bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging
Authors: Jomova Klaudia , Raptova Renata , Alomar Suliman Y. , Alwasel Saleh H. , Nepovimova Eugenie , Kuca Kamil , Valko Marian
Published: August 2023

A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress (“bad stress”). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s and Parkinson’s diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.
3D bioprinting in plastic and reconstructive surgery: current concepts, progress, and clinical application
Authors: Alawi Seyed Arash , Matschke Jan , Muallah David , Gelinksy Michael , Dragu Adrian
Published: August 2023

Background

Bioprinting is one of the most rapidly developing fields in medicine. Plastic and reconstructive surgery will be affected enormously by bioprinting, due to its original purpose of restoring injured or lost tissue. This article in particular has the purpose to analyze the current state of bioprinted tissues as well as research engagement for its application in plastic and reconstructive surgery.

Material and methods

A systematic search for the time span between 2000 and 2022 was performed on EMBASE, PubMed, Scopus, and Web of Science databases according to the PRISMA Guidelines. Criteria for the selection of publications were in vitro, animal in vivo, and human in vivo studies where three-dimensional bioprinting of tissue was performed. We extracted data such as (a) author’s country of origin, (b) in vitro study, (c) animal in vivo study, and (d) human in vivo study and categorized the publications by topics such as (1) neural tissue, (2) vascularization, (3) skin, (4) cartilage, (5) bone, and (6) muscle. Additionally, recent discoveries of in vivo animal trials were summarized.

Results

Out of a pool of 1.629 articles, only 29 publications met our criteria. Of these publications, 97% were published by university institutions. Publications from China (28%, n=8), the USA (28%, n=8), and Germany (10%, n=3) led the publication list on 3D bioprinting. Concerning the publications, 45% (n=13) were in vitro studies, 52% (n=15) in vivo studies on animal models, and 3% (n=1) pilot clinical studies on humans as reported by Zhou et al. (EBioMedicine 28: 287–302, 2018). Regarding the classification of topics, our study revealed that publications were mainly in the field of 3D printing of cartilage (n=13, 39%), skin (n=7, 21%), bone (n=6, 18%), and vascularization (n=5, 15%).

Conclusions

To this date, it has not been yet possible to bioprint whole tissue systems. However, the progress in three-dimensional bioprinting is rapid. There are still some challenges, which need to be overcome regarding cell survival before and during the printing process, continuation of architecture of bioprinted multilinear cells, and long-term stabilization and survival of complex tissues.

Level of evidence: Not ratable.
[99mTc]Tc-PentixaTec: development, extensive pre-clinical evaluation, and first human experience
Authors: Konrad Matthias , Rinscheid Andreas , Wienand Georgine , Nittbaur Bernd , Wester Hans-Jürgen , Janzen Tilman , Lapa Constantin , Pfob Christian Helmut , Schottelius Margret
Published: August 2023

Purpose

The clinical success non-invasive imaging of CXCR4 expression using [68 Ga]Ga-PentixaFor-PET warrants an expansion of the targeting concept towards conventional scintigraphy/SPECT with their lower cost and general availability. To this aim, we developed and comparatively evaluated a series of 99mTc-labeled cyclic pentapeptides based on the PentixaFor scaffold.

Methods

Six mas3-conjugated CPCR4 analogs with different 4-aminobenzoic acid (Abz)-D-Ala-D-Arg-aa3 linkers (L1–L6) as well as the corresponding HYNIC- and N4-analogs of L6-CPCR4 were synthesized via standard SPPS. Competitive binding studies (IC50 and IC50inv) were carried out using Jurkat T cell lymphoma cells and [125I]FC-131 as radioligand. Internalization kinetics were investigated using hCXCR4-overexpressing Chem-1 cells. Biodistribution studies and small animal SPECT/CT imaging (1 h p.i.) were carried out using Jurkat xenograft bearing CB17/SCID mice. Based on the preclinical results, [99mTc]Tc-N4-L6-CPCR4 ([99mTc]Tc-PentixaTec) was selected for an early translation to the human setting. Five patients with hematologic malignancies underwent [99mTc]Tc-N4-L6-CPCR4 SPECT/planar imaging with individual dosimetry.

Results

Of the six mas3-conjugated peptides, mas3-L6-CPCR4 (mas3-dap-r-a-Abz-CPCR4) showed the highest CXCR4 affinity (IC50 = 5.0 ± 1.3 nM). Conjugation with N4 (N4-L6-CPCR4) further improved hCXCR4 affinity to 0.6 ± 0.1 nM. [99mTc]Tc-N4-L6-CPCR4 also showed the most efficient internalization (97% of total cellular activity at 2 h) and the highest tumor accumulation (8.6 ± 1.3% iD/g, 1 h p.i.) of the compounds investigated. Therefore, [99mTc]Tc-N4-L6-CPCR4 (termed [99mTc]Tc-PentixaTec) was selected for first-in-human application. [99mTc]Tc-PentixaTec was well tolerated, exhibits a favorable biodistribution and dosimetry profile (2.1–3.4 mSv per 500 MBq) and excellent tumor/background ratios in SPECT and planar imaging.

