bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Cadherin-11 in pancreatic ductal adenocarcinoma alters tumor-immune microenvironment
Authors: Sebastian Aimy , Martin Kelly A. , Peran Ivana , Hum Nicholas R. , Leon Nicole F. , Amiri Beheshta , Wilson Stephen P. , Coleman Matthew A. , Wheeler Elizabeth K. , Byers Stephen W. , Loots Gabriela G.
Published: October 2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the top five deadliest forms of cancer with very few treatment options. The 5-year survival rate for PDAC is 10% following diagnosis. Cadherin 11 (Cdh11), a cell-to-cell adhesion molecule, has been suggested to promote tumor growth and immunosuppression in PDAC, and Cdh11 inhibition significantly extended survival in mice with PDAC. However, the mechanisms by which Cdh11 deficiency influences PDAC progression and anti-tumor immune responses have yet to be fully elucidated. To investigate Cdh11-deficiency induced changes in PDAC tumor microenvironment (TME), we crossed p48-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC) mice with Cdh11+/- mice and performed single-cell RNA sequencing (scRNA-seq) of the non-immune (CD45-) and immune (CD45+) compartment of KPC tumor-bearing Cdh11 proficient (KPC-Cdh11+/+) and Cdh11 deficient (KPC-Cdh11+/-) mice. Our analysis showed that Cdh11 is expressed primarily in cancer-associated fibroblasts (CAFs) and at low levels in epithelial cells undergoing epithelial-to-mesenchymal transition (EMT). Cdh11 deficiency altered the molecular profile of CAFs, leading to a decrease in the expression of myofibroblast markers such as Acta2 and Tagln and cytokines such as Il6, Il33 and Midkine (Mdk). We also observed a significant decrease in the presence of monocytes/macrophages and neutrophils in KPC-Cdh11+/- tumors while the proportion of T cells was increased. Additionally, myeloid lineage cells from Cdh11-deficient tumors had reduced expression of immunosuppressive cytokines that have previously been shown to play a role in immune suppression. In summary, our data suggests that Cdh11 deficiency significantly alters the fibroblast and immune microenvironments and contributes to the reduction of immunosuppressive cytokines, leading to an increase in anti-tumor immunity and enhanced survival.
Dehydroalanine and dehydrobutyrine in aging and cataractous lenses reveal site-specific consequences of spontaneous protein degradation
Authors: Paredes Jessica , Wang Zhen , Patel Purvi , Rose Kristie L. , Schey Kevin L.
Published: October 2023

Introduction

Protein post-translational modifications (PTMs) have been associated with aging and age-related diseases. PTMs are particularly impactful in long-lived proteins, such as those found in the ocular lens, because they accumulate with age. Two PTMs that lead to protein-protein crosslinks in aged and cataractous lenses are dehydroalanine (DHA) and dehydrobutyrine (DHB); formed from cysteine/serine and threonine residues, respectively. The purpose of this study was to quantitate DHA and DHB in human lens proteins as a function of age and cataract status.

Methods

Human lenses of various ages were divided into five donor groups: transparent lenses (18–22-year-old, 48–64-year-old, and 70–93-year-old) and cataractous human lenses of two age groups (48–64-year-old lenses, and 70–93-year-old lenses) and were subjected to proteomic analysis. Relative DHA and DHB peptide levels were quantified and compared to their non-modified peptide counterparts.

Results

For most lens proteins containing DHA or DHB, higher amounts of DHA- and DHB-modified peptides were detected in aged and cataractous lenses. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in age-related nuclear cataract (ARNC), (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. There was no indication that DHA or DHB levels were dependent on lens region. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins.

Discussion

DHA and DHB formation may induce structural effects that make proteins less soluble in water that leads to age-related protein insolubility and possibly aggregation and light scattering.
VeryFastCCD: a high frame rate soft X-ray detector
Authors: Goldschmidt Azriel , Grace Carl , Joseph John , Krieger Amanda , Tindall Craig , Denes Peter
Published: October 2023

Direct X-ray detection in silicon has been transformative for scattering experiments in biology and materials science. While bump-bonded hybrid pixels have been attractive for hard X-ray detection, the challenge for single photon soft X-ray detection is sufficiently low noise. CCD structures on thick, high-resistivity silicon have been successfully used as sensors over the range of soft to hard X-rays at storage rings and FELs. The VeryFastCCD is a high frame rate, column-parallel CCD sensor with 48 μm pixels. Combined with 256-channel custom readout ASICs, frame rates of 5–10 kHz have been achieved with readout noise as low as 20 e and full-well capacity >4 × 105 e/pixel. Thin (10 nm and 100 nm) entrance window contact processes have also been developed which provide >85% quantum efficiency for 285 eV X-rays. Systems are currently being developed for several beamlines at the upgraded Advanced Light Source.
DRI-Net: segmentation of polyp in colonoscopy images using dense residual-inception network
Authors: Lan Xiaoke , Chen Honghuan , Jin Wenbing
Published: October 2023

