bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational design of rasagiline derivatives: Searching for enhanced antioxidant capability
Authors: Reina Miguel , Guzmán‐López Eduardo Gabriel , Galano Annia
Published: September 2022

A set of new rasagiline derivatives is presented. They were designed to be antioxidant compounds with the potential to be used for treating neurodegenerative disorders. They are expected to be multifunctional molecules that can help reduce oxidative stress, which is thought to contribute to neurodegenerative disorders. The CADMA‐Chem computational protocol was used to produce rasagiline derivatives and to evaluate their likeliness as oral drugs and antioxidants. Three of them were identified as the most promising ones. They are proposed to be better free radical scavengers than rasagiline. In addition, they are expected to keep the parent's molecule neuroprotective capability. Hopefully, the results presented here would promote further experimental and theoretical investigations on these compounds.
Assessment of flood regulation service based on source–sink landscape analysis in urbanized watershed
Authors: Zhou Kejing , Jiao Sheng , Han Zongwei , Liu Yicun
Published: September 2022

Facing climate change and rapid urbanization, urban flooding has exposed human and properties to increasing disaster risks. The attention from researchers and decision‐makers to understand the key role of flood regulation service (FRS) in flood management has arisen. However, the mechanism of FRS supply–demand is little known from landscape scale. The FRS assessment methodology considering interacts between source, sink, and flow landscape was proposed in this study. The spatial distributions of surface runoff generation, runoff reduction capacity, and flood inundation were mapped using one‐dimensional rainfall–runoff method SCS‐CN and two‐dimensional flood propagation model CADDIES. Four 3‐hour designed rainfall scenarios ranging from nuisance to extreme events (3a, 11a, 56a, and 100a) were simulated. The Liuyang River Watershed in Changsha Municipality, China was selected for case study. The results showed that, the differences of runoff reduction coefficient and runoff generation volume between vegetation and built‐up landscape have shortened. The peak flood depth, extent of flood inundation, and peak flood velocity have increased continuously with the growing rainfall intensity. The number of source–sink mismatch catchment was the highest under 56 and 100a, and the most of source‐sink match catchments were observed under 3a. Under four rainfall scenarios, the changes of source–sink relationships were witnessed and the potentials of flow zone in source–sink mismatch catchments have increased. The FRS management framework concerning supply–demand connections has been proposed based on source–sink–flow analysis. These findings could provide a scientific basis for sustainable urban flood management and disaster risk mitigation.
One‐pot Synthesis of Propargylamines using Aldehydes‐Amines‐Acetylene via an Efficient Nickel‐Based Silica‐Coated Magnetic Nanocatalyst
Authors: Yadav Priya , Gupta Radhika , Arora Gunjan , Srivastava Anju , Sharma Rakesh K.
Published: September 2022

This work discloses the fabrication and characterization of a highly efficient and magnetically retrievable nickel‐based silica‐coated nanocatalyst that has been utilized to obtain relatively large number of biologically significant propargylamines via one pot fashion. A facile co‐precipitation approach was employed for obtaining spherical and disperse Fe3O4 nanoparticles, which were further modified using suitable protecting and functionalizing agents. The successful formation of nanocatalyst was thoroughly investigated by various physio‐chemical techniques such as FT‐IR, SEM, TEM, XRD, VSM, XPS, ICP‐MS and ED‐XRF The present strategy offered greener reaction condition, broad substrate scope, short reaction time and reusability up to seven runs without any appreciable loss in its catalytic activity. Moreover, it is noteworthy that this atom economical methodology does not require any co‐catalyst or activator. Hence, the outcomes of the present methodology prove the nanocatalyst is a suitable candidate for the development of green and sustainable chemical processes.
Phytochemical Profiling, Antioxidants, Antimicrobial and Anti‐Proliferative Effect of Senna hirsuta against PC‐3 Human Prostate Cancer Cells
Authors: Ramasubramanian Arumugam , Venkatachalam Karthikeyan , Chellaiah Ijin , Chinnathambi Pothiraj , Palanichamy Ayyappan , Nguyen Van‐Huy , Paulraj Balaji
Published: September 2022

The phytochemical profile, antioxidant, antibacterial, and cytotoxicity of Senna hirsuta (M−Sh) leaf extracts were investigated in human prostate cancer PC‐3 cell lines. Antioxidant bioactive components like phenolics, tannins, and flavonoids were measured at 15.36±0.19, 2.97±0.11, and 19.77±0.51, respectively. An intense dose‐dependent radical scavenging activity was observed for M−Sh with 83 % in 500 μg/mL for DPPH. M−Sh boosted ABTS radical inhibition from 35 % at 100 μg/ml to 70 % at 500 μg/ml, whereas hydroxyl radical scavenging was 96 % at 500 μg/ml, significantly greater than butylated hydroxytoluene (91.91 %). The maximum NO scavenging activity of M−Sh was 83 %, and the lipid peroxidation inhibition was 87 % at 500 μg/ml. The M−Sh exhibited antibacterial efficacy against Escherichia coli (25 mm), Bacillus subtilis (24 mm), and Staphylococcus aureus (21 mm). The MTT assay was used to study anti‐proliferative activity, which inhibited PC‐3 cell growth with an IC50 of 257.13 μg/mL over 24 hours. These results demonstrate that M−Sh inhibits PC‐3 cell proliferation by shedding from the surface and assuming a spherical shape. Additionally, the morphology of PC‐3 cells showed shrinkage, blebbing membrane condensation, and nuclear chromatin margination, indicating that M−Sh was cytotoxic to PC‐3 Cells.
Synergistic Effect of Drug Delivery System Combining DOX and V9302 on Gastric Cancer Cells**
Authors: Duan Qianqian , Zhang Qi , Shi Jiaying , Zhang Boye , Zhou Lan , Sang Shengbo , Xue Juanjuan
Published: September 2022

