bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Expression of NOTCH-1 and Its Molecular Targets in Response to Metronomic Followed by Conventional Therapy in a Patient with Advanced Triple-Negative Breast Cancer
Authors: Ilari Alice , Cogliati Viola , Sherif Noorhan , Grassilli Emanuela , Ramazzotti Daniele , Cordani Nicoletta , Cazzaniga Giorgio , Di Bella Camillo , Lavitrano Marialuisa , Cazzaniga Marina Elena , Cerrito Maria Grazia
Published: January 2024

A group of 27 patients diagnosed with metastatic triple-negative breast cancer (mTNBC) was randomly distributed into two groups and underwent different lines of metronomic treatment (mCHT). The former group (N 14) received first-line mCHT and showed a higher overall survival rate than the second group (N 13), which underwent second-line mCHT. Analysis of one patient still alive from the first group, diagnosed with mTNBC in 2019, showed a complete metabolic response (CMR) after a composite approach implicating first-line mCHT followed by second-line epirubicin and third-line nab-paclitaxel, and was chosen for subsequent molecular characterization. We found altered expression in the cancer stemness-associated gene NOTCH-1 and its corresponding protein. Additionally, we found changes in the expression of oncogenes, such as MYC and AKT, along with their respective proteins. Overall, our data suggest that a first-line treatment with mCHT followed by MTD might be effective by negatively regulating stemness traits usually associated with the emergence of drug resistance.
Nuclear VANGL2 Inhibits Lactogenic Differentiation
Authors: Rubio Stefany , Molinuevo Rut , Sanz-Gomez Natalia , Zomorrodinia Talieh , Cockrum Chad S. , Luong Elina , Rivas Lucia , Cadle Kora , Menendez Julien , Hinck Lindsay
Published: January 2024

Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing cell patterning and polarity. Asymmetrically localized on the plasma membrane of cells, transmembrane PCP proteins are trafficked by endocytosis, suggesting they may have intracellular functions that are dependent or independent of their extracellular role, but whether these functions extend to transcriptional control remains unknown. Here, we show the nuclear localization of transmembrane, PCP protein, VANGL2, in the HCC1569 breast cancer cell line, and in undifferentiated, but not differentiated, HC11 cells that serve as a model for mammary lactogenic differentiation. The loss of Vangl2 function results in upregulation of pathways related to STAT5 signaling. We identify DNA binding sites and a nuclear localization signal in VANGL2, and use CUT&RUN to demonstrate recruitment of VANGL2 to specific DNA binding motifs, including one in the Stat5a promoter. Knockdown (KD) of Vangl2 in HC11 cells and primary mammary organoids results in upregulation of Stat5a, Ccnd1 and Csn2, larger acini and organoids, and precocious differentiation; phenotypes are rescued by overexpression of Vangl2, but not Vangl2ΔNLS. Together, these results advance a paradigm whereby PCP proteins coordinate tissue morphogenesis by keeping transcriptional programs governing differentiation in check.
Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFNγ and GM-CSF
Authors: Ravelojaona Marion , Girouard Julie , Kana Tsapi Emmanuelle Stella , Chambers Megan , Vaillancourt Cathy , Van Themsche Céline , Thornton Catherine A. , Reyes-Moreno Carlos
Published: January 2024

Interleukin-6 (IL-6) superfamily cytokines play critical roles during human pregnancy by promoting trophoblast differentiation, invasion, and endocrine function, and maintaining embryo immunotolerance and protection. In contrast, the unbalanced activity of pro-inflammatory factors such as interferon gamma (IFNγ) and granulocyte–macrophage colony-stimulating factor (GM-CSF) at the maternal–fetal interface have detrimental effects on trophoblast function and differentiation. This study demonstrates how the IL-6 cytokine family member oncostatin M (OSM) and STAT3 activation regulate trophoblast fusion and endocrine function in response to pro-inflammatory stress induced by IFNγ and GM-CSF. Using human cytotrophoblast-like BeWo (CT/BW) cells, differentiated in villous syncytiotrophoblast (VST/BW) cells, we show that beta-human chorionic gonadotrophin (βhCG) production and cell fusion process are affected in response to IFNγ or GM-CSF. However, those effects are abrogated with OSM by modulating the activation of IFNγ-STAT1 and GM-CSF-STAT5 signaling pathways. OSM stimulation enhances the expression of STAT3, the phosphorylation of STAT3 and SMAD2, and the induction of negative regulators of inflammation (e.g., IL-10 and TGFβ1) and cytokine signaling (e.g., SOCS1 and SOCS3). Using STAT3-deficient VST/BW cells, we show that STAT3 expression is required for OSM to regulate the effects of IFNγ in βhCG and E-cadherin expression. In contrast, OSM retains its modulatory effect on GM-CSF-STAT5 pathway activation even in STAT3-deficient VST/BW cells, suggesting that OSM uses STAT3-dependent and -independent mechanisms to modulate the activation of pro-inflammatory pathways IFNγ-STAT1 and GM-CSF-STAT5. Moreover, STAT3 deficiency in VST/BW cells leads to the production of both a large amount of βhCG and an enhanced expression of activated STAT5 induced by GM-CSF, independently of OSM, suggesting a key role for STAT3 in βhCG production and trophoblast differentiation through STAT5 modulation. In conclusion, our study describes for the first time the critical role played by OSM and STAT3 signaling pathways to preserve and regulate trophoblast biological functions during inflammatory stress.
Analysing the Influence of Fibers on Fresh Concrete Rheometry by the Use of Numerical Simulation
Authors: Gerland Florian , Vaupel Tim , Schomberg Thomas , Wünsch Olaf
Published: January 2024

