time, length of hospital stay (LoS), hemoglobin drop, postoperative urinary retention (PUR), Clavien-Dindo Classification (CDC), and the Combined Complication Index (CCI), were evaluated. Results: There was no difference in mean hemoglobin drop (2.2 vs. 1.9 g/dL, p = 0.34), yet endoscopic surgery showed superiority in mean operation time (109 vs. 154 min, p < 0.001), mean postoperative catheterization time (3.3 vs. 7.2 days, p < 0.001), and mean LOS (5.4 vs. 8.4 days, p < 0.001). Complication rates evaluated by CDC (p = 0.11) and CCI (p = 0.89) were similar in both groups. Within the documented complications, transfusion rate (0 vs. 3, p = 0.08) and the occurrence of PUR (1 vs. 2, p = 0.5) showed no significant difference. Conclusion: ThuLEP and RASP show similar perioperative efficacy and a low rate of complications. ThuLEP had shorter operation times, shorter catheterization time, and a shorter LoS.
Dual Diagnosis of Trichohepatoenteric Syndrome and Lipoid Proteinosis in a Turkish Child
Authors: Eser Hatice Ceren , Ayyildiz Emecen Durdugul , Topyildiz Ezgi , Isik Esra , Edeer Karaca Neslihan , Atik Tahir , Aksu Guzide , Ozkinay Ferda , Kutukculer Necil
Published: August 2023

Introduction: Trichohepatoenteric syndrome (THES) is caused by pathogenic mutations in TTC37 and SKIV2L genes and characterized by intractable diarrhea, facial dysmorphism, hair abnormality, immunodeficiency, and skin abnormalities. Lipoid proteinosis is caused by pathogenic mutations in ECM1 gene and characterized by deposition of hyaline-like material in various tissues resulting in heterogenous clinical findings. Case Presentation: Four years after the diagnosis and management of THES, due to new clinical findings, another reason for underlying features of the patient was considered. WES was performed and a homozygous c.507delT (p.Arg171GlyfsTer7) mutation in the ECM1 gene was detected. Conclusion: This case provides an example of co-existence of multiple genetic defects in a single patient born to consanguineous parents.
Dilemmas in the Management of an Infant with Neuroblastoma Metastasized to the Muscles
Authors: van Heerden Jaques , van den Akker Machiel , Verlooy Joris , Van Roy Nadine , Laureys Geneviève , Norga Koen
Published: August 2023

The risk stratification of infants with metastatic neuroblastoma (NB) has evolved over time from stage 4/M or IVs/4S/MS/Ms according to various staging systems. Despite these developments for some genetic aberrations, the prognostic value and the impact of soft tissue metastases in infants are not fully understood, nor well described in the different classification systems, hampering the definitions to uniformly treat patients and predict prognosis. A literature review on staging of infants with M/MS disease was performed at the occasion of the diagnosis of NB in an 8-month-old boy who presented with atypical metastatic sites in soft tissue and an aberrant tumor biology. The definitions of stage 4/4S/4s/M/MS/Ms were evaluated and compared to enable tumor risk stratification and inform management. International NB groups use different criteria for defining stage of infants with metastasized NB, resulting in differences in management. Limited literature is available on soft tissue metastases, especially muscular metastases, and is poorly incorporated into management guidelines mainly due to the lack of data. The uncertain prognosis of rare genetic aberrancies may add to the difficulties in treatment decisions. In some rare cases of NB in infants, the international treatment classification is not sufficient for staging and treatment decisions. Based on tumor progression, biology of unknown significance and a lack of evidence to classify a child under 12 months with NB and multiple muscular metastases, the patient was treated as stage 4/M and intermediate-risk protocols with a favorable outcome.