Conclusion

The successive optimization of the amino acid composition of the linker structure and the N-terminal 99mTc-labeling strategies (mas3 vs HYNIC vs N4) has provided [99mTc]Tc-PentixaTec as a novel, highly promising CXCR4-targeted SPECT agent for clinical application. With its excellent CXCR4 affinity, efficient internalization, high uptake in CXCR4-expressing tissues, suitable clearance/biodistribution characteristics, and favorable human dosimetry, it holds great potential for further clinical use.

Graphical abstract
Can penguins (Spheniscidae) see in the ultraviolet spectrum?
Authors: Hadden Peter W. , Vorobyev Misha , Hadden William H. , Bonadonna Francesco , McGhee Charles N.J. , Zhang Jie
Published: August 2023

It has been postulated that ultraviolet reflectance is important in mate choice in King Penguins Aptenodytes patagonicus, although not in other penguin species that do not have body parts that reflect UV light. However, this theory has been challenged. Here we aimed to determine the transmission of the ocular media in the large King Penguin as well as the smallest penguin, the Little Penguin Eudyptula minor, and a medium-sized penguin, the Gentoo Penguin Pygoscelis papua, to determine if the penguin eye is capable of seeing ultraviolet light. In all species the cornea absorbed the most damaging rays at 300 nm or below but it was the lens that predominantly determined the transmission of light between 300 and 400 nm. The lenses of a young King Penguin absorbed almost all light less than 370 nm and had 50% transmission at 406 nm, thus ultraviolet perception in the King Penguin is very limited. In contrast, 50% lenticular transmission was 329 nm in the Little Penguin and 367 nm in the Gentoo. Therefore, we suspect that ultraviolet light may be more important in the behaviour of smaller penguins than in the King Penguin, where it is unlikely to play a significant role.
Influence of noninvasive brain stimulation on connectivity and local activation: a combined tDCS and fMRI study
Authors: Claaß Luise Victoria , Hedrich Annika , Reinelt Janis , Sehm Bernhard , Villringer Arno , Schlagenhauf Florian , Kaminski Jakob
Published: August 2023

The effect of transcranial direct current stimulation (tDCS) on neurobiological mechanisms underlying executive function in the human brain remains elusive. This study aims at examining the effect of anodal and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) in comparison with sham stimulation on resting-state connectivity as well as functional activation and working memory performance. We hypothesized perturbed fronto-parietal resting-state connectivity during stimulation and altered working memory performance combined with modified functional working memory-related activation. We applied tDCS with 1 mA for 21 min over the DLPFC inside an fMRI scanner. During stimulation, resting-state fMRI was acquired and task-dependent fMRI during working memory task performance was acquired directly after stimulation. N = 36 healthy subjects were studied in a within-subject design with three different experimental conditions (anodal, cathodal and sham) in a double-blind design. Seed-based functional connectivity analyses and dynamic causal modeling were conducted for the resting-state fMRI data. We found a significant stimulation by region interaction in the seed-based ROI-to-ROI resting-state connectivity, but no effect on effective connectivity. We also did not find an effect of stimulation on task-dependent signal alterations in working memory activation in our regions of interest and no effect on working memory performance parameters. We found effects on measures of seed-based resting-state connectivity, while measures of effective connectivity and task-based connectivity did not show any stimulation effect. We could not replicate previous findings of tDCS stimulation effects on behavioral outcomes. We critically discuss possible methodological limitations and implications for future studies.
Modeling decompression paths in a basaltic andesite magma using the nucleation and growth of plagioclase microlites
Authors: Marshall Aaron A. , Andrews Benjamin J.
Published: August 2023