Measuring the flow properties of fiber-laden fresh concrete poses a substantial challenge because not only the fraction of fibers but also their orientation process during the measurement influence the measured quantities. Numerical simulations of the flow in a ball probe rheometer are used to determine the fiber orientation process during the measurement of the flow properties and its influence on the measured variables. Through analytical considerations and comparison with measurement results, it can be shown that the constitutive law applied can reproduce the real flow behavior very well, taking the fiber orientation into account. At the same time, it is investigated why no orientation influence on the torque is recognizable in the experimental measurement curves, although the orientation process demonstrably exceeds the duration of the measurement process. The results show that fluid inertia is overcome before the recognizable onset of fiber orientation, and the spatially inhomogeneous flow minimises the impact of the orientation process on torque. The simulation model aligns well with experimental outcomes, indicating a linear increase in effective viscosity with increasing fiber volume fraction. The findings can be used to accurately measure the objective material parameters of the orientation-considering constitutive law using ball probe rheometers, so that an accurate prediction of the flow process of fresh concrete with fibers is made possible, for example for the simulation of formwork fillings.
Natural Deep Eutectic Solvents as a Novel Bio-Based Matrix for Ready-to-Use Natural Antioxidants-Enriched Ingredients: Extraction and Formulation Optimization
Authors: Boudesocque-Delaye Leslie , Ardeza Iron Mike , Verger Alexis , Grard Roxane , Théry-Koné Isabelle , Perse Xavier , Munnier Emilie
Published: January 2024

The escalating consumer demand for sustainable cosmetic ingredients poses distinct challenges, particularly concerning their stability within the final formulation. Although natural resources offer a pool of antioxidant molecules with diverse structures and polarities, achieving stabilization combined with a comprehensive antioxidant profile often proves incompatible with practical preformulation considerations. Notably, Calendula, which is rich in both polar (glycosylated flavonoids) and nonpolar (carotenoids) antioxidants, is a standout candidate. Nevertheless, the market lacks an ingredient embodying this diversity, primarily due to the limited polarity range of available usable solvents. Natural deep eutectic solvents (NaDESs) emerge as a promising solution. This study explores NaDES technology with the goal of developing a unique Calendula extract enriched in both polarities of antioxidants, a composition that is unattainable with traditional solvents. A screening of 12 NaDESs with varying polarities highlighted a NaDES based on betaine and glycerol as particularly effective, outperforming ethanol. Leveraging response surface methodology, an optimal mechanical stirring procedure for extraction was identified. The resulting extract showed a total flavonoid content of 45.42 ± 0.85 mg eq rutin/g of biomass and a total carotenoid content of 383.54 ± 4.73 µg/g biomass. It was then incorporated into a sustainable cream (1% and 10%wt) using an innovative mixing technology. The resulting creams demonstrated stability over 90 days, with no significant deviations in pH or rheological properties compared to the control, and a droplet size that was inferior to 10 µm. This study lays the foundation for pioneering natural antioxidant cocktail-loaded ingredients that are suitable for eco-friendly cosmetic formulations, substantiating the viability of integrating environmentally friendly ingredient-based solvents.
Addressing Inequality in the COVID-19 Pandemic in Africa: A Snapshot from Clinical Symptoms to Vaccine Distribution
Authors: Pêgo Ana Catarina , Lima Illyane Sofia , Gozzelino Raffaella
Published: January 2024

On 30 January 2020, WHO declared COVID-19 a public health emergency of global concern. COVID-19 became pandemic on 11 March 2020, and spread unprecedently. No country was prepared to face its impact. Major fears started to be expressed for Africa, where dramatic consequences were expected, due to the weakness of health systems. In this review, we related major concerns, at that time but still present, regarding the limited resources in terms of qualified physicians and researchers, as well as the scarce funds to purchase essential medical equipment and improve hospital infrastructures. The difficulties to provide proper care became an undeniable mark of inequality, highlighting the need to empower local capacity and raise preparedness against infection outbreaks. The transmissibility of genetic variants affecting African nations, the immunopathology underlying comorbidities, sequelae, and pre-existing conditions, often related to changes in iron metabolism and enhancing COVID-19 severity, were described. The obstacles in adopting standardized prevention measures were highlighted, along with testing capacity biases and inequity of healthcare access and vaccine distribution. By providing a better understanding of the COVID-19 pandemic in Africa, we draw attention to the need for collaborative efforts to leverage the quality of healthcare and research in this continent.
Ecological and Public Advantages of a Dual Flagship Strategy: Giant Panda and Snow Leopard
Authors: Yue Ying , Wang Yihong , Ye Ziyi , Zhang Chengcheng , Qiu Lan , Xu Qiang , He Xin , Ma Chendi , Yang Biao , Yang Zhisong , Dai Qiang
Published: January 2024

