bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning nomogram based on Gd-EOB-DTPA MRI for predicting early recurrence in hepatocellular carcinoma after hepatectomy
Authors: Yan Meng , Zhang Xiao , Zhang Bin , Geng Zhijun , Xie Chuanmiao , Yang Wei , Zhang Shuixing , Qi Zhendong , Lin Ting , Ke Qiying , Li Xinming , Wang Shutong , Quan Xianyue
Published: February 2023

Objectives

The accurate prediction of post-hepatectomy early recurrence in patients with hepatocellular carcinoma (HCC) is crucial for decision-making regarding postoperative adjuvant treatment and monitoring. We aimed to explore the feasibility of deep learning (DL) features derived from gadoxetate disodium (Gd-EOB-DTPA) MRI, qualitative features, and clinical variables for predicting early recurrence.

Methods

In this bicentric study, 285 patients with HCC who underwent Gd-EOB-DTPA MRI before resection were divided into training (n = 195) and validation (n = 90) sets. DL features were extracted from contrast-enhanced MRI images using VGGNet-19. Three feature selection methods and five classification methods were combined for DL signature construction. Subsequently, an mp-MR DL signature fused with multiphase DL signatures of contrast-enhanced images was constructed. Univariate and multivariate logistic regression analyses were used to identify early recurrence risk factors including mp-MR DL signature, microvascular invasion (MVI), and tumor number. A DL nomogram was built by incorporating deep features and significant clinical variables to achieve early recurrence prediction.

Results

MVI (p = 0.039), tumor number (p = 0.001), and mp-MR DL signature (p < 0.001) were independent risk factors for early recurrence. The DL nomogram outperformed the clinical nomogram in the training set (AUC: 0.949 vs. 0.751; p < 0.001) and validation set (AUC: 0.909 vs. 0.715; p = 0.002). Excellent DL nomogram calibration was achieved in both training and validation sets. Decision curve analysis confirmed the clinical usefulness of DL nomogram.

Conclusion

The proposed DL nomogram was superior to the clinical nomogram in predicting early recurrence for HCC patients after hepatectomy.

Key Points

• Deep learning signature based on Gd-EOB-DTPA MRI was the predominant independent predictor of early recurrence for hepatocellular carcinoma (HCC) after hepatectomy.

• Deep learning nomogram based on clinical factors and Gd-EOB-DTPA MRI features is promising for predicting early recurrence of HCC.

• Deep learning nomogram outperformed the conventional clinical nomogram in predicting early recurrence.
Femtosecond tunable-wavelength photoassisted cold field emission
Authors: Haindl Rudolf , Köster Kerim , Gaida John H. , Franz Maximilian , Feist Armin , Ropers Claus
Published: February 2023

We demonstrate photoassisted cold field emission (PFE) from a tungsten tip induced by tunable-wavelength low-power femtosecond laser excitation. The emission current from the apex of the (310)-oriented single-crystalline emitter is shown to linearly depend on the incident laser power, while the effective work function is reduced by the respective photon energy. Our results promote the implementation of the linear regime in laser-triggered cold field emission for ultrafast transmission electron microscopy.
Disparities in pediatric drug-resistant epilepsy care
Authors: LoPresti Melissa A. , Zhang Lu , Lam Sandi
Published: February 2023

Introduction

Epilepsy affects millions of children worldwide, with 20–40% experiencing drug-resistant epilepsy (DRE) who are recommended for epilepsy surgery evaluation and may benefit from surgical management. However, many patients live with DRE for multiple years prior to surgical epilepsy referral or treatment or are never referred at all.

Objective

We aimed to describe factors associated with referral for epilepsy surgery in the USA, in order to identify disparities in DRE, characterize why they may exist, and recognize areas for improvement.

Methods

Pediatric patients diagnosed with DRE between January 1, 2004 and December 31, 2020 were identified from the Pediatric Health Information System (PHIS) Database. Patients treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery were studied regarding access to epilepsy surgery and disparities in care. This study used chi-square tests to determine associations between treatment time and preoperative factors. Preoperative factors studied included epilepsy treatment type, age, sex, race/ethnicity, insurance type, geographic region, patient type, epilepsy type, and presence of pediatric complex chronic conditions (PCCCs).

Results

A total of 18,292 patients were identified; 10,240 treated with ASMs, 5019 treated with ASMs + VNS, and 3033 treated with ASMs + cranial epilepsy surgery. Sex was not found to significantly vary among groups. There was significant variation in age, census region, race/ethnicity, patient type, presence of PCCCs, diagnosis, and insurance (p < 0.001). Those treated surgically, either with VNS or cranial epilepsy surgery, were 2 years older than those medically treated. Additionally, those medically treated were less likely to be living in the Midwest (25.46%), identified as non-Hispanic white (51.78%), have a focal/partial epilepsy diagnosis (8.74%), and be privately insured (35.82%).

