bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing Severe Cancer Pain with Oxycodone/Naloxone Treatment: A Literature Review Update
Authors: Formenti Paolo , Umbrello Michele , Pignataro Mauro , Sabbatini Giovanni , Dottorini Lorenzo , Gotti Miriam , Brenna Giovanni , Menozzi Alessandro , Terranova Gaetano , Galimberti Andrea , Pezzi Angelo
Published: May 2024

Severe cancer pain substantially affects patients’ quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone’s prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients’ quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.
The Presence of Ganglionic Acetylcholine Receptor Antibodies in Sera from Patients with Functional Gastrointestinal Disorders: A Preliminary Study
Authors: Nakane Shunya , Mukaino Akihiro , Okumura Yoshiaki , Hirosawa Hiroaki , Higuchi Osamu , Matsuo Hidenori , Kainuma Mosaburo , Nakatsuji Yuji
Published: May 2024

Background: Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. Objective: To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. Materials and Methods: We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. Results: Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. Conclusions: We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.
Spatiotemporal Evolution and Transformation Regulation Strategies of Rural Residential Land on the Grand Canal (China)
Authors: Li Jintao , Chu Lei
Published: May 2024

Land use is an embodiment of human socio-economic activities and represents a bridge between these activities and natural systems. Rural residential land represents a space for rural residents to reside in and exhibits spatial characteristics that evolve over time, which is proof of rural socio-economic development. As one of the most developed regions in China, cities along the Beijing–Hangzhou Canal experienced significant changes in rural residential land use from 1990 to 2020. This paper analyses the spatial differentiation of rural residential land in 21 cities on the Grand Canal. Then, it explores the driving factors of this land using spatial grid analysis and the geographic detector model. According to the spatial differentiation characteristics and the driving factors of rural residential land, the study proposed an improved potential model for rural residential land improvement. Lastly, it proposes three different forms of rural residential land based on the results. The study found that (1) the change in rural residential land in the northern part of the Grand Canal was more volatile than that in the southern part. The change in rural residential land from 1990 to 2020 conformed to the pattern of cultivated land–rural residential land–urban construction land. (2) Based on the driving factors of rural residential land, the land is divided into one-dimensional cities, two-dimensional cities, and three-dimensional cities. Circular, linear, and scattered cities of different sizes were affected by socio-economic factors, transportation accessibility, and the natural environment, respectively. (3) Based on the potential scale of rural residential land consolidation, different types of development strategies were proposed through research, including constructing large-scale villages, relocating and reconstructing new villages, and constructing high-quality villages, respectively. Enhancing the scientific planning of rural residential land and its efficiency and tapping into the potential of land consolidation can offer the protection of agricultural land and the integration of urban and rural areas in the new era.
microRNA and the Post-Transcriptional Response to Oxidative Stress during Neuronal Differentiation: Implications for Neurodevelopmental and Psychiatric Disorders
Authors: Khavari Behnaz , Barnett Michelle M. , Mahmoudi Ebrahim , Geaghan Michael P. , Graham Adam , Cairns Murray J.
Published: May 2024

Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks.
Risk Stratification with Sarculator and MSKCC in Patients with Primary and Secondary Angiosarcoma
Authors: Steubing Yonca , Ahmadi Nilofar , Puscz Flemming , Wolff Alexander , Hinzmann Jannik , Reinkemeier Felix , Schmidt Sonja Verena , Sogorski Alexander , Von Glinski Maxi , Becerikli Mustafa , Füth Maria , Zuchowski Jessica , Brüggenhorst Hannah , Huyghebaert Tom , Stricker Ingo , Lehnhardt Marcus , Wallner Christoph
Published: May 2024