Individual chemotherapeutic drugs usually suffered drug resistance in the cancer treatment, and the combination therapy has aroused great interest which can reduce the resistance. Glutamine inhibitor (V9302) and chemotherapy drug doxorubicin (DOX) were combined for the first time to construct a pH‐sensitive multi‐mode synergistic treatment system BSA@CDs‐V9302/DOX. The synergistic rate CI value of the drugs was less than 1, indicating the combination therapy showed a synergistic effect on reducing cancerous cell viability. In addition, compared with the high toxicity and rapid release of free drug DOX and the poor solubility of glutamine inhibitor V9302, the BSA@CDs‐V9302/DOX administration system not only retains the pharmacological activity of V9302 and DOX, but also has an excellent time‐dependence which is more suitable for continuous treatment. BSA@CDs‐V9302/DOX drug delivery system has excellent long‐term tracing ability, which has a high application value in biomedical field.
In Situ‐Illuminated X‐Ray Photoelectron Spectroscopy Investigation of S‐Scheme Ta2O5/ZnIn2S4 Core–Shell Hybrid Nanofibers for Highly Efficient Solar‐Driven CO2 Overall Splitting
Authors: Wang Kai , Shao Xiuli , Cheng Qiang , Li Ke , Le Xiaoying , Wang Guohong , Wang Hukun
Published: September 2022

Exploring and designing highly efficient solar‐driven CO2 overall splitting photocatalysts toward carbon neutrality is still challenging. Herein, a novel core–shell Ta2O5/ZnIn2S4 heterojunction photocatalyst is fabricated where ZnIn2S4 nanosheets are deposited on mesoporous Ta2O5 nanofibers via electrospinning and hydrothermal methods. In situ‐illuminated X‐ray photoelectron spectra analysis and density functional theory calculation imply that the photoelectrons in ZnIn2S4 can transfer to Ta2O5 though a 2D/1D interface, accelerating the separation of photogenerated electron–hole pairs driven by the built‐in electric field under illumination, coupling the S‐scheme charge transfer mechanism. As a result, the total yield of CO2 overall splitting (including CO and CH4) over ZISTO0.1 is about 4.1 and 5.74 times that of pristine Ta2O5 nanofibers and ZnIn2S4 nanosheets, respectively. This work may pave a promising strategy of designing heterojunction photocatalysts with S‐scheme pathways toward solar fuel generation.
Hierarchical fuzzy‐based Quality of Experience (QoE)‐aware application placement in fog nodes
Authors: Mirampalli Sreenivasu , Srirama Satish Narayana , Wankar Rajeev , Chillarige Raghavendra Rao
Published: September 2022

Fog computing or a fog network is a decentralized network placed in between data source and the cloud to minimize the network latency issues and thus support in‐time service delivery, of Internet of Things (IoT) applications. However, placing computational tasks of IoT applications in fog infrastructure is a challenging task. State of the art focuses on quality of service and quality of experience (QoE) based application placement. In this article, we design hierarchical fuzzy based QoE‐aware application placement strategy for mapping IoT applications with compatible instances in the fog network. The proposed method considers user application expectation parameters and metrics of available fog instances, and assigns the priority of applications using hierarchical fuzzy logic. The method later uses Hungarian maximization assignment algorithm to map applications with compatible instances. The simulation results of the proposed policy show better performance over the existing baseline algorithms in terms of resource gain (RG), processing time reduction ratio (PTRR), and similarly network relaxation ratio. When considering 10 applications in the fog network, our proposed method simulation results show 70.00%, 22.44%, 37.83% improvement in RG, and 28.46%, 37.5%, 23.07% improvement in PTRR, when compared with QoE‐aware, randomized, FIFO algorithms, respectively.
Natural swietenine attenuates diabetic nephropathy by regulating the NF‐κB/NLRP3/Caspase‐1 signaling pathways: In vivo and in vitro study
Authors: Duan Jingyu , He Liangliang , Deng Wenhao , Lu Mengyuan , Zhai Yutong , Pei Feilong , Liu Shuang , Zhang Chunping
Published: September 2022