Plagioclase microlites in a magma nucleate and grow in response to melt supersaturation (Δϕplag). The resultant frozen plagioclase crystal size distribution (CSD) preserves the history of decompression pathways (dP/dt). SNGPlag is a numerical model that calculates the equilibrium composition of a decompressing magma and nucleates and grows plagioclase in response to an imposed Δϕplag. Here, we test a new version of SNGPlag calibrated for use with basaltic andesite magmas and model dP/dt for the ca. 12.6 ka Curacautín eruption of Llaima volcano, Chile. Instantaneous nucleation (Nplag) and growth (Gplag) rates of plagioclase were computed using the experimental results of Shea and Hammer (J Volcanol Geotherm Res 260:127–145, 10.1016/j.jvolgeores.2013.04.018, 2013) and used for SNGPlag modeling of basaltic andesite composition. Maximum Nplag of 6.1 × 105 cm h−1 is achieved at a Δϕplag of 44% and the maximum Gplag of 27.4 μm h−1 is achieved at a Δϕplag of 29%. Our modeled log dP/dtavg range from 2.69 ± 0.09 to 6.89 ± 0.96 MPa h−1 (1σ) with an average duration of decompression from 0.87 ± 0.25 to 16.13 ± 0.29 h assuming a starting pressure Pi of 110–150 MPa. These rates are similar to those derived from mafic decompression experiments for other explosive eruptions. Using assumptions for lithostatic pressure gradients (dP/dz), we calculate ascent rates of < 1–6 m s−1. We conducted a second set of Monte Carlo simulations using Pi of 15–30 MPa to investigate the influence of shallower decompression, resulting in log dP/dtavg from 2.86 ± 0.49 to 6.00 ± 0.86 MPa h−1. The dP/dt modeled here is two orders of magnitude lower than those calculated by Valdivia et al. (Bull Volcanol, 10.1007/s00445-021-01514-8, 2022) for the same eruption using a bubble number density meter, and suggests homogeneous nucleation raises dP/dt by orders of magnitude in the shallow conduit. Our modeling further supports the rapid-ascent hypothesis for driving highly explosive mafic eruptions.
A real-time Arabic avatar for deaf–mute community using attention mechanism
Authors: Mosa Diana T. , Nasef Nada A. , Lotfy Mohamed A. , Abohany Amr A. , Essa Reham M. , Salem Ahmed
Published: August 2023

Speech-impaired people use Sign Language (SL), an efficient natural form of communication, all over the world. This paper aims to use deep learning technology in the realm of SL translation and identification. In order to ease communication between hearing-impaired and sighted individuals and to enable the social inclusion of hearing-impaired people in their daily lives, it presents a transformer as a neural machine translation model. The article details the creation of a machine translation system that converts Arabic audio and text into Arabic Sign Language (ArSL) automatically. It does this by utilizing an animated character to produce the correct sign for each spoken word. Since Arabic has few resources, it was challenging to obtain an Arabic-Sign dataset, so we created our own Arabic–Arabic sign gloss, which consists of 12,187 pairs, to train the model. We use bidirectional encoder representations from transformers as an embedding layer to interpret input text tokens and represent an appropriate natural language vector space for deep learning models. To represent the structure of each Arabic word, the Ferasa Part-of-Speech Tagging module was used and then the extracted rules from the ArSL structure were applied. This paper shows a detailed description of a natural language translator (for converting an Arabic word sequence into a sequence of signs belonging to the ArSL) and a 2D avatar animation module (for playing back the signs). In our prototype, we train the software-based module using the attention mechanism. The evaluation was carried out in our developed Arabic sentences with the corresponding Arabic gloss. The proposed model achieves promising results and indicates significant improvements to direct communication between hearing and deaf people, with a training accuracy of 94.71% and an 87.04% testing accuracy for Arabic–Arabic sign gloss translation.
Experimental Study of the Effects of Borehole Size, Borehole Roughness, and Installation Pressure on the Pull Load Capacity of Inflatable Rockbolts
Authors: Li Charlie C. , Aure Andreas , Knox Greig
Published: August 2023

An inflatable rockbolt is a steel tube that has been rolled into an omega shape. During installation, water is injected into the tube, which expands the profile of the rockbolt, generating a radial force against the borehole wall. This reinforces the rock mass through the friction at the bolt–rock interface. This study aims to quantify the effects of borehole size, borehole roughness, and installation water pressure on the pull load capacity of the bolt. This was achieved through a series of pull tests under laboratory conditions. The test results showed that the load capacity was higher in boreholes that were either close to the initial profile diameter of the bolt or the fully unfolded diameter of the bolt, that were 26.8 mm and 38.7 mm, respectively, in the study. The load capacity and the radial stiffness of the bolt were lowest in the medium-sized boreholes (33 and 33.5 mm). In small boreholes, the shoulders of the bolt tongue are tightly compressed such that the outward elastic deformation of the bolt tube is locked in after installation. This deformation locking enhances the load capacity of the bolt. In addition, the load capacity was found to be higher in percussively drilled boreholes than in diamond-drilled boreholes. The additional friction angle of the percussive boreholes was back-calculated to be approximately 5.83°. The load capacity was also found to increase as the installation water pressure increases in the range of pressures tested. It was observed that the inflatable bolt was clamped against the borehole in three zones: on the two tongue shoulders and the side of the bolt opposite the tongue.
Immediate effect of caffeine on sympathetic nerve activity: why coffee is safe? A single-centre crossover study
Authors: Butler Jennifer M. , Frampton Christopher M. , Moore Grant , Barclay Murray L. , Jardine David L.
Published: August 2023

Purposes

Habitual coffee drinking is ubiquitous and generally considered to be safe despite its transient hypertensive effect. Our purpose was to determine the role of the sympathetic nervous system in the hypertensive response.