Colorectal cancer is a common malignant tumor in the gastrointestinal tract, which usually evolves from adenomatous polyps. However, due to the similarity in color between polyps and their surrounding tissues in colonoscopy images, and their diversity in size, shape, and texture, intelligent diagnosis still remains great challenges. For this reason, we present a novel dense residual-inception network (DRI-Net) which utilizes U-Net as the backbone. Firstly, in order to increase the width of the network, a modified residual-inception block is designed to replace the traditional convolutional, thereby improving its capacity and expressiveness. Moreover, the dense connection scheme is adopted to increase the network depth so that more complex feature inputs can be fitted. Finally, an improved down-sampling module is built to reduce the loss of image feature information. For fair comparison, we validated all method on the Kvasir-SEG dataset using three popular evaluation metrics. Experimental results consistently illustrates that the values of DRI-Net on IoU, Mcc and Dice attain 77.72%, 85.94% and 86.51%, which were 1.41%, 0.66% and 0.75% higher than the suboptimal model. Similarly, through ablation studies, it also demonstrated the effectiveness of our approach in colorectal semantic segmentation.
Alternative carbon sources for the production of plant cellular agriculture: a case study on acetate
Authors: Hann Elizabeth C. , Harland-Dunaway Marcus , Garcia Adrian J. , Meuser Jonathan E. , Jinkerson Robert E.
Published: October 2023

Plant cellular agriculture aims to disrupt the way plant derived products are produced. Plant cell cultures are typically grown with sucrose as the primary carbon and energy source, but alternative carbon sources may have advantages over sucrose including less strain on food systems, lower costs, and more sustainable sourcing. Here we review carbon and energy sources that may serve as alternatives to sucrose in the cultivation of plant cell cultures. We identified acetate as a promising candidate and took the first steps to evaluate its potential for use in growing tobacco plant cell cultures. When added to media containing sucrose, acetate concentrations above 8 mM completely inhibit growth. Lower concentrations of acetate (2-4 mM) can support an increase in dry weight without sucrose but do not provide enough energy for substantial growth. 13C labeling indicates that tobacco plant cell cultures can incorporate carbon from exogenous acetate into proteins and carbohydrates. Analysis of transcriptome data showed that genes encoding glyoxylate cycle enzymes are expressed at very low levels compared to genes from the TCA cycle and glycolysis. Adaptive laboratory evolution experiments were able to increase tobacco cell cultures tolerance to acetate, demonstrating the potential for this type of approach going forward. Overall, our results indicate that acetate can be metabolized by plant cell cultures and suggest that further adaptive laboratory evolution or strain engineering efforts may enable acetate to serve as a sole carbon and energy source for tobacco plant cell cultures. This assessment of acetate provides a framework for evaluating other carbon and energy sources for plant cell cultures, efforts that will help reduce the costs and environmental impact, and increase the commercial potential of plant cellular agriculture.
Crop sensitivity to waterlogging mediated by soil temperature and growth stage
Authors: Xu Fu-Li , Hu Pei-Min , Wan Xiao , Harrison Matthew Tom , Liu Ke , Xiong Qin-Xue
Published: October 2023

Waterlogging constrains crop yields in many regions around the world. Despite this, key drivers of crop sensitivity to waterlogging have received little attention. Here, we compare the ability of the SWAGMAN Destiny and CERES models in simulating soil aeration index, a variable contemporaneously used to compute three distinct waterlogging indices, denoted hereafter as WI Destiny, WIASD1, and WIASD2. We then account for effects of crop growth stage and soil temperature on waterlogging impact by introducing waterlogging severity indices, WI Growth, which accommodates growth stage tolerance, and WI Plus, which accounts for both soil temperature and growth stage. We evaluate these indices using data collected in pot experiments with genotypes “Yang mai 11” and “Zheng mai 7698” that were exposed to both single and double waterlogging events. We found that WI Plus exhibited the highest correlation with yield (-0.82 to -0.86) suggesting that waterlogging indices which integrate effects of temperature and growth stage may improve projections of yield penalty elicited by waterlogging. Importantly, WI Plus not only allows insight into physiological determinants, but also lends itself to remote computation through satellite imagery. As such, this index holds promise in scalable monitoring and forecasting of crop waterlogging.
Scalable agritech growbox architecture
Authors: Kirwan R. F. , Abbas F. , Atmosukarto I. , Loo A. W. Y. , Lim J. H. , Yeo S.
Published: October 2023

Introduction: Urban farming has gained prominence in Singapore, offering opportunities for automation to enhance its efficiency and scalability. This study, conducted in collaboration with a leading Singaporean urban farming company, introduces an IoT-based automated farming system. This system incorporates an agnostic growbox and a web application dashboard for intelligent monitoring of crop growth. The presented approach provides an open-source and cost-effective solution for a scalable urban farming architecture. The agnostic growbox system offers both accessibility and scalability, utilizing cost-effective and modular hardware components with open-source software, thereby increasing customizability and accessibility compared to commercial growbox products. The authors anticipate that this approach will find diverse applications within the realm of urban farming, streamlining, and improving the efficiency of urban farming through automation.

