bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Aureobasidium in a sustainable economy
Authors: Rensink Stephanie , van Nieuwenhuijzen Elke J. , Sailer Michael F. , Struck Christian , Wösten Han A. B.
Published: February 2024

Aureobasidium is omnipresent and can be isolated from air, water bodies, soil, wood, and other plant materials, as well as inorganic materials such as rocks and marble. A total of 32 species of this fungal genus have been identified at the level of DNA, of which Aureobasidium pullulans is best known. Aureobasidium is of interest for a sustainable economy because it can be used to produce a wide variety of compounds, including enzymes, polysaccharides, and biosurfactants. Moreover, it can be used to promote plant growth and protect wood and crops. To this end, Aureobasidium cells adhere to wood or plants by producing extracellular polysaccharides, thereby forming a biofilm. This biofilm provides a sustainable alternative to petrol-based coatings and toxic chemicals. This and the fact that Aureobasidium biofilms have the potential of self-repair make them a potential engineered living material avant la lettre.

Key points

•Aureobasidium produces products of interest to the industry

•Aureobasidium can stimulate plant growth and protect crops

•Biofinish of A. pullulans is a sustainable alternative to petrol-based coatings

•Aureobasidium biofilms have the potential to function as engineered living materials
Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy
Authors: Li Jianying , Ma Anjun , Zhang Ruohan , Chen Yao , Bolyard Chelsea , Zhao Bao , Wang Cankun , Pich Thera , Li Wantong , Sun Nuo , Ma Qin , Wen Haitao , Clinton Steven K. , Carson William E. , Li Zihai , Xin Gang
Published: February 2024

Introduction

As one of the major components of the tumor microenvironment, tumor-associated macrophages (TAMs) possess profound inhibitory activity against T cells and facilitate tumor escape from immune checkpoint blockade therapy. Converting this pro-tumorigenic toward the anti-tumorigenic phenotype thus is an important strategy for enhancing adaptive immunity against cancer. However, a plethora of mechanisms have been described for pro-tumorigenic differentiation in cancer, metabolic switches to program the anti-tumorigenic property of TAMs are elusive.

Materials and methods

From an unbiased analysis of single-cell transcriptome data from multiple tumor models, we discovered that anti-tumorigenic TAMs uniquely express elevated levels of a specific fatty acid receptor, G-protein-coupled receptor 84 (GPR84). Genetic ablation of GPR84 in mice leads to impaired pro-inflammatory polarization of macrophages, while enhancing their anti-inflammatory phenotype. By contrast, GPR84 activation by its agonist, 6-n-octylaminouracil (6-OAU), potentiates pro-inflammatory phenotype via the enhanced STAT1 pathway. Moreover, 6-OAU treatment significantly retards tumor growth and increases the anti-tumor efficacy of anti-PD-1 therapy.

Conclusion

Overall, we report a previously unappreciated fatty acid receptor, GPR84, that serves as an important metabolic sensing switch for orchestrating anti-tumorigenic macrophage polarization. Pharmacological agonists of GPR84 hold promise to reshape and reverse the immunosuppressive TME, and thereby restore responsiveness of cancer to overcome resistance to immune checkpoint blockade.
Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells
Authors: Sueangoen Natthaporn , Grove Harald , Chuangchot Nisa , Prasopsiri Jaturawitt , Rungrotmongkol Thanyada , Sanachai Kamonpan , Darai Nitchakan , Thongchot Suyanee , Suriyaphol Prapat , Sa-Nguanraksa Doonyapat , Thuwajit Peti , Yenchitsomanus Pa-thai , Thuwajit Chanitra
Published: February 2024

Breast cancer stands as a formidable global health challenge for women. While neoantigens exhibit efficacy in activating T cells specific to cancer and instigating anti-tumor immune responses, the accuracy of neoantigen prediction remains suboptimal. In this study, we identified neoantigens from the patient-derived breast cancer cells, PC-B-142CA and PC-B-148CA cells, utilizing whole-genome and RNA sequencing. The pVAC-Seq pipeline was employed, with minor modification incorporating criteria (1) binding affinity of mutant (MT) peptide with HLA (IC50 MT) ≤ 500 nm in 3 of 5 algorithms and (2) IC50 wild type (WT)/MT > 1. Sequencing results unveiled 2513 and 3490 somatic mutations, and 646 and 652 non-synonymous mutations in PC-B-142CA and PC-B-148CA, respectively. We selected the top 3 neoantigens to perform molecular dynamic simulation and synthesized 9–12 amino acid neoantigen peptides, which were then pulsed onto healthy donor peripheral blood mononuclear cells (PBMCs). Results demonstrated that T cells activated by ADGRL1E274K, PARP1E619K, and SEC14L2R43Q peptides identified from PC-B-142CA exhibited significantly increased production of interferon-gamma (IFN-γ), while PARP1E619K and SEC14L2R43Q peptides induced the expression of CD107a on T cells. The % tumor cell lysis was notably enhanced by T cells activated with MT peptides across all three healthy donors. Moreover, ALKBH6V83M and GAAI823T peptides from PC-B-148CA remarkably stimulated IFN-γ- and CD107a-positive T cells, displaying high cell-killing activity against target cancer cells. In summary, our findings underscore the successful identification of neoantigens with anti-tumor T cell functions and highlight the potential of personalized neoantigens as a promising avenue for breast cancer treatment.
Synergistic combination therapy using cowpea mosaic virus intratumoral immunotherapy and Lag-3 checkpoint blockade
Authors: Karan Sweta , Jung Eunkyeong , Boone Christine , Steinmetz Nicole F.
Published: February 2024