Methods

In a single-centre crossover study, medical caregivers were studied after consumption of standard coffee (espresso), water and decaffeinated coffee (decaff) given in random order at least 1 month apart. Plasma caffeine levels, mean arterial pressure, heart rate, total peripheral resistance and muscle sympathetic activity were recorded. Baroreflex activity was assessed using burst incidence and RR interval changes to spontaneous blood pressure fluctuations.

Results

A total of 16 subjects (mean [± standard error] age 34.4 ± 2 years; 44% female) were recruited to the study. Three agents were studied in ten subjects, and two agents were studied in six subjects. Over a 120-min period following the consumption of standard coffee, mean (± SE) plasma caffeine levels increased from 2.4 ± 0.8 to 21.0 ± 4 µmol/L and arterial pressure increased to 103 ± 1 mmHg compared to water (101 ± 1 mmHg; p = 0.066) and decaff (100 ± 1 mmHg; p = 0.016). Peripheral resistance in the same period following coffee increased to 120 ± 4% of the baseline level compared to water (107 ± 4; p = 0.01) and decaff (109 ± 4; p = 0.02). Heart rate was lower after both coffee and decaff consumption: 62 ± 1 bpm compared to water (64 bpm; p = 0.01 and p = 0.02, respectively). Cardio-vagal baroreflex activity remained stable after coffee, but sympathetic activity decreased, with burst frequency of 96 ± 3% versus water (106 ± 3%; p = 0.04) and decaff (112 ± 3%; p = 0.001) despite a fall in baroreflex activity from – 2.2 ± 0.1 to – 1.8 ± 0.1 bursts/100 beats/mmHg, compared to water (p = 0.009) and decaff (p = 0.004).

Conclusion

The hypertensive response to coffee is secondary to peripheral vasoconstriction but this is not mediated by increased sympathetic nerve activity. These results may explain why habitual coffee drinking is safe.
Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial
Authors: Wheatley-Guy Courtney M. , Shea Meredith G. , Parks Jordan K. , Scales Robert , Goodman Brent P. , Butterfield Richard J. , Johnson Bruce D.
Published: August 2023

Purpose

Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC).

Methods

Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions.

Results

The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. − 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (− 11.38 vs. − 6.49, p = 0.09).

Conclusion

Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.
Non-breeding sites, loop migration and flight activity patterns over the annual cycle in the Lesser Grey Shrike Lanius minor from a north-western edge of its range
Authors: Adamík Peter , Wong Joanna B. , Hahn Steffen , Krištín Anton
Published: August 2023

The Lesser Grey Shrike is a typical Palaearctic songbird for which we have limited knowledge of its migration ecology. All that is known about its non-breeding movements is inferred from observational data of birds on passage. The few available ring recovery data do not link breeding and African non-breeding grounds. By deploying two types of loggers, light-level geolocators and multi-sensor loggers, on birds from a declining Slovak breeding population, we present the first direct evidence for non-breeding grounds, loop migration, stopover sites and the timing of annual cycle events. With barometric data, we provide details on flight altitudes during migration. The two tracked birds migrated in a clear anti-clockwise loop to S Africa. Autumn migration tracks went through the Balkan Peninsula, Mediterranean Sea towards Libya with unusually long stays around N Chad and Niger. The next stopovers were in Angola, and the main non-breeding sites were in Botswana. Spring migration commenced on March 29 and April 7 and the birds took routes along East African countries, with stopovers later in Somalia and Saudi Arabia, before crossing the eastern Mediterranean Sea. Nocturnal migration dominated, but for three days in August, while crossing the Sahara Desert, the bird extended flights into the day with a sudden increase in flight altitudes at dawn. Flight altitudes were higher during barrier crossing and during the last phase of spring migration compared to the remaining periods, with the most extreme event recorded at 4530 m asl.
Quantitative version of Weyl’s law
Authors: Savale Nikhil
Published: August 2023

We prove a general estimate for the Weyl remainder of an elliptic, semiclassical pseudodifferential operator in terms of volumes of recurrence sets for the Hamilton flow of its principal symbol. This quantifies earlier results of Volovoy (Comm Partial Differential Equations 15:1509–1563, 1990; Ann Global Anal Geom 8:127–136, 1990). Our result particularly improves Weyl remainder exponents for compact Lie groups and surfaces of revolution. And gives a quantitative estimate for Bérard’s Weyl remainder in terms of the maximal expansion rate and topological entropy of the geodesic flow.
Antidepressant Prescription Behavior Among Primary Care Clinician Providers After an Interprofessional Primary Care Psychiatric Training Program
Authors: Huo Shutong , Bruckner Tim A. , Xiong Glen L. , Cooper Emma , Wade Amy , Neikrug Ariel B. , Gagliardi Jane P. , McCarron Robert
Published: August 2023

