bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Magnetic Levitation Control Method under Elastic Track Conditions Based on Backstepping Method
Authors: Zhu Pengxiang , Zhang Te , Zhou Danfeng , Li Jie , Jin Yuxin , Li Qicai
Published: July 2024

The vehicle–guideway coupled self-excited vibration of maglev systems is a common control instability problem in maglev traffic while the train is suspended above flexible girders, and it seriously affects the suspension stability of maglev vehicles. In order to solve this problem, a nonlinear dynamic model of a single-point maglev system with elastic track is established in this paper, and a new and more stable adaptive backstepping control method combined with magnetic flux feedback is designed. In order to verify the control effect of the designed control method, a maglev vehicle–guideway coupled experimental platform with elastic track is built, and experimental verifications under rigid and elastic conditions are carried out. The results show that, compared with the state feedback controller based on the feedback linearization controller, the adaptive backstepping control law proposed in this paper can achieve stable suspension under extremely low track stiffness, and that it shows good stability and anti-interference abilities under elastic conditions. This work has an important meaning regarding its potential to benefit the advancement of commercial maglev lines, which may significantly enhance the stability of the maglev system and reduce the cost of guideway construction.
Numerical Solution to the Time-Fractional Burgers–Huxley Equation Involving the Mittag-Leffler Function
Authors: Hayat Afzaal Mubashir , Riaz Muhammad Bilal , Abbas Muhammad , Alosaimi Moataz , Jhangeer Adil , Nazir Tahir
Published: July 2024

Fractional differential equations play a significant role in various scientific and engineering disciplines, offering a more sophisticated framework for modeling complex behaviors and phenomena that involve multiple independent variables and non-integer-order derivatives. In the current research, an effective cubic B-spline collocation method is used to obtain the numerical solution of the nonlinear inhomogeneous time-fractional Burgers–Huxley equation. It is implemented with the help of a θ-weighted scheme to solve the proposed problem. The spatial derivative is interpolated using cubic B-spline functions, whereas the temporal derivative is discretized by the Atangana–Baleanu operator and finite difference scheme. The proposed approach is stable across each temporal direction as well as second-order convergent. The study investigates the convergence order, error norms, and graphical visualization of the solution for various values of the non-integer parameter. The efficacy of the technique is assessed by implementing it on three test examples and we find that it is more efficient than some existing methods in the literature. To our knowledge, no prior application of this approach has been made for the numerical solution of the given problem, making it a first in this regard.
The Assessment of the Overall Lifetime Performance Index of Chen Products with Multiple Components
Authors: Wu Shu-Fei , Huang Yu-Lun
Published: July 2024

Process capability indices are widely utilized to evaluate process performance and drive continuous improvements in quality and productivity. Among these indices, the the-larger-the-better lifetime performance index is particularly noteworthy. For products with multiple components, an overall lifetime performance index is used, since it is a monotonically increasing function of the overall conforming rate and the relationship with each individual lifetime performance index can be determined. For products with the lifetime of the ith component following the Chen distribution, we investigate the maximum likelihood estimator for the overall lifetime performance index and the individual lifetime performance index based on the progressive type I interval censoring sample. Their asymptotic distributions for all lifetime performance indices are also derived. Once the target level for the overall lifetime performance index is specified, the desired level of individual lifetime performance index can be specified. By using the maximum likelihood estimator as the test statistic, a testing procedure to test whether the overall lifetime performance index has reached the target level is developed. The power analysis of the testing procedure is shown with figures, and some findings are summarized. At last, we use one practical example with two components to demonstrate how to implement this testing algorithmic procedure to test if the overall production process has reached the pre-assigned target level.
Medial Rectus Disinsertion for the Management of Large-Angle Sensory Esotropia
Authors: Han So Young , Chun Bo Young , Lee Hye Jin , Kim Hyun Kyung , Kwon Mi Sun , Lee Ho Seok , Rhiu Soolienah
Published: July 2024

Background and Objectives: The aim of the report is to report the outcomes of the medial rectus (MR) disinsertion procedure for the management of large-angle esotropia (ET) patients. Materials and Methods: This is a retrospective case series of patients with large-angle ET who underwent an MR disinsertion procedure between March 2012 to April 2022. The procedure happened accidentally during muscle surgery. The demographic and clinical data, including sex, age, visual acuity, pre- and postoperative angle of strabismus, duction limitations, results of intraoperative forced duction tests, and follow-up duration were collected from medical records. Results: Five patients were enrolled in this study. The mean age was 62.2 ± 9.8 years, and the mean follow-up was 24.8 ± 8.7 months. The ET at the primary position of gaze was 92.0 ± 17.9 prism diopters (PD) before MR disinsertion and 38.0 ± 29.5 PD after MR disinsertion only. Abduction deficiency was −4 before after MR disinsertion, which improved to −1 at the last follow-up. Conclusions: The results of MR disinsertion were not as frustrating as anticipated. MR disinsertion may be considered in patients with large-angle sensory ET who refuse surgery on the opposite eye.
High Strain Rate Deformation Behavior of Gradient Rolling AZ31 Alloys
Authors: Li Yingjie , Yu Hui , Liu Chao , Liu Yu , Yu Wei , Xu Yuling , Jiang Binan , Shin Kwangseon , Yin Fuxing
Published: July 2024