Swietenine (Swi), isolated from Swietenia macrophylla King ameliorates inflammation and oxidative stress, and diabetic nephropathy has a close connection with them. So the effects of Swi on diabetic nephropathy and its mechanism of action was explored. We divided human mesangial cells into five groups and determined the expression of NF‐κB and NLRP3 inflammasomes in each group. The levels of inflammatory factors IL‐1β and IL‐18 were also measured. To explore the relationship between NF‐κB and NLRP3, we added PDTC, a specific NF‐κB inhibitor, and LPS, and divided the experimental groups into seven groups. We measured the expressions of NF‐κB and NLRP3, and then added MCC950, a specific inhibitor of NLRP3 and LPS, the expression of NLRP3, Caspase‐1, and IL‐1β and IL‐18 were measured. Animals divided into four groups and administered over 8 weeks. Protein excretion, creatinine, urea nitrogen, and uric acid were measured. Swi down regulated the expression of NF‐κB, NLRP3, and Caspase‐1. It reduced the levels of IL‐1β and IL‐18. PDTC decreased the expression of NF‐κB and NLRP3. Compared with the HG + PDTC group, the expression of NF‐κB and NLRP3 in the HG + Swi + PDTC group decreased significantly. After adding lipopolysaccharide, the expression of NF‐κB and NLRP3 increased, but this situation was reversed after adding Swi. After adding LPS, the expression of NLRP3 and Caspase‐1 increased, and the levels of IL‐1β and IL‐18 also increased, but this situation was reversed after the addition of Swi. Swi significantly improved the renal function of mice with diabetic nephropathy and inhibited the activation of NF‐κB and the NLRP3 inflammasome and reduced inflammation by regulating the NF‐κB/NLRP3/Caspase‐1 signaling pathway, thereby improving diabetic nephropathy.
Comparison and optimisation of screening cutoff values for Mycoplasma bovis antibody ELISAs using serum from youngstock
Authors: Bokma Jade , Stuyvaert Sabrina , Pardon Bart
Published: September 2022

Background

Mycoplasma bovis‐associated disease can cause tremendous production losses, welfare issues and high antimicrobial use. Therefore, screening cattle for M. bovis antibodies before entering the herd is a popular and possibly cost‐efficient way to reduce disease introduction. However, interpretation of results can be challenging due to variable accuracy between tests and populations. This study's objectives were to compare the diagnostic test accuracy of three commercially available M. bovis antibody ELISAs (ID‐screen, Bio K302 and Bio K432) and to explore optimal cutoff values for screening purposes.

Methods

A prospective diagnostic test accuracy study was performed on 170 serum samples from youngstock using Bayesian latent class modelling. Samples were categorised using manufacturer and generated cutoff values.

Results

Using the manufacturers' guidelines, ID‐screen, Bio K432 and Bio K302 showed 97.6%, 67.4% and 33.6% sensitivity, and 78.8%, 97.6% and 99.1% specificity, respectively. Optimised cutoffs resulted in 94.8%, 82.6% and 78.3% sensitivity, and 94.2%, 92.5% and 79.4% specificity, respectively.

Conclusions

The highest diagnostic accuracy for detecting M. bovis antibodies was obtained by ID‐screen (≥110%). However, by adjusting cutoff values, the sensitivity of Bio‐X tests could be markedly increased, making these tests also applicable as screening tools.

Limitations

Interpretation needs to be careful as antibodies may be linked to both infectious and non‐infectious status.
Psychological and social well‐being of bony fishes in zoos and aquariums
Authors: Oldfield Ronald G. , Bonano Patrick E.
Published: September 2022

Research on the behavior of animals in zoos has been conducted for decades and observations have provided information that has improved the psychological and social well‐being of animals. However, research on fishes in zoos and aquariums seems to be lacking. Here we assess the current state of research on fishes in zoos and aquariums by surveying peer‐reviewed literature. Our assessment differs from previous surveys in that we examine the taxonomic classes Chondrichthyes (sharks and rays) and Osteichthyes (bony fishes) separately. Our survey finds that bony fishes have been drastically underrepresented in zoo journals, more so than chondrichthyans, revealing an urgent need for zoos and aquariums to conduct research on the behavior of the bony fishes in their care, to ensure a positive state of psychological and social well‐being. To plot a course for the future, we discuss the few studies that have been conducted on the behavior of bony fishes in zoos and aquariums, and we discuss research conducted on bony fishes in food‐fish aquaculture and biomedicine to identify the types of studies that could be conducted in zoos and aquariums. We conclude that data‐driven analyses of fish behavior could aid in development of evidence‐based practices that enhance the well‐being of bony fishes in zoos and aquariums, just as they already do for terrestrial animals.
Vorticity and Vortex Kinematics
Authors: Deville Michel O.
Published: September 2022

The concepts of vorticity and circulation are introduced. The three-dimensional governing equation for the vorticity is obtained. The generation of vorticity on the solid walls is analyzed in detail. For irrotational flows, the modeling rests upon Bernoulli equation. The flow behind a grid solved by Kovasznay provides a benchmark solution for numerical simulation. The chapter ends with the Taylor–Green vortex described by Clebsch potentials.
Plane Irrotational Flows of Perfect Fluid
Authors: Deville Michel O.
Published: September 2022