Conclusions

We studied a large administrative US database examining variables associated with surgical epilepsy evaluation and management. We found significant variation in treatment associated with age, US census region, race/ethnicity, patient type, presence of PCCCs, diagnosis, and health insurance type. We believe that these disparities in care are related to access and social determinants of health, and we encourage focused outreach strategies to mitigate these disparities to broaden access and improve outcomes in children in the USA with DRE.
Technical aspects of percutaneous endovascular arteriovenous fistula creation with the Ellipsys® Vascular Access System. Preliminary results after 16 patients
Authors: Liebetrau Dominik , Zerwes Sebastian , Kerndl Hagen , Schaal Jochen , Hyhlik-Dürr Alexander
Published: February 2023

Purpose

Technical aspects are crucial for planning and performing endovascular arteriovenous fistula (AVF) creation. The Ellipsys® Vascular Access System represents a minimal invasive method for the creation of a proximal forearm fistula. This report summarizes the essential elements for AVF creation with the Ellipsys® Vascular Access System and investigates feasibility, efficacy, and safety procedures conducted on 16 patients.

Materials and methods

We performed a retrospective analysis of patients who underwent endovascular AVF creation with the Ellipsys® Vascular Access System between May 2020 and March 2022 at a tertiary referral center.

Results

The median age was 67.5 years (47–86 years). The mean BMI was 31.4 kg/m2. AV fistula was created on 15/16 patients on their left arm. The technical success was 100%. The mean operation time was 24.2 min. There were no complications associated with the procedure. All patients were examined after 30 days (± 5 days). Primary patency after 30 days was 94% (15/16). The mean fistula flow was 681.1 mL/min and the mean AVF diameter was 6.1 mm. Thirteen out of 15 patients met the criteria for potential hemodialysis.

Conclusion

With the Ellipsys Vascular Access System exist an additional possibility of an AV fistula creation. Based on above findings, the Ellipsys® Vascular Access System represents a feasible, safe, and effective method for AVF creation.
Eccentric muscle contractions: from single muscle fibre to whole muscle mechanics
Authors: Tomalka André
Published: February 2023

Eccentric muscle loading encompasses several unique features compared to other types of contractions. These features include increased force, work, and performance at decreased oxygen consumption, reduced metabolic cost, improved energy efficiency, as well as decreased muscle activity. This review summarises explanatory approaches to long-standing questions in terms of muscular contraction dynamics and molecular and cellular mechanisms underlying eccentric muscle loading. Moreover, this article intends to underscore the functional link between sarcomeric components, emphasising the fundamental role of titin in skeletal muscle. The giant filament titin reveals versatile functions ranging from sarcomere organisation and maintenance, providing passive tension and elasticity, and operates as a mechanosensory and signalling platform. Structurally, titin consists of a viscoelastic spring segment that allows activation-dependent coupling to actin. This titin-actin interaction can explain linear force increases in active lengthening experiments in biological systems. A three-filament model of skeletal muscle force production (mediated by titin) is supposed to overcome significant deviations between experimental observations and predictions by the classic sliding-filament and cross-bridge theories. Taken together, this review intends to contribute to a more detailed understanding of overall muscle behaviour and force generation—from a microscopic sarcomere level to a macroscopic multi-joint muscle level—impacting muscle modelling, the understanding of muscle function, and disease.
The efficacy of insulin degludec and insulin glargine over NPH insulin among toddlers and preschoolers with type 1 diabetes using glycemic variability and time in range
Authors: Elhabashy Safinaz Adel , Sakr Eman Mohamed , Salah Nouran Yousef
Published: February 2023

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2–6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group.

Conclusion: Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group.

What is Known:• Insulin therapy is the mainstay of T1D management.• Optimal insulin therapy for young children with T1D should provide
effective glycemic.

What is New:• Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower
coefficient of variation, HbA1c and IDD and significantly higher time in range.• Insulin degludec and insulin glargine have better safety in the term of
less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and
preschoolers with T1D.
Hybrid laparoscopic versus fully robot-assisted minimally invasive esophagectomy: an international propensity-score matched analysis of perioperative outcome
Authors: Jung Jin-On , de Groot Eline M. , Kingma B. Feike , Babic Benjamin , Ruurda Jelle P. , Grimminger Peter P. , Hölzen Jens P. , Chao Yin-Kai , Haveman Jan W. , van Det Marc J. , Rouanet Philippe , Benedix Frank , Li Hecheng , Sarkaria Inderpal , van Berge Henegouwen Mark I. , van Boxel Gijs I. , Chiu Philip , Egberts Jan-Hendrik , Sallum Rubens , Immanuel Arul , Turner Paul , Low Donald E. , Hubka Michal , Perez Daniel , Strignano Paolo , Biebl Matthias , Chaudry M. Asif , Bruns Christiane J. , van Hillegersberg Richard , Fuchs Hans F. ,   UGIRA Study Group
Published: February 2023

Background

Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE).

