bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse initial‐value problems for time fractional diffusion equations in fractional Sobolev spaces
Authors: Tuan Nguyen Huy , Tran Bao‐Ngoc
Published: September 2024

We study the time fractional diffusion equation , , in a bounded domain with an elliptic operator and a locally Lipschitz nonlinearity on fractional Sobolev spaces, subjected to the homogeneous Dirichlet boundary condition. Data have not been measured at the initial time , but at a final time , that is, is given instead of . The problem is, therefore, called an inverse initial‐value problem. We first establish the well‐posedness of this problem on fractional Sobolev spaces and the regularity of the solution by assuming only the local Lipschitz continuity of . Second, an susceptible‐infected (shortly, SI) model with heterogeneity and a Navier–Stokes equation have been exemplified. Finally, a spatial ‐estimate for the solution and its gradient has been provided. The essential tools are asymptotic behaviours of Mittag–Leffler functions, fractional power spaces, fractional Sobolev spaces and embedding, weighted functional spaces, and estimates for heat semigroup.
Measurement of blood–brain barrier water exchange rate using diffusion‐prepared and multi‐echo arterial spin labelling: Comparison of quantitative values and age dependence
Authors: Morgan Catherine A. , Thomas David L. , Shao Xingfeng , Mahroo Amnah , Manson Tabitha J. , Suresh Vinod , Jansson Deidre , Ohene Yolanda , Günther Matthias , Wang Danny J. J. , Tippett Lynette J. , Dragunow Michael
Published: September 2024

Water exchange rate (Kw) across the blood–brain barrier (BBB) is an important physiological parameter that may provide new insight into ageing and neurodegenerative disease. Recently, two non‐invasive arterial spin labelling (ASL) MRI methods have been developed to measure Kw, but results from the different methods have not been directly compared. Furthermore, the association of Kw with age for each method has not been investigated in a single cohort. Thirty participants (70% female, 63.8 ± 10.4 years) were scanned at 3 T with Diffusion‐Prepared ASL (DP‐ASL) and Multi‐Echo ASL (ME‐ASL) using previously implemented acquisition and analysis protocols. Grey matter Kw, cerebral blood flow (CBF) and arterial transit time (ATT) were extracted. CBF values were consistent; approximately 50 ml/min/100 g for both methods, and a strong positive correlation in CBF from both methods across participants (r = 0.82, p < 0.001). ATT was significantly different between methods (on average 147.7 ms lower when measured with DP‐ASL compared to ME‐ASL) but was positively correlated across participants (r = 0.39, p < 0.05). Significantly different Kw values of 106.6 ± 19.7 min−1 and 306.8 ± 71.7 min−1 were measured using DP‐ASL and ME‐ASL, respectively, and DP‐ASL Kw and ME‐ASL Kw were negatively correlated across participants (r = −0.46, p < 0.01). Kw measured using ME‐ASL had a significant linear relationship with age (p < 0.05). In conclusion, DP‐ASL and ME‐ASL provided estimates of Kw with significantly different quantitative values and inconsistent dependence with age. We propose future standardisation of modelling and fitting methods for DP‐ASL and ME‐ASL, to evaluate the effect on Kw quantification. Also, sensitivity and bias analyses should be performed for both approaches, to assess the effect of varying acquisition and fitting parameters. Lastly, comparison with independent measures of BBB water transport, and with physiological and clinical biomarkers known to be associated with changes in BBB permeability, are essential to validate the ASL methods, and to demonstrate their clinical utility.
An investigation on the wear properties of the photocurable components produced by additive manufacturing for dentistry applications: Combined influences of UV exposure time, building direction, and sliding loads
Authors: Bolat Çağın , Salmaz Serkan
Published: September 2024

Additive manufacturing (AM) of polymers is a highly versatile technology that can be applied to many independent sectors like automotive, aviation, medicine, and dentistry. Since it has great potential for rapid prototyping, clean‐process concepts, and the ability to produce complex shapes, the layer‐by‐layer printing method is one of the most promising alternatives for future industrial production efforts. In that sense, different from the previous studies, this work aims to elucidate the friction and wear properties of the special dental samples manufactured via photopolymerization‐based AM technology according to both for printing parameters, and dry sliding test variables. Also, this is the first initiation to examine the combined influences of the UV exposure time, building direction, and sliding force on the surface roughness, hardness, friction coefficient, wear rate, and main plastic damage mechanism of the printed samples. The results showed that the maximum average hardness value was detected as 89.8 Shore D for vertically built samples printed with 8 s exposure time. In addition, vertically printed samples exhibited better wear resistance than the horizontal samples and the rising exposure time generally affected affirmatively the hardness levels of the samples. The lowest volume loss of 78 mm3 belonged to the vertical sample at 5 N. Further, increasing test force levels caused a decrease in the friction coefficient results and triggered the volume loss increase in the samples. Among all samples, the calculated friction coefficient values changed between 0.3 and 0.87. On the other side, scanning electron microscopy (SEM), and energy‐dispersive spectroscopy (EDS) analyses pointed out that ascending exposure times led to the altering contact surface matchings determining the final volume loss outcomes.

Highlights

To obtain better surface quality, vertical printing was a useful option.

Horizontally printed samples exhibited higher friction coefficients.