A dynamic impact test was performed on as-rolled AZ31 alloys with gradient microstructure under various strains. The microstructural evolution and mechanical properties were systematically investigated. As the strain rate gradually increased, an increasing number of twins were formed, facilitating dynamic recrystallization (DRX), and the mechanical properties were also gradually improved. The microstructure became heterogeneous at higher strain rates, but the peak stress decreased. The impact process resulted in a significantly higher performance due to microstructural refinement, work hardening by dislocations, and precipitates. In addition, both the adiabatic shear band and the adjacent crack experienced a temperature rise that exceeded the recrystallization temperature of the alloys. This observation also explains the presence of ultrafine recrystallized grains within the adiabatic shear band and the appearance of molten metal around the crack.
A First-Principles Study of the Structural, Elastic, and Mechanical Characteristics of Mg2Ni Subjected to Pressure Conditions
Authors: Xiao Chuncai , Liu Lei , Liu Shihuan , Lai Zhangli , Liu Yuxin , Zeng Xianshi , Liao Luliang
Published: July 2024

This study employs first-principles calculations to examine structural, elastic, and mechanistic relationships of Mg2Ni alloys under varying conditions of pressure. The investigation encompasses Young’s modulus, bulk modulus, shear modulus, Poisson’s ratio, and anisotropy index, as well as sound velocity, Debye temperature, and related properties. Our findings indicate that the lattice parameters of Mg2Ni in its ground state are in agreement with values obtained experimentally and from the literature, confirming the reliability of the calculated results. Furthermore, a gradual decrease in the values of the lattice parameters a/a0 and c/c0 is observed with increasing pressure. Specifically, the values for C13 and C33 decrease at a hydrostatic pressure of 5 GPa, while C11 and C13 increase when the external hydrostatic pressure exceeds 5 GPa. All other elastic constants exhibit a consistent increasing trend with increasing pressure between 0 and 30 GPa, with C11 and C12 increasing at a faster rate than C44 and C66. In the 0–30 GPa pressure range, Mg2Ni satisfies the mechanical stability criterion, indicating its stable existence under these conditions. Additionally, the Poisson’s ratio of Mg2Ni consistently exceeds 0.26 over a range of pressures from 0 to 30 GPa, signifying ductility and demonstrating consistency with the value of B/G. The hardness of Mg2Ni increases within the pressure range of 0–5 GPa, but decreases above 5 GPa. Notably, the shear anisotropy of Mg2Ni exhibits greater significance than the compressive anisotropy, with its anisotropy intensifying under higher pressures. Both the sound anisotropy and the Debye temperature of Mg2Ni demonstrate an increasing trend with rising pressure.
Research on Blast Furnace Ingredient Optimization Based on Improved Grey Wolf Optimization Algorithm
Authors: Liu Ran , Gao Zi-Yang , Li Hong-Yang , Liu Xiao-Jie , Lv Qing
Published: July 2024

Blast furnace ironmaking plays an important role in modern industry and the development of the economy. A reasonable ingredient scheme is crucial for energy efficiency and emission reduction in blast furnace production. Determining the right blast furnace ingredients is a complicated process; therefore, this study examines the optimization of the ingredient ratio. In this paper a model of the blast furnace ingredients is established by considering cost of per ton iron, CO2 emissions, and the theoretical coke ratio as the objective functions; ingredient parameters, process parameters, main and by-product parameters as variables; and the blast furnace smelting theory and equilibrium equation as constraints. Then, the model is solved by using an improved grey wolf optimization algorithm and an improved multi-objective grey wolf optimization algorithm. Using the data collected from the steel mill, the conclusion is that multi-objective optimization can consider the indexes of each target, so that the values of all the targets are excellent; we also compared the multi-objective solution results with the original production scheme of the steel mill, and we found that using the blast furnace ingredient scheme optimized in this study can reduce the cost of iron per ton, CO2 emissions per ton, and the theoretical coke ratio in blast furnace production by 350 CNY/t, 1000 kg/t, and 20 kg/t, respectively, compared with the original production plan. Thus, steel mill decision makers can choose the blast furnace ingredients according to different business strategies and the actual needs of steel mills can be better met.
Electro-Osmotic Flow and Mass Transfer through a Rough Microchannel with a Modulated Charged Surface
Authors: Qing Yun , Wang Jiaqi , Li Fengqin
Published: July 2024