Methods

This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers.

Results

After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group.

Conclusions

Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE.
Survey of window types for aggregation in stream processing systems
Authors: Verwiebe Juliane , Grulich Philipp M. , Traub Jonas , Markl Volker
Published: February 2023

In this paper, we present the first comprehensive survey of window types for stream processing systems which have been presented in research and commercial systems. We cover publications from the most relevant conferences, journals, and system whitepapers on stream processing, windowing, and window aggregation which have been published over the last 20 years. For each window type, we provide detailed specifications, formal notations, synonyms, and use-case examples. We classify each window type according to categories that have been proposed in literature and describe the out-of-order processing. In addition, we examine academic, commercial, and open-source systems with respect to the window types that they support. Our survey offers a comprehensive overview that may serve as a guideline for the development of stream processing systems, window aggregation techniques, and frameworks that support a variety of window types.
On the 2-rainbow independent domination numbers of some graphs
Authors: Gabrovšek Boštjan , Peperko Aljoša , Žerovnik Janez
Published: February 2023

By suitably adjusting the tropical algebra technique we compute the rainbow independent domination numbers of several infinite families of graphs including Cartesian products$$C_n \Box P_m$$Cn□Pmand$$C_n \Box C_m$$Cn□Cmfor allnand$$m\le 5$$m≤5, and generalized Petersen graphsP(n, 2) for$$n \ge 3$$n≥3.
COP 27 mit mageren Ergebnissen
Authors: Frenz Walter
Published: February 2023

Die Ergebnisse von Scharm El-Scheich wurden inzwischen verabschiedet. Sie sind so kurz wie dieser
Aufsatz: Im Wesentlichen wurde ein Entschädigungsfonds für die besonders vom Klimawandel betroffenen
Entwicklungsländer getroffen, aber noch ohne nähere Kontur. Dagegen scheiterte insbesondere der
Einstieg in den Ausstieg aus allen fossilen Energien.
Spheroids, organoids and kidneys-on-chips: how complex human cellular models have assisted in the study of kidney disease and renal ciliopathies
Authors: Dewhurst Rebecca Marie , Molinari Elisa , Sayer John A.
Published: February 2023

Kidney disease is one of the leading causes of morbidity worldwide, emphasizing the importance for physiologically accurate disease models. With most of the approved renal drugs failing to perform as well in human clinical trials as they did in animal testing, it is imperative that new and improved human-based models are developed to test these potential therapeutics. One option is to use patient derived cell lines, grown in both two-dimensional (2D) and three-dimensional (3D) structures, known as spheroids and organoids. Despite their contributions to the field, the lack of physiological accuracy, including the absence of fluid flow, and mechanistic effects in these 2D and 3D models means there is still room for improvement. Organ-on-a-chip (OOAC) technology offers itself as a potential candidate model to overcome these limitations. Over recent years OOAC technology has grown in popularity, with multiple organ systems, including lung, liver, and kidney described in the literature. In this review, traditional human cellular based models, including monolayer, spheroid and organoid models will be discussed. Human kidney-on-a-chip models will also be discussed, while exploring the advantages and potential limitations of this rapidly emerging field for the study of human kidney disease and drug testing.
Humanitarian management strategy for interstate movement of migrant workers in India during COVID-19 pandemic: an optimization based approach
Authors: Palit Niladri , Chaudhuri Atanu , Mishra Nishikant
Published: February 2023

India faced a unique situation during the ongoing COVID-19 pandemic when millions of migrant workers, in different states had to be transported to their home states as workplaces shut down. The governments in respective states faced challenges of minimizing economic impact while ensuring that the risk of infection was also kept under control. This paper develops models based on various secondary data from governmental and relevant non-governmental sources, trying to minimize the economic impact while keeping the rate of infection low and determining whether the migrant workforce should be allowed to stay in their workplace state or allowed to return to their home state. We found that the number of days of lockdown had a significant impact on the results. Fewer days of lockdown resulted in workers remaining in their work state as the preferred outcome, while a higher number of days of lockdown implied that people traveled to their home state and remain there. The proportion of workers who were willing to return to their work state played an important role on the results too. Beyond the threshold percentages of migrant workers returning to their work state, it became optimal for the government to encourage the workers to travel to their home state. However, this was mostly visible for moderate number of lockdown days as the effects on results were dominated by the impact from the number of lockdown days for too high or too low number of lockdown days. There is also an important trade-off between the budget and infection rate ‘R’ for the governments to consider. Minimizing the risk of infection requires an additional budget.
Will natura 2000 european network of protected areas support conservation of Southwestern Alps endemic flora under future climate?
Authors: Casazza Gabriele , Guerrina Maria , Dagnino Davide , Minuto Luigi
Published: February 2023