Primary care providers (PCPs) are increasingly called upon to screen for and treat depression. However, PCPs often lack the training to diagnose and treat depression. We designed an innovative 12-month evidence and mentorship-based primary care psychiatric training program entitled the University of California, Irvine (UCI) School of Medicine Train New Trainers Primary Care Psychiatry (TNT PCP) Fellowship and examined whether this training impacted clinician prescription rates for antidepressants. We retrieved information on 18,844 patients and 192 PCPs from a publicly insured health program in Southern California receiving care between 2017 and 2021. Of the 192 PCPs, 42 received TNT training and 150 did not. We considered a patient as exposed to the provider’s TNT treatment if they received care from a provider after the provider completed the 1-year fellowship. We utilized the number of antidepressant prescriptions per patient, per quarter-year as the dependent variable. Linear regression models controlled for provider characteristics and time trends. Robustness checks included clustering patients by provider identification. After PCPs completed TNT training, “exposed” patients received 0.154 more antidepressant prescriptions per quarter-year relative to expected levels (p < 0.01). Clustering of standard errors by provider characteristics reduced precision of the estimate (p < 0.10) but the direction and magnitude of the results were unchanged. Early results from the UCI TNT PCP Fellowship demonstrate enhanced antidepressant prescription behavior in PCPs who have undergone TNT training. A novel, and relatively low-cost, clinician training program holds the potential to empower PCPs to optimally deliver depression treatment.
A trust-region approach for computing Pareto fronts in multiobjective optimization
Authors: Mohammadi A. , Custódio A. L.
Published: August 2023

Multiobjective optimization is a challenging scientific area, where the conflicting nature of the different objectives to be optimized changes the concept of problem solution, which is no longer a single point but a set of points, namely the Pareto front. In a posteriori preferences approach, when the decision maker is unable to rank objectives before the optimization, it is important to develop algorithms that generate approximations to the complete Pareto front of a multiobjective optimization problem, making clear the trade-offs between the different objectives. In this work, an algorithm based on a trust-region approach is proposed to approximate the set of Pareto critical points of a multiobjective optimization problem. Derivatives are assumed to be known, allowing the computation of Taylor models for the different objective function components, which will be minimized in two main steps: the extreme point step and the scalarization step. The goal of the extreme point step is to expand the approximation to the Pareto front, by moving towards the extreme points of it, corresponding to the individual minimization of each objective function component. The scalarization step attempts to reduce the gaps on the Pareto front, by solving adequate scalarization problems. The convergence of the method is analyzed and numerical experiments are reported, indicating the relevance of each feature included in the algorithmic structure and its competitiveness, by comparison against a state-of-art multiobjective optimization algorithm.
Using a Service Lens to Better Understand Practices –and Vice Versa
Authors: Farshchian Babak A. , Mikalsen Marius
Published: August 2023

Many studies of practices involve service exchange, and many service researchers have discovered the central role that sociotechnical practices play in service –in particular, within the service-dominant logic school of thought. In this paper, we propose an analytical lens that builds on this mutual interest to understand complex practices involving service exchange. Practice researchers can gain new insights regarding practices embedded in service ecosystems. At the same time, service researchers can better explain actor behavior by looking deeper at sociotechnical practices. We develop a concept toolbox based on practice and service-dominant logic research literature. We illustrate the usefulness of the toolbox through an interpretative case study of public service to include children with disabilities in leisure activities. Seeing practices as parts of larger multi-stakeholder service ecosystems 1) can help us better explain behavior in those practices and understand how they are affected by other overlapping practices, 2) brings forward the importance of value and how multiple actors need to interact in order to create value for each other, and 3) enriches service-dominant logic with a focus on sociotechnical aspects that are central to many practice studies.
Enhancing Swedish Toddlers’ Learning Opportunities Through Interactions with Pictures and Narrative Designed for Numerical Learning Purposes
Authors: Björklund Camilla , Palmér Hanna
Published: August 2023

The aim of this study is to deepen the understanding of how preschool teachers can use representations of different kinds to bring fore the mathematical content that may be afforded in pictures and narrative designed for numerical learning purposes. Seventy-three video documentations of reading sessions with 27 toddlers (1–3 years of age) over the course of three semesters were analyzed with a focus on number-oriented actions that, theoretically, would facilitate toddlers’ learning of numbers. In the reading sessions the teachers extended the content of the pictures and the narrative in different ways, and how one and the same picture was handled was shown to impact on what was made possible for the children to discern. Three different objects of learning—identifying numbers, comparing numbers, and operating on numbers—were made visible. Further, the use of gestures strengthened the possibility for the children to make connections within and between representations. This contributes to our understanding of the importance of using representations and gestures with a pedagogical purpose.
Iterated AGM Revision Based on Probability Revision
Authors: Hansson Sven Ove
Published: August 2023