Methods: The study employs an integrated solution that incorporates an image analytics approach for the proficient and accurate classification of crop disease phenotypes, specifically targeting chlorosis and tip burn in lettuce crops. This approach is designed to be hardware- and software-efficient, obviating the necessity for extensive image datasets for model training. The image analytics approach is compared favourably with a machine learning approach, evaluating the accuracy of categorization using the same dataset. Additionally, the approach is assessed in terms of time and cost efficiency in comparison to machine learning techniques.

Results: The image analytics approach demonstrated notable scalability, time efficiency, and accuracy in the detection of crop diseases within urban farming. Early detection, particularly of chlorosis and tip burn, proves critical in mitigating crop wastage. The results indicate that the integrated solution provided a reliable and effective means of disease classification, with significant advantages over traditional machine learning approaches in terms of time and cost efficiency.

Discussion: The presented IoT-based automated farming system, incorporating the agnostic growbox and image analytics approach, holds promise for revolutionizing urban farming practices. Its open-source nature, coupled with cost-effectiveness and scalability, positions it as a practical solution for urban farming architecture. The system's ability to efficiently detect and classify crop diseases, particularly chlorosis and tip burn, offers a substantial contribution to reducing wastage and enhancing crop yield. Overall, this approach paves the way for a more efficient and sustainable future for urban farming through the integration of automation and advanced analytics. Further exploration and implementation of this technology in diverse urban farming settings is warranted.
Serendipita indica as a Plant Growth Promoter and Biocontrol Agent against Black Rot Disease in Cabbage Grown in a Phytotron
Authors: Saleem Sana , Ragasova Lucia Nedorost , Tekielska Dorota , Fidurski Maciej , Sekara Agnieszka , Pokluda Robert
Published: October 2023

Serendipita indica, a mutualistic root endophytic fungus, has gained attention for its potential to enhance plant health and resistance to various stresses. This study investigated the impact of S. indica (strain DSM 11827) on plant growth promotion and the management of black rot disease. This is a devastating bacterial ailment caused by Xanthomonas campestris pv. campestris, which affects cruciferous crops worldwide. The experiment was conducted under sterile conditions in a phytotron for 10 weeks. It involved the substrate and seed inoculation of S. indica in a cabbage crop. The findings suggested that S. indica establishes mutualistic relationships with cruciferous plants, positively influencing their growth while simultaneously reducing their susceptibility to black rot disease. Plant morphological and physiological parameters were enhanced by S. indica application. Additionally, bio stress markers were also enhanced in response to black rot disease. Moreover, disease severity was reduced by 27.9% and 18.8% in the substrate and seeds treated with S. indica, respectively. However, our findings did not report any antagonistic effect between S. indica and two pathogens, i.e., Xanthomonas campestris pv. campestris and Alternaria brassicicola under the in vitro test, suggesting that the suppression of black rot disease in cabbage seedlings was induced indirectly by S. indica. This study, therefore, underscores the promising prospect of utilizing S. indica to promote crop productivity and combat the destructive impact of black rot disease in cruciferous plants, contributing to more sustainable and resilient agriculture.
Spatial–Temporal Dynamics of Grassland Net Primary Productivity and Its Driving Mechanisms in Northern Shaanxi, China
Authors: Chen Yaxian , Lin Ziqi , Chen Xu , Liu Yangyang , Jian Jinshi , Zhang Wei , Han Peidong , Wang Zijun
Published: October 2023

Grasslands, a vital ecosystem and component of the global carbon cycle, play a significant role in evaluating ecosystem health and monitoring the global carbon balance. In this study, based on the Carnegie–Ames–Stanford Approach (CASA) model, we estimated the Net Primary Productivity (NPP) of grasslands in northern Shaanxi from 2000 to 2020. Employing trend analysis, stability analysis, multiple regression analysis, and residual analysis, the research examined the dynamic changes of grassland NPP and its response to climatic and human factors. Key findings include: (1) Grassland NPP showed a significant increasing trend during 2000–2020, with high-coverage grasslands showing a higher rate of increase than medium and low-coverage grasslands. (2) Most grasslands (>90%) exhibited unstable growth and high NPP fluctuation. (3) While temperature, precipitation, and radiation undulate, the trends were not significant. Rainfall and radiation emerged as dominant factors affecting NPP, with temperature suppressing NPP increase to some extent. (4) Policies like returning farmland to grassland had a positive impact on grassland recovery, vegetation productivity, and regional ecosystem health.
The Electric Spatula: Killing Weeds with Pulsed Microshocks from a Flat-Plate Electrode
Authors: Bloomer Daniel J. , Harrington Kerry C. , Ghanizadeh Hossein , James Trevor K.
Published: October 2023