This chapter treats the theory of irrotational flows of perfect fluids by the use of complex variables. The theory is based on a complex velocity and the related concepts like circulation, flow rate, complex potential. Several simple examples are given. More elaborated is the flow around a circular cylinder with and without circulation . Using conformal mapping and especially the Joukowski transformation, it is possible to consider an aerodynamics application, namely the flow around an airfoil. Blasius theorem allows for the computation of the forces and moment generated by the flow around an immersed body. It is applied to the case of the cylinder and Joukowski profile.
Boundary Layer
Authors: Deville Michel O.
Published: September 2022

The Prandtl’s equations for laminar boundary layer are obtained via dimensional analysis. The case of the flat plate is treated as a suitable example for the development of the boundary layer on a simple geometry. Various thicknesses are introduced. The integration of Prandtl’s equation across the boundary layer produces the von Kármán integral equation which allows the elaboration of the approximate von Kármán-Pohlhausen method where the velocity profile is given as a polynomial. The use of a third degree polynomial for the flat plate demonstrates the feasibility of the approach.
Introducing the Diagrammatic Semiotic Mode
Authors: Hiippala Tuomo , Bateman John A.
Published: September 2022

As the use and diversity of diagrams across many disciplines grows, there is an increasing interest in the diagrams research community concerning how such diversity might be documented and explained. In this article, we argue that one way of achieving increased reliability, coverage, and utility for a general classification of diagrams is to draw on recently developed semiotic principles developed within the field of multimodality. To this end, we sketch out the internal details of what may tentatively be termed the diagrammatic semiotic mode. This provides a natural account of how diagrammatic representations organising lines of research integrate natural language, various forms of graphics, diagrammatic elements such as arrows, lines and other expressive resources into coherent organisations, while still respecting the crucial diagrammatic contributions of visual organisation. We illustrate the proposed approach using two recent diagram corpora and show how a multimodal approach supports the empirical analysis of diagrammatic representations, especially in identifying diagrammatic constituents and describing their interrelations in a manner that may be generalised across diagram types and be used to characterise distinct kinds of functionality.
How to Build and Convert Complex Propositions in the Marlo Diagram
Authors: López Aznar Marcos Bautista
Published: September 2022

Marlo diagrams are a novel method of representing logical propositions that the author has used successfully with hundreds of high school students for instructional purposes. The examples of construction and conversion of complex diagrams that we offer in this work have a double objective: on the one hand, we hope that the reader becomes familiar with our notation, which, due to its novelty, is complex for those not initiated in our diagrams. On the other hand, we want to illustrate how our graphic conversions are articulated with those of natural language, always preserving the conclusions that follow from the premises.
Taming the Irrational Through Musical Diagrams – from Boethius to Oresme and Nemorarius
Authors: Muzzulini Daniel
Published: September 2022

Boethius and his followers used diagrammatic methods to estimate musical intervals with epimoric ratios, they determined geometric number sequences with triangular tables, and they treated the converse problem of dividing musical intervals equally. The collection of mathematical manuscripts Codex Basel F II 33 (ca. 1360) contains treatises by Nicolaus Oresme, Jordanus Nemorarius and others. Images in Nemorarius’ treatise combine number triangles into complex spider webs and they display recursive algorithms. Oresme diagrams make use of irrational ratios. These little known images and their relationship to music theory are the focus of this paper.
Learning Flexible Translation Between Robot Actions and Language Descriptions
Authors: Özdemir Ozan , Kerzel Matthias , Weber Cornelius , Lee Jae Hee , Wermter Stefan
Published: September 2022

Handling various robot action-language translation tasks flexibly is an essential requirement for natural interaction between a robot and a human. Previous approaches require change in the configuration of the model architecture per task during inference, which undermines the premise of multi-task learning. In this work, we propose the paired gated autoencoders (PGAE) for flexible translation between robot actions and language descriptions in a tabletop object manipulation scenario. We train our model in an end-to-end fashion by pairing each action with appropriate descriptions that contain a signal informing about the translation direction. During inference, our model can flexibly translate from action to language and vice versa according to the given language signal. Moreover, with the option to use a pretrained language model as the language encoder, our model has the potential to recognise unseen natural language input. Another capability of our model is that it can recognise and imitate actions of another agent by utilising robot demonstrations. The experiment results highlight the flexible bidirectional translation capabilities of our approach alongside with the ability to generalise to the actions of the opposite-sitting agent.
Business Process Simulation with Differentiated Resources: Does it Make a Difference?
Authors: López-Pintado Orlenys , Dumas Marlon
Published: September 2022