Flagship species’ conservation strategies hold significant prominence in biodiversity preservation. The giant panda, a globally recognized species, has drawn attention to its benefits and constraints as a flagship species. This study aimed to assess the potential benefits of a dual flagship strategy using both the giant panda and snow leopard, compared to an approach solely using the giant panda. We identified the number of potential beneficiary species based on their habitat overlap with the giant panda and snow leopard in Sichuan and Gansu, China. Subsequently, we examined public preferences for these two flagships and their influencing factors through questionnaire surveys within and outside China. The dual flagship strategy covered the habitats of more species and amplified existing protection for those species already benefiting from giant panda conservation efforts. The giant panda was commonly perceived as “Adorable”, “Innocent”, and “Rare”, while perceptions of the snow leopard leaned towards “Mighty”, “Mysterious”, and “Rare”. Though the giant panda is widely favored, the survey indicates a notable preference for snow leopards among a proportion of respondents. The dual flagship strategy offers expanded wildlife habitat coverage and benefits a broader range of species. Moreover, the combined appeal of the snow leopard and giant panda, each possessing unique charm and symbolism, holds the potential to garner broader societal interest and support. This study may serve as a reference for policy decisions in the Giant Panda National Park and other similar protected areas, optimizing conservation management and outreach initiatives for flagship species strategies. It may also benefit conservation strategies centered on other flagship species.
High-Altitude Precision Landing by Smartphone Video Guidance Sensor and Sensor Fusion
Authors: Silva Cotta Joao Leonardo , Gutierrez Hector , Bertaska Ivan R. , Inness John P. , Rakoczy John
Published: January 2024

This paper describes the deployment, integration, and demonstration of the Smartphone Video Guidance Sensor (SVGS) as novel technology for autonomous 6-DOF proximity maneuvers and high-altitude precision landing of UAVs via sensor fusion. The proposed approach uses a vision-based photogrammetric position and attitude sensor (SVGS) to support the precise automated landing of a UAV from an initial altitude above 100 m to ground, guided by an array of landing beacons. SVGS information is fused with other on-board sensors at the flight control unit to estimate the UAV’s position and attitude during landing relative to a ground coordinate system defined by the landing beacons. While the SVGS can provide mm-level absolute positioning accuracy depending on range and beacon dimensions, the proper operation of the SVGS requires a line of sight between the camera and the beacon, and readings can be disturbed by environmental lighting conditions and reflections. SVGS readings can therefore be intermittent, and their update rate is not deterministic since the SVGS runs on an Android device. The sensor fusion of the SVGS with on-board sensors enables an accurate and reliable update of the position and attitude estimates during landing, providing improved performance compared to state-of-art automated landing technology based on an infrared beacon, but its implementation must address the challenges mentioned above. The proposed technique also shows significant advantages compared with state-of-the-art sensors for High-Altitude Landing, such as those based on LIDAR.
Hyperspectral Image Shadow Enhancement Using Three-Dimensional Dynamic Stochastic Resonance and Classification Based on ResNet
Authors: Liu Xuefeng , Kou Yangyang , Fu Min
Published: January 2024

Classification is an important means of extracting rich information from hyperspectral images (HSIs). However, many HSIs contain shadowed areas, where noise severely affects the extraction of useful information. General noise removal may lead to loss of spatial correlation and spectral features. In contrast, dynamic stochastic resonance (DSR) converts noise into capability that enhances the signal in a way that better preserves the image’s original information. Nevertheless, current one-dimensional and 2D DSR methods fail to fully utilize the tensor properties of hyperspectral data and preserve the complete spectral features. Therefore, a hexa-directional differential format is derived in this paper to solve the system’s output, and the iterative equation for HSI shadow enhancement is obtained, enabling 3D parallel processing of HSI spatial–spectral information. Meanwhile, internal parameters are adjusted to achieve optimal resonance. Furthermore, the residual neural network 152 model embedded with the convolutional block attention module is proposed to diminish information redundancy and leverage data concealed within shadow areas. Experimental results on a real-world HSI demonstrate the potential performance of 3D DSR in enhancing weak signals in HSI shadow regions and the proposed approach’s effectiveness in improving classification.
Deep Neural Network Confidence Calibration from Stochastic Weight Averaging
Authors: Cao Zongjing , Li Yan , Kim Dong-Ho , Shin Byeong-Seok
Published: January 2024

Overconfidence in deep neural networks (DNN) reduces the model’s generalization performance and increases its risk. The deep ensemble method improves model robustness and generalization of the model by combining prediction results from multiple DNNs. However, training multiple DNNs for model averaging is a time-consuming and resource-intensive process. Moreover, combining multiple base learners (also called inducers) is hard to master, and any wrong choice may result in lower prediction accuracy than from a single inducer. We propose an approximation method for deep ensembles that can obtain ensembles of multiple DNNs without any additional costs. Specifically, multiple local optimal parameters generated during the training phase are sampled and saved by using an intelligent strategy. We use cycle learning rates starting at 75% of the training process and save the weights associated with the minimum learning rate in every iteration. Saved sets of the multiple model parameters are used as weights for a new model to perform forward propagation during the testing phase. Experiments on benchmarks of two different modalities, static images and dynamic videos, show that our method not only reduces the calibration error of the model but also improves the accuracy of the model.
Red Dragon Fruit Peels: Effect of Two Species Ratio and Particle Size on Fibre Quality and Its Application in Reduced-Fat Alpaca-Based Sausages
Authors: Corimayhua-Silva Andrés A. , Elías-Peñafiel Carlos , Rojas-Ayerve Tatiana , Guevara-Pérez Américo , Farfán-Rodríguez Lucero , Encina-Zelada Christian R.
Published: January 2024