In this paper, we investigate the electro-osmotic flow (EOF) and mass transfer of a Newtonian fluid propelled by a pressure gradient and alternating current (AC) electric field in a parallel microchannel with sinusoidal roughness and modulated charged surfaces. The two-wall roughness is described by in-phase or out-of-phase sine functions with a small amplitude δ. By employing the method of perturbation expansion, the semi-analytical solutions of the Poisson–Boltzmann (P–B) equation based on the Debye–Hückel approximation and the modified Navier–Stokes (N–S) equation are obtained. The numerical solution of the concentration equation is obtained by the finite difference method. The effects of sinusoidal roughness, modulated charged surface, and the AC electric field on the potential field, velocity field, and concentration field are discussed. Under the influence of the modulated charged surface and sinusoidal roughness, vortices are generated. The velocity oscillates due to the effect of the AC electric field. The results indicate that solute diffusion becomes enhanced when the oscillation Reynolds number is below a specific critical value, and it slows down when the oscillation Reynolds number exceeds this critical value.
DEMIGOD: A Low-Cost Microcontroller-Based Closed-Loop System Integrating Nanoengineered Sweat-Based Glucose Monitoring and Controlled Transdermal Nanoemulsion Release of Hypoglycemic Treatment with a Software Application for Noninvasive Personalized Diabetes Care
Authors: Fiska Vasiliki , Papanikolaou Eirini , Patila Michaela , Prodromidis Mamas I. , Trachioti Maria G. , Tzianni Eleni I. , Spyrou Konstantinos , Angelidis Pantelis , Tsipouras Markos G.
Published: July 2024

This study endeavored to design and develop an innovative closed-loop diagnostic and therapeutic system with the following objectives: (a) the noninvasive detection of glucose concentration in sweat utilizing nanonengineered screen-printed biosensors; (b) the management of measured data through a specialized computer system comprising both hardware and software components, thereby enabling the precise control of therapeutic responses via a patch-based nanomedicine delivery system. This initiative addresses the significant challenges inherent in the management of diabetes mellitus, including the imperative need for glucose-level monitoring to optimize glycemic control. Leveraging chronoamperometric results as a foundational dataset and the in vivo hypoglycemic activity of nanoemulsion formulations, this research underscores the efficacy and accuracy of glucose concentration estimation, decision-making mechanism responses, and transdermal hypoglycemic treatment effects, within the proposed system.
Statics Performance and Heat Dissipation Evaluation of Lattice Structures Prepared by Laser Powder Bed Fusion
Authors: Bai Jingfei , Zhang Can , Li Ziche , Liao Ruobing , Men Zhengxing , Wang Liang , Ji Chen , Li Kun
Published: July 2024

This paper address the performance optimization of the battery heat sink module by analyzing the lattice structure of the battery heat sink module through in-depth modeling and simulation, and combining the laser powder bed fusion (LPBF)-forming technology with mechanical and corrosion resistance experiments for a comprehensive study. It is found that the introduction of the lattice skeleton significantly improves the thermal conductivity of the phase change material (PCM), realizing the efficient distribution and fast transfer of heat in the system. At the same time, the lattice skeleton makes the heat distribution in the heat exchanger more uniform, improves the utilization rate of the PCM, and helps to maintain the stability of the cell temperature. In addition, the melting of PCM in the lattice heat exchanger is more uniform, thus maximizing its latent heat capacity. In summary, by optimizing the lattice structure and introducing the lattice skeleton, this study successfully improves the performance of the battery heat dissipation system, which provides a strong guarantee for the high efficiency and stable operation of the battery, and provides new ideas and references for the development of the battery heat dissipation technology.
Optical Halo: A Proof of Concept for a New Broadband Microrheology Tool
Authors: Ramírez Jorge , Gibson Graham M. , Tassieri Manlio
Published: July 2024