Seeking an easy-to-deploy, energy-efficient, non-herbicide weed control method, we tested a flat-plate electrode to apply pulsed electric microshocks (PMS) to a grass and four broadleaf weed species. The method can be deployed via a hand-held unit or as part of a fully automated system to control escape weeds in field crops. The effectiveness of the treatments and the relative energy discharges when applying similar electric doses to the plant leaves or to the plant when pressed to the soil with a flat-plate electrode were compared. The method killed only half of the treated Lolium multiflorum “Winter Star” plants, well below our target rate, but significantly reduced growth rates and indicated that effective treatment of <1.0 MJ ha−1 for treating five plants m−2 is possible. Polygonum aviculare L., Amaranthus powellii S. Wats., Amaranthus deflexus, and Solanum nitidibaccatum Bitter plants were successfully controlled, with the energy required to kill 100% of seedlings varying from 0.1 to 0.9 MJ ha−1, indicating that broadleaf weeds are more susceptible. This easily met our target effectiveness and efficiency goals. The discharged energy increased when the electrode pressed the plant to a dry soil surface rather than to the leaves only and increased further when the electrode pressed the plant to a wet soil surface.
Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp.
Authors: de Lima Silva Maria Gabriely , de Lima Luciene Ferreira , Alencar Fonseca Victor Juno , Santos da Silva Lucas Yure , Calixto Donelardy Ana Cecília , de Almeida Ray Silva , de Morais Oliveira-Tintino Cícera Datiane , Pereira Bezerra Martins Anita Oliveira Brito , Ribeiro-Filho Jaime , Bezerra Morais-Braga Maria Flaviana , Tintino Saulo Relison , Alencar de Menezes Irwin Rose
Published: October 2023

The increasing antifungal resistance rates against conventional drugs reveal the urgent need to search for new therapeutic alternatives. In this context, natural bioactive compounds have a critical role in antifungal drug development. Since evidence demonstrates that abietic acid, a diterpene found in Pinus species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against Candida spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against Candida albicans (CA INCQS 40006), Candida krusei (CK INCQS 40095), and Candida tropicalis (CT INCQS 40042). The microdilution method was used to determine the IC50 and the cell viability curve. Minimum Fungicidal Concentration (MFC) was determined by subculture in a solid medium. The plasma membrane permeability was measured using a fluorescent SYTOX Green probe. While the IC50 of the drugs alone ranged between 1065 and 3255 μg/mL, the IC50 resulting from the combination of abietic acid and fluconazole ranged between 7563 and 160.1 μg/mL. Whether used in combination with fluconazole or isolated, abietic acid exhibited Minimum Fungicidal Concentration (MFC) values exceeding 1024 μg/mL against Candida albicans, Candida krusei and Candida tropicalis. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against Candida albicans and Candida tropicalis. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance.
A Modified Model for Identifying the Characteristic Parameters of Machine Joint Interfaces
Authors: Liu Kexian , Liu Junfeng , Wang Linfeng , Zhao Yuqian , Li Fei
Published: October 2023

The contact parameters of joint interfaces have a great influence on the dynamic performance of the machine tool, and the dynamic performance determines the machining precision of the machine tool. Therefore, it is important to accurately identify the contact parameters of joint interfaces to improve the machining precision of the machine tool. In this paper, a method of identifying the joint interface stiffness parameters based on a joint simulation in Matlab and Ansys is first proposed, and then stiffness parameters of joint interfaces between the bed and column of the precision grinding machine are identified by applying the method. Finally, the feasibility and high efficiency of the proposed method are proved by comparing the natural frequencies of the simulation and the experiment. In order to further analyze the influence of joint contact parameters on the performance of the joint interfaces, the theoretical model of the normal stiffness of the joint interfaces based on fractal geometry is amended and verified by taking into account the asperity interaction and elastic–plastic deformation. Then, the modified model is extended to a three-dimensional model, which is more in line with the actual situation. Finally, the influencing factors of the joint interface stiffness are analyzed. The conclusions of this paper are of great significance in the dynamic performance analysis and structural design of machine tools.
Immediate Versus Conventional Loading of Two-Implant Overdenture with Magnetic Attachments: A 5-Year Follow-Up on Patient-Reported Outcomes
Authors: Bui Trang Ngoc Huyen , Komagamine Yuriko , Namano Sahaprom , Miyayasu Anna , Sato Daisuke , Minakuchi Shunsuke , Kanazawa Manabu
Published: October 2023

Comprehensive, long-term studies on patient-reported outcomes for two-implant overdentures with magnetic attachments using immediate or conventional loading methods are lacking. This study aimed to provide 5-year follow-up data comparing patient-reported outcomes for mandibular overdentures supported by two implants with magnetic attachments under immediate or conventional loading. Nineteen edentulous mandible patients were randomly assigned to immediate (IG) or conventional loading groups (CG). Two implants were placed with prostheses, loaded on the same day (immediate) or three months later (conventional). Participants completed questionnaires (oral health-related quality of life (OHRQoL), patient general satisfaction, and patient’s denture assessment (PDA)) at baseline and yearly intervals for 5 years. Results showed no significant differences between IG and CG throughout the study. However, the within-group analysis revealed significant improvements in OHRQoL, patient satisfaction, and all PDA domains from the baseline to years 1–5. Regarding patient satisfaction, significant differences were observed between T1, T2, and T3 when compared with T0 of IG and T1-T0 of CG. Regarding PDA results of T4-T5, IG exhibited several significant differences compared to CG. In conclusion, this study suggests that two-implant overdentures with magnetic attachments, whether immediately or conventionally loaded, improve patient-reported outcomes. Immediate loading may have prolonged effects on the improvement of patient-reported outcomes.
Research on the Residual Stress Field of a Compression Bushing-Lug Plate in Cold Expansion Strengthening
Authors: Lin Zhongliang , Bai Qingshun , Wang Hongfei , Wu Baoquan , Li Wensheng
Published: October 2023