This research aimed to assess the influence of red dragon fruit peels ratio (RDF-PR) from two species, Hylocereus hybridum (HH) and Hylocereus undatus (HU), and particle size (PS) on quality parameters of red dragon fruit peel powder (RDF-PP) and its further application in emulsified alpaca-based sausages as partial substitutes of pork-back fat. A three-level full factorial design (nine treatments) was employed to evaluate the effect of RDF-PR (HH(0%):HU(100%), HH(50%):HU(50%), and HH(100%):HU(0%)) and PS (499–297, 296–177, and <177 µm) on the dependent variables: L*, a*, b*, C, h°, water-holding capacity, oil-holding capacity, swelling capacity, pectin yield, degree of esterification (analysed through FT-IR), and crude fibre content. The data analysed through a response surface methodology showed that treatment one (T1) is the best with the optimised conditions at 100% HU RDF-PR and PS of <177 µm. The statistical validation of T1 exhibited the highest water-holding capacity (32.1 g/g peel), oil-holding capacity (2.20 g oil/g peel), and pectin yield (27.1%). A completely randomised design (four formulations) was then used to assess the effect of partial replacement of pork-back fat by T1 in emulsified alpaca-based sausages on the colourimetric, physicochemical, and texture properties (hardness, chewiness, cohesiveness, springiness, adhesiveness, and adhesive force). Likewise, a sensory hedonic scale was employed to evaluate the appearance, colour, odour, flavour, texture, and overall acceptability of sausages. The results revealed that 65.7% of pork-back fat content was successfully replaced compared with a control formulation. Additionally, F3 showed significantly (p < 0.05) better colourimetric, physicochemical, and textural characteristics, such as lower hardness (34.8 N) and chewiness (21.7 N) and higher redness (a* = 19.3) and C (22.9), compared to a control formulation. This research presents RDF-PP as a promising fat substitute for developing healthier, reduced-fat meat products using fibre-rich agroindustry by-products.
Oxidative Modification, Structural Conformation, and Gel Properties of Pork Paste Protein Mediated by Oxygen Concentration in Modified Atmosphere Packaging
Authors: Liu Rui , Guan Wen , Lv Wei , Kang Zhuangli , Wang Qingling , Jin Duxin , Zhao Xinxin , Ge Qingfeng , Wu Mangang , Yu Hai
Published: January 2024

The objective of this study was to investigate the effect of pork oxidation through modified atmosphere packaging (MAP) on gel characteristics of myofibrillar proteins (MP) during the heat-induced gelation process. The pork longissimus thoracis (LT) was treated by MAP at varying oxygen concentrations (0, 20, 40, 60, and 80% O2) with a 5-day storage at 4 °C for the detection of MP oxidation and gel properties. The findings showed the rise of O2 concentration resulted in a significant increase of carbonyl content, disulfide bond, and particle size, and a decrease of sulfhydryl content and MP solubility (p < 0.05). The gel textural properties and water retention ability were significantly improved in MAP treatments of 0–60% O2 (p < 0.05), but deteriorated at 80% O2 level. As the concentration of O2 increased, there was a marked decrease in the α-helix content within the gel, accompanied by a simultaneous increase in β-sheet content (p < 0.05). Additionally, a judicious oxidation treatment (60% O2 in MAP) proved beneficial for crafting dense and uniform gel networks. Our data suggest that the oxidation treatment of pork mediated by O2 concentration in MAP is capable of reinforcing protein hydrophobic interaction and disulfide bond formation, thus contributing to the construction of superior gel structures and properties.
The Effect of Sex on the Chemical and Mineral Composition of the Meat, Bone and Liver of Giraffe (Giraffa giraffa angolensis)
Authors: Hoffman Louwrens Christiaan , Silberbauer Bianca L. , Needham Tersia , Bureš Daniel , Kotrba Radim , Strydom Philip E.
Published: January 2024

Consumers tend to buy meat based on visual physical characteristics, which are affected by the chemical composition of the meat, and there is very little known about the chemical composition of the meat of giraffe. This study therefore aims to broaden the knowledge base on the chemical composition of giraffe meat, rib bone and liver. Eight different muscles from 15 giraffes were analyzed to determine the chemical composition, yielding an average moisture of 77.2 ± 0.09 g/100 g meat, an average protein of 20.8 ± 0.09 g/100 g meat, an average intramuscular fat (IMF) of 1.4 ± 0.03 g/100 g meat and an average ash of 1.1 ± 0.01 g/100 g meat. There was a significant interaction between sex and muscle for the moisture, protein and ash contents, while only muscle had an effect on the fat content. The mineral content of the bone, liver and Longissimus thoracis et lumborum muscle was also analyzed, and bone was found to be a rich source of calcium (highest concentration), whilst the liver had the highest concentration of iron. The chemical composition of the giraffe meat was such that it could be classified as lean meat.
Addressing the Audience and Making History: Soliloquies in Richard III
Authors: Hopkins Lisa
Published: January 2024