Close connections between probability theory and the theory of belief change emerge if the codomain of probability functions is extended from the real-valued interval [0, 1] to a hyperreal interval with the same limits. Full beliefs are identified as propositions with a probability at most infinitesimally smaller than 1. Full beliefs can then be given up, and changes in the set of full beliefs follow a pattern very close to that of AGM revision. In this contribution, iterated revision is investigated. The iterated changes in the set of full beliefs generated by repeated revisions of a hyperreal probability function can, semantically, be modelled with the same basic structure as the sphere models of belief change theory. The changes on the set of full beliefs induced by probability revision satisfy the Darwiche–Pearl postulates for iterated belief change.
An analytical model for the static behaviour of honeycomb sandwich plates with auxetic cores using higher-order shear deformation theories
Authors: Karimi Mahdi , Khoshgoftar Mohammad Javad , Karimi Mohammad , Mirzaali Mohammad Javad , Javanbakht Zia
Published: August 2023

This paper presents an analytical model to investigate the static behaviour of sandwich plates comprised of two isotropic face sheets and a honeycomb core. Through-thickness transverse shear stresses were considered using a unified displacement field with which various plate theories were implemented, i.e., exponential, third-order, hyperbolic, sinusoidal, fifth-order, Mindlin, and the classic plate theory. The equilibrium equations of a simply-supported sandwich panel were derived using the principle of virtual work and Navier solution was obtained under static transverse loading. After validating of the model, various mechanical and geometrical parameters were varied to characterise the behaviour of the structure under regular and auxetic response. It was found that the auxeticity of the core strongly affects the mechanical response, e.g., in controlling deflection, in-plane anisotropy, and Poisson’s ratio. Cell wall angle was found to be most critical parameter that can be used to adjust anisotropy, out-of-plane shear modulus, transverse shear stress distribution, and deflection of the panel. Also the cell aspect ratio controls the sensitivity of the core response to other geometrical variations. In terms of the higher-order theories, the deflection-dependent parameter of the unified formulation seems to have more control of maximum deflection compared to independent rotations. Auxeticity of the core showed some benefits in controlling anisotropy, deflection and providing additional out-of-plane shear rigidity. Overall, since there is not one-to-one relationship between specific values of Poisson’s ratio, anisotropy, and shear rigidity, careful design considerations must be invested to obtain a correct mechanical response.
A comparative exergy-based assessment of direct air capture technologies
Authors: Hoseinpoori Sina , Pallarès David , Johnsson Filip , Thunman Henrik
Published: August 2023

The 6th Assessment of the IPCC underlined the need for urgent measures for carbon dioxide removal from the atmosphere, so as to meet the 1.5 °C goal by the end of this century. One option to achieve this is direct air capture (DAC) technologies. This work assesses the thermodynamic performances of different categories of DAC technologies, i.e., adsorption-based, absorption-based, ion exchange, and electrochemical. An exergy analysis is performed on the DAC processes in each category to identify hotspots for efficiency loss within the system. The results show that the consumption of materials is responsible for 5–40% of the exergy consumption of the most-developed DAC processes. Despite their greater use of materials compared to absorption-based processes, adsorption-based processes, together with ion exchange technologies, have the highest exergy efficiencies of the DAC technologies investigated. Moreover, the results highlight the importance of limiting material consumption and electrifying large-scale DAC plants, which cannot run exclusively on waste heat from industrial processes.
The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma
Authors: He Cheng , Teng Xiao , Wang Luming , Ni Miaoqi , Zhu Linhai , Liu Jiacong , Lv Wang , Hu Jian
Published: August 2023

Esophageal carcinoma (EC) is always diagnosed at advanced stage and its the mortality rate remains high. The patients usually miss the best opportunity for treatment because of non-specific symptoms and the survival rates are low. N6-methyladenosine (m6A) the predominant modification in eukaryotic messenger RNA(mRNA), serves vital roles in numerous bioprocess. This chemical modification is dynamic, reversible and consists of three regulators: m6A methyltransferases (writers), demethylases (erasers) and m6A-binding proteins (readers). Recently, a growing number of evidences have indicated relationships between m6A and EC. Whereas, lacking of cognition about the molecular mechanism of m6A modification in esophageal carcinoma. We will focus on the biological function roles of m6A modification in the tumorigenesis and development of EC. Recent studies showed that immunotherapy had a positive impact on EC. The relationship between m6A and immunotherapy in EC deserves further research and discussion. We will also discuss the potential clinical applications regarding diagnosis, treatment and prognosis of m6A modification for EC and provide perspectives for further studies.
Low bleeding acceptance is associated with increased death risk in patients with atrial fibrillation on oral anticoagulation
Authors: Rusin Gabriela , Konieczyńska Małgorzata , Natorska Joanna , Malinowski Krzysztof Piotr , Undas Anetta
Published: August 2023