Curing time positively impacted the wear resistance for both orientations.

Grooves and debris parts were observed on surfaces with low exposure times.
Psychosis following phenibut‐assisted withdrawal
Authors: Bicknell Marcus , Bachra Joshua , Rhinds David
Published: September 2024

Phenibut is less frequently used in the UK compared with heroin, cocaine, crack, cannabis, ketamine or alcohol but is currently not covered by the UK drugs legislation. It is widely available on the internet, and its popularity is increasing, particularly among younger, internet‐savvy patients. This case describes a patient who developed psychosis during medically assisted withdrawal from phenibut.
Imperfect Measurement Devices Impact the Security of Tomography‐Based Source‐Independent Quantum Random Number Generator
Authors: Li Yuanhao , Fei Yangyang , Wang Weilong , Meng Xiangdong , Wang Hong , Duan Qianheng , Han Yu , Ma Zhi
Published: September 2024

Source‐independent quantum random number generators (SI‐QRNGs) can generate secure random numbers with untrusted and uncharacterized sources. Recently, a tomography‐based SI‐QRNG protocol has garnered significant attention for its higher randomness generation rate[Phys. Rev. A 99, 022328 (2019)], achieved through measurements utilizing three mutually unbiased bases. However, imperfect and inadequately characterized measurement devices would impact the security and performance of this protocol. In this work, considering the imperfect basis modulation, afterpulse effect and detection efficiency mismatch, it is demonstrated that the imperfect measurement devices would reduce the extractable randomness and lead to the incorrect estimation of the conditional min‐entropy. Additionally, the influences of the finite‐size effect and the performances of the protocol based on different parameter estimation methods are investigated and compared. To guarantee the security of generated random numbers, accurate conditional min‐entropy estimation methods that are compatible with imperfect factors are also developed. The work emphasizes the significance of considering the imperfections in measurement devices and establishing tighter bounds for parameter estimation, especially in high‐speed systems, thereby enhancing the robustness and performance of the protocol.
Environmental Factors Associated With Fish Reproduction in Regulated Rivers
Authors: Griffen Erik M. , Weber Michael J.
Published: September 2024

Humans have extensively altered rivers to accommodate anthropogenic uses. Dams modify river flow and temperature regimes important for lotic fish reproduction. Yet, assessments of fish production in relation to environmental conditions in regulated rivers are lacking but are needed to guide experimental environmental flows. We evaluated the effects of water temperature and discharge on larval Catostomidae, Sciaenidae, and Clupeidae production to inform environmental flow management. We sampled ichthyoplankton from April through June on the Des Moines and Iowa rivers prior to (2014–2015) and after (2021–2022) an experimental environmental flow was incorporated on the Des Moines River. We used a hurdle model to assess the effects of water temperature, discharge, and discharge variation on larval presence (logistic regression) and density (linear regression). Larval Catostomidae were captured once water temperatures exceeded 15°C, Sciaenidae appeared when water temperature surpassed 18°C, while Clupeidae appeared when water temperature exceeded 20°C. The probability of larval Sciaenidae and Clupeidae presence increased with discharge variation while densities were both positively associated with discharge and discharge variation. The probability of Sciaenidae and Catostomidae larval presence increased with water temperature. Interactions between water temperature and discharge influenced Clupeidae presence and Catostomidae density. The probability of Clupeidae presence increased with discharge at warmer water temperatures. Catostomidae densities increased with discharge at cool water temperature (13°C) and decreased with discharge at warm (25°C) temperatures. Our results provide information about the effects of discharge, discharge variation, and water temperature driving larval fish production in anthropogenically altered rivers to guide environmental flow management.
Did court dismiss due process case?
Authors: Lyerly Eric
Published: September 2024

John Doe was an Iranian graduate student at Virginia Polytechnic Institute and State University.
Stem‐Cell‐Based Small‐Diameter Blood Vessels with 3D Printing
Authors: Wang Yifan , Wang Xinhuan , Chen Jun , Wallace Gordon , Gu Qi
Published: September 2024

Cardiovascular disease has emerged as the leading cause of death worldwide. Since coronary arteries, carotid arteries, and other blood vessels are prone to narrowing, small‐diameter artificial blood channels offer a crucial solution for restoring blood flow. Ideal grafts must emulate the structure of natural blood vessels, possess adequate mechanical strength, ensure long‐term patency, and incorporate functional cells with minimal immunogenicity. Enhanced cell sources and engineering methods are vital for the creation of functional small‐diameter blood vessels (SDBVs). Among potential cell sources, stem cells stand out due to their ability to differentiate into multiple cell types, self‐renew, and exhibit low immunogenicity. Additionally, three‐dimensionally (3D) printed vascular stents have attracted widespread attention for their precision and controllable bioink application. The need for tissue‐engineered blood vessels is currently rising, and innovative design concepts integrating stem cells and 3D printing present promising solutions. Herein, the construction requirements of vascular grafts are reviewed, current status of using stem cells as a cell source and 3D printing as an engineering strategy is described, and prospects and challenges for the development of SDBVs in the medical field are discussed.
What affects carotid intima media thickness more, diabetes or smoking: An ultrasound based study
Authors: Rasheed Awais , Riaz Umair , Khawaja Shayan Rashid , Jamil Akhtar , Dawood Sabiha , Tazeen Anjum , Anjum Muhammad Nawaz , Fatima Zareen
Published: September 2024

Background

Both diabetes mellitus (DM) and cigarette smoking have been implicated in affecting carotid intima‐media thickness (CIMT) and plaque formation. The study aimed to evaluate and compare the effects of these risk factors on CIMT.