Immune checkpoint therapy (ICT) for cancer can yield dramatic clinical responses; however, these may only be observed in a minority of patients. These responses can be further limited by subsequent disease recurrence and resistance. Combination immunotherapy strategies are being developed to overcome these limitations. We have previously reported enhanced efficacy of combined intratumoral cowpea mosaic virus immunotherapy (CPMV IIT) and ICT approaches. Lymphocyte-activation gene-3 (LAG-3) is a next-generation inhibitory immune checkpoint with broad expression across multiple immune cell subsets. Its expression increases on activated T cells and contributes to T cell exhaustion. We observed heightened efficacy of a combined CPMV IIT and anti-LAG-3 treatment in a mouse model of melanoma. Further, LAG-3 expression was found to be increased within the TME following intratumoral CPMV administration. The integration of CPMV IIT with LAG-3 inhibition holds significant potential to improve treatment outcomes by concurrently inducing a comprehensive anti-tumor immune response, enhancing local immune activation, and mitigating T cell exhaustion.
Human identification: an investigation of 3D models of paranasal sinuses to establish a biological profile on a modern UK population
Authors: Robles Madeline , Nakhaeizadeh Sherry , Rando Carolyn , Morgan Ruth M.
Published: February 2024

Medical imaging is a valuable source for facilitating empirical research and provides an accessible gateway for developing novel forensic anthropological methods for analysis including 3D modelling. This is especially critical for the United Kingdom (UK), where methods developed from modern UK populations do not currently exist. This study introduces a new approach to assist in human identification using 3D models of the paranasal sinuses. The models were produced from a database of 500 modern CT scans provided by University College London Hospital. Linear measurements and elliptic Fourier coefficients taken from 1500 three-dimensional models across six ethnic groups assessed by one-way ANOVA and discriminant function analysis showed a range of classification rates with certain rates reaching 75–85.7% (p < 0.05) in correctly classifying age and sex according to size and shape. The findings offer insights into the potential for employing paranasal sinuses as an attribute for establishing the identification of unknown human remains in future crime reconstructions.
Long-term results after surgical basal cell carcinoma excision in the eyelid region: revisited
Authors: Told Reinhard , Reumueller Adrian , Kreminger Judith , Lackner Birgit , Kuchar Andreas , Schmidt-Erfurth Ursula , Dunavoelgyi Roman
Published: February 2024

The aim of the study was to readdress basal cell carcinoma (BCC) in the periocular region to prove the efficacy of histologically controlled surgical treatment and to identify high-risk characteristics.

Retrospective analysis of 451 microscopically controlled BCC excisions in the periocular region. Tumor location, tumor size, AJCC 7 classification, and histological results were recorded. The same procedure was followed for recurrences.

A recurrence rate of 5.0% was observed after the first microscopically controlled excision. Recurrent BCCs show a shift from nodular to sclerosing BCC as the primary histological type as well as a change in primary location from lower eyelid to medial canthus. The frequency of BCC with deep extension increased from 7.3% to 24.7%, and 57.1% after the second and third operations, respectively. The recurrence rate increased to 9.5% and 42.9%, after the second and third operations, respectively.

In conclusion, we are facing the same challenges in surgical BCC treatment as 30 years ago. The distribution of periocular BCC location, histologic subtype and recurrence rates mirror the literature und the general consensus. The recurrence rate increases with every operation needed. Sclerosing BCCs with deep extension at the medial canthus bear the greatest risk for recurrence. In such cases, centers of expertise should be consulted and additional treatment options should be considered.
Approximation of Almost Diagonal Non-linear Maps by Lattice Lipschitz Operators
Authors: Arnau Roger , Calabuig Jose M. , Erdoğan Ezgi , Sánchez Pérez Enrique A.
Published: February 2024

Lattice Lipschitz operators define a new class of nonlinear Banach-lattice-valued maps that can be written as diagonal functions with respect to a certain basis. In the n-dimensional case, such a map can be represented as a vector of size n of real-valued functions of one variable. In this paper we develop a method to approximate almost diagonal maps by means of lattice Lipschitz operators. The proposed technique is based on the approximation properties and error bounds obtained for these operators, together with a pointwise version of the interpolation of McShane and Whitney extension maps that can be applied to almost diagonal functions. In order to get the desired approximation, it is necessary to previously obtain an approximation to the set of eigenvectors of the original function. We focus on the explicit computation of error formulas and on illustrative examples to present our construction.
Two years of neurosurgical intraoperative MRI in Sweden - evaluation of use and costs
Authors: Kaijser Magnus , Frisk Henrik , Persson Oscar , Burström Gustav , Suneson Annika , El-Hajj Victor Gabriel , Fagerlund Michael , Edström Erik , Elmi-Terander Adrian
Published: February 2024

Background

The current shortage of radiology staff in healthcare provides a challenge for departments all over the world. This leads to more evaluation of how the radiology resources are used and a demand to use them in the most efficient way. Intraoperative MRI is one of many recent advancements in radiological practice. If radiology staff is performing intraoperative MRI at the operation ward, they may be impeded from performing other examinations at the radiology department, creating costs in terms of exams not being performed. Since this is a kind of cost whose importance is likely to increase, we have studied the practice of intraoperative MRI in Sweden.