Background: Sarculator and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms are freely available risk prediction scores for surgically treated patients with primary sarcomas. Due to the rarity of angiosarcomas, these scores have only been tested on small cohorts of angiosarcoma patients. In neither the original patient cohort upon which the Sarculator is based nor in subsequent studies was a distinction made between primary and secondary angiosarcomas, as the app is intended to be applied to primary sarcomas. Therefore, the objective of our investigation was to assess whether the Sarculator reveals a difference in prognosis and whether such differentiation aligns with actual clinical data. Patients and Methods: Thirty-one patients with primary or secondary soft tissue angiosarcoma, treated at our Sarcoma Center from 2001 to 2023, were included in the study. Actual survival rates were compared with nomogram-derived data for predicted 5-year survival (Sarculator), as well as 4-, 8- and 12-year sarcoma-specific death probabilities (MSKCC). Harrell’s c-index was utilized to assess predictive validity. Results: In total, 31 patients were analyzed. The actual overall 5-year survival was 22.57% with a predicted 5-year survival rate of 25.97%, and the concordance index was 0.726 for the entire cohort. The concordance index results from MSKCC for angiosarcoma patients were below 0.7 indicating limited predictive accuracy in this cohort, particularly when compared to Sarculator. Summary: Nomogram-based predictive models are valuable tools in clinical practice for rapidly assessing prognosis. They can streamline the decision-making process for adjuvant treatments and improve patient counselling especially in the treatment of rare and complicated tumor entities such as angiosarcomas.
Atrial Fibrillation and Heart Failure
Authors: Cismaru Gabriel , Negru Alina-Gabriela
Published: May 2024

Recent years have witnessed progress in the management of heart failure through the development of SGLT2 inhibitors and angiotensin receptor neprilysin inhibitors [...]
The Importance of In Vivo Reflectance Confocal Microscopy in a Case of Desmoplastic Melanoma
Authors: Cristescu Miruna Ioana , Popa Liliana Gabriela , Cozma Elena Codruta , Celarel Ana Maria , Popa Valentin Tudor , Lupu Mihai , Voiculescu Vlad Mihai
Published: May 2024

Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma.
The Utilization of the SaLux19-Based Loop-Mediated Isothermal Amplification (LAMP) Assay for the Rapid and Sensitive Identification of Minute Amounts of a Biological Specimen
Authors: Ruszova Ema , Vanek Daniel , Stühmer Walter , Khaznadar Ziad , Subhashini Nidhi
Published: May 2024

Our research has developed a highly sensitive and simple assay to detect small amounts of animal and human biological material in less than 40 min. The handheld SaLux19 device developed at the Max Planck Institute of Experimental Medicine in Göttingen, Germany, was used to validate our concept. The proposed system uses isothermal amplification of DNA in a rapid assay format. Our results show that the assay can detect Sus scrofa nucleic acids with very high sensitivity and specificity. This detection system has potential for forensic scenarios.
Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders
Authors: Balan Irina , Boero Giorgia , Chéry Samantha Lucenell , McFarland Minna H. , Lopez Alejandro G. , Morrow A. Leslie
Published: May 2024

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.
Application of Logistic Regression to Analyze The Economic Efficiency of Vehicle Operation in Terms of the Financial Security of Enterprises
Authors: Grzelak Malgorzata , Owczarek Paulina , Stoica Ramona-Monica , Voicu Daniela , Vilău Radu
Published: May 2024

Background: A measurable feature of the efficiency of vehicle use in transportation companies is the revenue from transport orders, which has a significant impact on their profitability. Therefore, it is important to skillfully analyze the parameters related to the operation of vehicles and their impact on the bottom line. Transportation companies, when managing their operations, take steps to reduce operating costs. The above makes a large number of studies available in the literature on the analysis of vehicle damage or wear of system components, as well as ways to predict them. However, there is a lack of studies treating the impact of the parameters of specific orders on economic efficiency, which is a research niche undertaken in the following study. Methods: The purpose of this article was to analyze the economic efficiency of vehicle operation in terms of the financial security of enterprises. The main research problem was formulated in the form of the question of how the various parameters of a transport order affect its profitability. During our study, critical analysis of the literature, mathematical modeling and inference were used. A detailed analysis of transport orders executed by SMEs (small and medium-sized enterprises), which are characterized by a fleet of light commercial vehicles with a capacity of up to 3.5 t, was carried out in the FMCG (Fast-Moving Consumer Good) industry in Poland in 2021–2022. Due to the binary variable form, a logistic regression model was elaborated. The estimated parameters of the model and the calculated odds ratios made it possible to assess the influence of the selected factors on the profitability of orders. Results: Among other things, it was shown that in the case of daily vehicle mileage, the odds quotient indicates that with each additional kilometer driven, the probability of profitability of an order increases by 1%. Taking into account the speed of travel, it is estimated that with an increase in its value by 1 km/h, the probability of profitability of an order decreases by 3%. On the other hand, an increase in cargo weight by 1 kg makes the probability of a profitable order increase by 9%. Conclusion: Through this study, the limited availability of low-cost analytical tools that can be applied during transportation fleet management in SME companies was confirmed, as was the use of simple and non-expansive mathematical models. At the same time, they are not “black boxes” and therefore enable drawing and implementing model conclusions into operations. The results obtained can help shape the overall strategy of companies in the area of vehicle operation and can support the decision-making process related to the management of subsequent orders, indicating those that will bring the highest profit. The above is very important for SME companies, which often operate on the verge of profitability.
Gauss’ Second Theorem for F12(1/2)-Series and Novel Harmonic Series Identities
Authors: Li Chunli , Chu Wenchang
Published: May 2024

