bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Complex Strengthening on the Continuous Cooling Transformation Behavior of High-Strength Rebar
Authors: You Jingtian , Li Zhiying , Wang Jie , Li Changrong , Zeng Zeyun , Li Shiwang , Huang Sheng
Published: December 2022

The effects of niobium and composite strengthening on the phase transformation characteristics and precipitation behavior of continuous cooling transformation of high-strength rebar during thermal deformation and subsequent cooling were investigated. The results show that when the cooling rate was within 0.3–5 °C/s, ferrite transformation and pearlite transformation occurred in the experimental steels. The Nb content increased to 0.062 wt.%, and the starting temperature of the ferrite transformation decreased. Meanwhile, the ferrite phase transformation zone gradually expanded, and the pearlite phase transformation zone gradually narrowed with the increase in the cooling rate. When the cooling rate was 1 °C/s, bainite transformation began to occur, and the amount of transformation increased with the increase in the cooling rate. It was found that the main precipitates in the experimental steels were (Nb, Ti, V)C, with an average particle size of about 10–50 nm. When the Nb content was increased to 0.062 wt.% and the cooling rate was increased to 5 °C/s, the ferrite grain size was reduced from 19.5 to 7.5 μm, and the particle size of the precipitate (Nb, Ti, V)C could be effectively reduced. The strength of the steel was significantly improved, but the elongation of the steel was reduced. However, the comprehensive mechanical properties of 0.062 wt.% Nb experimental steel was significantly improved at a cooling rate of 5 °C/s.
Design of a Novel LLE for Energy Saving
Authors: Garcia Miguel , Gómez Fabio , Magadán Andrea , Arias Manuel , Martínez Eladio , Blanco Andrés
Published: December 2022

Powering lower limb assistance/augmentation systems throughout long time periods is one of the major challenges in such an area. Researchers have proposed many solutions to diminishing energy consumption in such systems, many of which rely on the user’s biomechanics, that is, the design is intended to take advantage of the user’s inertia to spare/store energy in some subphases of the walking cycle and use or release it in the subphases with the greatest energy requirement. We have approached this issue and developed a lower limb exoskeleton that would spare up to 47% of the energy required throughout the walking cycle. We have achieved this by adding a clutch at the hip to set it passive during the stance phase. Such a mechanism could be implemented in a wide range of lower limb exoskeletons with successful results.
Intelligent Prediction of Customer Churn with a Fused Attentional Deep Learning Model
Authors: Liu Yunjie , Shengdong Mu , Jijian Gu , Nedjah Nadia
Published: December 2022

In recent years, churn rates in industries such as finance have increased, and the cost of acquiring new users is more than five times the cost of retaining existing users. To improve the intelligent prediction accuracy of customer churn rate, artificial intelligence is gradually used. In this paper, the bidirectional long short-term memory convolutional neural network (BiLSTM-CNN) model is integrated with recurrent neural networks (RNNs) and convolutional neural networks (CNNs) in parallel, which well solves the defective problem that RNNs and CNNs run separately, and it also solves the problem that the output results of a long short-term memory network (LSTM) layer in a densely-connected LSTM-CNN (DLCNN) model will ignore some local information when input to the convolutional layer. In order to explore whether the attention bidirectional long short-term memory convolutional neural network (AttnBLSTM-CNN) model can perform better than BiLSTM-CNN, this paper uses bank data to compare the two models. The experimental results show that the accuracy of the AttnBiLSTM-CNN model is improved by 0.2%, the churn rate is improved by 1.3%, the F1 value is improved by 0.0102, and the AUC value is improved by 0.0103 compared with the BLSTM model. Therefore, introducing the attention mechanism into the BiLSTM-CNN model can further improve the performance of the model. The improvement of the accuracy of the user churn prediction model can warn of the possibility of user churn in advance and take effective measures in advance to prevent user churn and improve the core competitiveness of financial institutions.
Semantic Segmentation of UAV Images Based on Transformer Framework with Context Information
Authors: Kumar Satyawant , Kumar Abhishek , Lee Dong-Gyu
Published: December 2022

With the advances in Unmanned Aerial Vehicles (UAVs) technology, aerial images with huge variations in the appearance of objects and complex backgrounds have opened a new direction of work for researchers. The task of semantic segmentation becomes more challenging when capturing inherent features in the global and local context for UAV images. In this paper, we proposed a transformer-based encoder-decoder architecture to address this issue for the precise segmentation of UAV images. The inherent feature representation of the UAV images is exploited in the encoder network using a self-attention-based transformer framework to capture long-range global contextual information. A Token Spatial Information Fusion (TSIF) module is proposed to take advantage of a convolution mechanism that can capture local details. It fuses the local contextual details about the neighboring pixels with the encoder network and makes semantically rich feature representations. We proposed a decoder network that processes the output of the encoder network for the final semantic level prediction of each pixel. We demonstrate the effectiveness of this architecture on UAVid and Urban Drone datasets, where we achieved mIoU of 61.93% and 73.65%, respectively.
Privacy Protection Practice for Data Mining with Multiple Data Sources: An Example with Data Clustering
Authors: O’Shaughnessy Pauline , Lin Yan-Xia
Published: December 2022