Objective

To compare sonographically measured carotid arterial intima‐media thickness among non‐diabetic and non‐smoker control group with smokers and diabetics.

Materials and Methods

This cross‐sectional analytical study was conducted over 9 months. Sonographic measurement of CIMT was done in 143 participants, divided into three groups: non‐diabetic non‐smokers, diabetics, and smokers. Data were analyzed using MEDCALC.

Results

Mean CIMT values differed significantly among the three groups (p value = .000001) bilaterally. CIMT correlated strongly positively with age in Group I (r = .38, p = .018) and Group III (r = .35, p = .008) but not in Group II (r = .002, p = .98).

Conclusion

The study concludes that both smoking and diabetes contribute to the intimal thickening. However, smoking may have a more pronounced effect on CIMT thickening than diabetes. This underscores the importance of addressing smoking cessation in cardiovascular risk management.
Inkjet‐Printed Flexible and Transparent Ti3C2Tx/TiO2 Composite Films: A Strategy for Photoelectrically Controllable Photocatalytic Degradation
Authors: Ji Ziying , Wu Yiran , Liu Lu , Zheng Wei , Wu Meng , Li Yuexia , Sun Zhengming , Ying Guobing
Published: September 2024

The 2D Ti3C2Tx MXene has a large specific surface area, abundant functional groups, and low work function, which has potential in the field of photocatalytic materials. However, the manufacturing of controllable films with high photocatalytic properties and desirable transmittance is a challenging task. Herein, low‐cost, large‐scale, and rapid preparation of Ti3C2Tx/TiO2 flexible composite films have been successfully prepared by inkjet printing technology, which can be applied in complex and special environments, as well as in photoelectrically controllable places for photocatalytic performance. With the increase of the anatase TiO2, the transmittance of Ti3C2Tx/TiO2 films increases from 55.37% to 73.27% at 780 nm, corresponding to the square resistance of 1.112–206.496 kΩ sq−1 and the figure of merit of 0.48–0.005. When the amount of anatase TiO2 is 15%, the film has the best photocatalytic effect on methylene blue (MB) dye, reaching 68.94%. After five cycles of testing, the degradation efficiency of MB dye decreases by only 5.68%, showing that the film has good cycling stability. This work provides a new research direction for photoelectrically controllable photocatalytic degradation in complex and special environments.
Development of multilayer composite film based on protein‐polysaccharides with the addition of onion waste extracts and their impact on the shallot quality
Authors: Thivya P. , Reddy N. Bhanu Prakash , Sinija V. R.
Published: September 2024

At present, multilayer composite film is attractive in the production of biodegradable films due to its essential film properties. The current study mainly focused on overcoming the problems of poor water barrier and mechanical strength observed in monolayer films (SA‐CMC and G/SA‐CMC) made from gluten (G), sodium alginate (SA), and carboxymethylcellulose (CMC). The film was developed with the addition of onion waste extracts (OWEs), primarily from peel and stalk, to enhance functional properties. The multilayer composite film consists of three layers: an outer layer made of G, an inner layer made of SA, CMC, and a middle layer made of G/SA‐CMC. The developed composite film exhibited improved physical properties (thickness: 0.348–0.629 mm and moisture: 20.889%–21.403%), mechanical properties (tensile strength: 21.943–20.640 MPa), and barrier properties (WVP: 0.212–0.516 g/m.s.Pa × 10−14) compared to monolayer films (SA‐CMC and G/SA‐CMC). The addition of OWEs enhanced the multilayer film's phenolic (20.076 and 36.175 mgGAE/g) and antioxidant activity (73.850% and 42.667%). The study found that the multilayer control film had minimal changes in weight loss (9.75% ± 0.18%) and firmness (6.68 ± 0.64 N) compared to OWEs‐added films (9.93% ± 0.49–10.02% ± 0.14% and 6.61 ± 0.37 to 6.64 ± 0.18 N). However, fresh‐peeled shallot onion packed with control film exhibited higher bacterial counts (6.70 ± 0.42 CFU/g) and yeast and mold counts (5.08 ± 0.20 CFU/g) than those packed with the OWEs‐added film (6.49 ± 0.28–6.56 ± 0.27 CFU/g and 4.75 ± 0.18–4.89 ± 0.21 CFU/g), indicating that OWEs protect the onions from microbial degradation. Overall, the multilayer control film (without OWEs) showed better results for storing the fresh‐peeled shallot onion at 4°C for 21 days.