Business process simulation is a versatile technique to predict the impact of one or more changes on the performance of a process. Mainstream approaches in this space suffer from various limitations, some stemming from the fact that they treat resources as undifferentiated entities grouped into resource pools. These approaches assume that all resources in a pool have the same performance and share the same availability calendars. Previous studies have acknowledged these assumptions, without quantifying their impact on simulation model accuracy. This paper addresses this gap in the context of simulation models automatically discovered from event logs. The paper proposes a simulation approach and a method for discovering simulation models, wherein each resource is treated as an individual entity, with its own performance and availability calendar. An evaluation shows that simulation models with differentiated resources more closely replicate the distributions of cycle times and the work rhythm in a process than models with undifferentiated resources.
Learning Analytics in Open, Distance, and Digital Education (ODDE)
Authors: Prinsloo Paul
Published: September 2022

Data, and specifically student data, has always been an integral part of good teaching as well as providing evidence for strategic and operational planning, resource allocation, pedagogy, and student support. As Open, Distance, and Digital Education (ODDE) become increasingly datafied, institutions have access to greater volumes, variety, and granularity of student data, from more diverse sources than ever before. This provides huge opportunity for institutions, and specifically educators and course support teams, to better understand learning, and provide more appropriate and effective student support.

With the emergence of learning analytics (LA) in 2011, the measurement, collection, analysis, and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs, gained momentum, both as research focus and practice. Since then, LA have become institutionalized in many higher education institutions, mostly in residential institutions located in the Global North, and established a prolific presence in research on student learning in digitized environments. While LA has become institutionalized in the Open University (UK), it remains an emerging research focus and practice in many ODDE institutions across the world.

This chapter considers the implications of LA for ODDE research and practice by first providing a brief overview of the evolution of LA, and specifically the theoretical influences in this evolution. A selection of major research findings and discourses in LA are then discussed, before the chapter is concluded with some open questions for a research agenda for LA in ODDE.
Emergent metric space-time from matrix theory
Authors: Brahma Suddhasattwa , Brandenberger Robert , Laliberte Samuel
Published: September 2022

Abstract

The IKKT matrix model yields an emergent space-time. We further develop these ideas and give a proposal for an emergent metric. Based on previous numerical studies of this model, we provide evidence that the emergent space-time is continuous and infinite in extent, both in space and in time, and that the metric is spatially flat. The time evolution describes the transition from a string-theoretic emergent phase to a phase in which the SO(9) symmetry of the model is spontaneously broken to SO(6) × SO(3), with three dimensions of space expanding, becoming classical and at later times evolving like in a radiation-dominated universe, and the remaining six dimensions of space stabilized at the string scale. We speculate on how this analysis can be extended to yield an early universe cosmology which, in addition to the above-mentioned properties, also leads to a roughly scale-invariant spectrum of cosmological fluctuations and gravitational waves.
Potent anticancer activity of a novel iridium metallodrug via oncosis
Authors: Ortega-Forte Enrique , Hernández-García Samanta , Vigueras Gloria , Henarejos-Escudero Paula , Cutillas Natalia , Ruiz José , Gandía-Herrero Fernando
Published: September 2022

Oncosis (from Greek ónkos, meaning “swelling”) is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers.

Graphical abstract
Spline-based shape optimization of large-scale composite leaf spring models using Bayesian strategies with multiple constraints
Authors: Winter Jens , Fiebig Sierk , Franke Thilo , Bartz Ronald , Vietor Thomas
Published: September 2022

The presented paper describes a shape optimization workflow using Bayesian strategies. It is applied to a novel automotive axle system consisting of leaf springs made from glass fiber reinforced plastics (GFRP). Besides the primary objectives of cost and mass reduction, the assembly has to meet multiple technical constraints with respect to various loading conditions. The related large-scale finite element model is fully parameterized by splines, hence the general shape of the guide curve as well as the spring’s height, width and material properties can be altered by the corresponding workflow. For this purpose, a novel method is developed to automatically generate high-quality meshes depending on the geometry of the respective springs. The size and complexity of the model demands the implementation of efficient optimization techniques with a preferably small number of required response function evaluations. Therefore, an existing optimization framework is extended by state-of-the-art Bayesian methods, including different kernel combinations and multiple acquisition function approaches, which are then tested, evaluated and compared. To properly address the use of GFRP as spring material in the objective function, an appropriate cost model is derived. Emerging challenges, such as conflicting targets regarding direct material costs and potential lightweight measures, are considered and investigated. The intermediate steps of the developed optimization procedure are tested on various sample functions and simplified models. The entire workflow is finally applied to the complete model and evaluated. Concluding, ideas and possibilities in improving the optimization process, such as the use of models with varying complexity, are discussed.
Towards automatic classification of cardiovascular magnetic resonance Task Force Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy
Authors: Bourfiss Mimount , Sander Jörg , de Vos Bob D. , te Riele Anneline S. J. M. , Asselbergs Folkert W. , Išgum Ivana , Velthuis Birgitta K.
Published: September 2022

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed according to the Task Force Criteria (TFC) in which cardiovascular magnetic resonance (CMR) imaging plays an important role. Our study aims to apply an automatic deep learning-based segmentation for right and left ventricular CMR assessment and evaluate this approach for classification of the CMR TFC.