In the age of data, data mining provides feasible tools with which to handle large datasets consisting of data from multiple sources. However, there is limited research on retrieving statistical information from data when data are confidential and cannot be shared directly. In this paper, we address this problem and propose a framework for performing data analysis using data from multiple sources without revealing true values for privacy purposes. The proposed framework includes three steps. First, data custodians individually mask data before publishing; then, the masked data collection is used to reconstruct the density function of the original dataset, from which resampled values are generated; last, existing data mining techniques are applied directly to the resampled data. This framework utilises the technique of reconstructing an original density function from noise-masked data using the moment-based density estimation method, which plays an essential role. Simulation studies show that the proposed framework performs well; analysis results from the resampled data are comparable to those of the original data when the density of the original data is estimated well. The proposed framework is demonstrated in data clustering analysis using the example of a real-life Australian soybean dataset. Results from the k-means algorithms with two and three fitted clusters are presented to show that cluster analysis using resampled data can well replicate that of the original data.
Sharp Estimates for Proximity of Geometric and Related Sums Distributions to Limit Laws
Authors: Bulinski Alexander , Slepov Nikolay
Published: December 2022

The convergence rate in the famous Rényi theorem is studied by means of the Stein method refinement. Namely, it is demonstrated that the new estimate of the convergence rate of the normalized geometric sums to exponential law involving the ideal probability metric of the second order is sharp. Some recent results concerning the convergence rates in Kolmogorov and Kantorovich metrics are extended as well. In contrast to many previous works, there are no assumptions that the summands of geometric sums are positive and have the same distribution. For the first time, an analogue of the Rényi theorem is established for the model of exchangeable random variables. Also within this model, a sharp estimate of convergence rate to a specified mixture of distributions is provided. The convergence rate of the appropriately normalized random sums of random summands to the generalized gamma distribution is estimated. Here, the number of summands follows the generalized negative binomial law. The sharp estimates of the proximity of random sums of random summands distributions to the limit law are established for independent summands and for the model of exchangeable ones. The inverse to the equilibrium transformation of the probability measures is introduced, and in this way a new approximation of the Pareto distributions by exponential laws is proposed. The integral probability metrics and the techniques of integration with respect to sign measures are essentially employed.
The Re-Localization of Proteins to or Away from Membranes as an Effective Strategy for Regulating Stress Tolerance in Plants
Authors: Ku Yee-Shan , Cheng Sau-Shan , Cheung Ming-Yan , Law Cheuk-Hin , Lam Hon-Ming
Published: December 2022

The membranes of plant cells are dynamic structures composed of phospholipids and proteins. Proteins harboring phospholipid-binding domains or lipid ligands can localize to membranes. Stress perception can alter the subcellular localization of these proteins dynamically, causing them to either associate with or detach from membranes. The mechanisms behind the re-localization involve changes in the lipidation state of the proteins and interactions with membrane-associated biomolecules. The functional significance of such re-localization includes the regulation of molecular transport, cell integrity, protein folding, signaling, and gene expression. In this review, proteins that re-localize to or away from membranes upon abiotic and biotic stresses will be discussed in terms of the mechanisms involved and the functional significance of their re-localization. Knowledge of the re-localization mechanisms will facilitate research on increasing plant stress adaptability, while the study on re-localization of proteins upon stresses will further our understanding of stress adaptation strategies in plants.
The Application of the Nanofiltration Membrane NF270 for Separation of Fermentation Broths
Authors: Tomczak Wirginia
Published: December 2022

The potential for nanofiltration (NF) in removing both relatively low molecular weight (MW) organic species and charged solutes from complex media is noteworthy. The main aim of the current work was to improve understanding of the separation mechanisms of fermentation broths components in the NF process. For this purpose, the experimental investigations were performed using the commercial polyamide NF270 membrane. The feed solution was ultrafiltered 1,3-propanediol (1,3-PD) broths. The separation results were analyzed and discussed in light of the detailed characteristics of both the membrane and the broth components. It has been noted that the membrane ensured the complete 1,3-PD permeability and significant rejection of some feed components. A thorough analysis showed that the retention of carboxylic acids was based on both the Donnan effect and sieve mechanism, according to the following order: succinic acid > lactic acid > acetic acid > formic acid. Indeed, acids retention increased with increasing charged acids ions valency, Stokes radius (rS) as well as MW, and decreasing diffusion coefficient (D). In turn, for ions, the following orders retention was determined: SO42− = PO43− > Cl− and Ca2+ > Na+ > NH4+ ~ K+. It indicated that the ions retention increased with increasing ions charge density, hydrated radius (rH), and hydration energy (Eh). It showed that the separation of the ions was based on the Donnan exclusion, sieving effect, and dielectric exclusion.
Preliminary Assessment of Asymmetric Triangular Riblet Microstructures for Drag Deduction and Fouling Resistance: Numerical Modeling, Fabrication, and Performance Evaluation
Authors: Hamilton Benjamin W. , Tutunea-Fatan Remus O. , Bordatchev Evgueni V.
Published: December 2022