Methods

The study includes data from the first four hospitals in Sweden that installed MRI scanners adjacent to the operating theaters. In addition, we included data from Karolinska University Hospital in Solna where intraoperative MRI is carried out at the radiology department.

Results

Scanners that were moved into the operation theater and doing no or few other scans were used 11–12% of the days. Stationary scanners adjacent to the operation room were used 35–41% of the days. For scanners situated at the radiology department doing intraoperative scans interspersed among all other scans, the proportion was 92%.

Conclusion

Our study suggests that performing exams at the radiology department rather than at several locations throughout the hospital may be an efficient approach to tackle the simultaneous trends of increasing demands for imaging and increasing staff shortages at radiology departments.
Effect of meniscus modelling assumptions in a static tibiofemoral finite element model: importance of geometry over material
Authors: Yao Jiacheng , Crockett John , D’Souza Mathias , A. Day Gavin , K. Wilcox Ruth , C. Jones Alison , Mengoni Marlène
Published: February 2024

Finite element studies of the tibiofemoral joint have increased use in research, with attention often placed on the material models. Few studies assess the effect of meniscus modelling assumptions in image-based models on contact mechanics outcomes. This work aimed to assess the effect of modelling assumptions of the meniscus on knee contact mechanics and meniscus kinematics. A sensitivity analysis was performed using three specimen-specific tibiofemoral models and one generic knee model. The assumptions in representing the meniscus attachment on the tibia (shape of the roots and position of the attachment), the material properties of the meniscus, the shape of the meniscus and the alignment of the joint were evaluated, creating 40 model instances. The values of material parameters for the meniscus and the position of the root attachment had a small influence on the total contact area but not on the meniscus displacement or the force balance between condyles. Using 3D shapes to represent the roots instead of springs had a large influence in meniscus displacement but not in knee contact area. Changes in meniscus shape and in knee alignment had a significantly larger influence on all outcomes of interest, with differences two to six times larger than those due to material properties. The sensitivity study demonstrated the importance of meniscus shape and knee alignment on meniscus kinematics and knee contact mechanics, both being more important than the material properties or the position of the roots. It also showed that differences between knees were large, suggesting that clinical interpretations of modelling studies using single geometries should be avoided.
TET2 mutations contribute to adverse prognosis in acute myeloid leukemia (AML): results from a comprehensive analysis of 502 AML cases and the Beat AML public database
Authors: Pan Xin’an , Chang Yingjun , Ruan Guorui , Zhou Songhai , Jiang Hao , Jiang Qian , Huang Xiaojun , Zhao Xiao-Su
Published: February 2024

Despite the high incidence of tet methylcytosine dioxygenase 2 (TET2) mutations in acute myeloid leukemia (AML), the prognostic implications of these mutations in three AML risk groups based on the 2022 ELN AML risk classification are still unclear. A total of 502 consecutive de novo AML patients who had next-generation sequencing data available between March 2011 and July 2021 at the Peking University Institute of Hematology were enrolled in this study. Univariate and multivariate Cox regression analyses were performed to explore the prognostic impact of TET2 mutations in the above cohort and the Beat AML cohort. Of the 502 total AML patients, 76 (15.1%) carried TET2 mutations. Multivariate analysis revealed TET2 mutations as independent risk factor for overall survival (OS) in both the total AML cohort (OR = 1.649, p = 0.009) and in the 2022 ELN intermediate-risk cohort (HR = 1.967, p = 0.05). Analysis of RNA-seq data from the Beat AML study revealed 1042 differentially expressed genes (DEGs) between the TET2-mutant and TET2 wild-type groups. The results of enrichment analysis indicated the DEGs to be notably enriched in categories related to the PI3K-Akt signaling pathway. Collectively, our findings indicate that mutations in TET2 are prognostically disadvantageous in AML patients. Assessment of TET2 mutational status contributes to the stratification of intermediate-risk AML patients. Multiple genes and pathways of potential therapeutic relevance may be differentially modulated by TET2 mutations in AML.
Interpretable Radiomic Signature for Breast Microcalcification Detection and Classification
Authors: Prinzi Francesco , Orlando Alessia , Gaglio Salvatore , Vitabile Salvatore
Published: February 2024