Two summation theorems concerning the F12(1/2)-series due to Gauss and Bailey will be examined by employing the “coefficient extraction method”. Forty infinite series concerning harmonic numbers and binomial/multinomial coefficients will be evaluated in closed form, including eight conjectured ones made by Z.-W. Sun. The presented comprehensive coverage for the harmonic series of convergence rate “1/2” may serve as a reference source for readers.
Synchronization in a Three Level Network of All-to-All Periodically Forced Hodgkin–Huxley Reaction–Diffusion Equations
Authors: Ambrosio B. , Aziz-Alaoui M. A. , Oujbara A.
Published: May 2024

This article focuses on the analysis of dynamics emerging in a network of Hodgkin–Huxley reaction–diffusion equations. The network has three levels. The three neurons in level 1 receive a periodic input but do not receive inputs from other neurons. The three neurons in level 2 receive inputs from one specific neuron in level 1 and all neurons in level 3. The neurons in level 3 (all other neurons) receive inputs from all other neurons in levels 2 and 3. Furthermore, the right-hand side of pre-synaptic neurons is connected to the left-hand side of the post-synaptic neurons. The synchronization phenomenon is observed for neurons in level 3, even though the system is initiated with different functions. As far as we know, it is the first time that evidence of the synchronization phenomenon is provided for spatially extended Hodgkin–Huxley equations, which are periodically forced at three different sites and embedded in such a hierarchical network with space-dependent coupling interactions.
Lp-Norm for Compositional Data: Exploring the CoDa L1-Norm in Penalised Regression
Authors: Saperas-Riera Jordi , Mateu-Figueras Glòria , Martín-Fernández Josep Antoni
Published: May 2024

The Least Absolute Shrinkage and Selection Operator (LASSO) regression technique has proven to be a valuable tool for fitting and reducing linear models. The trend of applying LASSO to compositional data is growing, thereby expanding its applicability to diverse scientific domains. This paper aims to contribute to this evolving landscape by undertaking a comprehensive exploration of the L1-norm for the penalty term of a LASSO regression in a compositional context. This implies first introducing a rigorous definition of the compositional Lp-norm, as the particular geometric structure of the compositional sample space needs to be taken into account. The focus is subsequently extended to a meticulous data-driven analysis of the dimension reduction effects on linear models, providing valuable insights into the interplay between penalty term norms and model performance. An analysis of a microbial dataset illustrates the proposed approach.
Enhancing Portfolio Allocation: A Random Matrix Theory Perspective
Authors: Vanni Fabio , Hitaj Asmerilda , Mastrogiacomo Elisa
Published: May 2024

This paper explores the application of Random Matrix Theory (RMT) as a methodological enhancement for portfolio selection within financial markets. Traditional approaches to portfolio optimization often rely on historical estimates of correlation matrices, which are particularly susceptible to instabilities. To address this challenge, we combine a data preprocessing technique based on the Hilbert transformation of returns with RMT to refine the accuracy and robustness of correlation matrix estimation. By comparing empirical correlations with those generated through RMT, we reveal non-random properties and uncover underlying relationships within financial data. We then utilize this methodology to construct the correlation network dependence structure used in portfolio optimization. The empirical analysis presented in this paper validates the effectiveness of RMT in enhancing portfolio diversification and risk management strategies. This research contributes by offering investors and portfolio managers with methodological insights to construct portfolios that are more stable, robust, and diversified. At the same time, it advances our comprehension of the intricate statistical principles underlying multivariate financial data.
Investigation of the Leaching Kinetics of Zinc from Smithsonite in Ammonium Citrate Solution
Authors: Chen Huiqin , Wu Dandan , Wang Ziang
Published: May 2024