Bleeding is the most feared complication of anticoagulation. We sought to investigate whether the bleeding risk acceptance has a prognostic value during long-term follow-up in the era of direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF). We studied 167 consecutive AF outpatients [aged 68.8 SD 10.6 years; 141 (84.4%) on DOACs]. The bleeding acceptance was assessed based on the Bleeding Ratio defined as the declared maximum number of major bleedings that a patient would be willing to accept to prevent one major stroke. We recorded cerebrovascular ischemic events, major or clinically relevant non-major bleeds (CRNMB), and mortality. A median Bleeding Ratio was 4 (IQR 2–5). During follow-up of 946 patient-years, cerebrovascular ischemic events and/or death were observed in 28 patients (3.3%/ year) and major bleeding or CRNMB in 33 (4.6%/ year). The Bleeding Ratio was lower in patients who experienced cerebrovascular events or death (p = 0.004), but not bleeding. Patients with the Bleeding Ratio 0–3 were more often non-persistent to the OAC therapy, and more likely to have cerebrovascular event or die than those with higher bleeding acceptance (odds ratio 2.55; 0.95% CI 1.08–6.02) which was driven by the impact on mortality. The multiple Cox proportional hazards model showed that lower Bleeding Ratio, higher CHA2DS2-VASc score, and older age predicted cerebrovascular events or death during follow-up. AF patients who are willing to accept fewer serious bleedings to avoid major stroke during anticoagulation are more likely to experience death and/or cerebrovascular ischemic events, but not bleeding, what might be related to non-persistence.
PoroTwin: A Digital Twin for a FluidFlower Rig
Authors: Keilegavlen Eirik , Fonn Eivind , Johannessen Kjetil , Eikehaug Kristoffer , Both Jakub W. , Fernø Martin , Kvamsdal Trond , Rasheed Adil , Nordbotten Jan M.
Published: August 2023

We present a framework for integrated experiments and simulations of tracer transport in heterogeneous porous media using digital twin technology. The physical asset in our setup is a meter-scale FluidFlower rig. The digital twin consists of a traditional physics-based forward simulation tool and a correction technique which compensates for mismatches between simulation results and observations. The latter augments the range of the physics-based simulation and allows us to bridge the gap between simulation and experiments in a quantitative sense. We describe the setup of the physical and digital twin, including data transfer protocols using cloud technology. The accuracy of the digital twin is demonstrated on a case with artificially high diffusion that must be compensated by the correction approach, as well as by simulations in geologically complex media. The digital twin is then applied to control tracer transport by manipulating fluid injection and production in the experimental rig, thereby enabling two-way coupling between the physical and digital twins.
Five Years Measuring the Muck: Evaluating Interannual Variability of Nutrient Loads From Tidal Flooding
Authors: Macías-Tapia Alfonso , Mulholland Margaret R. , Selden Corday R. , Loftis J. Derek , Bernhardt Peter W.
Published: August 2023

Due to sea level rise, tidal flooding is now common in low-lying coastal systems around the world. Yet, the contribution of tidal flooding to non-point source nutrient loads and their impact on the quality of adjacent waters remains poorly constrained. Here, we quantified dissolved nutrient loading and Enterococcus abundance during annual autumnal king tides (i.e., perigean spring tides), between 2017 and 2021, in a sub-watershed of the lower Chesapeake Bay. To calculate nutrient loading from tidal flooding, we used geospatial inundation depths from a street-level hydrodynamic model to estimate floodwater volumes during each of the five sampling events and the difference between nutrient concentrations in floodwater and pre-flood measurements. Results showed that dissolved nutrient concentrations were higher in floodwaters than in estuarine waters and resulted in dissolved nitrogen and phosphorus loads that reached 58.4 × 103 kg and 14.4 × 103 kg, respectively. We compared our load estimates to the tributary-specific total and land-based federal allocations (i.e., total maximum daily loads (TMDL)) for total nitrogen (TN) and total phosphorus (TP). Even the more conservative calculations indicate that inputs of dissolved nutrients during a single tidal flooding event can exceed 100% of the annual load allocation. Additionally, more than 80% of the floodwater samples collected each year showed Enterococcus abundance that exceeded the threshold for recreational water use in Virginia (104 MPN 100 ml−1). Failing to account for non-point source loading of nutrients and contaminants from tidal flooding as sea level rises could result in worsening eutrophication and deterioration of coastal economies and the health of coastal communities around the world.
Does the Location in Science and Technology Parks Foster the Employment Growth of Firms?
Authors: da Silva Martins Júlio Paulo , Rodríguez-Gulías María Jesús , Rodeiro-Pazos David , Rios-Rodríguez Raul
Published: August 2023