Breast microcalcifications are observed in 80% of mammograms, and a notable proportion can lead to invasive tumors. However, diagnosing microcalcifications is a highly complicated and error-prone process due to their diverse sizes, shapes, and subtle variations. In this study, we propose a radiomic signature that effectively differentiates between healthy tissue, benign microcalcifications, and malignant microcalcifications. Radiomic features were extracted from a proprietary dataset, composed of 380 healthy tissue, 136 benign, and 242 malignant microcalcifications ROIs. Subsequently, two distinct signatures were selected to differentiate between healthy tissue and microcalcifications (detection task) and between benign and malignant microcalcifications (classification task). Machine learning models, namely Support Vector Machine, Random Forest, and XGBoost, were employed as classifiers. The shared signature selected for both tasks was then used to train a multi-class model capable of simultaneously classifying healthy, benign, and malignant ROIs. A significant overlap was discovered between the detection and classification signatures. The performance of the models was highly promising, with XGBoost exhibiting an AUC-ROC of 0.830, 0.856, and 0.876 for healthy, benign, and malignant microcalcifications classification, respectively. The intrinsic interpretability of radiomic features, and the use of the Mean Score Decrease method for model introspection, enabled models’ clinical validation. In fact, the most important features, namely GLCM Contrast, FO Minimum and FO Entropy, were compared and found important in other studies on breast cancer.
Optimizing biodiesel production from waste with computational chemistry, machine learning and policy insights: a review
Authors: Osman Ahmed I. , Nasr Mahmoud , Farghali Mohamed , Rashwan Ahmed K. , Abdelkader Adel , Al-Muhtaseb Ala’a H. , Ihara Ikko , Rooney David W.
Published: February 2024

The excessive reliance on fossil fuels has resulted in an energy crisis, environmental pollution, and health problems, calling for alternative fuels such as biodiesel. Here, we review computational chemistry and machine learning for optimizing biodiesel production from waste. This article presents computational and machine learning techniques, biodiesel characteristics, transesterification, waste materials, and policies encouraging biodiesel production from waste. Computational techniques are applied to catalyst design and deactivation, reaction and reactor optimization, stability assessment, waste feedstock analysis, process scale-up, reaction mechanims, and molecular dynamics simulation. Waste feedstock comprise cooking oil, animal fat, vegetable oil, algae, fish waste, municipal solid waste and sewage sludge. Waste cooking oil represents about 10% of global biodiesel production, and restaurants alone produce over 1,000,000 m3 of waste vegetable oil annual. Microalgae produces 250 times more oil per acre than soybeans and 7–31 times more oil than palm oil. Transesterification of food waste lipids can produce biodiesel with a 100% yield. Sewage sludge represents a significant biomass waste that can contribute to renewable energy production.
Integration of satellite SAR and optical acquisitions for the characterization of the Lake Sarez landslides in Tajikistan
Authors: Nardini Olga , Confuorto Pierluigi , Intrieri Emanuele , Montalti Roberto , Montanaro Thomas , Robles Javier Garcia , Poggi Francesco , Raspini Federico
Published: February 2024

Tajikistan is an area characterized by several lakes created after rockfalls and moraine deposits collapsed due to its geographic position on the collisional area of the Euro-Asian and Indian tectonic plates. In 1911, a violent earthquake generated the Usoi dam, which led to the creation of Lake Sarez. The purpose of the article is to provide an overview of the ground deformation of the two landslides that affect and threaten the area of Lake Sarez exploiting the combination of two different techniques, the interferometric synthetic aperture radar (InSAR) method with the SqueeSAR approach and optical image analysis through the use of COSI-Corr software. The combination of these two techniques turned out to be useful and provide more information because InSAR method balances lack the optical analysis and vice versa giving the possibility to obtain a complete overview of the displacement of the area. Moreover, InSAR data have been used to reconstruct the geometry and depth of the sliding surface of a potential landslide that could affect the lake, generating a wave that could overtop the dam and affect the villages downstream.
On the Impact of Residual Strains in the Stress Analysis of Patient-Specific Atherosclerotic Carotid Vessels: Predictions Based on the Homogenous Stress Hypothesis
Authors: Mastrofini Alessandro , Marino Michele , Karlöf Eva , Hedin Ulf , Gasser T. Christian
Published: February 2024

The identification of carotid atherosclerotic lesion at risk for plaque rupture, eventually resulting in cerebral embolism and stroke, is of paramount clinical importance. High stress in the fibrous plaque cap has been proposed as risk factor. However, among others, residual strains influence said stress predictions, but quantitative and qualitative implications of residual strains in this context are not well explored. We therefore propose a multiplicative kinematics-based Growth and Remodeling (G&R) framework to predict residual strains from homogenizing tissue stress and then investigate its implication on plaque stress. Carotid vessel morphology of four patients was reconstructed from clinical Computed Tomography-Angiography (CT-A) images and equipped with heterogeneous tissue constitutive properties assigned through a histology-based artificial intelligence image segmentation tool. As compared to a purely elastic analysis and depending on patient-specific morphology and tissue distributions, the incorporation of residual strains reduced the maximum wall stress by up to $$30\%$$