Highlights

Onion waste extracts have potent high antioxidant and antimicrobial properties

Multilayer film's physical, mechanical, barrier, and functional properties improved

Addition of onion waste extracts increased the film's antimicrobial activity

Control film showed a better effect for storing fresh‐peeled shallot onion

Developed film can store fresh‐peeled shallot onion for 21 days at 4°C.
Targeting specific brain districts for advanced nanotherapies: A review from the perspective of precision nanomedicine
Authors: Sierri Giulia , Patrucco Michela , Ferrario Davide , Renda Antonio , Comi Susanna , Ciprandi Matilde , Fontanini Veronica , Sica Francesco Saverio , Sesana Silvia , Costa Verdugo Marta , Kravicz Marcelo , Salassa Luca , Busnelli Marta , Re Francesca
Published: September 2024

Numerous studies are focused on nanoparticle penetration into the brain functionalizing them with ligands useful to cross the blood–brain barrier. However, cell targeting is also crucial, given that cerebral pathologies frequently affect specific brain cells or areas. Functionalize nanoparticles with the most appropriate targeting elements, tailor their physical parameters, and consider the brain's complex anatomy are essential aspects for precise therapy and diagnosis. In this review, we addressed the state of the art on targeted nanoparticles for drug delivery in diseased brain regions, outlining progress, limitations, and ongoing challenges. We also provide a summary and overview of general design principles that can be applied to nanotherapies, considering the areas and cell types affected by the most common brain disorders. We then emphasize lingering uncertainties that hinder the translational possibilities of nanotherapies for clinical use. Finally, we offer suggestions for continuing preclinical investigations to enhance the overall effectiveness of precision nanomedicine in addressing neurological conditions.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Learning Branching-Time Properties in CTL and ATL via Constraint Solving
Authors: Bordais Benjamin , Neider Daniel , Roy Rajarshi
Published: September 2024

We address the problem of learning temporal properties from the branching-time behavior of systems. Existing research in this field has mostly focused on learning linear temporal properties specified using popular logics, such as Linear Temporal Logic (LTL) and Signal Temporal Logic (STL). Branching-time logics such as Computation Tree Logic (CTL) and Alternating-time Temporal Logic (ATL), despite being extensively used in specifying and verifying distributed and multi-agent systems, have not received adequate attention. Thus, in this paper, we investigate the problem of learning CTL and ATL formulas from examples of system behavior. As input to the learning problems, we rely on the typical representations of branching behavior as Kripke structures and concurrent game structures, respectively. Given a sample of structures, we learn concise formulas by encoding the learning problem into a satisfiability problem, most notably by symbolically encoding both the search for prospective formulas and their fixed-point based model checking algorithms. We also study the decision problem of checking the existence of prospective ATL formulas for a given sample. We implement our algorithms in a Python prototype and have evaluated them to extract several common CTL and ATL formulas used in practical applications.
A Zonotopic Dempster-Shafer Approach to the Quantitative Verification of Neural Networks
Authors: Goubault Eric , Putot Sylvie
Published: September 2024

The reliability and usefulness of verification depend on the ability to represent appropriately the uncertainty. Most existing work on neural network verification relies on the hypothesis of either set-based or probabilistic information on the inputs. In this work, we rely on the framework of imprecise probabilities, specifically p-boxes, to propose a quantitative verification of ReLU neural networks, which can account for both probabilistic information and epistemic uncertainty on inputs. On classical benchmarks, including the ACAS Xu examples, we demonstrate that our approach improves the tradeoff between tightness and efficiency compared to related work on probabilistic network verification, while handling much more general classes of uncertainties on the inputs and providing fully guaranteed results.
A obustness fication Tool for uantum Machine Learning Models
Authors: Lin Yanling , Guan Ji , Fang Wang , Ying Mingsheng , Su Zhaofeng
Published: September 2024

Adversarial noise attacks present a significant threat to quantum machine learning (QML) models, similar to their classical counterparts. This is especially true in the current Noisy Intermediate-Scale Quantum era, where noise is unavoidable. Therefore, it is essential to ensure the robustness of QML models before their deployment. To address this challenge, we introduce VeriQR, the first tool designed specifically for formally verifying and improving the robustness of QML models, to the best of our knowledge. This tool mimics real-world quantum hardware’s noisy impacts by incorporating random noise to formally validate a QML model’s robustness. VeriQR supports exact (sound and complete) algorithms for both local and global robustness verification. For enhanced efficiency, it implements an under-approximate (complete) algorithm and a tensor network-based algorithm to verify local and global robustness, respectively. As a formal verification tool, VeriQR can detect adversarial examples and utilize them for further analysis and to enhance the local robustness through adversarial training, as demonstrated by experiments on real-world quantum machine learning models. Moreover, it permits users to incorporate customized noise. Based on this feature, we assess VeriQR using various real-world examples, and experimental outcomes confirm that the addition of specific quantum noise can enhance the global robustness of QML models. These processes are made accessible through a user-friendly graphical interface provided by VeriQR, catering to general users without requiring a deep understanding of the counter-intuitive probabilistic nature of quantum computing.
Parameterized Verification of Round-Based Distributed Algorithms via Extended Threshold Automata
Authors: Baumeister Tom , Eichler Paul , Jacobs Swen , Sakr Mouhammad , Völp Marcus
Published: September 2024