Several species of plants and animals demonstrate an ability to resist the accumulation of contaminants natural to their environments. To explain this phenomenon, mechanisms that facilitate fouling resistance have to be deciphered. Along these lines, this study is focused on the correlation between drag reduction and fouling resistance for underwater surfaces. This was accomplished by means of a novel microtopography inspired by fish-scales and conceived as a series of asymmetric triangular microgrooves oriented in the spanwise direction. A parametric study involving Large Eddy simulations was carried out to determine the most effective dimensions of the riblets and the results obtained have indicated a 9.1% drag reduction with respect to a flat reference surface. Following this, functional samples were fabricated in acrylic by means of a multi-axis micromachining center and diamond tooling. Surface quality and form accuracy of the fabricated samples were assessed with an optical microscope and optical profilometer. Finally, the fouling resistance of the samples was assessed by subjecting them to a flow of contaminated water. The results demonstrate that a relationship exists between the relative size of the particle and the fouling resistance of the microstructured surface.
Diode Laser and Polyimide Tape Enables Cheap and Fast Fabrication of Flexible Microfluidic Sensing Devices
Authors: Thaweeskulchai Thana , Schulte Albert
Published: December 2022

Wearable devices are a new class of healthcare monitoring devices designed for use in close contact with the patient’s body. Such devices must be flexible to follow the contours of human anatomy. With numerous potential applications, a wide variety of flexible wearable devices have been created, taking various forms and functions. Therefore, different fabrication techniques and materials are employed, resulting in fragmentation of the list of equipment and materials needed to make different devices. This study attempted to simplify and streamline the fabrication process of all key components, including microfluidic chip and flexible electrode units. A combination of diode laser CNC machine and polyimide tape is used to fabricate flexible microfluidic chip and laser-induced graphene (LIG) electrodes, to create flexible microfluidic sensing devices. Laser ablation on polyimide tape can directly create microfluidic features on either PDMS substrates or LIG electrodes. The two components can be assembled to form a flexible microfluidic sensing device that can perform basic electrochemical analysis and conform to curved surfaces while undergoing microfluidic flow. This study has shown that simple, commonly available equipment and materials can be used to fabricate flexible microfluidic sensing devices quickly and easily, which is highly suitable for rapid prototyping of wearable devices.
Recent Trends and Opportunities for the Targeted Immuno-Nanomaterials for Cancer Theranostics Applications
Authors: John Clyde , Jain Kaahini , Masanam Hema Brindha , Narasimhan Ashwin Kumar , Natarajan Arutselvan
Published: December 2022

The targeted delivery of cancer immunotherapies has increased noticeably in recent years. Recent advancements in immunotherapy, particularly in blocking the immune checkpoints (ICs) axis, have shown favorable treatment outcomes for multiple types of cancer including melanoma and non-small-cell lung cancer (NSLC). Engineered micromachines, including microparticles, and nanoplatforms (organic and inorganic), functionalized with immune agonists can effectively deliver immune-targeting molecules to solid tumors. This review focuses on the nanomaterial-based strategies that have shown promise in identifying and targeting various immunological markers in the tumor microenvironment (TME) for cancer diagnosis and therapy. Nanomaterials-based cancer immunotherapy has improved treatment outcomes by triggering an immune response in the TME. Evaluating the expression levels of ICs in the TME also could potentially aid in diagnosing patients who would respond to IC blockade therapy. Detecting immunological checkpoints in the TME using noninvasive imaging systems via tailored nanosensors improves the identification of patient outcomes in immuno-oncology (IO). To enhance patient-specific analysis, lab-on-chip (LOC) technology is a rapid, cost-effective, and accurate way of recapitulating the TME. Such novel nanomaterial-based technologies have been of great interest for testing immunotherapies and assessing biomarkers. Finally, we provide a perspective on the developments in artificial intelligence tools to facilitate ICs-based nano theranostics toward cancer immunotherapy.
Hydrogen Sensor Based on NTC Thermistor with Pt-Loaded WO3/SiO2 Coating
Authors: Sun Changwei , Xu Ben , Li Ping
Published: December 2022