Methods

We included 227 subjects suspected of ARVC who underwent CMR. Subjects were classified into (1) ARVC patients fulfilling TFC; (2) at-risk family members; and (3) controls. To perform automatic segmentation, a Bayesian Dilated Residual Neural Network was trained and tested. Performance of automatic versus manual segmentation was assessed using Dice-coefficient and Hausdorff distance. Since automatic segmentation is most challenging in basal slices, manual correction of the automatic segmentation in the most basal slice was simulated (automatic−basal). CMR TFC calculated using manual and automatic−basal segmentation were compared using Cohen’s Kappa (κ).

Results

Automatic segmentation was trained on CMRs of 70 subjects (39.6 ± 18.1 years, 47% female) and tested on 157 subjects (36.9 ± 17.6 years, 59% female). Dice-coefficient and Hausdorff distance showed good agreement between manual and automatic segmentations (≥ 0.89 and ≤ 10.6 mm, respectively) which further improved after simulated correction of the most basal slice (≥ 0.92 and ≤ 9.2 mm, p < 0.001). Pearson correlation of volumetric and functional CMR measurements was good to excellent (automatic (r = 0.78–0.99, p < 0.001) and automatic−basal (r = 0.88–0.99, p < 0.001) measurements). CMR TFC classification using automatic−basal segmentations was comparable to manual segmentations (κ 0.98 ± 0.02) with comparable diagnostic performance.

Conclusions

Combining automatic segmentation of CMRs with correction of the most basal slice results in accurate CMR TFC classification of subjects suspected of ARVC.

Graphical abstract
Efficacy and safety of long-term botulinum toxin treatment for acquired cervical dystonia: a 25-year follow-up
Authors: Petracca Martina , Lo Monaco Maria Rita , Ialongo Tamara , Di Stasio Enrico , Cerbarano Maria Luana , Maggi Loredana , De Biase Alessandro , Di Lazzaro Giulia , Calabresi Paolo , Bentivoglio Anna Rita
Published: September 2022

Botulinum toxin A (BoNT/A) is the first-line treatment for idiopathic cervical dystonia (ICD) and is widely used in the clinical setting. To date, scanty data are available on the effectiveness of BoNT in treating acquired cervical dystonia (ACD). Here we present a long-term follow-up of ACD patients treated with BoNT/A that focused on safety and efficacy. The study included subjects who had received at least six treatments of three commercially available BoNT/A drugs [abobotulinumtoxinA (A/Abo), incobotulinumtoxinA (A/Inco) and onabotulinumtoxinA (A/Ona)]. Safety and efficacy were assessed based on patients' self-reports regarding adverse effects (AE), duration of improvement of dystonia and/or pain relief. Global clinical improvement was measured on a six-point scale. 23 patients with ACD were administered 739 treatments (A/Abo in 235, A/Inco in 72, A/Ona in 432) with a mean number of treatments of 31 ± 20 (range 6–76) and duration of 10 ± 6 weeks (range 2–25). The mean dose was 737 ± 292 U for A/Abo, 138 ± 108 U for A/Inco and 158 ± 80 U for A/Ona. The average benefit duration was 89 ± 26 (A/Abo), 88 ± 30 days (A/Inco), and 99 ± 55 days (A/Ona) (p = 0.011); global clinical improvement for all sessions was 4 ± 1. ANOVA one-way analysis indicated that A/Ona had the best profile in terms of duration (p < 0.05), whereas A/Abo had the best pain relief effect (p = 0.002). Side effects were reported in 9% of treatments (67/739), with ten treatments (1%) complicated by two side effects. Most side effects were rated mild to moderate; severe side effects occurred following three treatments with the three different BoNT; two required medical intervention. No allergic reactions were reported. Even after 25 years of repeated treatments, all serotypes of BoNT demonstrate positive effects in treating ACD with long-lasting efficacy and safety.
Heterozygous variants in the DVL2 interaction region of DACT1 cause CAKUT and features of Townes–Brocks syndrome 2
Authors: Christians Anne , Kesdiren Esra , Hennies Imke , Hofmann Alejandro , Trowe Mark-Oliver , Brand Frank , Martens Helge , Gjerstad Ann Christin , Gucev Zoran , Zirngibl Matthias , Geffers Robert , Seeman Tomáš , Billing Heiko , Bjerre Anna , Tasic Velibor , Kispert Andreas , Ure Benno , Haffner Dieter , Dingemann Jens , Weber Ruthild G.
Published: September 2022