Threshold automata are a computational model that has proven to be versatile in modeling threshold-based distributed algorithms and enabling their completely automatic parameterized verification. We present novel techniques for the verification of threshold automata, based on well-structured transition systems, that allow us to extend the expressiveness of both the computational model and the specifications that can be verified. In particular, we extend the model to allow decrements and resets of shared variables, possibly on cycles, and the specifications to general coverability. While these extensions of the model in general lead to undecidability, our algorithms provide a semi-decision procedure. We demonstrate the benefit of our extensions by showing that we can model complex round-based algorithms such as the phase king consensus algorithm and the Red Belly Blockchain protocol (published in 2019), and verify them fully automatically for the first time.
Nonlinear Craig Interpolant Generation Over Unbounded Domains by Separating Semialgebraic Sets
Authors: Wu Hao , Wang Jie , Xia Bican , Li Xiakun , Zhan Naijun , Gan Ting
Published: September 2024

Interpolation-based techniques become popular in recent years, as they can improve the scalability of existing verification techniques due to their inherent modularity and local reasoning capabilities. Synthesizing Craig interpolants is the cornerstone of these techniques. In this paper, we investigate nonlinear Craig interpolant synthesis for two polynomial formulas of the general form, essentially corresponding to the underlying mathematical problem to separate two disjoint semialgebraic sets. By combining the homogenization approach with existing techniques, we prove the existence of a novel class of non-polynomial interpolants called semialgebraic interpolants. These semialgebraic interpolants subsume polynomial interpolants as a special case. To the best of our knowledge, this is the first existence result of this kind. Furthermore, we provide complete sum-of-squares characterizations for both polynomial and semialgebraic interpolants, which can be efficiently solved as semidefinite programs. Examples are provided to demonstrate the effectiveness and efficiency of our approach.
The crucial role of beta-catenin in the osteoprotective effect of semaglutide in an ovariectomized rat model of osteoporosis
Authors: Abo-Elenin Mohannad Hakam Hamed , Kamel Rehab , Nofal Shahira , Ahmed Amany Ali Eissa
Published: September 2024

Postmenopausal osteoporosis is a common chronic medical illness resulting from an imbalance between bone resorption and bone formation along with microarchitecture degeneration attributed to estrogen deficiency and often accompanied by other medical conditions such as weight gain, depression, and insomnia. Semaglutide (SEM) is a recently introduced GLP-1 receptor agonist (GLP-1RA) for the treatment of obesity and type 2 diabetes mellitus by mitigating insulin resistance. It has been discovered that the beneficial effects of GLP-1 are associated with alterations in lipolysis, adipogenesis, and anti-inflammatory processes. GLP-1 analogs transmit signals directly to adipose tissue. Mesenchymal stem cells (MSCs) are multidisciplinary cells that originate from bone marrow, migrate to injury sites, and promote bone regeneration. MSCs can differentiate into osteoblasts, adipose cells, and cartilage cells. Our aim is to investigate the role of semaglutide on bone formation and the Wnt signaling pathway. Osteoporosis was induced in female rats by ovariectomy, and the ovariectomized rats were treated with alendronate as standard treatment with a dose of 3 mg/kg orally and semaglutide with two doses (150 mcg/kg and 300 mcg/kg) S.C. for 10 successive weeks. Semaglutide ameliorates bone detrimental changes induced by ovariectomy. It improves bone microarchitecture and preserves bone mineral content. Semaglutide ameliorates ovariectomy-induced osteoporosis and increases the expression of β-catenin, leading to increased bone formation and halted receptor activator of nuclear factor kappa-Β ligand (RANKL’s) activation. Semaglutide can be used as a potential prophylactic and therapeutic drug against osteoporosis, possibly by activating Wnt signaling and decreasing bone resorption.

Graphical Abstract
Identification of novel protein biomarkers and therapeutic targets for ankylosing spondylitis using human circulating plasma proteomics and genome analysis
Authors: Zhou Zhongxian , Liu Chong , Feng Sitan , Chen Jiarui , Chen Tianyou , Zhu Jichong , Wu Shaofeng , Zhou Chenxing , Huang Chengqian , Xue Jiang , Qin Xiaopeng , Zhan Xinli
Published: September 2024

The proteome serves as the primary basis for identifying targets for treatment. This study conducted proteomic range two-sample Mendelian randomization (MR) analysis to pinpoint potential protein markers and treatment targets for ankylosing spondylitis (AS). A total of 4907 data points on circulating protein expression were collected from a large-scale protein quantitative trait locus investigation involving 35,559 individuals. Using data from a Finnish study on AS as the outcome, the dataset comprised 166,144 individuals of European ancestry (1462 cases and 164,682 controls), and causal relationships were determined through bidirectional Mendelian randomization of two samples. Proteins were further validated and identified through single-cell expression analysis, certain cells showing enriched expression levels were detected, and possible treatment targets were optimized. Increased HERC5 expression predicted by genes was related to increased AS risk, whereas the expression of the remaining five circulating proteins, AIF1, CREB3L4, MLN, MRPL55, and SPAG11B, was negatively correlated with AS risk. For each increase in gene-predicted protein levels, the ORs of AS were 2.11 (95% CI 1.44–3.09) for HERC5, 0.14 (95% CI 0.05–0.41) for AIF1, 0.48 (95% CI 0.34–0.68) for CREB3L4, 0.54 (95% CI 0.42–0.68) for MLN, 0.23 (95% CI 0.13–0.38) for MRPL55, and 0.26 (95% CI 0.17–0.39) for SPAG11B. The hypothesis of a reverse causal relationship between these six circulating proteins and AS is not supported. Three of the six protein-coding genes were expressed in both the AS and healthy control groups, while CREB3L4, MLN, and SPAG11B were not detected. Increased levels of HERC5 predicted by genes are related to increased AS risk, whereas the levels of the remaining five circulating proteins, AIF1, CREB3L4, MLN, MRPL55, and SPAG11B, negatively correlate with AS risk. HERC5, AIF1, and MRPL55 are potential therapeutic targets for AS. This study advanced the field by employing a novel combination of proteomic range two-sample MR analysis and single-cell expression analysis to identify potential protein markers and therapeutic targets for AS. This approach enabled a comprehensive understanding of the causal relationships between circulating proteins and AS, which has not been extensively explored in previous studies.