A novel hydrogen sensor based on a negative temperature coefficient (NTC) thermistor with Pt-loaded WO3/SiO2 coating is proposed and demonstrated experimentally. When the Pt-loaded WO3/SiO2 film is exposed to the mixture of air and H2, the exothermic reactions caused by hydrogen and WO3 with the cooperation of the Pt catalyst raise the local temperature of the NTC thermistor and lower its resistance. Hence, hydrogen concentration can be measured by monitoring the voltage across the NTC thermistor in a series circuit. The proposed device has a rapid response time, high sensitivity, and excellent repeatability to hydrogen as well as immunity to humidity, a compact size, a low manufacturing cost, and is easy to use.
Prediction of Dispersion Rate of Airborne Nanoparticles in a Gas-Liquid Dual-Microchannel Separated by a Porous Membrane: A Numerical Study
Authors: Sheidaei Zohreh , Akbarzadeh Pooria , Guiducci Carlotta , Kashaninejad Navid
Published: December 2022

Recently, there has been increasing attention toward inhaled nanoparticles (NPs) to develop inhalation therapies for diseases associated with the pulmonary system and investigate the toxic effects of hazardous environmental particles on human lung health. Taking advantage of microfluidic technology for cell culture applications, lung-on-a-chip devices with great potential in replicating the lung air–blood barrier (ABB) have opened new research insights in preclinical pathology and therapeutic studies associated with aerosol NPs. However, the air interface in such devices has been largely disregarded, leaving a gap in understanding the NPs’ dynamics in lung-on-a-chip devices. Here, we develop a numerical parametric study to provide insights into the dynamic behavior of the airborne NPs in a gas–liquid dual-channel lung-on-a-chip device with a porous membrane separating the channels. We develop a finite element multi-physics model to investigate particle tracing in both air and medium phases to replicate the in vivo conditions. Our model considers the impact of fluid flow and geometrical properties on the distribution, deposition, and translocation of NPs with diameters ranging from 10 nm to 900 nm. Our findings suggest that, compared to the aqueous solution of NPs, the aerosol injection of NPs offers more efficient deposition on the substrate of the air channel and higher translocation to the media channel. Comparative studies against accessible data, as well as an experimental study, verify the accuracy of the present numerical analysis. We propose a strategy to optimize the affecting parameters to control the injection and delivery of aerosol particles into the lung-on-chip device depending on the objectives of biomedical investigations and provide optimized values for some specific cases. Therefore, our study can assist scientists and researchers in complementing their experimental investigation in future preclinical studies on pulmonary pathology associated with inhaled hazardous and toxic environmental particles, as well as therapeutic studies for developing inhalation drug delivery.
Multiple Sources of Indosinian Granites and Constraints on the Tectonic Evolution of the Paleo-Tethys Ocean in East Kunlun Orogen
Authors: Chen Guochao , Pei Xianzhi , Li Ruibao , Li Zuochen , Chen Youxin , Liu Chengjun , Pei Lei
Published: December 2022

Numerous Indosinian granitoids occur in the East Kunlun Orogen (EKO). The Indosinian was a key transitional period associated with the evolution of the Paleo-Tethys Ocean. Here, we study the relationship between the petrogenesis of the granitoids and the regional tectonic setting based on a comprehensive analysis of the petrology, geochronology, and geochemistry of typical granitoids in the eastern part of the EKO. The Indosinian granitoid compositions are dominated by quartz diorites, granodiorites, monzogranites, porphyritic monzogranites, and syenogranites. Early Indosinian granitoids are large, granitic batholiths, while the middle and late Indosinian granitoids are smaller in size. From the early Indosinian to late Indosinian, the granitoids show a transition from a medium-K calc-alkaline to high-K calc-alkaline composition. They are enriched in light rare earth elements (LREEs) and large-ion lithophile elements (LILEs) and depleted in high-field-strength elements (HFSEs), especially for the Helegangxilikete and the Kekeealong plutons. The late Indosinian granitoids have relatively low Y and Yb contents, high Sr contents, and high La/Yb and Sr/Y ratios, which suggests adakitic affinity. The zircon saturation temperatures of the early Indosinian syenogranite and the Keri syenogranite are above 800 °C. The zircon saturation temperatures of other Indosinian granites (average 749 °C) are lower than those of the biotite and amphibole partial melting experiment. In the early Indosinian (255–240 Ma), numerous granitoids were the products of the partial melting of the juvenile lower crust by mafic magma underplating. This underplating is geodynamically related to the continuous subduction of a branch of Paleo-Tethys Ocean, with slab break-off, rapid upwelling, and mantle decompression. In the middle Indosinian (240–230 Ma), the compression that accompanied the continent–continent collision was not conducive to fluid activity, and hence, the formation of magma could be attributed to dehydration partial melting of muscovite, biotite, or amphibole. In the late Indosinian (230–200 Ma), the delamination of thickened crust would provide heat and channels for fluid migration, leading to a flare-up of the magmas. The composition and petrogenesis of the Indosinian granitoids in the eastern EKO are the result of processes associated with the subduction, collisional, and post-collisional stages, during the evolution of the Paleo-Tethys Ocean.
Mechanism and Application of Hydraulic Fracturing in the High-Level Thick and Hard Gangue Layer to Improve Top Coal Caving in Fully Mechanized Caving Mining of an Ultra-Thick Coal Seam
Authors: Luo Hongye , Liang Shun , Yao Qiangling , Hao Yisong , Li Xuehua , Wang Furong , Chen Xiaoyu , Yang Miao
Published: December 2022