30
%

and resulted in a fundamentally different distribution of stress across the atherosclerotic wall. Regardless residual strains homogenized tissue stresses, the fibrous plaque cap may persistently be exposed to spots of high stress. In conclusion, the incorporation of residual strains in biomechanical studies of atherosclerotic carotids may be important for a reliable assessment of fibrous plaque cap stress.
Soil quality: an indicator of recovery in a nature reserve in the Colombian Andes
Authors: González O. F. , Baquero-Echeverri S. , Caicedo-García J. P. , Loaiza-Usuga J. C. , Polanía J.
Published: February 2024

Soils provide essential ecosystem services for the existence of ecosystems and biodiversity. It is crucial to understand their quality through the evaluation of ecological processes. However, only some studies estimate the effectiveness of ecosystem restoration based on evaluating soil quality (SQ) indicators. This research evaluated the five most common land-use scenarios in Andean ecosystems within the Natural Reserve of the Civil Society (RNSC) “La Montaña Mágica” under natural forest, coffee plantation, badlands, and active and passive restoration. The main objective was to analyze the physical, chemical, and biological characteristics concerning land use, establish the baseline for SQ indicators in different land use activities, and determine the status of restoration systems for other land uses in the study site. ANOVA and Dunnett's test evaluated SQ parameters. In passive and active restoration, soil bulk density, porosity, and the number of individuals and families of macroinvertebrates were improved. The latter presented low pH and aluminum values but increased potassium compared to other soil uses. The restoration strategies favored changes in SQ indicators due to the contribution of organic carbon, a developed root system, and the recirculation of nutrients in the edaphic system. This study provided information on changes in SQ with soil usage as a practical tool to evaluate ecological restoration methods in natural areas of the eastern Colombian Andes.
A review on graph neural networks for predicting synergistic drug combinations
Authors: Besharatifard Milad , Vafaee Fatemeh
Published: February 2024

Combinational therapies with synergistic effects provide a powerful treatment strategy for tackling complex diseases, particularly malignancies. Discovering these synergistic combinations, often involving various compounds and structures, necessitates exploring a vast array of compound pairings. However, practical constraints such as cost, feasibility, and complexity hinder exhaustive in vivo and in vitro experimentation. In recent years, machine learning methods have made significant inroads in pharmacology. Among these, Graph Neural Networks (GNNs) have gained increasing attention in drug discovery due to their ability to represent complex molecular structures as networks, capture vital structural information, and seamlessly handle diverse data types. This review aims to provide a comprehensive overview of various GNN models developed for predicting effective drug combinations, examining the limitations and strengths of different models, and comparing their predictive performance. Additionally, we discuss the datasets used for drug synergism prediction and the extraction of drug-related information as predictive features. By summarizing the state-of-the-art GNN-driven drug combination prediction, this review aims to offer valuable insights into the promising field of computational pharmacotherapy.
Dynamic cultivation of human mesenchymal stem/stromal cells for the production of extracellular vesicles in a 3D bioreactor system
Authors: Almeria Ciarra , Weiss René , Keck Maike , Weber Viktoria , Kasper Cornelia , Egger Dominik
Published: February 2024

Purpose

3D cell culture and hypoxia have been demonstrated to increase the therapeutic effects of mesenchymal stem/stromal cells (MSCs)-derived extracellular vesicles (EVs). In this study, a process for the production of MSC-EVs in a novel 3D bioreactor system under normoxic and hypoxic conditions was established and the resulting EVs were characterized.

Methods

Human adipose-derived MSCs were seeded and cultured on a 3D membrane in the VITVO® bioreactor system for 7 days. Afterwards, MSC-EVs were isolated and characterized via fluorescence nanoparticle tracking analysis, flow cytometry with staining against annexin V (Anx5) as a marker for EVs exposing phosphatidylserine, as well as CD73 and CD90 as MSC surface markers.

Results

Cultivation of MSC in the VITVO® bioreactor system demonstrated a higher concentration of MSC-EVs from the 3D bioreactor (9.1 × 109 ± 1.5 × 109 and 9.7 × 109 ± 3.1 × 109 particles/mL) compared to static 2D culture (4.2 × 109 ± 7.5 × 108 and 3.9 × 109 ± 3.0 × 108 particles/mL) under normoxic and hypoxic conditions, respectively. Also, the particle-to-protein ratio as a measure for the purity of EVs increased from 3.3 × 107 ± 1.1 × 107 particles/µg protein in 2D to 1.6 × 108 ± 8.3 × 106 particles/µg protein in 3D. Total MSC-EVs as well as CD73−CD90+ MSC-EVs were elevated in 2D normoxic conditions. The EV concentration and size did not differ significantly between normoxic and hypoxic conditions.