Graphical Abstract
Physical aspects of epithelial cell–cell interactions: hidden system complexities
Authors: Pajic-Lijakovic Ivana , Milivojevic Milan , McClintock Peter V. E.
Published: September 2024

The maintenance of homeostasis and the retention of ordered epithelial cell self-organization are essential for morphogenesis, wound healing, and the spread of cancer across the epithelium. However, cell–cell interactions in an overcrowded environment introduce a diversity of complications. Such interactions arise from an interplay between the cell compressive and shear stress components that accompany increased cell packing density. They can lead to various kinds of cell rearrangement such as: the epithelial-to-mesenchymal cell state transition; live cell extrusion; and cell jamming. All of these scenarios of cell rearrangement under mechanical stress relate to changes in the strengths of the cell–cell and cell–matrix adhesion contacts. The objective of this review study is twofold: first, to provide a comprehensive summary of the biological and physical factors influencing the effects of cell mechanical stress on cell–cell interactions, and the consequences of these interactions for the status of cell–cell and cell–matrix adhesion contacts; and secondly, to offer a bio-physical/mathematical analysis of the aforementioned biological aspects. By presenting these two approaches in conjunction, we seek to highlight the intricate nature of biological systems, which manifests in the form of complex bio-physical/mathematical equations. Furthermore, the juxtaposition of these apparently disparate approaches underscores the importance of conducting experiments to determine the multitude of parameters that contribute to the development of these intricate bio-physical/mathematical models.
Minimizing delays of patient transports with incomplete information: A modeling approach based on the vehicle routing problem
Authors: Adelhütte Dennis , Braun Kristin , Liers Frauke , Tschuppik Sebastian
Published: September 2024

We investigate a challenging task in ambulatory care, the minimizing of delays of patient transports. In practice, a limited number of vehicles is available for non-rescue transports. Furthermore, the dispatcher rarely has access to complete information when establishing a transport plan for dispatching the vehicles. If additional transport is requested on demand then schedules need to be updated, which can lead to long delays. We model the scheduling of patient transports as a vehicle routing problem with general time windows and solve it as a mixed-integer linear problem that is modified whenever additional transport information becomes available. We propose a modeling approach that is designed to determine fair and stable plans. Furthermore, we show that the model can easily be modified when transports need to satisfy additional requirements, e.g., during pandemics, exemplarily the Covid-19 pandemic. To show the applicability and efficiency of our modeling approach, we conduct a numerical study using historical data from the region of Middle Franconia. The results reveal and show that, by applying mathematical optimization—or, to be more precise by solving mixed-integer linear problem formulations—one can significantly decrease delays and have considerable potential for optimized patient transports.
Digitale Gesundheitsanwendungen – was sollten wir als Rheumatolog:innen wissen
Authors: Knitza Johannes , Krusche Martin , Chehab Gamal , Specker Christof , Richter Jutta G.
Published: September 2024

Digitale Gesundheitsanwendungen (DiGA) revolutionieren die Patientenversorgung durch verbesserten Zugang zu evidenzbasierter Therapie und fördern aktives Selbstmanagement. Die kontinuierlich wachsende Anzahl an DiGA ermöglicht es Patient:innen, durch digitale Unterstützung eigenständiger zu handeln. Die budgetneutrale Verordnung und Kostenübernahme durch gesetzliche Krankenkassen senken finanzielle Barrieren für Behandler:innen und Patient:innen. Erste Studien belegen, dass DiGA erfolgreich zur Behandlung von Komorbiditäten und rheumatischen Erkrankungen eingesetzt werden können. Mehrere DiGA für entzündlich-rheumatische Erkrankungen befinden sich in fortgeschrittener Entwicklung. Die Identifikation geeigneter Patient:innen und die Unterstützung durch Shared Decision Making (SDM) sind entscheidend für die erfolgreiche Implementierung. Herausforderungen bestehen weiterhin in der Adhärenz und Akzeptanz der Anwendungen. Dieser Artikel bietet einen Überblick über die Verordnung in der Praxis, erste Daten und Erfahrungen aus der rheumatologischen Versorgungsrealität und berichtet über aktuelle Entwicklungen.
Extraction and Purification of Biopolymers from Marine Origin Sources Envisaging Their Use for Biotechnological Applications
Authors: Carvalho Duarte Nuno , Gonçalves Cristiana , Sousa Rita O. , Reis Rui L. , Oliveira J. Miguel , Silva Tiago H.
Published: September 2024