Few plays make such varied or such bravura use of soliloquies as Shakespeare’s Richard III. The opening forty-one-line monologue by Richard himself allows an actor to show what he can do and to capture his audience and offers a view on processes of historical causation: having started with six uses of the word ‘our’, Richard not only moves on to say ‘I’ nine times (supplemented by ‘my’ and ‘me’), but also explains that his plans are going to affect the future of others, too. His plot to set his brothers against each other is going to change the course of history; moreover, it will do so by using the stalking-horse of a prophecy, a form of speech which presumes that the future is already unalterably fixed. Other soliloquies in the play also offer insights into historical process. This paper examines the differing tonality of the play’s soliloquies and the kind of information offered in them to argue that while Richard III officially subscribes to Tudor myths of the past, it not only implicitly urges the audience to a more sceptical take, but in fact raises questions about whether we can ever be sure about how history was made.
Short-Term Impact of Low-Intensity Exercise with Blood Flow Restriction on Mild Knee Osteoarthritis in Older Adults: A Pilot Study
Authors: Kim Kang-Ho , Kang Seung-Ho , Kim Nackhwan , Choi Jaehyeong , Kang Seok
Published: January 2024

This pilot study aimed to investigate the immediate impact of low-intensity exercises with blood flow restriction (BFR) on older adults with knee osteoarthritis (KOA). Fifteen patients with KOA who were over 50 years old, participated and underwent low-intensity resistance knee exercises at 30% of their one-repetition maximum with BFR three times/week for two weeks. Pre- and post-exercise assessments included pain levels, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, isokinetic knee strength, lower extremity muscle volume (via leg circumference and muscle thickness), functional performance tests (timed up-and-go [TUG] and sit-to-stand [STS]), skeletal muscle index (SMI) using bioelectrical impedance analysis, and handgrip strength (HGS). Post-exercise, there was a significant reduction in pain. WOMAC scores showed significant improvements across all three domains: pain, stiffness, and physical function. In the TUG and STS tests, completion times were significantly reduced. Thigh and calf circumferences, as well as thigh muscle thickness significantly increased after exercise. Post-exercise SMI and HGS also significantly increased. However, isokinetic knee strength did not show significant changes. In conclusion, low-intensity BFR exercises provide immediate benefits in symptoms and physical performance for patients with KOA, potentially inducing local and systemic muscle mass increase, even after a short-term intervention.
Assessing the Suitability of Fractal Dimension for Measuring Graphic Complexity Change in Schematic Metro Networks
Authors: Lan Tian , Wu Zhiwei , Sun Chenzhen , Cheng Donglin , Shi Xing , Zeng Guangjun , Zhang Hong , Peng Qian
Published: January 2024

Schematization is a process of generating schematic network maps (e.g., metro network maps), where the graphic complexity of networks is usually reduced. In the past two decades, various automated schematization methods have been developed. A quantitative and accurate description of the complexity variation in the schematization is critical to evaluate the usability of schematization methods. It is noticed that fractal dimension (F) has been widely used to analyze the complexity of geographic objects, and this indicator may be appropriate for this purpose. In some existing studies, although F has been employed to describe the complexity variation, the theoretical and experimental basis for adopting this approach is inadequate. In this study, experiments based on 26 Chinese cities’ metro networks showed that the F of all these metro networks have decreased in schematization, and a significant positive correlation exists between the F of original networks and the reduction of F after schematization. The above results were verified to have similar trends with the subjective opinions of participants in a psychological questionnaire. Therefore, it can be concluded that F can quantitatively measure the complexity change of networks in schematization. These discoveries provide the basis for using F to evaluate the usability of schematization methods.
Identification of the Major Facilitator Superfamily Efflux Pump KpsrMFS in Klebsiella pneumoniae That Is Down-Regulated in the Presence of Multi-Stress Factors
Authors: He Wei , Jiang Minzhi , Li Ying , Ge Xizhen
Published: January 2024

Efflux pumps play important roles in bacterial detoxification and some of them are stress-response elements that are up-regulated when the host is treated with antibiotics. However, efflux pumps that are down-regulated by stimulations are rarely discovered. Herein, we analyzed multiple transcriptome data and discovered a special (Major Facilitator Superfamily) MFS efflux pump, KpsrMFS, from Klebsiella pneumoniae, which was down-regulated when treated with antibiotics or extra carbon sources. Interestingly, overexpression of kpsrmfs resulted in halted cell growth in normal conditions, while the viable cells were rarely affected. The function of KpsrMFS was further analyzed and this efflux pump was determined to be a proton-driven transporter that can reduce the intracellular tetracycline concentration. In normal conditions, the expression of kpsrmfs was at a low level, while artificial overexpression of it led to increased endogenous reactive oxygen species (ROS) production. Moreover, by comparing the functions of adjacent genes of kpsrmfs, we further discovered another four genes that can confer similar phenotypes, indicating a special regulon that regulates cell growth. Our work provides new insights into the roles of efflux pumps and suggests a possible regulon that may regulate cell growth and endogenous ROS levels.
Neurobiology of Stress-Induced Nicotine Relapse
Authors: Wang Xinyu , Chen Yun , Dong Jing , Ge Jing , Liu Xiaoliu , Liu Jianfeng
Published: January 2024

Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, the relapse rate remains very high. Among the factors that could induce nicotine relapse, stress might be the most important one. In the last decades, preclinical studies have generated many new findings that lead to a better understanding of stress-induced relapse of nicotine-seeking. Several molecules such as α3β4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated receptor 1, and neuropeptide systems (corticotropin-releasing factor and its receptors, dynorphine and kappa opioid receptor) have been linked to stress-induced nicotine relapse. In this review, we discuss recent advances in the neurobiology, treatment targets, and potential therapeutics of stress-induced nicotine relapse. We also discuss some factors that may influence stress-induced nicotine relapse and that should be considered in future studies. In the final section, a perspective on some research directions is provided. Further investigation on the neurobiology of stress-induced nicotine relapse will shed light on the development of new medicines for controlling smoking and will help us understand the interactions between the stress and reward systems in the brain.
Homology Modeling, Molecular Dynamics Simulation, and Prediction of Bovine TLR2 Heterodimerization
Authors: Mansouri Alireza , Yousef Mohamed Samy , Kowsar Rasoul , Miyamoto Akio
Published: January 2024

Toll-like receptor 2 (TLR2) is a major membrane-bound receptor with ligand and species specificity that activates the host immune response. Heterodimerization of TLR2 with TLR1 (TLR2/1) or TLR6 (TLR2/6), triggered by ligand binding, is essential to initiating the signaling pathway. Bovine TLR2 (bTLR2) heterodimerization has not been defined yet compared with human and mouse TLR2s (hTLR2 and mTLR2). The aim of the present study was to model bovine TLRs (TLRs 1, 2 and 6) and create the heterodimeric forms of the bovine TLR2 using molecular dynamics (MD) simulations. We compared the intermolecular interactions in bTLR2/1-PAM3 and bTLR2/6-PAM2 with the hTLR2 and mTLR2 complexes through docking simulations and subsequent MD analyses. The present computational findings showed that bTLR2 dimerization could have a biological function and activate the immune response, similar to hTLR2 and mTLR2. Agonists and antagonists that are designed for hTLR2 and mTLR2 can target bTLR2. However, the experimental approaches to comparing the functional immune response of TLR2 across species were missing in the present study. This computational study provides a structural analysis of the bTLR2 interaction with bTLR1 and bTLR6 in the presence of an agonist/antagonist and reveals the three-dimensional structure of bTLR2 dimerization. The present findings could guide future experimental studies targeting bTLR2 with different ligands and lipopeptides.
Health and Benefits of Dog Companionship in Women over 50 Years Old
Authors: Kluess Heidi A. , Jones Rebecca L.
Published: January 2024

Background: The purpose of this study was to investigate the health and wellness benefits of dog companionship in a population of women over 50 years old. Methods: This study used a combination of an online survey (n = 284 self-identified dog companions, n = 71 non-dog companions) and in-person fitness testing (n = 24 dog companions and n = 7 non-dog companions). In-person testing included the 6 min walk, handgrip strength, and chair stand tests. Results: From the questionnaire: Dog companions were 61 ± 7 years old and non-dog companions were 58 ± 6 years old. Dog companions reported 3 ± 2 medical diagnoses and 2 ± 1 medications, but non-dog companions only reported 2 ± 1 medical diagnoses and 1 ± 1 medications (p < 0.001). Satisfaction with life scores and interpersonal communication competence scores were higher for dog companions compared to non-dog companions (p < 0.001). Dog companions and non-dog companions reported similar amounts of time per week on vigorous activity. However, the number of days per week in which dog companions participated in moderate activity was higher than in non-dog companions (p < 0.05). Dog companions also reported walking more days per week and for a longer time than non-dog companions (p < 0.05). There were no differences in the in-person testing (6 min walk, handgrip strength, chair stand tests) between groups. Conclusions: When the in-person testing scores were compared to national standards, the women in this study were average to above average. Overall, women over 50 that own dogs walk more and have better life satisfaction, compared to non-dog companions.
Headache Attributed to Refractive Error: Improvement after Topography-Guided Photorefractive Keratectomy with Corneal Cross-Linking in Patients with Keratoconus
Authors: Khoo Nigel Terk-Howe , Burgos-Blasco Barbara , Antoniou Angelique , Jenkins Bronwyn , Fraser Clare L. , Moloney Gregory
Published: January 2024