Most patients with congenital anomalies of the kidney and urinary tract (CAKUT) remain genetically unexplained. In search of novel genes associated with CAKUT in humans, we applied whole-exome sequencing in a patient with kidney, anorectal, spinal, and brain anomalies, and identified a rare heterozygous missense variant in the DACT1 (dishevelled binding antagonist of beta catenin 1) gene encoding a cytoplasmic WNT signaling mediator. Our patient’s features overlapped Townes–Brocks syndrome 2 (TBS2) previously described in a family carrying a DACT1 nonsense variant as well as those of Dact1-deficient mice. Therefore, we assessed the role of DACT1 in CAKUT pathogenesis. Taken together, very rare (minor allele frequency ≤ 0.0005) non-silent DACT1 variants were detected in eight of 209 (3.8%) CAKUT families, significantly more frequently than in controls (1.7%). All seven different DACT1 missense variants, predominantly likely pathogenic and exclusively maternally inherited, were located in the interaction region with DVL2 (dishevelled segment polarity protein 2), and biochemical characterization revealed reduced binding of mutant DACT1 to DVL2. Patients carrying DACT1 variants presented with kidney agenesis, duplex or (multi)cystic (hypo)dysplastic kidneys with hydronephrosis and TBS2 features. During murine development, Dact1 was expressed in organs affected by anomalies in patients with DACT1 variants, including the kidney, anal canal, vertebrae, and brain. In a branching morphogenesis assay, tubule formation was impaired in CRISPR/Cas9-induced Dact1−/− murine inner medullary collecting duct cells. In summary, we provide evidence that heterozygous hypomorphic DACT1 variants cause CAKUT and other features of TBS2, including anomalies of the skeleton, brain, distal digestive and genital tract.
Experimental evaluation of laparoscopic laser speckle contrast imaging to visualize perfusion deficits during intestinal surgery
Authors: Heeman Wido , Wildeboer Aurelia C. L. , Al-Taher Mahdi , Calon Joost E. M. , Stassen Laurents P. S. , Diana Michele , Derikx Joep P. M. , van Dam Gooitzen M. , Boerma E. Christiaan , Bouvy Nicole D.
Published: September 2022

Background

Ischemia at the site of an intestinal anastomosis is one of the most important risk factors for anastomotic leakage (AL). Consequently, adequate intestinal microperfusion is essential for optimal tissue oxygenation and anastomotic healing. As visual inspection of tissue viability does not guarantee an adequate objective evaluation of intestinal microperfusion, surgeons are in dire need of supportive tools to decrease anastomotic leakage after colorectal surgery.

Methods

In this feasibility study, laparoscopic laser speckle contrast imaging (LSCI) was used to evaluate intestinal microperfusion in an experimental ischemic bowel loop model. Both large and small ischemic loops were created from the small intestine of a pig; each loop was divided into 5 regions of interest (ROI) with varying levels of ischemia. Speckle contrast and local capillary lactate (LCL) was measured in all ROIs.

Results

Both real-time visualization of intestinal microperfusion and induced perfusion deficits was achieved in all bowel loops. As a result, the emergence of regions of intestinal ischemia could be predicted directly after iatrogenic perfusion limitation, whereas without LSCI signs of decreased intestinal viability could only be seen after 30 minutes. Additionally, a significant relation was found between LCL and LSCI.

Conclusion

In conclusion, LSCI can achieve real-time intraoperative visualization of intestinal microperfusion deficits, allowing for accurate prediction of long-term postoperative ischemic complications. With this revealing capacity, LSCI could potentially facilitate surgical decision-making when constructing intestinal anastomoses in order to mitigate ischemia-related complications such as AL.
Exercise training as part of multidisciplinary rehabilitation in cancer survivors: an observational study on changes in physical performance and patient-reported outcomes
Authors: Weemaes Anouk T. R. , Weijenberg Matty P. , Lenssen Antoine F. , Beelen Milou
Published: September 2022

Purpose

To describe changes in physical performance and patient-reported outcomes in cancer survivors who participated in an exercise program as part of usual-care multidisciplinary rehabilitation and the influence of training adaptations during the coronavirus-19 (COVID-19) pandemic.

Methods

In an observational cohort study, cancer survivors underwent usual-care multidisciplinary rehabilitation including a 10-week exercise program. During the COVID-19 pandemic, the exercise program was adapted with reduced training time and frequency. Mean changes and 95% confidence intervals in physical performance (peak oxygen uptake (VO2peak), peak work rate during a steep ramp test (SRT-WRpeak), 6-min walking distance, muscle strength) and patient-reported outcomes (health-related quality of life, fatigue, anxiety, and depression) were assessed between the start and the end of the exercise program. Linear regression analysis, adjusting for baseline levels of outcomes, was used to investigate differences in changes in outcomes between participants who underwent the original and the adapted program.

Results

All outcomes statistically significantly improved over time, regardless of adaptations in the exercise program. VO2peak increased with 9.6% and 7.7% in the original and adapted program, respectively. Significant smaller improvements were observed in SRT-WRpeak (− 3.9%) and upper body muscle strength (− 10.8%) after participation in the adapted compared to the original program. No significant between-group differences were observed for other outcomes.

Conclusion

Physical performance and patient-reported outcomes statistically and clinically significantly improved in cancer survivors who participated in an exercise program as part of usual-care multidisciplinary rehabilitation. Improvements of performance outcomes were smaller since the training adaptations, though only significant for SRT-WRpeak and upper body strength.
Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial
Authors: Tabernero Josep , Hoff Paulo M. , Shen Lin , Ohtsu Atsushi , Shah Manish A. , Siddiqui Asna , Heeson Sarah , Kiermaier Astrid , Macharia Harrison , Restuccia Eleonora , Kang Yoon-Koo
Published: September 2022

Background

Dual-targeted anti-HER2 therapy significantly improves outcomes in HER2-positive breast cancer and could be beneficial in other HER2-positive cancers. JACOB’s end-of study analyses aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy for previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer.