Conclusion

The production of MSC-EVs in a 3D bioreactor system under hypoxic conditions resulted in increased EV concentration and purity. This system could be especially useful in screening culture conditions for the production of 3D-derived MSC-EVs.
Derivative-free search approaches for optimization of well inflow control valves and controls
Authors: Bellout Mathias C. , Silva Thiago L. , Bakke Jan Øystein Haavig , Berg Carl Fredrik
Published: February 2024

Decisions regarding problem conceptualization, search approach, and how best to parametrize optimization methods for practical application are key to successful implementation of optimization approaches within georesources field development projects. This work provides decision support regarding the application of derivative-free search approaches for concurrent optimization of inflow control valves (ICVs) and well controls. A set of state-of-the-art approaches possessing different search features is implemented over two reference cases, and their performance, resource requirements, and specific method configurations are compared across multiple problem formulations for completion design. In this study, problem formulations to optimize completion design comprise fixed ICVs and piecewise-constant well controls. The design is optimized by several derivative-free methodologies relying on parallel pattern-search (tAPPS), population-based stochastic sampling (tPSO) and trust-region interpolation-based models (tDFTR). These methodologies are tested on a heterogeneous two-dimensional case and on a realistic case based on a section of the Olympus benchmark model. Three problem formulations are applied in both cases, i.e., one formulation optimizes ICV settings only, while two joint configurations also treat producer and injector controls as variables. Various method parametrizations across the range of cases and problem formulations exploit the different search features to improve convergence, achieve final objectives and infer response surface features. The scope of this particular study treats only deterministic problem formulations. Results outline performance trade-offs between parallelizable algorithms (tAPPS, tPSO) with high total runtime search efficiency and the local-search trust-region approach (tDFTR) providing effective objective gains for a low number of cost function evaluations. tAPPS demonstrates robust performance across different problem formulations that can support exploration efforts, e.g., during a pre-drill design phase while multiple independent tDFTR runs can provide local tuning capability around established solutions in a time-constrained post-drill setting. Additional remarks regarding joint completion design optimization, comparison metrics, and relative algorithm performance given the varying problem formulations are also made.
Explaining the Stylized Facts of Foreign Exchange Markets with a Simple Agent-based Version of Paul de Grauwe’s Chaotic Exchange Rate Model
Authors: Mignot Sarah , Westerhoff Frank
Published: February 2024

We propose a simple agent-based version of Paul de Grauwe’s chaotic exchange rate model. In particular, we assume that each speculator follows his own technical and fundamental trading rule. Moreover, a speculator’s choice between these two trading philosophies depends on his individual assessment of current market circumstances. Our agent-based model setup is able to explain a number of important stylized facts of foreign exchange markets, including bubbles and crashes, excess volatility, fat-tailed return distributions, serially uncorrelated returns and volatility clustering. A stability and bifurcation analysis of its deterministic skeleton provides us with useful insights that foster our understanding of exchange rate dynamics.
Latest pharmaceutical approaches across the spectrum of heart failure
Authors: Bismpos Dimitrios , Wintrich Jan , Hövelmann Julian , Böhm Michael
Published: February 2024

Despite major advances in prevention and medical therapy, heart failure (HF) remains associated with high morbidity and mortality, especially in older and frailer patients. Therefore, a complete, guideline-based treatment is essential, even in HF patients with conditions traditionally associated with a problematic initiation and escalation of the medical HF therapy, such as chronic kidney disease and arterial hypotension, as the potential adverse effects are overcome by the overall decrease of the absolute risk. Furthermore, since the latest data suggest that the benefit of a combined medical therapy (MRA, ARNI, SGLT2i, beta-blocker) may extend up to a LVEF of 65%, further trials on these subgroups of patients (HFmrEF, HFpEF) are needed to re-evaluate the guideline-directed medical therapy across the HF spectrum. In particular, the use of SGLT2i was recently extended to HFpEF patients, as evidenced by the DELIVER and EMPEROR-preserved trials. Moreover, the indication for other conservative treatments in HF patients, such as the intravenous iron supplementation, was accordingly strengthened in the latest guidelines. Finally, the possible implementation of newer substances, such as finerenone, in guideline-directed medical practice for HF is anticipated with great interest.
Examine the Impact of Contextual, Personal, and Behavioral Factors on High School Teachers’ Engagement in Teaching Science Using an Integrated STEM Approach
Authors: Sokha Khut
Published: February 2024

Teachers’ self-efficacy, attitude, and engagement are influenced by various factors, encompassing personal, school contextual, and behavioral aspects. Nevertheless, prior studies have not thoroughly explored the intricate relationship between teachers’ self-efficacy, attitudes, and engagement, particularly in the context of teaching science through an integrated STEM approach (ISTEMA). Drawing upon the Social Cognitive Theory and the Theory of Planned Behavior, this study proposes a structural equation model that incorporates school contextual factors: school administrative support and peer or collegial support, along with the personal factor—teachers’ STEM discipline knowledge to predict teachers’ self-efficacy in teaching science through ISTEMA. It also considers school administrative support and teachers’ self-efficacy to teach science through an ISTEMA as predictors for teachers’ attitudes and engagement in the implementation of ISTEMA. Additionally, school administrative support, teachers’ self-efficacy to teach science through ISTEMA, and teachers’ attitude to teach science through ISTEMA are regarded as behavioral factors that predict engagement in the implementation of ISTEMA. The survey was administered to 452 high school teachers hailing from four distinct regions and Phnom Penh City, Cambodia. The results of the full structural equation modeling (SEM) analysis revealed that changes in teachers’ STEM discipline knowledge and peer or collegial support may correspondingly lead to changes in teachers’ self-efficacy to teach science through an ISTEMA (SE), with an indirect effect of school administrative support (AD) on SE via teachers’ STEM discipline knowledge. The enhancement of SE and teachers’ attitude to teach science through an ISTEMA (ATT) significantly influences teachers’ engagement to teach science through an ISTEMA (EGG), whereas AD has a direct impact on engagement and an indirect one via teachers’ self-efficacy and attitude. Furthermore, SE directly and indirectly affects engagement through teachers’ attitude. These findings hold profound significance in shaping policies related to teacher training in integrated STEM education and theoretical foundation for future studies.
Ochratoxin A induces mitochondrial dysfunction, oxidative stress, and apoptosis of retinal ganglion cells (RGCs), leading to retinal damage in mice
Authors: Fu Miao , Chen Yuanyuan , Yang Anhuai
Published: February 2024