Biopolymers are a versatile and diverse class of materials that has won high interest due to their potential application in several sectors of the economy, such as cosmetics, medical materials/devices, and food additives. In the last years, the search for these compounds has explored a wider range of marine organisms that have proven to be a great alternative to mammal sources for these applications and benefit from their biological properties, such as low antigenicity, biocompatibility, and biodegradability, among others. Furthermore, to ensure the sustainable exploitation of natural marine resources and address the challenges of 3R’s policies, there is a current necessity to valorize the residues and by-products obtained from food processing to benefit both economic and environmental interests. Many extraction methodologies have received significant attention for the obtention of diverse polysaccharides, proteins, and glycosaminoglycans to accomplish the increasing demands for these products. The present review gives emphasis to the ones that can be obtained from marine biological resources, as agar/agarose, alginate and sulfated polysaccharides from seaweeds, chitin/chitosan from crustaceans from crustaceans, collagen, and some glycosaminoglycans such as chondroitin sulfate and hyaluronic acids from fish. It is offered, in a summarized and easy-to-interpret arrangement, the most well-established extraction and purification methodologies used for obtaining the referred marine biopolymers, their chemical structure, as well as the characterization tools that are required to validate the extracted material and respective features. As supplementary material, a practical guide with the step-by-step isolation protocol, together with the various materials, reagents, and equipment, needed for each extraction is also delivered is also delivered. Finally, some remarks are made on the needs still observed, despite all the past efforts, to improve the current extraction and purification procedures to achieve more efficient and green methodologies with higher yields, less time-consuming, and decreased batch-to-batch variability.

Graphical Abstract
Chip-scale atomic clock (CSAC) aided GNSS in urban canyons
Authors: Meng Yang , Weng Duojie , Yang Cheng , Chen Wu , Hou Zhiyu
Published: September 2024

In urban canyons, the reflections and obstructions of Global Navigation Satellite System (GNSS) signals frequently lead to significant errors in measurements, the number of which can be larger than that of the correct measurements. This leads to a severe degradation of GNSS performance in urban canyons. Various fault detection and exclusion (FDE) algorithms have been developed to cope with these outliers caused by multipath effects. Most of these FDE algorithms check the consistency among measurements. However, in urban canyons, their effectiveness is significantly compromised by the lack of fault-free measurements. There is an urgent need to develop new constraints for enhancing GNSS FDE performance. In recent years, the advent of Chip-Scale Atomic Clock (CSAC), known for their affordability and high frequency stability, offers a promising solution for accurately predicting receiver clock errors. Additionally, using city maps to establish height constraints is another way to increase redundancy. The purpose of this study is to improve the GNSS positioning accuracy in urban canyons with the aid of CSAC and city map data. A novel FDE algorithm is developed to search for positions through the constraints of height and receiver clock. Extensive tests were conducted in urban canyons to evaluate the performance of the system. Results showed that the positioning accuracy can be improved from tens of meters to less than 6 m.
The value of perfect information for the problem: a sensitivity analysis
Authors: Boncompte Pons Mercedes , Guerrero Manzano María del Mar
Published: September 2024

This paper examines problems in decision theory where the number of alternatives and states of nature are finite. Previous studies have defined the concept of “the value of perfect information for the problem” (VPIP). This metric allows us to obtain an upper bound on the amount a decision-maker would be willing to pay for perfect information under the specific conditions of a problem. This bound is particularly important when the decision is unrepeatable, providing a more accurately adjusted measure than the one traditionally obtained with “the expected value of perfect information” (EVPI). Supported by linear programming, this work proposes a sensitivity analysis of these bounds by seeking to identify the intervals in which the problem values can vary without essentially modifying the structure of the problem. Specifically, the study aims to determine how this variation might affect the EVPI and VPIP bounds, as well as the difference in the price a decision-maker would be willing to pay for perfect information if any of the problem values were altered. By identifying alternatives and scenarios taking into account the role they play in the problem, this research classifies the data involved in a finite decision problem to ensure the conclusions can be understood as generally as possible. Although the proposed sensitivity analysis is applied to the oil-drilling problem, a classic in decision theory, the conclusions of this work have potential applications in improving environmental decision-making processes.
Does Knee Arthroplasty Have a Beneficial Effect on Return to Work in Patients with Knee Osteoarthritis who Receive Long-Term Disability Benefits in the Netherlands?
Authors: Cheng Titi J. , Nieuwenhuijsen Karen , Kuijer P. Paul F. M.
Published: September 2024

Purpose

Optimal timing of knee arthroplasty (KA) is complex: operating at a younger age increases life time risk of revision, while delay results in an increased risk of job loss. This study evaluates whether disability benefits recipients due to knee osteoarthritis have an increased odds of returning to work (RTW) following KA.

Methods

A retrospective cohort study was performed among long-term disability benefits recipients due to knee osteoarthritis using data of the Dutch Employee Insurance Agency. Logistic regression assessed whether recipients with KA had a higher odds of RTW in 10 years following start of disability benefits, compared to those without KA.

Results

A total of 159 participants were included. During 10-year follow up, 42% had received KA and 37% had returned to work. No association was observed between KA and RTW (OR 1.39, 95% CI 0.62–3.12). Prognostic factors for RTW were being the main breadwinner (OR 7.93, 95% CI 2.95–21.32) and classification as 100% work disability (OR 0.20, 95% CI 0.09–0.45).