Methods

Eligible patients were randomized 1:1 to pertuzumab/placebo plus trastuzumab and chemotherapy every 3 weeks. Primary endpoint: overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety.

Results

The intention-to-treat population comprised 388 patients in the pertuzumab arm and 392 in the placebo arm. The safety population comprised 385 and 388 patients, respectively. Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72–0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62–0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment. There was a trend for more favorable hazard ratios in certain subgroups related to HER2 amplification/overexpression. Safety was comparable between arms, except for serious and grade 3–5 adverse events, and any-grade diarrhea, which were more frequent with pertuzumab.

Conclusions

JACOB did not meet its primary endpoint. Nonetheless, the study continues to demonstrate some, albeit limited, evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up.

Trial registration NCT01774786; https://clinicaltrials.gov/ct2/show/NCT01774786.
Minimally invasive versus open transforaminal lumbar interbody fusion: a prospective, controlled observational study of short-term outcome
Authors: Hartmann Sebastian , Lang Anna , Lener Sara , Abramovic Anto , Grassner Lukas , Thomé Claudius
Published: September 2022

Instrumented stabilization with intersomatic fusion can be achieved by open (O-TLIF) or minimally invasive (MIS-TLIF) transforaminal surgical access. While less invasive techniques have been associated with reduced postoperative pain and disability, increased manipulation and insufficient decompression may contradict MIS techniques. In order to detect differences between both techniques in the short-term, a prospective, controlled study was conducted. Thirty-eight patients with isthmic or degenerative spondylolisthesis or degenerative disk disease were included in this prospective, controlled study (15 MIS-TLIF group vs. 23 O-TLIF group) after failed conservative treatment. Patients were examined preoperatively, on the first, third, and sixth postoperative day as well as after 2, 4, and 12 weeks postoperatively. Outcome parameters included blood loss, duration of surgery, pre- and postoperative pain (numeric rating scale [NRS], visual analog scale [VAS]), functionality (Timed Up and Go test [TUG]), disability (Oswestry Disability index [ODI]), and quality of life (EQ-5D). Intraoperative blood loss (IBL) as well as postoperative blood loss (PBL) was significantly higher in the O-TLIF group ([IBL O-TLIF 528 ml vs. MIS-TLIF 213 ml, p = 0.001], [PBL O-TLIF 322 ml vs. MIS-TLIF 30 ml, p = 0.004]). The O-TLIF cohort showed significantly less leg pain postoperatively compared to the MIS-TLIF group ([NRS leg 3rd postoperative day, p = 0.027], [VAS leg 12 weeks post-op, p = 0.02]). The MIS group showed a significantly better improvement in the overall ODI (40.8 ± 13 vs. 56.0 ± 16; p = 0.05). After 3 months in the short-term follow-up, the MIS procedure tends to have better results in terms of patient-reported quality of life. MIS-TLIF offers perioperative advantages but may carry the risk of increased nerve root manipulation with consecutive higher radicular pain, which may be related to the learning curve of the procedure.
Behavioral Addictions Questionnaire (BAQ): Validation of a New Tool for the Screening of Multiple Addictive Behaviors in the Italian Population
Authors: Mastropietro Stefania , Favieri Francesca , Forte Giuseppe , Locuratolo Nicoletta , Mannarelli Daniela , Pauletti Caterina , Fattapposta Francesco , Casagrande Maria
Published: September 2022

This study deals with the uncertainty in defining behavioral addictions (BAs). BAs are characterized by specific compulsive behaviors, regardless of potential negative consequences. However, to differentiate a behavior from a leisure activity to an addictive one is still an object of debate in the literature. Accordingly, this study aimed to assess the psychometric properties of the Behavioral Addictions Questionnaire (BAQ) as a possible screening tool for multiple BAs (i.e., shopping, food addiction, gambling, sex, work, exercise, Internet, videogames, and smartphone). BAQ aims to give a dimensional and quantitative assessment of addictive behaviors in a continuum, including both the adaptive and maladaptive features of the behaviors. Five hundred and seventy-six healthy adults (age range: 18–88) participated in the study, completing a survey including the BAQ questionnaire. Considering both exploratory and confirmatory factor analyses, statistical examination suggested good psychometric properties, with adequate validity in all its subscales (i.e., the goodness of fit). Moreover, also higher reliability was confirmed for each dimension detected (i.e., all alpha over 0.65). The BAQ represents a comprehensive screening instrument that benefits from appropriate validity and reliability for assessing BAs. Therefore, it can be used in clinical fields and research. Moreover, the feature of BAs on a continuum, and the severity index adopted by the study, can help from a preventive perspective. However, further validation of the BAQ is needed in other countries and contexts.