In this study, the response surface method is used to develop a model for analyzing and optimizing zinc leaching experiments. An investigation into the leaching kinetics of smithsonite in ammonium citrate solution is also conducted. A model of kinetics is studied in order to represent these effects. The experimental data show that an increase in the solution temperature, concentration, and stirring speed has a positive impact on the leaching rate, while an increase in the particle size has a negative impact on it. The optimal experimental conditions consist of a leaching temperature of 70 °C, ammonium citrate concentration of 5 mol/L, particle size of 38 µm, and rotational speed of 1000 rpm. Under these optimal conditions, the leaching rate of zinc from smithsonite is 83.51%. It is speculated that the kinetic model will change when the temperature is higher than 60 °C. When the temperature is lower than 60 °C, the leaching process is under the control of the shrinking core model of the surface chemical reactions. The calculated activation energy of the leaching reaction is equal to 42 kJ/mol. The model of the leaching process can be described by the following equation: 1−1−x1/3=k0⋅(C)0.6181⋅r0−0.5868⋅SS0.6901exp⁡−42/RT]t. This demonstrates that an ammonium citrate solution can be used in the leaching process of zinc in smithsonite as an effective and clean leaching agent.
Benchmarking L-PBF Systems for Die Production: Powder, Dimensional, Surface, Microstructural and Mechanical Characterisation
Authors: Costa Jose Manuel , Sequeiros Elsa Wellenkamp , Santos Ruben Filipe , Vieira Manuel Fernando
Published: May 2024

While conventional die manufacturing techniques often lead to limitations in production speed and design intricacy due to labour-intensive procedures like machining and casting, Additive Manufacturing (AM) emerges as a key player offering substantial potential for cost reduction and process improvement in mass production. This study benchmarks four leading Laser Powder Bed Fusion (L-PBF) systems for producing maraging steel (EN 1.2709) dies. Despite the shared material and technology, variations in dimensional accuracy, surface finish, and microstructure were observed among the maraging steel parts. SEM/EDS, EBSD, hardness testing, and dimensional analysis revealed system-specific performance differences. Additionally, select parts underwent heat treatment and tensile testing, demonstrating the impact of post-processing on mechanical properties. These results offer valuable guidance for industrial stakeholders considering AM, highlighting the importance of supplier selection and process optimisation for achieving consistent part quality and unlocking the full potential of AM technologies.
The Effect of Ultrafine-Grained (UFG) Structure Formed by Equal-Channel Angular Pressing in AA7075 on Wear and Friction in Sliding against Steel and Ceramic Counterbodies
Authors: Filippov Andrey V. , Tarasov Sergei Y. , Filippova Ekaterina O.
Published: May 2024

The mechanical characteristics and sliding friction behaviors of AA7075 samples were studied in regard to structural states formed in them by ECAP and depending on the ECAP pass number. In addition, the effect of a counterbody’s material on the tribological characteristics of the samples was investigated by the examples of AISI 52100 steel, alumina Al2O3 and silicon nitride Si3N4. Vibration acceleration and acoustic emission signals with parameters such as acoustic emission energy and median frequency were used for characterizing the sliding regimes. The structural state and mechanical properties of the ECAPed AA7075 samples significantly affected their wear behaviors in dry sliding. The counterbody material had a significant influence on the formation of a transfer layer and the subsurface deformation of samples. The dynamic behavior of the tribosystem was studied and the relationship between the sliding parameters, vibrometry and acoustic emission signals was established.
Long Short-Term Memory Parameter Optimization Based on Improved Sparrow Search Algorithm for Molten Iron Quality Prediction
Authors: Zhang Ziwen , Zhang Ruiyao , Zhou Ping
Published: May 2024