The thick and hard gangue layer has long been one of the key obstacles affecting the coal recovery rate in the fully mechanized top-coal caving mining of ultra-thick coal seams, and it is also one key factor restricting the development of the technology used for such work. In this study, to improve the poor top coal cavability and low recovery rate in fully mechanized caving mining of ultra-thick coal seams containing thick and hard gangue layers, the fully mechanized caving mining of longwall working face 42,108 of the Qinggangping Coal Mine is the engineering setting. Then, through a combination of theoretical analysis, numerical simulation, and field practice, a mechanical model of the cantilever beam with uniform load for fracture of the gangue layer is developed. Next, the mechanical action mechanism and influence of the gangue layer and thickness on the fracture of the cantilever beam are analyzed, and a method of pre-fracturing and weakening high-level thick and hard gangue layers using hydraulic fracturing technology is proposed. Finally, using RFPA2D-flow numerical simulation, the key technical parameters of hydraulic fracturing in the working face are designed and applied to field practice. The results show the following: After the high-level thick and hard gangue layer is treated by hydraulic fracturing technology, the amount of fractured gangue behind the support increases, while that of big coal blocks decreases significantly, and the overall fragmentation of top coal is at a reasonable level. In addition, after taking hydraulic fracturing technical measures during the mining period of the working face, the average recovery rate of the working face is 86.6%. This is an increase of 6.5% over the previous area without hydraulic fracturing.
Electrical Contact Resistance of Large-Area Graphene on Pre-Patterned Cu and Au Electrodes
Authors: Blecha Tomáš , Vlčková Živcová Zuzana , Sonia Farjana J. , Mergl Martin , Volochanskyi Oleksandr , Bodnár Michal , Rous Pavel , Mizohata Kenichiro , Kalbáč Martin , Frank Otakar
Published: December 2022

Contact resistance between electrically connected parts of electronic elements can negatively affect their resulting properties and parameters. The contact resistance is influenced by the physicochemical properties of the connected elements and, in most cases, the lowest possible value is required. The issue of contact resistance is also addressed in connection with the increasingly frequently used carbon allotropes. This work aimed to determine the factors that influence contact resistance between graphene prepared by chemical vapour deposition and pre-patterned Cu and Au electrodes onto which graphene is subsequently transferred. It was found that electrode surface treatment methods affect the resistance between Cu and graphene, where contact resistance varied greatly, with an average of 1.25 ± 1.54 kΩ, whereas for the Au electrodes, the deposition techniques did not influence the resulting contact resistance, which decreased by almost two orders of magnitude compared with the Cu electrodes, to 0.03 ± 0.01 kΩ.
Isocaloric Diets with Different Protein-Carbohydrate Ratios: The Effect on Sleep, Melatonin Secretion and Subsequent Nutritional Response in Healthy Young Men
Authors: Saidi Oussama , Rochette Emmanuelle , Del Sordo Giovanna , Peyrel Paul , Salles Jérôme , Doré Eric , Merlin Etienne , Walrand Stéphane , Duché Pascale
Published: December 2022

This study aimed to determine the short-term effect of two isocaloric diets differing in the ratio of protein–carbohydrate on melatonin levels, sleep, and subsequent dietary intake and physical activity in healthy young men. Twenty-four healthy men took part in a crossover design including two sessions of three days on isocaloric diets whether high-protein, low-carbohydrate (HPLC) or low-protein, high-carbohydrate (LPHC) followed by 24-h free living assessments. Sleep was measured by ambulatory polysomnography pre-post-intervention. Melatonin levels were assessed on the third night of each session on eight-point salivary sampling. Physical activity was monitored by accelerometry. On day 4, participants reported their 24-h ad-libitum dietary intake. LPHC resulted in better sleep quality and increased secretion of melatonin compared to HPLC. A significant difference was noted in sleep efficiency (p < 0.05) between the two sessions. This was mainly explained by a difference in sleep onset latency (p < 0.01) which was decreased during LPHC (PRE: 15.8 ± 7.8 min, POST: 11.4 ± 4.5 min, p < 0.001). Differences were also noted in sleep staging including time spent on REM (p < 0.05) and N1 (p < 0.05). More importantly, REM latency (PRE: 97.2 ± 19.9 min, POST 112.0 ± 20.7 min, p < 0.001) and cortical arousals (PRE: 7.2 ± 3.9 event/h, POST 8.5 ± 3.3 event/h) increased in response to HPLC diet but not LPHC. On day 4, 24-h ad-libitum energy intake was higher following HPLC compared to LPHC (+64 kcal, p < 0.05) and explained by increased snacking behavior (p < 0.01) especially from carbohydrates (p < 0.05). Increased carbohydrates intake was associated with increased cortical arousals.
Omics as a Tool to Help Determine the Effectiveness of Supplements
Authors: Steg Anna , Oczkowicz Maria , Smołucha Grzegorz
Published: December 2022