Networks of protected areas (PAs) are globally recognized as playing a key role for in situ conservation of species. Despite a high potential for biodiversity conservation, PAs may not mitigate the current biodiversity loss because they do not consider climate change impact. In fact, because PAs have static geographical boundaries, they may hardly keep pace with dynamics in species distribution caused by the climate change, which was not considered when they were designed. In this study, we used species distribution modelling of 85 plant taxa endemic or subendemic to Southwestern Alps to evaluate the effectiveness of PAs network in protecting endemics under future climate change scenarios. PAs cover roughly the 30% of the Southwestern Alps. PAs will harbour more expected distribution range of taxa in the future than today, probably because they occur in high altitude areas rich in endemics that have been climatically stable areas in the past and that will likely remain relatively climatically buffered in the future. Moreover, PAs are distributed to poorly cover expected range of endemics at low and middle elevation, which are threatened by urbanization and climate change. We recommend additional protection at low and middle elevation, considering the future climatic suitability of species.
Evaluating the suitability of granular anammox biomass for nitrogen removal from vegetable tannery wastewater
Authors: Polizzi C. , Lotti T. , Ricoveri A. , Mori G. , Gabriel D. , Munz G.
Published: February 2023

In the present study, the potential inhibitory effect of biologically pre-treated vegetable tannery wastewater (TW) on anammox granular biomass was evaluated. Beside high organic and chemicals load, vegetable TW are characterised by high salinity and high tannins concentration, the latter belonging to a group of bio-refractory organic compounds, potentially inhibitory for several bacterial species. Recalcitrant tannin-related organic matters and salinity were selected as the two potential inhibitory factors and studied either for their separate and combined effect. Parallel batch tests were performed, with biomass acclimated and non-acclimated to salinity, testing three different conditions: non-saline control test with non-acclimated biomass (CT); saline control test with acclimated biomass (SCT); vegetable tannery wastewater test with acclimated biomass (TWT). Compared with non-saline CT, the specific anammox activity in tests SCT and TWT showed a reduction of 28 and 14%, respectively, suggesting that salinity, at conductivity values of 10 mS/cm (at 25 °C), was the main impacting parameter. As a general conclusion, the study reveals that there is no technical limitation for the application of the anammox process to vegetable TW, but preliminary biomass acclimation as well as regular biomass activity monitoring is recommended in case of long-term applications. To the best of our knowledge, this is the first work assessing the impact of vegetable TW on anammox biomass.
The grammar of interactive explanatory model analysis
Authors: Baniecki Hubert , Parzych Dariusz , Biecek Przemyslaw
Published: February 2023

The growing need for in-depth analysis of predictive models leads to a series of new methods for explaining their local and global properties. Which of these methods is the best? It turns out that this is an ill-posed question. One cannot sufficiently explain a black-box machine learning model using a single method that gives only one perspective. Isolated explanations are prone to misunderstanding, leading to wrong or simplistic reasoning. This problem is known as the Rashomon effect and refers to diverse, even contradictory, interpretations of the same phenomenon. Surprisingly, most methods developed for explainable and responsible machine learning focus on a single-aspect of the model behavior. In contrast, we showcase the problem of explainability as an interactive and sequential analysis of a model. This paper proposes how different Explanatory Model Analysis (EMA) methods complement each other and discusses why it is essential to juxtapose them. The introduced process of Interactive EMA (IEMA) derives from the algorithmic side of explainable machine learning and aims to embrace ideas developed in cognitive sciences. We formalize the grammar of IEMA to describe human-model interaction. It is implemented in a widely used human-centered open-source software framework that adopts interactivity, customizability and automation as its main traits. We conduct a user study to evaluate the usefulness of IEMA, which indicates that an interactive sequential analysis of a model may increase the accuracy and confidence of human decision making.
Capability Approach and Inclusion: Developing a Context Sensitive Design for Biobased Value Chains
Authors: Asveld Lotte , Robaey Zoë Houda , Francke Sara , Osseweijer Patricia
Published: February 2023