Blast furnace (BF) ironmaking is a key process in iron and steel production. Because BF ironmaking is a dynamic time series process, it is more appropriate to use a recurrent neural network for modeling. The long short-term memory (LSTM) network is commonly used to model time series data. However, its model performance and generalization ability heavily depend on the parameter configuration. Therefore, it is necessary to study parameter optimization for the LSTM model. The sparrow search algorithm (SSA) holds advantages over traditional optimization algorithms in several aspects, such as no need for prior knowledge, fewer parameters, fast convergence, and high scalability. However, the algorithm still faces some challenges, such as the tendency to become trapped in the local optimum and the imbalance between global search ability and local search ability. Therefore, on the basis of SSA, this study examined the Levy flight strategy, sine search strategy, and step size factor adjustment strategy to improve it. This algorithm, improved by three strategies, is called the improved sparrow search algorithm (ISSA). Then, the ISSA-LSTM model was established. Furthermore, considering the limitations of SSA in dealing with multi-objective problems, the fast non-dominated sorting genetic algorithm (NSGAII) was introduced, and the ISSA-NSGAII model was established. Finally, experimental validation was performed using real blast furnace operation data, which demonstrated the proposed algorithm’s superiority in parameter optimization for the LSTM model and prediction for real industrial data.
Study of Tensile and Compressive Behavior of ECO-Mg97Gd2Zn1 Alloys Containing Long-Period Stacking Ordered Phase with Lamellar Structure
Authors: Garcés Gerardo , Medina Judit , Pérez Pablo , Barea Rafael , Lim Hyunkyu , Kim Shae K. , Maawad Emad , Schell Norbert , Adeva Paloma
Published: May 2024

A suitable heat treatment in the Mg97Gd2Zn1 (at.%) alloy in the as-cast condition results, after extrusion at high temperature, in a two-phase lamellar microstructure consisting of magnesium grains with thin lamellar shape precipitates and long fibers of the 14H-Long-Period Stacking Ordered (LPSO) phase elongated in the extrusion direction. The magnesium matrix is not fully recrystallized and highly oriented coarse non-dynamically recrystallized (non-DRXed) grains (17% volume fraction) elongated along the extrusion direction remain in the material. The deformation mechanisms of the extruded alloy have been studied measuring the evolution of the internal strains during in situ tension and compression tests using synchrotron diffraction radiation. The data demonstrate that the macroscopic yield stress is governed by the activation of the basal slip system in the randomly oriented equiaxed dynamic recrystallized (DRXed) grains. Non-DRXed grains, due to their strong texture, are favored oriented for the activation of tensile twinning. However, the presence of lamellar-shape precipitates strongly delays the propagation of lenticular thin twins through these highly oriented grains and they have no effect on the onset of the plastic deformation. Therefore, the tension–compression asymmetry is low since the plasticity mechanism is independent of the stress mode.
Parametric Optimization of Friction Stir Welding of AA6061-T6 Samples Using the Copper Donor Stir-Assisted Material Method
Authors: Al-Allaq Aiman H. , Maniscalco Joseph , Bhukya Srinivasa Naik , Wu Zhenhua , Elmustafa Abdelmageed
Published: May 2024

This study presents an optimization of the process parameters for the effect of copper (Cu) donor material percentage on the friction stir welding (FSW) of AA6061-T6 alloy. Extensive factorial experiments were conducted to determine the significance of the rotational speed (ω), the transverse speed (v), the interface coefficient of friction (μ), and the Cu donor material percentage in the plunge, left, right, and downstream zones. Design Expert 13 software was used to identify the number of simulation experiments to be conducted using the Abaqus simulation software. From Design Expert 13, which is a thorough multi-objective optimization analysis software, we were able to identify ideal welding parameters such as a rotational speed of 1222 rpm, transverse speed of 1.1 mm/s, the coefficient of friction of 0.9, and a 19% donor material percentage for the plunge zone. Significant findings demonstrate that increasing the Cu donor material substantially reduced the temperature from 502 °C to 134 °C when the Cu content is increased from 0% to 50%. This integrated modeling and optimization approach provides a practical procedure to identify the best experimental parameters for the process and a new understanding to guide advances for high-quality FSW of aluminum alloys. This work offers a methodology for optimizing the FSW parameters aligned with multifaceted thermomechanical physics.
Dynamics of Serum Inflammatory Markers and Adipokines in Patients: Implications for Monitoring Abnormal Body Weight: Preliminary Research
Authors: Zimowska Malwina , Rolbiecka Marta , Antoniak-Pietrynczak Klaudia , Jaskulak Marta , Zorena Katarzyna
Published: May 2024