There has been considerable interest in dietary supplements in the last two decades. Companies are releasing new specifics at an alarming pace, while dietary supplements are one of the less-studied substances released for public consumption. However, access to state-of-the-art and high-throughput techniques, such as the ones used in omics, make it possible to check the impact of a substance on human transcriptome or proteome and provide answers to whether its use is reasonable and beneficial. In this review, the main domains of omics are briefly introduced. The review focuses on the three most widely used omics techniques: NGS, LC-MS, NMR, and their usefulness in studying dietary supplements. Examples of studies are described for some of the most commonly supplemented substances, such as vitamins: D, E, A, and plant extracts: resveratrol, green tea, ginseng, and curcumin extract. Techniques used in omics have proven to be useful in studying dietary supplements. NGS techniques are helpful in identifying pathways that change upon supplementation and determining polymorphisms or conditions that qualify for the necessity of a given supplementation. LC-MS techniques are used to establish the serum content of supplemented a compound and its effects on metabolites. Both LC-MS and NMR help establish the actual composition of a compound, its primary and secondary metabolites, and its potential toxicity. Moreover, NMR techniques determine what conditions affect the effectiveness of supplementation.
Mediterranean Alcohol-Drinking Patterns and All-Cause Mortality in Women More Than 55 Years Old and Men More Than 50 Years Old in the “Seguimiento Universidad de Navarra” (SUN) Cohort
Authors: Barbería-Latasa María , Bes-Rastrollo Maira , Pérez-Araluce Rafael , Martínez-González Miguel Ángel , Gea Alfredo
Published: December 2022

Background: Most of the available epidemiological evidence on alcohol and chronic disease agrees on recommending alcohol abstention to young people, but some controversy exists about the most appropriate recommendation for alcohol abstention for people of older ages. A growing body of evidence suggests that the pattern of alcohol consumption is likely to be a strong effect modifier. The Mediterranean Alcohol Drinking Pattern (MADP) represents a score integrating several dimensions of drinking patterns (moderation, preference for red wine, drinking with meals, and avoiding binge drinking). Our aim was to clarify this issue and provide more precise recommendations on alcohol consumption. Methods: We prospectively followed-up 2226 participants (men older than 50 years and women older than 55 years at baseline) in the Seguimiento Universidad de Navarra (SUN) cohort. We classified participants into three categories of adherence to the MADP score (low, moderate, and high), and we added a fourth category for abstainers. Cox regression models estimated multivariable-adjusted hazard ratios (HR) of all-cause death and 95% confidence intervals (CI) using low MADP adherence as the reference category. Results: The strongest reduction in risk of mortality was observed for those with high adherence to the MADP, with an HR of 0.54 (95% CI: 0.37–0.80). The moderate adherence group (HR = 0.65, 95% CI: 0.44–0.96) and the abstention group (HR = 0.60, 95% CI: 0.36–0.98) also exhibited lower risks of mortality than the low MADP adherence group. Conclusions: based on the available evidence, a public health message can be provided to people older than 50 years as follows: among those who drink alcohol, high adherence to the MADP score could substantially reduce their risk of all-cause mortality.
Intermittent Fasting Alleviates Risk Markers in a Murine Model of Ulcerative Colitis by Modulating the Gut Microbiome and Metabolome
Authors: Wu Jingjing , Man Da , Shi Ding , Wu Wenrui , Wang Shuting , Wang Kaicen , Li Yating , Yang Liya , Bian Xiaoyuan , Wang Qiangqiang , Li Lanjuan
Published: December 2022