Biomass such as crops and agricultural waste is increasingly used as the primary resource for products like bioplastics and biofuels. Incorporating the needs, knowledge, skills and values of biomass producers in the design of global value chains – the steps involved in creating any finished product from design to delivery – can contribute to sustainability, reliability and fairness. However, how to involve biomass producers, especially if they are resource poor, remains a challenge. To make sure that inclusion in global biobased value chains is both fair and effective, the capabilities of relevant actors need to be taken into account, especially of those producing biomass. Access to resources determines to what extent a specific actor can participate in a global value chain. Therefore, differences in capabilities should be a central consideration when new (biobased) value chains are designed. Using the capability approach as an ethical framework to realize inclusion, we discern three complementary strategies for setting up inclusive value chains. Firstly, designing for local conversion factors second, providing adaptive design for new capabilities, and third, investing in local conversion factors. Applying these strategies can lead to context-sensitive design of biorefineries that allow for true inclusion of local stakeholders. We support these claims with reference to case-studies of sugarcane production in Jamaica, modified tobacco in South Africa and the non-edible parts of corn (stover) in the US.
Extraction of phytostimulant molecules from Scenedesmus almeriensis using different extractor systems
Authors: Navarro-López Elvira , Gallardo-Rodríguez Juan José , del Carmen Cerón-García María , Gallego-López Inmaculada , Acién-Fernández Francisco Gabriel , Molina-Grima Emilio
Published: February 2023

There is an increasing demand for bio-based fertilizers and phytostimulants. Microalgae biomass contains a number of compounds that have positive effects on plant growth (for instance, phenolic compounds). Other valuable substances are simultaneously produced in the biomass, enabling a biorefinery approach to be applied. Downstream processing optimization for sustainable economic biostimulant production must involve the use of microalgal wet paste instead of dry biomass. The present study investigated the effect of different parameters, such as the solvent, temperature, and time, on the extraction of biostimulant molecules from Scenedesmus almeriensis microalgal biomass. The extraction process optimization was determined by calculating the germination index in the watercress seed bioassays. Since phenols and other bioactives are extracted together, and purification should be avoided, biological methods are preferred for assessing biostimulation. Water was compared to organic solvents of lower polarity such as acetone, ethanol (96%), and an ethanol:hexane:water (76:18:6 v/v/v) mixture. Different solvent extraction ratios (0.5–8 mL solvent g−1 of dry biomass), temperatures (25–50 ºC), and extraction times (0.5–6 h) were tested, after which the best combination was selected for each solvent. The optimal conditions were obtained with organic green solvents (acetone or ethanol), which resulted in a Germination Index above 120% (at least 20% above the distilled water control). Consequently, from a biorefinery perspective, this process was considered to be the most suitable for microalgal biomass exploitation.

Graphical Abstract
Bioanalytical Validated Spectrofluorimetric Method for the Determination of Prucalopride succinate in Human Urine Samples and Its Greenness Evaluation
Authors: Saad Marwa T. , Zaazaa Hala E. , Fattah Taghreed A. , Boltia Shereen A.
Published: February 2023

An economical & eco-friendly spectrofluorometric method has been developed for the determination of prucalopride succinate (PRU) in human urine on the basis of the drug’s native fluorescence. The type of solvent and the wavelengths of excitation and emission have been carefully selected for optimal experimental conditions. In deionized water, the fluorescence intensity was measured at λ emission 362 nm upon excitation at 310 nm. This bio-validated method was carried out using 30uL urine without any preliminary steps. The calibration curve for prucalopride succinate shows a linear relationship in a concentration range of 0.75–5.5 µg/mL. Accuracy and precision were obtained using 4 quality control samples which are: 0.75 μg/ mL (LLOQ), 2.25 μg/mL (QCL), 2.5 μg/mL (QCM) & 4.125 µg/mL (QCH). The validation of this proposed technique obeys European Medicines Agency (EMA) Guidelines for validating bioanalytical methods and the greenness assessment was evaluated according to the Analytical GAPI approach.
A natural regularization of the adsorption integral equation with Langmuir-kernel
Authors: Arnrich Steffen , Kalies Grit
Published: February 2023

Adsorption integral equations are used to compute adsorption energy distributions by measured total isotherms. Since these types of equations are Fredholm integral equations of the first kind on bounded domains, they are unstable or ill-posed, respectively. Hence, there is a need for regularization. In this work, we present general regularizations based on the fourier transform for a special kernel, the Langmuir kernel. The regularization parameters are chosen as zeros or minimizers of simple functions depending on the mean absolute error of a transformed total isotherm. In difference to many other solutions proposed, an explicit error and convergence analysis is made. Additionally, we consider adsorption energy distributions with sharp peaks or for ideal adsorbents. Here, we construct a regularization for computing averages of the adsorption energy distribution and the maximal approximation error is estimated uniformly.
Guidelines for RBF-FD Discretization: Numerical Experiments on the Interplay of a Multitude of Parameter Choices
Authors: Le Borne Sabine , Leinen Willi
Published: February 2023