This study aimed to investigate the influence of abnormal body weight on inflammatory markers and adipokine levels across varied body mass index (BMI) categories. The cohort included 46 participants categorized into normal BMI (group I; n = 19), overweight (group II; n = 14), and obesity (group III; n = 13). Inflammatory markers (hsCRP and IL-6) and adipokines (Adiponectin, Leptin, Nesfatin-1, and Zinc-α2-glycoprotein) were assessed to discern effective indicators of inflammation in individuals with abnormal body weight. Additionally, the full lipid profile was also assessed (total cholesterol, triglycerides, LDL-C, HDL-C). The results indicated significant biochemical changes, particularly in IL-6 and Leptin levels, in participants with a BMI over 25. The levels of ZAG protein were negatively correlated with the HDL-C and LDC-L levels with statistical significance (Pearson: −0.57, p = 0.001, and Pearson: −0.41, p = 0.029, for HDL-C and LDL-C, respectively), suggesting that the level of ZAG is also inversely proportional to the amount of cholesterol. Statistical analyses revealed decreased Zinc-α2-glycoprotein (ZAG) levels and increased Adiponectin, Leptin, and IL-6 levels in individuals with abnormal body weight. Correlation analyses demonstrated a statistically significant upward trend for IL-6 (p = 0.0008) and Leptin (p = 0.00001), with a similar trend observed for hsCRP without statistical significance (p = 0.113). IL-6 levels in the overweight group were 158.71% higher than in the normal-weight group, while the obese group exhibited a 229.55% increase compared to the normal-weight group. No notable changes have been recorded for the levels of Nesfatin-1. Based on our results, we propose IL-6, Leptin, and ZAG as potential biomarkers for monitoring interventions and assessing patient conditions in those with abnormal BMIs. Further research with a larger patient cohort is warranted to validate these correlations in overweight and obese individuals.
Depth of Interbreed Difference in Postmortem Bovine Muscle Determined by CE-FT/MS and LC-FT/MS Metabolomics
Authors: Muroya Susumu , Horiuchi Yuta , Iguchi Kazuki , Higuchi Takuma , Sakamoto Shuji , Ojima Koichi , Matsukawa Kazutsugu
Published: May 2024

Japanese Brown (JBR) cattle have moderately marbled beef compared to the highly marbled beef of Japanese Black (JBL) cattle; however, their skeletal muscle properties remain poorly characterized. To unveil interbreed metabolic differences over the previous results, we explored the metabolome network changes before and after postmortem 7-day aging in the trapezius muscle of the two cattle breeds by employing a deep and high-coverage metabolomics approach. Using both capillary electrophoresis (CE) and ultra-high-performance liquid chromatography (UHPLC)–Fourier transform mass spectrometry (FT/MS), we detected 522 and 384 annotated peaks, respectively, across all muscle samples. The CE-based results showed that the cattle were clearly separated by breed and postmortem age in multivariate analyses. The metabolism related to glutathione, glycolysis, vitamin K, taurine, and arachidonic acid was enriched with differentially abundant metabolites in aged muscles, in addition to amino acid (AA) metabolisms. The LC-based results showed that the levels of bile-acid-related metabolites, such as tauroursodeoxycholic acid (TUDCA), were high in fresh JBR muscle and that acylcarnitines were enriched in aged JBR muscle, compared to JBL muscle. Postmortem aging resulted in an increase in fatty acids and a decrease in acylcarnitine in the muscles of both cattle breeds. In addition, metabolite set enrichment analysis revealed that JBR muscle was distinctive in metabolisms related to pyruvate, glycerolipid, cardiolipin, and mitochondrial energy production, whereas the metabolisms related to phosphatidylethanolamine, nucleotide triphosphate, and AAs were characteristic of JBL. This suggests that the interbreed differences in postmortem trapezius muscle are associated with carnitine/acylcarnitine transport, β-oxidation, tricarboxylic acid cycle, and mitochondrial membrane stability, in addition to energy substrate and AA metabolisms. These interbreed differences may characterize beef quality traits such as the flavor intensity and oxidative stability.
A Novel Low-Temperature Extrusion Method for the Fused Filament Fabrication of Fluoroelastomer Compounds
Authors: Periyasamy Mookkan , Campbell Ronald , Mead Joey M. , Kazmer David O. , Banerjee ShibShankar , Mubasshir AA , Phaen Leeda A. , Kodra Stiven
Published: May 2024