The accurate acquisition of the residual stress field is the key to clarifying the cold expansion strengthening mechanism of compression bushings, optimizing the extrusion process parameters, and improving the structural fatigue life. In the actual cold expansion strengthening process, the resultant distribution of residual stresses is influenced by the relative extrusion amount, mandrel structure, material properties, and extrusion speed. In this article, the distribution patterns of residual stress after cold extrusion are investigated through a combination of finite element simulation and experimental measurements using a micro-region stress tester. To examine the redistribution law of the stress field of cold expansion reinforcement under external load, the compression bushing-lug-plate-reinforced structure is loaded and unloaded. The results show that large circumferential residual compressive stresses are distributed in the hole wall of the compression bushing after cold expansion. Radial residual stresses are also compressive stresses, although the values are small. In addition, the reinforced structure after cold extrusion presents a large difference in the stress redistribution rules compared with cold extrusion after the load is applied and removed.
Deep Reinforcement Learning-Based Approach for Video Streaming: Dynamic Adaptive Video Streaming over HTTP
Authors: Souane Naima , Bourenane Malika , Douga Yassine
Published: October 2023

Dynamic adaptive video streaming over HTTP (DASH) plays a crucial role in delivering video across networks. Traditional adaptive bitrate (ABR) algorithms adjust video segment quality based on network conditions and buffer occupancy. However, these algorithms rely on fixed rules, making it challenging to achieve optimal decisions considering the overall context. In this paper, we propose a novel deep-reinforcement-learning-based approach for DASH streaming, with the primary focus of maintaining consistent perceived video quality throughout the streaming session to enhance user experience. Our approach optimizes quality of experience (QoE) by dynamically controlling the quality distance factor between consecutive video segments. We evaluate our approach through a comprehensive simulation model encompassing diverse wireless network environments and various video sequences. We also conduct a comparative analysis with state-of-the-art methods. The experimental results demonstrate significant improvements in QoE, ensuring users enjoy stable, high-quality video streaming sessions.
Analysis of the Effect of Pulse Width on Nonlinear Thomson Scattering from an Applied Magnetic Field
Authors: Wang Haokai , Gu Feiyang , Zhang Yi , Wang Yubo , Tian Youwei
Published: October 2023

The effects of magnetic fields on electron dynamics, spatially radiated power, and radiation spectra in tightly focused circularly polarized laser pulses are studied in detail. The laser wavelength λ0=1 μm. As the pulse width increases from λ0 to 6λ0, the electron dynamics, spatially radiated power, and spectral properties stabilize, and the benefit that can be enhanced by increasing the pulse width decreases continuously, i.e., saturation is reached. However, although the benefits are better at pulse widths equal to 6λ0, to obtain high-energy, highly collimated X-rays, tightly focused circularly polarized laser pulses with larger pulse widths is better.
Probabilistic Interval Ordering Prioritized Averaging Operator and Its Application in Bank Investment Decision Making
Authors: Ruan Chuanyang , Gong Shicheng , Chen Xiangjing
Published: October 2023

Probabilistic interval ordering, as a helpful tool for expressing positive and negative information, can effectively address multi-attribute decision-making (MADM) problems in reality. However, when dealing with a significant number of decision-makers and decision attributes, the priority relationships between different attributes and their relative importance are often neglected, resulting in deviations in decision outcomes. Therefore, this paper combines probability interval ordering, the prioritized aggregation (PA) operator, and the Gauss–Legendre algorithm to address the MADM problem with prioritized attributes. First, considering the significance of interval priority ordering and the distribution characteristics of attribute priority, the paper introduces probability interval ordering elements that incorporate attribute priority, and it proposes the probabilistic interval ordering prioritized averaging (PIOPA) operator. Then, the probabilistic interval ordering Gauss–Legendre prioritized averaging operator (PIOGPA) is defined based on the Gauss–Legendre algorithm, and various excellent properties of this operator are explored. This operator considers the priority relationships between attributes and their importance level, making it more capable of handling uncertainty. Finally, a new MADM method is constructed based on the PIOGPA operator using probability intervals and employs the arithmetic–geometric mean (AGM) algorithm to compute the weight of each attribute. The feasibility and soundness of the proposed method are confirmed through a numerical example and comparative analysis. The MADM method introduced in this paper assigns higher weights to higher-priority attributes to establish fixed attribute weights, and it reduces the impact of other attributes on decision-making results. It also utilizes the Gauss AGM algorithm to streamline the computational complexity and enhance the decision-making effectiveness.
Crystal Structures Reveal Hidden Domain Mechanics in Protein Kinase A (PKA)
Authors: Welsh Colin L. , Conklin Abigail E. , Madan Lalima K.
Published: October 2023