Conclusions

KA has no beneficial effect on RTW among patients with knee osteoarthritis granted long-term disability in the Netherlands. For RTW, KA is probably best performed within the two years of paid sick leave before long-term disability is assessed in the Netherlands.
A numerical algorithm for the computation of the noncentral beta distribution function
Authors: Egorova Vera , Gil Amparo , Segura Javier , Temme Nico M.
Published: September 2024

The noncentral beta distribution function is a generalization of the central beta distribution (the regularized incomplete beta function) that includes a noncentrality parameter. This paper describes an algorithm and provides a Matlab implementation for calculating the noncentral beta distribution function. Through a series of numerical tests, we demonstrate that the algorithm is accurate and efficient across a wide range of parameters.
Virtual Assessment of Physical Activity–Related Built Environment in Soweto, South Africa: What Is the Role of Contextual Familiarity?
Authors: Godongwana Motlatso , Gama Khulu , Maluleke Vongani , Micklesfield Lisa K. , Odekunle Damilola , Wasnyo Yves Florent , Elouna Boris , Ngwa Edwin , Lopes Adalberto , Balarabe Muhammad Rabiu , Coringrato Eva , McGushin Alice , Oni Tolu , Foley Louise , Canelas Tiago
Published: September 2024

Understanding how urban environments shape physical activity is critical in rapidly urbanizing countries such as South Africa. We assessed the reliability of virtual audits for characterizing urban features related to physical activity in Soweto, South Africa. We used the Microscale Audit of Pedestrian Streetscapes Global tool to characterize pedestrian-related features from Google Street View images in four neighborhoods of Soweto. Neighborhoods were selected to represent different levels of deprivation. Inter-rater reliability was analyzed according to the rater’s familiarity with the local area. The results show a higher inter-rater reliability was observed among auditors with greater contextual familiarity. Many measurements however generated inconclusive results due to either low variability in the raters’ responses or the absence of the features in the streets. It is evident from our findings that virtual audits are efficient tools that can be used to assess the built environment. However, to ensure meaningful use of these tools in diverse settings, we recommend that auditors comprise of people with contextual familiarity.
Pathways to survive in abrupt adversities: a configurational approach to understanding the resilience of new venture teams
Authors: Liu Jian , Harms Rainer
Published: September 2024

New venture teams (NVTs) face challenges caused by adversity, making team resilience crucial for venture survival. While team resilience factors have been identified, we do not yet understand how they combine. We examine their combinations from a configurational approach. Based on a fsQCA analysis of team resilience factors in thirty-eight NVTs and five follow-up in-depth case interviews, we explore how team resilience factors combine to form particular team resilience pathways for survival in adversity. Our analysis reveals three pathways: relaxed team improvisers, validated team visionaries, and relational team connectors. The theoretical implications include enhancing the framework regarding the resilience of NVTs and introducing a new causal mechanism based on the causal complexity of team resilience factors.
The Effect of Metallic Nanoparticles Supplementation in Semen Extender on Post-thaw Quality and Fertilizing Ability of Egyptian Buffalo (Bubalus bubalis) Spermatozoa
Authors: Khalil Wael A. , El-Rais Mohamed S. , Hegazy Mohamed M. , Hassan Mahmoud A. E. , El-Raghi Ali A. , El-Moghazy Mostafa M.
Published: September 2024

Nanomaterials offer several promising prospects in the field of farm animal reproduction, encompassing a broad range of applications such as transgenesis and the precise delivery of substances to sperm cells, antimicrobial, antioxidants properties as well as their potent role in improving cryopreservation methods. The aim of the present study is to explore the effect of supplementing the semen extender with 10 µg/mL nano gold (Au-NPs10), 10 µg/mL nano silver (Ag-NPs10), 1 µg/mL nano selenium (Se-NPs1), and 100 µg/mL nano zinc oxide (ZnO-NPs100) on sperm characteristics and kinematics parameters, acrosome integrity, oxidative biomarkers, morphological and apoptosis-like changes of frozen-thawed buffalo bull sperm, and, ultimately, their fertilizing capacity. The results revealed that all aforementioned nano materials significantly improved viability, progressive motility, membrane integrity, acrosome integrity, and kinematic parameters as well as apoptosis-like changes of post-thawed buffalo bull sperm compared to the control (p < 0.05). No discernible effects were observed on sperm ultrastructure morphology measures as a response to the addition of these metallic nanoparticles to the extender. The values of caspase 3 significantly decreased by 64.22, 45.99, 75.59, and 49.39% in Au-NPs10, Ag-NPs10, Se-NPs1, and ZnO-NPs100 treated groups, respectively, compared to the control. The addition of 100 µg ZnO-NPs to the extender significantly decreased the total count of bacteria, fungi, and yeast compared to the control (p < 0.05). The AuNPs10 and SeNPs1 treated groups showed lower content of malondialdehyde, hydrogen peroxide, and nitric oxide concentrations and higher values of total antioxidant capacity of post-thawed extended semen (p < 0.05). Pregnancy rates increased by 17.5, 20, and 30% in buffalo cows inseminated with sperm treated with ZnO-NPs100, Se-NPs1, and Au-NPs10, respectively, compared to the control group. The present results indicate that the freezing extender supplemented with metallic nanoparticles can be an effective strategy to enhance the cryotolerance and fertility potential of buffalo bull sperm.