Purpose

Ochratoxin A (OTA) contamination of food and feed is a serious problem worldwide. OTA is considered a carcinogen and immunotoxic, nephrotoxic, and neurotoxic mycotoxin. The present study aims to determine the toxic effects of OTA on retinal ganglion cells (RGCs) and assess the resulting impairment of retinal function in mice.

Methods

RGC-5 cells were exposed to OTA (100 and 200 μg/L) for 3 days, and the mice were fed OTA-contain (100 and 200 μg/kg) diets for 4 weeks. Antioxidant indices were detected by spectrophotometer. The apoptosis of RGC-5 cells was determined by flow cytometry. Mitochondrial morphology and mitochondrial membrane potential were detected by immunofluorescence. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function.

Results

The oxidative-antioxidant balance suggested that OTA-induced severe oxidative stress, including increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the OTA-exposed RGC-5 cells, and the reduced activity of superoxide dismutase (SOD) and glutathione-S-transferase (GST) in the OTA exposed group. Furthermore, OTA exposure led to remarkable apoptosis in RGC-5 cells. The mitochondrial detection showed that OTA caused significant mitochondrial membrane potential reduction and mitochondrial fragmentation, which may be the cause of apoptosis of RGC-5 cells. Additionally, in vivo experiments demonstrated that OTA resulted in significant death of RGCs and subsequent retinal dysfunction in mice.

Conclusion

Ochratoxin A induces mitochondrial dysfunction, oxidative stress, and RGCs death in mice.
Higher incidence of meibomian gland dysfunction in postmenopausal women with primary acquired nasolacrimal duct obstruction
Authors: Wang Guoping , Jin Haili , Sheng Yonghong , Ji Feng , Liu Yin , Han Linfeng , Wang Xiaohu , Chen Xianjie , Ding He , Liu Jing , Fu Qingqing
Published: February 2024

Purpose

This study aimed to investigate the incidence of meibomian gland dysfunction (MGD) in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) and enables ophthalmologists to pay attention to ocular surface damage before surgery.

Methods

165 postmenopausal women with PANDO and 115 postmenopausal women with a normal lacrimal drainage system were enrolled in this prospective study. Based on the results of lacrimal duct irrigation and age, the participants were further subdivided. The incidence of different severities of MGD in different groups was calculated and analyzed by the chi-squared test.

Results

The incidence of MGD in the PANDO group was 81.21%, and in the control group, it was 46.96%, which was significantly higher in the presence of PANDO (p < 0.001). The incidence of severe MGD in the complete and incomplete PANDO groups was higher than that in the control group (all p < 0.05), and no significant differences were observed between the complete and incomplete PANDO groups. The incidence of moderate MGD was significantly higher in the complete PANDO group than in the control group (p < 0.001). When age was considered an independent variable, the results revealed a significant value for patients aged < 70 years (p < 0.001).

Conclusions

Our study revealed a prodominantly high incidence of MGD in postmenopausal women with PANDO, especially in a complete PANDO or aged < 70 years. Ophthalmologists need to pay close attention to MGD in postmenopausal women with PANDO.
Let’s Walk: A Quasi-Experimental Multi-Component Intervention to Improve Physical Activity and Social Engagement for Older Chinese American Adults
Authors: Katigbak Carina , Cheng Ssu-Fang , Matz Christina , Jimison Holly
Published: February 2024

Physical activity (PA) is critical for healthy aging, yet < 16% of U.S. older adults meet federal recommendations for moderate to vigorous PA. Asian Americans are a rapidly growing segment of the older adult population, who are less likely to meet these guidelines, and are frequently under-represented in clinical trials. This quasi-experimental pilot study evaluated the feasibility, acceptability, and preliminary effectiveness of a culturally tailored walking program to improve PA and social engagement for older Chinese Americans in Boston, MA. Participants at two community organizations were assigned to an enhanced walking or walking only condition for 12 weeks. Mixed effect repeated measures analysis addressed the study aims. The enhanced walking group (intervention) had fewer steps at baseline and less of a reduction in steps by 12 weeks as compared with the walking only (control) condition. Mean social engagement scores were significantly higher at 12 weeks (p = .03) for the intervention group. A culturally tailored walking intervention was feasible and acceptable for older Chinese Americans, improving social engagement and PA scores.
“Illness Calls for Stories”: Care, Communication, and Community in the COVID-19 Patient Narrative
Authors: Crocker Rosalind
Published: February 2024