Cyclic-AMP-dependent protein kinase A (PKA) is a critical enzyme involved in various signaling pathways that plays a crucial role in regulating cellular processes including metabolism, gene transcription, cell proliferation, and differentiation. In this study, the mechanisms of allostery in PKA were investigated by analyzing the vast repertoire of crystal structures available in the RCSB database. From existing structures of murine and human PKA, we elucidated the conformational ensembles and protein dynamics that are altered in a ligand-dependent manner. Distance metrics to analyze conformations of the G-loop were proposed to delineate different states of PKA and were compared to existing structural metrics. Furthermore, ligand-dependent flexibility was investigated through normalized B′-factors to better understand the inherent dynamics in PKA. The presented study provides a contemporary approach to traditional methods in engaging the use of crystal structures for understanding protein dynamics. Importantly, our studies provide a deeper understanding into the conformational ensemble of PKA as the enzyme progresses through its catalytic cycle. These studies provide insights into kinase regulation that can be applied to both PKA individually and protein kinases as a class.
Efficacy of Sub-Gingivally Delivered Propolis Nanoparticle in Non-Surgical Management of Periodontal Pocket: A Randomized Clinical Trial
Authors: Sahu Sushree Ambika , Panda Saurav , Das Abhaya Chandra , Mishra Lora , Rath Satchidananda , Sokolowski Krzysztof , Kumar Manoj , Mohanty Rinkee , Nayak Rashmita , Satpathy Anurag , Lapinska Barbara
Published: October 2023

Naturally sourced products like propolis are commonly employed for the non-surgical treatment of periodontal pockets. The use of nanoparticle formulations of these natural remedies has the potential to improve treatment outcomes. The aim of the present study was to evaluate the efficacy of sub-gingivally delivered propolis nanoparticles in the non-surgical management of periodontal pockets. Forty patients diagnosed with periodontitis presenting at least one periodontal pocket with a probing pocket depth between 4 and 6 mm were selected. Patients were randomly assigned into the control group (n = 20), which received scaling and root planing (SRP) and saline (SRP + Saline), and the test group (n = 20), which received SRP and sub-gingivally delivered propolis nanoparticles (PRO) into the periodontal pocket (SRP + PRO). The clinical parameters recorded were plaque index (PI), gingival index (GI), relative attachment loss (RAL), probing pocket depth (PPD), and bleeding on probing (BOP). They were assessed at baseline, one month, and three months post therapy. The results indicated that there was a significant improvement in clinical parameters (p < 0.05) in the test sites compared with the control sites at the end of the study. The gingival index at one month and three months was found to be significantly better in the SRP + PRO group than the SRP + Saline group, with a p value of <0.001. The BOP, PPD, and RAL showed significant improvement with the SRP + PRO group at the end of the 3-month follow-up with p values of 0.0001, 0.001, and 0.05, respectively. The subgingival delivery of propolis nanoparticles showed promising results as an adjunct to SRP in patients with periodontitis presenting periodontal pockets.
Total 25-Hydroxyvitamin D Is an Independent Marker of Left Ventricular Ejection Fraction in Heart Failure with Reduced and Mildly Reduced Ejection Fraction
Authors: Szabo Timea Magdolna , Nagy Előd Ernő , Kirchmaier Ádám , Heidenhoffer Erhard , Gábor-Kelemen Hunor-László , Frăsineanu Marius , Cseke Judit , Germán-Salló Márta , Frigy Attila
Published: October 2023

Vitamin D emerged as an important prognostic biomarker in heart failure (HF), with currently highly debated therapeutic implications. Several trials on vitamin D supplementation in HF showed improvements in left ventricular (LV) remodeling and function and health-related quality of life (HRQoL), which did not translate into mid- to long-term beneficial effects regarding physical performance and mortality. We addressed total 25-hydroxyvitamin D (25(OH)D), serum albumin, and uric acid (UA) levels, focusing mainly on vitamin D deficiency, as potential markers of LV systolic dysfunction in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Seventy patients with LVEF < 50% were comprehensively evaluated using ECG, echocardiography, lung ultrasound (LUS), blood sampling, and the six-minute walk test (6MWT). HRQoL was also assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Statistically significant positive correlations were found between LVEF, 25(OH)D, serum UA, and albumin, respectively (p = 0.008, p = 0.009, and p = 0.001). Serum UA (7.4 ± 2.4 vs. 5.7 ± 2.1, p = 0.005), NT-proBNP levels (1090.4 (675.2–2664.9) vs. 759.0 (260.3–1474.8), p = 0.034), and MLHFQ scores (21.0 (14.0–47.0) vs. 14.5 (4.5–25.5), p = 0.012) were significantly higher, whereas 25(OH)D concentrations (17.6 (15.1–28.2) vs. 22.7 (19.5–33.8), p = 0.010) were lower in subjects with severely reduced LVEF. Also, 25(OH)D was independently associated with LVEF in univariate and multiple regression analysis, maintaining its significance even after adjusting for confounders such as age, NT-proBNP, the presence of chronic coronary syndrome, hypertension, and anemia. According to our current findings, 25(OH)D is closely associated with LVEF, further supporting the need to establish correct vitamin D supplementation schemes and dietary interventions in HF. The changes in LVEF, 25(OH)D, serum UA, and albumin levels in HFrEF and HFmrEF indicate a similar pathophysiological background.
MicroRNA and Protein Cargos of Human Limbal Epithelial Cell-Derived Exosomes and Their Regulatory Roles in Limbal Stromal Cells of Diabetic and Non-Diabetic Corneas
Authors: Verma Nagendra , Khare Drirh , Poe Adam J. , Amador Cynthia , Ghiam Sean , Fealy Andrew , Ebrahimi Shaghaiegh , Shadrokh Odelia , Song Xue-Ying , Santiskulvong Chintda , Mastali Mitra , Parker Sarah , Stotland Aleksandr , Van Eyk Jennifer E. , Ljubimov Alexander V. , Saghizadeh Mehrnoosh
Published: October 2023