Purpose: To investigate if topography-guided photorefractive keratectomy (TGPRK) alleviates headache, particularly headache attributed to refractive errors (HARE) in keratoconus. Methods: Patients diagnosed with keratoconus undergoing TGPRK for refractive correction were included. Best spectacle corrected visual acuity (BSCVA) using the logMAR scale and refractive error were measured. Patients answered a questionnaire exploring headaches, characteristics, treatment, and the Headache Impact Test (HIT-6) before and 6 months after the surgery. Results: 40 patients were included. Preoperatively, 24 patients (60%) met criteria for headaches: five for migraine, 14 for HARE, and five for tension-type headache (TTH). Patients with headaches preoperatively were more likely to require bilateral TGPRK, and the mean sphere and cylindrical power were higher. Postoperatively, 15 out of the 24 patients of the headache group experienced complete resolution of headaches, and only nine patients met diagnostic criteria for headaches: two for migraine, six for HARE, and one for TTH. The number of headaches reduced from 4.4 ± 2.4 to 0.5 ± 0.7 days/week (p < 0.001). Headache duration decreased from 108.5 ± 100.7 min to 34.4 ± 63.5 min (p = 0.002). Postoperatively, the consumption of analgesia decreased. The HIT-6 revealed an improvement in the quality-of-life post-procedure (p < 0.001). Conclusions: Surgical correction of irregular astigmatism in patients with keratoconus can alleviate or resolve headaches in a large proportion of patients, resulting in an improvement in their quality of life. Physicians should consider keratoconus in patients fitting criteria for HARE not alleviated by spectacle correction and suboptimal vision in glasses.
Impact of Skeletal Muscle Mass on Physical Function and Locomotive Syndrome of Pre- and Postoperative Adult Spinal Deformity
Authors: Ohba Tetsuro , Oda Kotaro , Tanaka Nobuki , Go Goto , Haro Hirotaka
Published: January 2024

Background: The purpose of this study is to identify the relationship between locomotive syndrome (LS) status, physical performance and limb and trunk skeletal muscle mass before and after surgery in adult spinal surgery (ASD) patients. Methods: A retrospective observational investigation of 63 consecutive patients with ASD who underwent spinal surgery was conducted. The total skeletal muscle mass of the arms and legs was considered a measure of the total appendicular skeletal muscle mass measured with whole-body dual-energy X-ray absorptiometry. All data pertaining to the physical performance tests and LS were collected preoperatively with follow-up one year postoperatively. Results: Gait speed, the one-leg standing test and the stand-up test were significantly improved one year after surgery compared to preoperative measurements. The lower extremity skeletal muscle mass predominantly influences physical function improvement including gait stride, one-leg standing and the stand-up test after ASD surgery. Conclusions: This study is the first to show that assessing lower extremity muscles prior to ASD surgery is useful in predicting postoperative recovery.
How to Manage Advanced Differentiated Thyroid Cancer: Step-by-Step Analysis from Two Italian Tertiary Referral Centers
Authors: Sartori Paola Vincenza , Andreani Sara , De Pasquale Loredana , Pauna Iuliana , Bulfamante Antonio Mario , Aiello Paolo Salvatore Lorenzo , Melcarne Rossella , Giacomelli Laura , Boniardi Marco
Published: January 2024

Background: Differentiated thyroid carcinoma (DTC) has an excellent prognosis; however, advanced disease is associated with a worse prognosis and is relatively common. Surgery followed by RAI treatment remains the mainstream treatment for a large majority of patients with high- and intermediate-risk DTC, but its benefits should be carefully weighed against the potential for harm. The aim of this paper is to critically review the experience in treating advanced DTC at two tertiary referral centers in Italy. Methods: Retrospective analysis of 300 patients who underwent surgery for ADTC over 30 years. Results: The complication rate was 50.33%. A total of 135 patients (45%) remained at regular follow-up, 118 (87.4%) were alive, while 17 (12.6%) were deceased. The mean overall survival at 12 years was 84.8% with a mean of 238 months. Eleven patients (8.1%) experienced a relapse after a median of 13 months. Conclusions: ADTC patients adequately treated can achieve prolonged survival even in the case of metastasis or disease relapse. Patients with ADTC should be referred to high-volume centers with the availability of an extended multidisciplinary team to receive tailored treatment.
How Reliable Is Breast Volume Assessment When the Patient Is Lying Flat?—Volumetric Assessment of Breast Volume Using a Vectra H2 Handheld Device in Different Positions
Authors: Macek Aljosa , Leitsch Sebastian , Koban Konstantin Christoph , Mayer Julius Michael , Loucas Rafael , Holzbach Thomas
Published: January 2024

(1) Background: Three-dimensional (3D) volumetric assessment is receiving increased recognition in breast surgery. It is commonly used for preoperative planning and postoperative control with the patient standing in an upright position. Recently, intraoperative use was evaluated with patients in the supine position. The aim of this prospective study was to evaluate the volumetric changes in 3D surface imaging depending on the patient’s position. (2) Methods: 3D volumetric analysis was performed using a Vectra-H2 device with patients in standing, sitting, and supine positions. A total of 100 complete datasets of female breasts were included in the study. The measured volumes of each evaluated breast (n = 200) were compared between the three positions. (3) Results: The mean difference between the 3D volumetric assessments of the sitting and standing positions per breast was 7.15 cc and, thus, statistically insignificant (p = 0.28). However, the difference between supine and standing positions, at 120.31 cc, was significant (p < 0.01). (4) Conclusions: The 3D volumetric assessment of breasts in the supine position did not statistically correlate with the validated assessment of breast volume in the standing position while breast volume in the sitting position is reliable and correlates with the assessment of a standing patient. We conclude that intraoperative volumetric assessment should be performed with patients in an upright sitting position.
Uncommon Blepharitis
Authors: Di Zazzo Antonio , Giannaccare Giuseppe , Villani Edoardo , Barabino Stefano
Published: January 2024