One of the main objectives of science and technology parks (STPs) is to contribute to regional development through the creation of skilled jobs in the territory where they are located. However, despite the expansion of these infrastructures over the last decades and the governmental support they receive, there is very little empirical evidence on how these infrastructures affect the employment growth of the firms located there. The aim of this paper is to examine whether the location in STPs has positive effects on employment growth at the firm level. We analysed a sample of 553 Portuguese firms located on STPs and a control group of the same size of comparable firms located outside STPs, applying a dynamic panel data model methodology. The empirical evidence does not allow to prove that location in STPs has positive effects on employment growth, which raises the need to rethink the policies supporting these parks.
Designing Expert-Augmented Clinical Decision Support Systems to Predict Mortality Risk in ICUs
Authors: Chen Johannes , Lowin Maximilian , Kellner Domenic , Hinz Oliver , Adam Elisabeth Hannah , Ippolito Angelo , Wenger-Alakmeh Katharina
Published: August 2023

One of the most critical infrastructures during the COVID-19 pandemic are intensive care units (ICU). ICU’s crucial task is to preserve the lives of patients and mitigate the pandemic’s impact on the population. However, most ICUs plan only one day ahead. This short-term planning becomes an obstacle during disaster situations since physicians need to decide efficiently and ensure the timely treatment of high-risk patients. Integrating machine learning (ML) systems for clinical decision support could improve this process by predicting the mortality risk of critically ill patients. Several ML approaches tackling this problem have already shown promising results. However, these systems mostly neglect the integration of explicit domain knowledge, which is crucial to ensure prediction quality and adaptability. Otherwise, black-box systems might base their decision on confounding variables and improper relationships. Following design science research, we utilize a unique dataset of patients diagnosed with SARS-CoV-2 in ICU care to design a clinical decision support system by combining ML and expert knowledge in the form of a severity score. We show that by augmenting the system with expert knowledge, its overall performance improves compared to the baseline approach.
Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: interplay between nuclear factor-kappa β and cathepsin B
Authors: Hassan Donia M. , El-Kamel Amal H. , Allam Eman A. , Bakr Basant A. , Ashour Asmaa A.
Published: August 2023

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder associated with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (TAN) is a phytomedicine with a documented activity in treating many CNS disorders, particularly PD owing to its unique anti-inflammatory and antioxidant effect. However, its clinical utility is limited by its poor aqueous solubility, short half-life, and hence low concentration reaching targeted cells. This work aimed to develop a biocompatible chitosan-coated nanostructured lipid carriers (CS-NLCs) for effective brain delivery of TAN for PD management. The proposed nanosystem was successfully prepared using a simple melt-emulsification ultra-sonication method, optimized and characterized both in vitro and in vivo in a rotenone-induced PD rat model. The developed TAN-loaded CS-NLCs (CS-TAN-NLCs) showed good colloidal properties (size ≤ 200 nm, PDI ≤ 0.2, and ζ-potential + 20 mV) and high drug entrapment efficiency (> 97%) with sustained release profile for 24 h. Following intranasal administration, CS-TAN-NLCs succeeded to achieve a remarkable antiparkinsonian and antidepressant effect in diseased animals compared to both the uncoated TAN-NLCs and free TAN suspension as evidenced by the conducted behavioral tests and improved histopathological findings. Furthermore, biochemical evaluation of oxidative stress along with inflammatory markers, nuclear factor-kabba β (NF-Kβ) and cathepsin B further confirmed the potential of the CS-TAN-NLCs in enhancing brain delivery and hence the therapeutic effect of TAN of treatment of PD. Accordingly, CS-TAN-NLCs could be addressed as a promising nano-platform for the effective management of PD.

Graphical abstract
Empirical model to assess leaching of pesticides in soil under a steady-state flow and tropical conditions
Authors: Mosquera-Vivas C. S. , Celis-Ossa R. E. , González-Murillo C. A. , Obregón-Neira N. , Martínez-Cordón M. J. , Guerrero-Dallos J. A. , García-Santos G.
Published: August 2023

An empirical model of leaching of pesticides was developed to simulate the concentration of fungicides throughout unsaturated soil. The model was based on chemical reactions and the travel time of a conservative tracer to represent the travel time required for water to flow between soil layers. The model’s performance was then tested using experimental data from dimethomorph and pyrimethanil applied to the soil under field and laboratory conditions. The empirical model simulated fungicide concentration on soil solids and in soil solution at different depths over time (mean square error between 2.9 mg2 kg−2 and 61mg2 kg−2) using sorption percentages and degradation rates under laboratory conditions. The sorption process was affected by the organic carbon, clay, and the effective cation exchange capacity of the soil. The degradation rate values of dimethomorph (0.039 d−1–0.009 d−1) and pyrimethanil (0.053 d−1–0.004 d−1) decreased from 0 to 40 cm and then remained constant in deeper soil layers (60–80 cm). Fungicide degradation was a critical input in the model at subsurface layers. The model was determined to be a reliable mathematical tool to estimate the leachability of pesticides in tropical soil under a steady-state flow. It may be extended to other substances and soils for environmental risk assessment projects.

Graphical abstract