Epithelial and stromal/mesenchymal limbal stem cells contribute to corneal homeostasis and cell renewal. Extracellular vesicles (EVs), including exosomes (Exos), can be paracrine mediators of intercellular communication. Previously, we described cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos in non-diabetic (N) and diabetic (DM) limbal epithelial cells (LECs). Presently, we quantify the miRNA and proteome profiles of human LEC-derived Exos and their regulatory roles in N- and DM-LSC. We revealed some miRNA and protein differences in DM vs. N-LEC-derived Exos’ cargos, including proteins involved in Exo biogenesis and packaging that may affect Exo production and ultimately cellular crosstalk and corneal function. Treatment by N-Exos, but not by DM-Exos, enhanced wound healing in cultured N-LSCs and increased proliferation rates in N and DM LSCs vs. corresponding untreated (control) cells. N-Exos-treated LSCs reduced the keratocyte markers ALDH3A1 and lumican and increased the MSC markers CD73, CD90, and CD105 vs. control LSCs. These being opposite to the changes quantified in wounded LSCs. Overall, N-LEC Exos have a more pronounced effect on LSC wound healing, proliferation, and stem cell marker expression than DM-LEC Exos. This suggests that regulatory miRNA and protein cargo differences in DM- vs. N-LEC-derived Exos could contribute to the disease state.
Parent Perspectives: Part 1—Considerations for Changing the NICU Culture
Authors: DiBari Jessica N. , Rouse LaToshia
Published: October 2023

While publications that aim to reflect the parent perspective are increasingly common in the medical literature, few are authored by parents in their own words. As mothers with lived and professional experience in the Neonatal Intensive Care Unit (NICU), we believe this perspective is vital to improving health outcomes. We are writing from a life course health development framework that regards health as an active process that develops over time with the integration of physical, social, emotional, and relational components. Health development trajectories are shaped by the family and community ecosystems that surround each child. This means that the child’s ability to thrive is strongly linked to the family’s health and well-being. These links are not being given sufficient attention in clinical practice. Psychological distress, trauma, and grief are common family experiences in the NICU. Left unaddressed, they can negatively impact parent-child bonding. Drawing on life course principles, we make a series of recommendations for changes to practice to enable NICUs to better serve children and families, and better prepare families for the post-NICU experience. These include setting a positive tone in the NICU, creating a nurturing, personalized environment; addressing the social determinants of health; supporting families to develop a ‘growth’ mindset; and communicating in an optimistic, positive manner. Building trust is key to ensuring families feel supported and can be promoted through establishing equitable collaborative models of care. Peer support, doulas, and community health worker engagement can facilitate early interactions crucial to the child’s developmental progress and family healing.
Clinical and Paraclinical Characteristics of Endobronchial Pulmonary Squamous Cell Carcinoma—A Brief Review
Authors: Matache Radu Serban , Stanciu-Gavan Camelia , Pantile Daniel , Iordache Adrian Mihail , Bejgăneanu Andreea Octavia , Șerboiu Crenguța Sorina , Nemes Alexandra Floriana
Published: October 2023

Background: Endobronchial squamous cell carcinoma is one of the most common types of tumors located inside the tracheobronchial tree. Patients often present in advanced stages of the disease, which most often leads to a targeted therapeutic attitude of pneumonectomy. Practicing lung parenchyma-preserving surgery led us to undertake this review. Materials and methods: We used three search platforms—SCIENCE, MEDLINE, and PubMed—in order to identify studies presenting case reports, investigations, and reviews on endobronchial squamous cell carcinoma. We identified the clinical and paraclinical features of endobronchial squamous cell carcinoma. All the selected articles were in English and addressed the clinical criteria of endobronchial squamous cell carcinoma, autofluorescence bronchoscopy in endobronchial squamous cell carcinoma, imaging features of endobronchial squamous cell carcinoma, blood tumor markers specific to lung squamous cell carcinoma, and histopathological features of endobronchial squamous cell carcinoma. Results: In total, 73 articles were analyzed, from which 48 articles were selected as bibliographic references. We present the criteria used for the identification of endobronchial squamous cell carcinoma in order to highlight its main characteristics and the most reliable technologies that can be used for the detection of this type of cancer. Conclusions: The current literature review highlights the clinical and paraclinical characteristics of endobronchial squamous cell carcinoma. It aims to open new paths for research and early detection with respect to the frequent practice of lung parenchymal preservation surgery.
Anomaly Detection Using an Ensemble of Multi-Point LSTMs
Authors: Lee Geonseok , Yoon Youngju , Lee Kichun
Published: October 2023