Blepharitis is a common chronic inflammatory condition affecting the eyelid margins; the pathophysiology of blepharitis is complex and not fully understood. The disease is anatomically divided into anterior (inflammation of eyelashes) and posterior (meibomian gland dysfunction) types. Diagnosis relies on clinical examination, revealing characteristic features like scurf, vascular changes, and meibomian gland dysfunction. The main goals of blepharitis treatment are symptom relief, recurrence prevention, and complication risk minimization. Treatment options include lid hygiene, topical and systemic antibiotics, topical corticosteroids, and omega-3 supplements. However, it is important to highlight reported cases of blepharitis as side effects of systemic therapies, particularly in the context of chemotherapy, bortezomib, cetuximab, TNFα inhibitors, and dupilumab. It is crucial to monitor patients undergoing such treatments regularly and attentively in order to promptly set up adequate supportive therapy. Of even more importance is future research on the pathophysiological mechanisms responsible for the occurrence of these ocular side effects in order to find a nosological cure for the issue.
Psychophysiological Effects of Slow-Paced Breathing on Adolescent Swimmers’ Subjective Performance, Recovery States, and Control Perception
Authors: Merlin Quentin , Vacher Philippe , Mourot Laurent , Levillain Guillaume , Martinent Guillaume , Nicolas Michel
Published: January 2024

This study examined the effect of a Slow-Paced Breath (i.e., 6 breaths per minute) without Biofeedback (SPB-NoHRVB) protocol on semi-elite adolescent swimmers’ psychological and physiological states during a seven-week ecological training period. A linear mixed-effects multilevel regression analysis approach was used with 13 adolescent national-level swimmers. Athletes were randomly assigned to an intervention group (n = 7) and a control group (n = 6). Seven waves of assessments were completed weekly during a seven-week training preparation in ecological conditions. During the protocol, swimmers completed subjective quantitative measures (RESTQ-36-R-Sport; cognitive perceived stress and control states about the training process, training subjective performance, and subjective internal training load) and physiological heart rate (HR) (HR of exercise, absolute and normalized HR recovery during the first 60 s of recovery; HRR60 and nHRR60) and heart rate variability (HRV) (MeanRR, RMSSD, LFnu and HFnu, LF/HF ration) tests (through a submaximal heart rate (5′-5′ test) once a week. Results revealed that the SPB-NoHRVB protocol significantly predicts biopsychosocial recovery states, cognitive perception of control, and training subjective performance (i.e., a significant effect of the SPB-NoHRVB protocol with the dependent variables simple time trajectories). However, no significant effects were found for biopsychosocial stress scales, cognitively perceived stress, HR, or HRV markers. Our results suggest that SPB-NoHRVB induces simple evolutions over time for crucial variables in athletes’ adaptation to the training process (i.e., cognitive appraisals and biopsychosocial states). In contrast, it highlights that SPB-NoHRVB does not induce better stress states. This specific effect on the resource component is an exciting result that will be discussed in the manuscript.
Turbulent Characteristics of a Submerged Reef under Various Current and Submergence Conditions
Authors: Kuang Cuiping , Li Hongyi , Zheng Yuhua , Xing Wei , Cong Xin , Chen Jilong
Published: January 2024

Submerged Reefs (SRs) are a kind of artificial fish habitat that can protect coasts and maintain ecological biodiversity. In this study, the flow field of the SR is simulated by solving a Reynolds-averaged Navier–Stokes equation closed with the Realizable k-ε model based on the finite volume method. The turbulent characteristics of SRs under different inflow velocities and submergences in the vicinity of the SR are analyzed. The wake vorticities are the primary turbulent pattern within and around the SR. The back wake and vorticity are chosen as critical indicators to quantitatively assess the hydrodynamic characteristics induced by the SR. The results show: (1) as the main flow passes through the SR, the upwelling is produced in front of the SR and a large-scale wake region is formed behind the SR which contains a clockwise vortex; (2) the length of the wake region formed behind the SR is positively and linearly correlated with both the inflow velocity and submergence; (3) the dipole-type vorticity patterns are induced within the compartment of the SR, where the area and average value of high vorticity have a positive correlation with the flow velocity and a negative correlation with the submergence, respectively.
Utilizing Machine Learning Tools for Calm Water Resistance Prediction and Design Optimization of a Fast Catamaran Ferry
Authors: Nazemian Amin , Boulougouris Evangelos , Aung Myo Zin
Published: January 2024

The article aims to design a calm water resistance predictor based on Machine Learning (ML) Tools and develop a systematic series for battery-driven catamaran hullforms. Additionally, employing a machine learning predictor for design optimization through the utilization of a Genetic Algorithm (GA) in an expedited manner. Regression Trees (RTs), Support Vector Machines (SVMs), and Artificial Neural Network (ANN) regression models are applied for dataset training. A hullform optimization was implemented for various catamarans, including dimensional and hull coefficient parameters based on resistance, structural weight reduction, and battery performance improvement. Design distribution based on Lackenby transformation fulfills all of the design space, and sequentially, a novel self-blending method reconstructs new hullforms based on two parents blending. Finally, a machine learning approach was conducted on the generated data of the case study. This study shows that the ANN algorithm correlates well with the measured resistance. Accordingly, by choosing any new design based on owner requirements, GA optimization obtained the final optimum design by using an ML fast resistance calculator. The optimization process was conducted on a 40 m passenger catamaran case study that achieved a 9.5% cost function improvement. Results show that incorporating the ML tool into the GA optimization process accelerates the ship design process.