Clinical trials have demonstrated the health benefits of intermittent fasting (IF). However, the potential mechanism of IF in alleviating dextran sulfate sodium (DSS)-induced colitis is not fully understood. The present study was mainly designed to explore the dynamic changes in the gut microbiota and metabolome after short-term (2 weeks) or long-term (20 weeks) IF and therefore clarify the potential mechanisms by which IF ameliorates DSS-induced colitis in a murine model. Thirty-two C57BL/6 male mice were equally divided into four groups and underwent IF intervention for 2 weeks (SIF group, n = 8), 20 weeks (LIF group, n = 8), or were allowed free access to food for 2 weeks (SAL group, n = 8) or 20 weeks (LAL group, n = 8). The thirty-two C57BL/6 male mice were accepted for the diet intervention of 2 weeks of IF or fed ad libitum. Colitis was induced by drinking 2% DSS for 7 days. Our findings showed that short-term IF prominently elevates the abundance of Bacteroides, Muibaculum and Akkermansia (p < 0.001, p < 0.001, p < 0.001, respectively), and decreased the abundance of Ruminiclostridium (p < 0.05). Long-term IF, however, decreased the abundance of Akkermansia and obviously increased the abundance of Lactobacillus (p < 0.05, p < 0.001, respectively). Metabolites mainly associated with nucleoside, carbohydrate, amino acid, bile acid, fatty acid, polyol, steroid and amine metabolism were identified in the faeces using untargeted GC/MS. In particular, inosine was extremely enriched after short-term IF and long-term IF (p < 0.01, p < 0.01, respectively); butyrate, 2-methyl butyric acid and valeric acid were significantly decreased after short-term IF (p < 0.001, p < 0.001, p < 0.01, respectively); and 2-methyl butyric acid was significantly increased after long-term IF (p < 0.001). The abundance of lithocholic acid (LCA), one of the secondary bile acids, increased significantly after short-term and long-term IF based on UPLC–MS/MS (p < 0.001, p < 0.5, respectively). Of note, IF markedly mitigated DSS-induced acute colitis symptoms and down-regulated pro-inflammatory cytokines IL-1α, IL-6, keratinocyte-derived chemokine (KC) and G-CSF levels in the serum (p < 0.01, p < 0.001, p < 0.05, p < 0.001, respectively). Furthermore, a correlation analysis indicated that the disease activity index (DAI) score and serum levels of IL-1α, IL-6, KC, and G-CSF were negatively correlated with the relative abundance of Akkermansia and the faecal metabolites LCA and inosine. This study confirmed that IF altered microbiota and reprogramed metabolism, which was a promising development in the attempt to prevent DSS-induced colitis. Moreover, our findings provide new insights regarding the correlations among the mucosal barrier dysfunction, metabolome, and microbiome.
Dietary Patterns, Dietary Interventions, and Mammographic Breast Density: A Systematic Literature Review
Authors: Pastore Elisa , Caini Saverio , Bendinelli Benedetta , Palli Domenico , Ermini Ilaria , de Bonfioli Cavalcabo’ Nora , Assedi Melania , Ambrogetti Daniela , Fontana Miriam , Masala Giovanna
Published: December 2022

Background: Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD. Methods: We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD. Results: In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., “fruit-vegetable-cereal” and “salad-sauce-pasta/grains” patterns). Findings from intervention studies were in fair agreement with those from observational studies. Conclusions: While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD.
How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials
Authors: Kleinschmidt Alexander C. , Singh Ambrish , Hussain Salman , Lovell Gregory A. , Shee Anna Wong
Published: December 2022

Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA.
Injectable Nano Drug Delivery Systems for the Treatment of Breast Cancer
Authors: Kafle Urmila , Agrawal Satish , Dash Alekha K.
Published: December 2022

Breast cancer is the most diagnosed type of cancer, with 2.26 million cases and 685,000 deaths recorded in 2020. If left untreated, this deadly disease can metastasize to distant organs, which is the reason behind its incurability and related deaths. Currently, conventional therapies are used to treat breast cancer, but they have numerous shortcomings such as low bioavailability, short circulation time, and off-target toxicity. To address these challenges, nanomedicines are preferred and are being extensively investigated for breast cancer treatment. Nanomedicines are novel drug delivery systems that can improve drug stability, aqueous solubility, blood circulation time, controlled release, and targeted delivery at the tumoral site and enhance therapeutic safety and effectiveness. Nanoparticles (NPs) can be administered through different routes. Although the injectable route is less preferred than the oral route for drug administration, it has its advantages: it helps tailor drugs with targeted moiety, boosts payload, avoids first-pass metabolism, and improves the pharmacokinetic parameters of the active pharmaceutical ingredients. Targeted delivery of nanomedicine, closer to organelles such as the mitochondria and nuclei in breast cancer, reduces the dosage requirements and the toxic effects of chemotherapeutics. This review aims to provide the current status of the recent advances in various injectable nanomedicines for targeted treatment of breast cancer.
Development and Skin Penetration Pathway Evaluation Using Confocal Laser Scanning Microscopy of Microemulsions for Dermal Delivery Enhancement of Finasteride
Authors: Subongkot Thirapit , Charernsriwilaiwat Natthan , Chanasongkram Rattathammanoon , Rittem Kantawat , Ngawhirunpat Tanasait , Opanasopit Praneet
Published: December 2022

This study aimed to develop microemulsions using poloxamer 124 as a surfactant to improve the skin penetration of finasteride and to investigate the skin penetration pathways of these microemulsions by colocalization techniques using confocal laser scanning microscopy (CLSM). The prepared finasteride-loaded microemulsions had average particle sizes ranging from 80.09 to 136.97 nm with particle size distributions within acceptable ranges and exhibited negative surface charges. The obtained microemulsions could significantly increase the skin penetration of finasteride compared to a finasteride solution. According to the skin penetration pathway evaluation conducted with CLSM, the microemulsions were hair follicle-targeted formulations due to penetration via the transfollicular pathway as a major skin penetration pathway. Additionally, this study found that the microemulsions also penetrated via the intercluster pathway more than via the intercellular pathway and transcellular pathway. The intercluster pathway, intercellular pathway, and transcellular pathway were considered only minor pathways.
Total and Unbound Pharmacokinetics of Cefiderocol in Critically Ill Patients
Authors: Zahr Noël , Urien Saik , Llopis Benoit , Noé Gaëlle , Tissot Nadine , Bihan Kevin , Junot Helga , Marin Clémence , Mansour Bochra , Luyt Charles-Edouard , Bleibtreu Alexandre , Funck-Brentano Christian
Published: December 2022