As technologies for storing time-series data such as smartwatches and smart factories become common, we are collectively accumulating a great deal of time-series data. With the accumulation of time-series data, the importance of time-series abnormality detection technology that detects abnormal patterns such as Cyber-Intrusion Detection, Fraud Detection, Social Networks Anomaly Detection, and Industrial Anomaly Detection is emerging. In the past, time-series anomaly detection algorithms have mainly focused on processing univariate data. However, with the development of technology, time-series data has become complicated, and corresponding deep learning-based time-series anomaly detection technology has been actively developed. Currently, most industries rely on deep learning algorithms to detect time-series anomalies. In this paper, we propose an anomaly detection algorithm with an ensemble of multi-point LSTMs that can be used in three cases of time-series domains. We propose our anomaly detection model that uses three steps. The first step is a model selection step, in which a model is learned within a user-specified range, and among them, models that are most suitable are automatically selected. In the next step, a collected output vector from M LSTMs is completed by stacking ensemble techniques of the previously selected models. In the final step, anomalies are finally detected using the output vector of the second step. We conducted experiments comparing the performance of the proposed model with other state-of-the-art time-series detection deep learning models using three real-world datasets. Our method shows excellent accuracy, efficient execution time, and a good F1 score for the three datasets, though training the LSTM ensemble naturally requires more time.
Historical Representations of University Students: Post-War Discourses in the Greek Student Press
Authors: Betsas Ioannis Stergios , Charalambous Dimitrios Philippos
Published: October 2023

In this article, we trace the histories of discourses concerning student identity in post-war Greece. Making use of the discourse-historical approach (DHA), textual data are analyzed in student journals published by students’ unions, factions and collectives of the University of Thessaloniki. Student identity is theorized as being constructed and negotiated in discourse, in close relation to sociopolitical context. In light of the discourse-historical approach it is assumed that the intensification of discursive strategies, such as nominations, predications and argumentations, and the reconceptualization of ingroup and outgroup dichotomy relate to student identity shifts. The findings from such an analysis detect successive shifts in student identity during the post-war period. Student identity is constructed upon the ‘Us’ and ‘Them’ dichotomy. Students sometimes self-identify as agents of change and at other times as followers or recipients thereof, while their discourse is tuned with domestic sociopolitical developments.
A Study on Blockchain Sandwich Attack Strategies Based on Mechanism Design Game Theory
Authors: Liang Yuxuan , Wang Xukang , Wu Ying Cheng , Fu Hongpeng , Zhou Mengjie
Published: October 2023

The rapid progression of Decentralized Finance (DeFi) has established Decentralized Exchanges (DEX) as critical elements in the financial landscape. Nevertheless, the open and transparent nature of DEX makes them susceptible to strategic manipulations, especially the sandwich attack. During such maneuvers, ill-intentioned actors exploit price slippage by positioning their transactions strategically around a target’s order to reap unfair profits. This paper introduces a ground-breaking framework rooted in mechanism design game theory to lessen the impact of sandwich attacks. The framework delineates the precise strategy of the sandwich attack and its repercussions, shedding light on the tactical aspects and utility functions pertinent to both the attackers and the ordinary traders, subsequently referred to as workers. The discussion extends to defining utility functions for both the market and the workers, emphasizing the benefits of liquidity provision for the market and the potential profits and losses for the workers. The proposal encourages adopting a market-centric mechanism design grounded in game theory, wherein the market, operating as the designer, creates rules to maximize its utility while considering the workers’ utility. Through a meticulous analysis of this game-theoretic approach, the study identifies optimum strategies for all the involved parties, demonstrating that these strategies can reach a balanced state. Further, this study presents a comparative view against existing research, highlighting the limitations of contemporary solutions and asserting the effectiveness of the proposed model in protecting the interests of both the market and the workers. Ultimately, this research furnishes stakeholders with new perspectives and instruments to thwart sandwich attacks and lays a foundation for creating resilient and fair decentralized trading infrastructures.
Improving the Therapeutic Relationship When Prescribing Antidepressants: A Pilot Study
Authors: Michel Konrad , Lutz-Beck Daniela , Engeroff Sylva
Published: October 2023

Studies indicate that the quality of the doctor–patient relationship moderates the effect of pharmacotherapy. To enhance the quality of the therapeutic relationship in the pharmacotherapy of depression, we developed a brief manual with interactive materials for residents in psychiatry and their patients. In a pilot study at a psychiatric university hospital’s outpatient department, we compared patient-centered treatment parameters of a first patient group treated as usual and a second patient group treated using the manual. The study had no influence on the choice of medication. In the manual group, patient satisfaction with the doctor–patient relationship increased significantly at the three-month follow-up. Depression parameters declined in both groups, without group differences. Continuation of antidepressant medication at six months was higher in the manual group. In conclusion, a simple intervention using written materials for doctors prescribing antidepressants improved doctors’ and patients’ satisfaction with treatment.