This creative-critical piece reflects on the practices of recording, communicating, and caring that took place on social media and in digital spaces during the COVID-19 pandemic. Using my own experience of contracting COVID-19 as a starting point, the piece looks at the ways in which epidemics have often been recorded in collaborative ways, with the personal, professional, and familial converging in historical texts that could be used as sources of medical authority. COVID-19 has similarly been immortalized across a variety of forms and by different communities. The piece particularly explores the ways in which collective epidemic experience has been represented online through autopathographical Tweets, TikTok cures, and group chat messages and the future purposes that such collaborative patient narratives can serve.
Urban 2D and 3D morphology and the pattern of ozone pollution: a 68-city study in China
Authors: Hong Shengyang , Wang Chengcong , Wang Wenjie , Zhang Peng , Guo Yujie , Ma Zijun , Hong Wenhai , Ren Zhibin
Published: February 2024

Context

Air pollution significantly impacts urban sustainable development and public health. Urban ozone pollution (UOP) is currently one of the most challenging tasks for urban air pollution control, and is possibly linked to urban morphology. However, the effect of urban two-dimensional (2D) (coverage or density, etc.) and three-dimensional (3D) (density + height, etc.) morphology on the UOP concentration remains unclear.

Objectives

The objective of this study was to explore the influence of urban morphology on UOP concentration and provide useful information to control urban air pollutants.

Methods

First, based on building height and remotely sensed UOP data from 68 Chinese cities, the general spatial pattern of urban 3D morphology and UOP was detected across different climate zones in China. Then, this study used variance decomposition to investigate the contribution of 2D and 3D urban morphology to UOP in China.

Results

The study showed that China's urban morphology was dominated by Medium Rise & Medium Density (MRMD). Large cities had higher UOP levels in summer, especially for the urban morphology with Low Rise & High Density (LRHD). Further, UOP concentrations were substantially higher in the southern temperate zone than in other climatic zones. Anthropogenic factors (rather than natural factors) were always the dominant factors influencing UOP across different seasons; specifically, urban 2D and 3D morphology can explain 40% of UOP variation. The effects of urban 3D and 2D morphologies on UOP concentrations varied seasonally. Urban 2D morphology dominated in spring, whereas 3D morphology dominated in winter.

Conclusions

Our study elucidates the effect of urban morphology on UOP and provides insights for sustainable urban development.
Sounds boring: the causal effect of boredom on self-administration of aversive stimuli in the presence of a positive alternative
Authors: Yusoufzai Morsal Khouwaga , Nederkoorn Chantal , Lobbestael Jill , Vancleef Linda
Published: February 2024

Previous studies demonstrated that boredom leads to increased self-administration of painful electric stimulation, a proxy for non-suicidal self-injury (NSSI). However, in these experimental studies, participants had no behavioral alternatives besides electric stimulation to break the monotony. A first aim in the current experimental study was to examine whether boredom still leads to self-administering aversive stimuli when positive behavioral alternatives are present. This boredom effect was furthermore compared to an anger induction. The second aim was to examine whether history of NSSI and negative urgency (i.e., the tendency to engage in impulsive action in response to negative emotions) positively moderate the link between boredom and self-administered aversive stimuli. In a between-subjects design using college students (N = 129), participants were randomly assigned to one of three emotion induction writing tasks (i.e., boredom, anger, neutral), during which frequency of self-administered positive (chirping birds) and aversive (screaming pig) sounds was measured. The latter was used as a proxy for NSSI behavior. Results showed that boredom led to increased selection of aversive sounds compared to the neutral and anger conditions, despite the presence of a positive alternative (i.e., positive sounds). No difference in frequency of selecting the aversive sounds was observed between the anger and neutral condition. Neither history of NSSI nor negative urgency moderated the effect of condition on self-administered aversive stimuli. The current results tentatively support a causal and specific link between boredom and NSSI, and warrant further examination of the role of boredom in maladaptive behaviors such as NSSI.
Time Series Prediction of ESN Based on Chebyshev Mapping and Strongly Connected Topology
Authors: Xie Minzhi , Wang Qianxue , Yu Simin
Published: February 2024

This paper introduces a novel approach called Chebyshev mapping and strongly connected topology for optimization of echo state network (ESN). To enhance the predictive performance of ESNs for time series data, Chebyshev mapping is employed to optimize the irregular input weight matrix. And the reservoir of the ESN is also replaced using an adjacency matrix derived from a digital chaotic system, resulting in a reservoir with strong connectivity properties. Numerical experiments are conducted on various time series datasets, including the Mackey–Glass time series, Lorenz time series and solar sunspot numbers, validating the effectiveness of the proposed optimization methods. Compared with the traditional ESNs, the optimization method proposed in this paper has higher predictive performance, and effectively reduce the reservoir’s size and model complexity.