There exist several discretization techniques for the numerical solution of partial differential equations. In addition to classical finite difference, finite element and finite volume techniques, a more recent approach employs radial basis functions to generate differentiation stencils on unstructured point sets. This approach, abbreviated by RBF-FD (radial basis function-finite difference), has gained in popularity since it enjoys several advantages: It is (relatively) straightforward, does not require a mesh and generalizes easily to higher spatial dimensions. However, its application is not quite as blackbox as it may appear at first sight. The computed solution might suffer severely from various sources of errors if RBF-FD parameters are not selected carefully. Through comprehensive numerical experiments, we study the influence of several of these parameters on the condition numbers of intermediate (local) weight matrices, on the condition number of the resulting (global) stiffness matrix and ultimately on the approximation error of the computed discrete solution to the partial differential equation. The parameters of investigation include the type of RBF (and its shape or other parameters if applicable), the degree of polynomial augmentation, the discretization stencil size, the underlying type of point set (structured/unstructured), and the total number of (interior and boundary) points to discretize the PDE, here chosen as a three-dimensional Poisson’s problem with Dirichlet boundary conditions. Numerical tests on a sphere as well as tests for the convection-diffusion equation are included in a supplement and demonstrate that the results obtained for the Laplace problem on a cube generalize to wider problem classes. The purpose of this paper is to provide a comprehensive survey on the various components of the basic algorithms for RBF-FD discretization and steer away from potential pitfalls such as computationally more expensive setups which not always lead to more accurate numerical solutions. We guide toward a compatible selection of the multitude of RBF-FD parameters in the basic version of RBF-FD. For many of its components we refer to the literature for more advanced versions.
A three-step approach for assessing landscape connectivity via simulated dispersal: African wild dog case study
Authors: Hofmann David D. , Cozzi Gabriele , McNutt John W. , Ozgul Arpat , Behr Dominik M.
Published: February 2023

Context

Dispersal of individuals contributes to long-term population persistence, yet requires a sufficient degree of landscape connectivity. To date, connectivity has mainly been investigated using least-cost analysis and circuit theory, two methods that make assumptions that are hardly applicable to dispersal. While these assumptions can be relaxed by explicitly simulating dispersal trajectories across the landscape, a unified approach for such simulations is lacking.

Objectives

Here, we propose and apply a simple three-step approach to simulate dispersal and to assess connectivity using empirical GPS movement data and a set of habitat covariates.

Methods

In step one of the proposed approach, we use integrated step-selection functions to fit a mechanistic movement model describing habitat and movement preferences of dispersing individuals. In step two, we apply the parameterized model to simulate dispersal across the study area. In step three, we derive three complementary connectivity maps; a heatmap highlighting frequently traversed areas, a betweenness map pinpointing dispersal corridors, and a map of inter-patch connectivity indicating the presence and intensity of functional links between habitat patches. We demonstrate the applicability of the proposed three-step approach in a case study in which we use GPS data collected on dispersing African wild dogs (Lycaon pictus) inhabiting northern Botswana.

Results

Using step-selection functions we successfully parametrized a detailed dispersal model that described dispersing individuals’ habitat and movement preferences, as well as potential interactions among the two. The model substantially outperformed a model that omitted such interactions and enabled us to simulate 80,000 dispersal trajectories across the study area.

Conclusion

By explicitly simulating dispersal trajectories, our approach not only requires fewer unrealistic assumptions about dispersal, but also permits the calculation of multiple connectivity metrics that together provide a comprehensive view of landscape connectivity. In our case study, the three derived connectivity maps revealed several wild dog dispersal hotspots and corridors across the extent of our study area. Each map highlighted a different aspect of landscape connectivity, thus emphasizing their complementary nature. Overall, our case study demonstrates that a simulation-based approach offers a simple yet powerful alternative to traditional connectivity modeling techniques. It is therefore useful for a variety of applications in ecological, evolutionary, and conservation research.

Graphical abstract
New antiproliferative 3-substituted oxindoles inhibiting EGFR/VEGFR-2 and tubulin polymerization
Authors: Ezelarab Hend A. A. , Ali Taha F. S. , Abbas Samar H. , Sayed Ahmed M. , Beshr Eman A. M. , Hassan Heba A.
Published: February 2023