Background: Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing strains. The pharmacokinetics of cefiderocol has been studied in healthy subjects and particularly in phase II and III studies. This retrospective study investigated intravenous cefiderocol population pharmacokinetics in adult patients treated by cefiderocol. Methods: We studied 55 consecutive patients hospitalized in an intensive care unit. Cefiderocol plasma samples were obtained on different occasions during treatment. Plasma concentration was assayed using mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2020R1. Results: A total of 205 plasma samples were obtained from 55 patients. Eighty percent of patients received cefiderocol for ventilator-associated pneumonia due to carbapenem-resistant Pseudomonas aeruginosa infection. Cefiderocol concentration time-courses were best fit to a two-compartment open model with first-order elimination. Elimination clearance was positively related to renal function (estimated by the CKD formula). Adding albumin plasma binding in the model significantly improved the model assuming a ~40% unbound drug fraction given a ~40 g/L albuminemia. The final model included CKD plus cefiderocol plasma binding effects. Fat-free mass was better than total body weight to influence, via the allometric rule, clearance and volume terms, but this effect was negligible. The final clearance based on free circulating drug (CLU) for a typical patient, CKD = 90, was 7.38 L/h [relative standard error, RSE, 22%] with a between-subject variability of 0.47 [RSE 10%] (exponential distribution). Conclusion: This study showed that albumin binding and CKD effects were significant predictors of unbound and total plasma cefiderocol concentrations. Our results indicate that individual adjustment of cefiderocol can be used to reach high minimum inhibitory concentrations based on an estimation of unbound drug concentration and optimize therapeutic efficacy.
Anti-Tumor Effects of Engineered VNP20009-Abvec-Igκ-mPD-1 Strain in Melanoma Mice via Combining the Oncolytic Therapy and Immunotherapy
Authors: Zhou De-Xi , Wang Xiao-He , Xu Xuan , Chen Wen-Jie , Wei Jing , Chen Ting-Tao , Wei Hong
Published: December 2022

Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors are the most promising treatments for malignant tumors currently, but the low response rate limits their further clinical utilization. To address this problem, our group constructed an engineered strain of VNP20009-Abvec-Igκ-mPD-1 [V-A-mPD-1 (mPD-1, murine PD-1)] to combine oncolytic bacterial therapy with immunotherapy. Further, we evaluated its growth performance and mPD-1 expression ability in vitro while establishing the melanoma mice model to explore its potential anti-cancer effects in tumor therapy. Our results indicated that the V-A-mPD-1 strain has superior growth performance and can invade B16F10 melanoma cells and express PD-1. In addition, in the melanoma mice model, we observed a marked reduction in tumor volume and the formation of a larger necrotic area. V-A-mPD-1 administration resulted in a high expression of mPD-1 at the tumor site, inhibiting tumor cell proliferation via the down-regulation of the expression of rat sarcoma (Ras), phosphorylated mitogen-activated protein kinase (p-MEK)/MEK, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK expression significantly inhibited tumor cell proliferation. Tumor cell apoptosis was promoted by down-regulating phosphoinositide 3 kinase (PI3K) and protein kinase B (AKT) signaling pathways, as evidenced by an increased Bcl-2-associated X protein/B cell lymphoma-2 (Bax/Bcl-2) expression ratio. Meanwhile, the expression levels of systemic inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were substantially reduced. In conclusion, our research demonstrated that V-A-mPD-1 has an excellent anti-tumor effect, prompting that the combined application of microbial therapy and immunotherapy is a feasible cancer treatment strategy.
Recent Advances in Metal–Organic-Framework-Based Nanocarriers for Controllable Drug Delivery and Release
Authors: Zong Ziao , Tian Guanghui , Wang Junli , Fan Chuanbin , Yang Fenglian , Guo Feng
Published: December 2022

Metal–organic frameworks (MOFs) have a good designability, a well-defined pore, stimulus responsiveness, a high surface area, and a controllable morphology. Up to now, various MOFs have been widely used as nanocarriers and have attracted lots of attention in the field of drug delivery and release because of their good biocompatibility and high-drug-loading capacity. Herein, we provide a comprehensive summary of MOF-based nanocarriers for drug delivery and release over the last five years. Meanwhile, some representative examples are highlighted in detail according to four categories, including the University of Oslo MOFs, Fe-MOFs, cyclodextrin MOFs, and other MOFs. Moreover, the opportunities and challenges of MOF-based smart delivery vehicles are discussed. We hope that this review will be helpful for researchers to understand the recent developments and challenges of MOF-based drug-delivery systems.