In this work, an additive manufacturing process for extruding fully compounded thermosetting elastomers based on fluorine-containing polymer compositions is reported. Additive manufacturing printers are designed with a dry ice container to precool filaments made from curable fluoroelastomer (FKM) and perfluoroelastomer (FFKM) compounds. A support tube guides the stiffened filament towards the printer nozzle. This support tube extends near the inlet to a printer nozzle. This approach allows low-modulus, uncured rubber filaments to be printed without buckling, a phenomenon common when 3D printing low-modulus elastomers via the fused deposition modeling (FDM) process. Modeling studies using thermal analyses data from a Dynamic Mechanical Analyzer (DMA) and a Differential Scanning Calorimeter (DSC) are used to calculate the Young’s modulus and buckling force, which helps us to select the appropriate applied pressure and the nozzle size for printing. Using this additive manufacturing (AM) method, the successful printing of FKM and FFKM compounds is demonstrated. This process can be used for the future manufacturing of seals or other parts from fluorine-containing polymers.
Long-Term Improvement in Cardiorespiratory Fitness Ameliorates Insulin Sensitivity beyond Changes in Visceral/Ectopic Fat among Men with Visceral Obesity
Authors: Murphy-Després Adrien , Chartrand Dominic J. , Lemieux Isabelle , Tremblay Angelo , Bergeron Jean , Poirier Paul , Alméras Natalie , Després Jean-Pierre
Published: May 2024

The SYNERGIE study documented the effects on cardiometabolic risk (CMR) indices of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by a 2-year maintenance period in men with visceral obesity. Improvements in CMR markers and a decrease in low-attenuation muscle (LAM) area were observed after 1 year. Despite a rebound in visceral adipose tissue (VAT) during the maintenance period, insulin resistance (IR) improved. We tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in IR. A health (n = 88; mean age 49.0 ± 8.2 years) and fitness (n = 72) evaluation was performed at 0, 1, and 3 years. Participants were classified into two groups based on their CRF response over the maintenance period (worsening: CRF− vs. maintenance/improvement: CRF+). During the maintenance period, changes in the psoas and core LAM areas correlated with changes in IR (r = 0.27; p < 0.05 and r = 0.34; p < 0.005) and changes in CRF (r = −0.31; p < 0.01 and r = −0.30; p < 0.05). IR improved in the CRF+ group (p < 0.05) but remained stable in the CRF− group. Men in the CRF+ group regained half of the changes in VAT volume and LAM at the psoas and mid-thigh compared to the CRF− group (p < 0.05). These results support the importance of targeting VAT and CRF/PA for the long-term management of CMR in men with visceral obesity.
The Tomato Variety Affects the Survival of Shigella flexneri 2a in Fruit Pericarp
Authors: Henriquez Tania , Guerra Simona , Nerini Marta , Purchase Diane , Marvasi Massimiliano
Published: May 2024

The presence of enteric pathogens in produce can serve as a significant means of transmitting infections to consumers. Notably, tomatoes, as a type of produce, have been implicated in outbreaks caused by various human pathogens, such as Salmonella enterica and pathogenic Escherichia coli. However, the survival characteristics of Shigella spp. in tomatoes have not been thoroughly investigated. In this study, we assess the survival of S. flexneri 2a in two distinct varieties of post-harvested tomatoes. S. flexneri 2a was used to inoculate both regular-sized Vine tomatoes and cherry-type Mini Plum tomatoes. Our findings reveal no significant difference in Shigella survival in the pericarp of both varieties on day 2 post-inoculation. However, a significant disparity emerges on day 6, where all recovered Shigella colonies exclusively belong to the Mini Plum variety, with none associated with the Vine type. When Shigella was inoculated into the locular cavity (deep inoculation), no significant difference between varieties was observed. Additionally, we investigate the potential role of the SRL pathogenicity island (SRL PAI) in the survival and fitness of S. flexneri 2a in post-harvested tomatoes. Our results indicate that while the SRL PAI is not linked to the survival of the strains in tomato, it does impact their fitness. These findings underscore the variability in Shigella strains’ survival capabilities depending on the tomato variety, highlighting the importance of understanding Shigella ecology beyond the human host and identifying molecular determinants influencing bacterial survival to mitigate the risk of future outbreaks. The significance of this data on Shigella persistence in fresh vegetables should not be underestimated, as even a small number of Shigella cells can pose a threat to the health of individuals.
Unveiling the Role of Tryptophan 2,3-Dioxygenase in the Angiogenic Process
Authors: Cecchi Marta , Anceschi Cecilia , Silvano Angela , Coniglio Maria Luisa , Chinnici Aurora , Magnelli Lucia , Lapucci Andrea , Laurenzana Anna , Parenti Astrid
Published: May 2024