New 3-substituted oxindole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of compounds 6a–j was evaluated against 60 NCI cell lines. Among these tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity, specifically against leukemia and breast cancer cell lines. Compound 6f was the most promising antiproliferative agent against MCF-7 (human breast cancer) with an IC50 value of 14.77 µM compared to 5-fluorouracil (5FU) (IC50 = 2.02 µM). Notably, compound 6f hampered receptor tyrosine EGFR fundamentally with an IC50 value of 1.38 µM, compared to the reference sunitinib with an IC50 value of 0.08 µM. Moreover, compound 6f afforded anti-tubulin polymerization activity with an IC50 value of 7.99 µM as an outstanding observable activity compared with the reference combretastatin A4 with an IC50 value of 2.64 µM. In silico molecular-docking results of compound 6f in the ATP-binding site of EGFR agreed with the in vitro results. Besides, the investigation of the physicochemical properties of compound 6f via the egg-boiled method clarified good lipophilicity, GIT absorption, and blood–brain barrier penetration properties.
Towed wheel shimmy suppression through a nonlinear tuned vibration absorber
Authors: Habib Giuseppe , Epasto Alberto
Published: February 2023

The implementation of the nonlinear tuned vibration absorber (NLTVA) for the suppression of shimmy vibration in towed wheels is addressed in this study. We adopt a modified straight tangent tyre model of a single-degree-of-freedom towed wheel system with an attached NLTVA. Stability analysis illustrated that the NLTVA can significantly improve the stability of the equilibrium of the wheel. Bifurcation analysis highlighted the existence of large bistable regions, which undermines the system’s safety. However, numerical continuation analysis, coupled with a dynamical integrity investigation, revealed that the addition of an intentional softening nonlinearity in the absorber restoring force characteristic enables the complete suppression of the bistable regions, also reducing the amplitude of shimmy oscillations in the unstable region. Quasiperiodic motions were also identified; however, their practical relevance seems marginal.
Specific alterations in riboproteomes composition of isonicotinic acid treated arabidopsis seedlings
Authors: Fakih Zainab , Plourde Mélodie B. , Nkouankou Charlène Eugénie Tomi , Fourcassié Victor , Bourassa Sylvie , Droit Arnaud , Germain Hugo
Published: February 2023

Plants have developed strategies to deal with the great variety of challenges they are exposed to. Among them, common targets are the regulation of transcription and translation to finely modulate protein levels during both biotic and abiotic stresses. Increasing evidence suggests that ribosomes are highly adaptable modular supramolecular structures which remodel to adapt to stresses. Each Arabidopsis thaliana ribosome consists of approximately 81 distinct ribosomal proteins (RPs), each of which is encoded by two to seven genes. To investigate the identity of ribosomal proteins of the small subunit (RPS) and of the large subunit (RPL) as well as ribosomes-associated proteins, we analysed by LC/MS/MS immunopurified ribosomes from A. thaliana leaves treated with isonicotinic acid (INA), an inducer of plant innate immunity. We quantified a total of 2084 proteins. 165 ribosome-associated proteins showed increased abundance while 52 were less abundant. Of the 52 identified RPS (from a possibility of 104 encoding genes), 15 were deregulated. Similarly, from the 148 possible RPL, 80 were detected and 9 were deregulated. Our results revealed potential candidates involved in innate immunity that could be interesting targets for functional genomic studies.
Tree-distance and tree-species effects on soil biota in a temperate agroforestry system
Authors: Vaupel Anna , Bednar Zita , Herwig Nadine , Hommel Bernd , Moran-Rodas Virna Estefania , Beule Lukas
Published: February 2023

Aims

Cropland agroforestry systems are land-use systems with numerous environmental advantages over monoculture croplands including promotion of soil life. This study aimed to investigate tree-species and tree-distance effects on soil biota in a temperate agroforestry system.

Methods

Our study was conducted at a paired alley-cropping and monoculture cropland system. The tree rows of the agroforestry system comprised of blocks of poplar Fritzi Pauley, poplar Max 1 or black locust. Within the agroforestry system, soil microbial and earthworm communities were collected along transects spanning from the center of the tree rows into the crop rows. Archaea, bacteria, and fungi were quantified using real-time PCR. The community composition of fungi and earthworms was deciphered using amplicon sequencing and morphological identification, respectively.

Results

Tree rows promoted the abundance of bacteria and earthworms, which we attribute mainly to tree litter input and the absence of tillage. Fungal community composition was altered by the tree rows, resulting in an increased proportion of ectomycorrhizal fungi in the tree-row associated mycobiome. The proportion of Blumeria graminis, the causal agent of powdery mildew, increased with increasing distance from the trees. We suggest that enhanced microbial antagonism, increased earthworm densities and/or altered microclimate contributed to the suppression of B. graminis in vicinity of the trees. Tree-species effect had a minor influence on the abundance and composition of soil communities at our study site.