Background: Indoleamine 2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO) are the two principals enzymes involved in the catabolization of tryptophan (Trp) into kynurenine (Kyn). Despite their well-established role in the immune escape, their involvement in angiogenesis remains uncertain. We aimed to characterize TDO and IDO1 in human umbilical venular endothelial cells (HUVECs) and human endothelial colony-forming cells (ECFCs). Methods: qRT-PCR and immunofluorescence were used for TDO and IDO1 expression while their activity was measured using ELISA assays. Cell proliferation was examined via MTT tests and in in vitro angiogenesis by capillary morphogenesis. Results: HUVECs and ECFCs expressed TDO and IDO1. Treatment with the selective TDO inhibitor 680C91 significantly impaired HUVEC proliferation and 3D-tube formation in response to VEGF-A, while IDO1 inhibition showed no effect. VEGF-induced mTor phosphorylation and Kyn production were hindered by 680C91. ECFC morphogenesis was also inhibited by 680C91. Co-culturing HUVECs with A375 induced TDO up-regulation in both cell types, whose inhibition reduced MMP9 activity and prevented c-Myc and E2f1 upregulation. Conclusions: HUVECs and ECFCs express the key enzymes of the kynurenine pathway. Significantly, TDO emerges as a pivotal player in in vitro proliferation and capillary morphogenesis, suggesting a potential pathophysiological role in angiogenesis beyond its well-known immunomodulatory effects.
From Eye Care to Hair Growth: Bimatoprost
Authors: Zeppieri Marco , Gagliano Caterina , Spadea Leopoldo , Salati Carlo , Chukwuyem Ekele Caleb , Enaholo Ehimare Samuel , D’Esposito Fabiana , Musa Mutali
Published: May 2024

Background: Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular hypertension. Its ability to reduce intraocular pressure has established it as a first-line treatment option, improving management and preventing vision loss. In dermatology, bimatoprost has shown promising results in the promotion of hair growth, particularly in the treatment of alopecia and hypotrichosis. Its mechanism of action, stimulating the hair cycle and prolonging the growth phase, has led to the development of bimatoprost-containing solutions for enhancing eyelash growth. Aim: The aim of our review is to provide a brief description, overview, and studies in the current literature regarding the versatile clinical use of bimatoprost in recent years. This can help clinicians determine the most suitable individualized therapy to meet the needs of each patient. Methods: Our methods involve a comprehensive review of the latest advancements reported in the literature in bimatoprost formulations, which range from traditional eye drops to sustained-release implants. These innovations offer extended drug delivery, enhance patient compliance, and minimize side effects. Results: The vast literature published on PubMed has confirmed the clinical usefulness of bimatoprost in lowering intraocular pressure and in managing patients with glaucoma. Numerous studies have shown promising results in dermatology and esthetics in promoting hair growth, particularly in treating alopecia and hypotrichosis. Its mechanism of action involves stimulating the hair cycle and prolonging the growth phase, leading to the development of solutions that enhance eyelash growth. The global use of bimatoprost has expanded significantly, with applications growing beyond its initial indications. Ongoing research is exploring its potential in glaucoma surgery, neuroprotection, and cosmetic procedures. Conclusions: Bimatoprost has shown immense potential for addressing a wide range of therapeutic needs through various formulations and advancements. Promising future perspectives include the exploration of novel delivery systems such as contact lenses and microneedles to further enhance drug efficacy and patient comfort. Ongoing research and future perspectives continue to shape its role in medicine, promising further advancements and improved patient outcomes.