Conclusions

In comparison to monoculture cropland, agroforestry benefits the abundance, diversity, and function of soil biota and may enhance soil suppressiveness.
A Spatial Analysis of Suicide Displacement at a High-Risk Cliff-Based Location Following Installation of a Means Restriction Initiative
Authors: Torok Michelle , Passioura Jason , Konings Paul , Wong Quincy , Qian Jiahui , Larsen Mark E.
Published: February 2023

Means restriction interventions are recognised as highly effective for the deterrence of suicide attempts by jumping. While such interventions can lead to significant reductions in suicide, it is unclear whether these reductions represent a displacement effect, whereby individuals are instead choosing to attempt suicide at other nearby locations which offer the same means. The potential displacement of suicides as an unintended consequence of means restriction has been relatively unexplored to date. The only studies exploring displacement effects have focused on bridges, which are relatively easily contained sites; no studies have yet explored displacement effects at cliff-based high risk suicide locations (hotspots). Using Australian coronial data for the period of 2006–2019, we undertook joinpoint and kernel density analysis of suicides by jumping at a well-known cliff-based hotspot in Sydney, Australia, to determine whether there was evidence of displacement to local and broader surrounding cliffs following the installation of a multi-component harm minimization intervention (the Gap Park Masterplan). While slight decreases were noted in the immediate area subject to the structural intervention in the post-implementation period, alongside slight increases in the surrounding cliffs, there was no evidence for statistically significant changes. While kernel density analyses did not identify the emergence of any new hotspot locations in the post-implementation period, three existing hotspot sites of concern were found in our total area of interest, with greater than expected growth in the density of one of the hotspots. While we found no persuasive evidence of displacement, ongoing monitoring of the cliff-based location where the structural interventions were implemented is needed to ensure the ongoing safety of the area.
Psychological interventions improve quality of life despite persistent pain in endometriosis: results of a 3-armed randomized controlled trial
Authors: Hansen K. E. , Brandsborg B. , Kesmodel U. S. , Forman A. , Kold M. , Pristed R. , Donchulyesko O. , Hartwell D. , Vase L.
Published: February 2023

Purpose

Despite standard medical treatment endometriosis is often associated with disabling pain and poor quality of life (QoL). Studies indicate that psychological interventions (PIs) may improve pain and QoL, yet studies on the effects of PIs for women with endometriosis are sparse and limited by low-quality study designs. Therefore, this study aimed, in a rigorous three-armed design, to evaluate the effect of PIs on chronic pelvic pain (CPP) and QoL in women with endometriosis.

Methods

This three-armed parallel, multi-center randomized controlled trial included fifty-eight endometriosis patients reporting severe CPP [≥ 5 for pain intensity measured on a 0–10-point numeric rating scale (NRS)]. Patients were randomly assigned to (1) Specific mindfulness- and acceptance-based psychological intervention (MY-ENDO), (2) Carefully matched non-specific psychological intervention (Non-specific), or (3) A wait-list control group (WL). The primary outcome was pelvic pain intensity/unpleasantness measured on NRS. Secondary outcomes included endometriosis-related quality of life, workability, pain acceptance, and endometriosis-related symptoms. Differences in outcomes between groups at post-treatment follow-up were analyzed using mixed linear models. Analyses were performed on an intention-to-treat basis.

Results

Compared to WL, psychological intervention (MY-ENDO + Non-specific) did not significantly reduce pain. However, psychological intervention did significantly improve the QoL-subscales ‘control and powerlessness’, ‘emotional well-being’, and ‘social support’ as well as the endometriosis-related symptoms ‘dyschezia’ and ‘constipation’. MY-ENDO was not superior to Non-specific.

Conclusions

Women with endometriosis may have significant and large effects of psychological intervention on QoL despite an ongoing experience of severe CPP.

Trial registration

12 April 2016, clinicaltrials.gov (NCT02761382), retrospectively registered.
Innovations, Challenges and Future Directions in Nature of Science Research: Reflections from Early Career Academics
Authors: Park Wonyong , Cullinane Alison , Gandolfi Haira , Alameh Sahar , Mesci Günkut
Published: February 2023

There has been sustained research interest in the role of early career researchers in advancing the field and the challenges that they face. However, efforts to document lived experiences of researchers working in a specific research area within science education have been scarce. This paper considers the meaning of innovation in the context of nature of science (NOS) research, drawing from a collective reflection of five early career academics from different backgrounds. After discussing the sources of our motivation to innovate in NOS research, we identify four distinct pathways of innovation. These pathways include (1) delving into specific aspects of NOS in greater depth, (2) exploring the interface of NOS and other established research areas, and (3) using NOS to address pressing social issues, and (4) expanding the methodological repertoire of NOS research. We illustrate these four modes of research innovation using examples from our own work. Barriers to early-career innovation such as the absence of NOS in curricula and initial teacher education, the lack of time to engage with practitioners to develop and implement instructional resources, and the underrepresentation of diverse education systems in NOS research literature are discussed.