Microrheology, the study of material flow at micron scales, has advanced significantly since Robert Brown’s discovery of Brownian motion in 1827. Mason and Weitz’s seminal work in 1995 established the foundation for microrheology techniques, enabling the measurement of viscoelastic properties of complex fluids using light-scattering particles. However, existing techniques face limitations in exploring very slow dynamics, crucial for understanding biological systems. Here, we present a proof of concept for a novel microrheology technique called “Optical Halo”, which utilises a ring-shaped Bessel beam created by optical tweezers to overcome existing limitations. Through numerical simulations and theoretical analysis, we demonstrate the efficacy of the Optical Halo in probing viscoelastic properties across a wide frequency range, including low-frequency regimes inaccessible to conventional methods. This innovative approach holds promise for elucidating the mechanical behaviour of complex biological fluids.
Synthesis of Mesoporous Silica Sol with Low Refractive Properties for Increasing Transmittance
Authors: Ko Han-San , Kang Misun , Lee Jong-tak , Bae Jae Young
Published: July 2024

Currently, coating with anti-reflective materials is an attractive approach to improve the quality of screen-based displays. In this study, mesoporous silica particles were systematically synthesized as a function of surfactant (i.e., CTAC-cetyltrimethylammonium chloride) concentration to serve as main coating fillers possessing low refractive indices. Precisely changing the amount of the CTAC surfactant, silica sol with an average diameter of 50 nm exhibits distinctively different specific surface areas, pore size, and pore volume. Prior to the preparation of final coating solutions containing these silica particle fillers, the percentage of solid content was optimized on a glass slide. The use of 50 wt% solid content exhibited the highest transmittance of light. Among various content levels of silica sol, the use of 3.5 wt% of silica particles in the solid content displayed the highest transmittance (i.e., best anti-reflectiveness). Under the almost identical coating layers prepared with the fixed amount of silica particles possessing different surface areas, pore size, and pore volume, it appears that the largest pore volume played the most important role in improving the anti-reflective properties. Experimentally understanding the key feature of low-refractive filler materials under the optimized conditions could provide a clear view to develop highly effective anti-reflective materials for various display applications.
Lacticaseibacillus casei IB1 Alleviates DSS-Induced Inflammatory Bowel Disease by Regulating the Microbiota and Restoring the Intestinal Epithelial Barrier
Authors: Lao Jianlong , Yan Shuping , Yong Yanhong , Li Yin , Wen Zhaohai , Zhang Xiaoyong , Ju Xianghong , Li Youquan
Published: July 2024

Inflammatory bowel disease (IBD) is becoming an increasingly serious health problem in humans and animals. Probiotics can inhibit the development of IBD. Due to the specificity of the strains, the function and mechanism of action of different strains are still unclear. Here, a DSS-induced colitis mouse model was utilized to investigate the ability and mechanism by which Lacticaseibacillus casei IB1 alleviates colitis. Treatment with L. casei IB1 improved DSS-induced colitis in mice, as indicated by increased body weight, colon length, and goblet cell numbers and decreased disease activity index (DAI), proinflammatory factor (TNF-α, IL-1β, and IL-6) levels, and histopathological scores after intake of IB1. IB1 supplementation also improved the expression of tight junction proteins and inhibited the activation of the MAPK and NF-κB signaling pathways to alleviate intestinal inflammation. In addition, IB1 rebalanced the intestinal microbial composition of colitis mice by increasing the abundance of Faecalibaculum and Alistipes and decreasing the abundance of Bacteroides and Escherichia_Shigella. In summary, L. casei IB1 showed great potential for relieving colitis by regulating the microbiota and restoring the epithelial barrier. It can be used as a potential probiotic for the prevention and treatment of UC in the future.
Effects of PEF on Cell and Transcriptomic of Escherichia coli
Authors: Kuang Jinyan , Lin Ying , Wang Li , Yan Zikang , Wei Jinmei , Du Jin , Li Zongjun
Published: July 2024

Pulsed electric field (PEF) is an up-to-date non-thermal processing technology with a wide range of applications in the food industry. The inactivation effect of PEF on Escherichia coli was different under different conditions. The E. coli inactivated number was 1.13 ± 0.01 lg CFU/mL when PEF was treated for 60 min and treated with 0.24 kV/cm. The treatment times were found to be positively correlated with the inactivation effect of PEF, and the number of E. coli was reduced by 3.09 ± 0.01 lg CFU/mL after 100 min of treatment. The inactivation assays showed that E. coli was inactivated at electrical intensity (0.24 kV/cm) within 100 min, providing an effective inactivating outcome for Gram-negative bacteria. The purpose of this work was to investigate the cellular level (morphological destruction, intracellular macromolecule damage, intracellular enzyme inactivation) as well as the molecular level via transcriptome analysis. Field Emission Scanning Electron Microscopy (TFESEM) and Transmission Electron Microscope (TEM) results demonstrated that cell permeability was disrupted after PEF treatment. Entocytes, including proteins and DNA, were markedly reduced after PEF treatment. In addition, the activities of Pyruvate Kinase (PK), Succinate Dehydrogenase (SDH), and Adenosine Triphosphatase (ATPase) were inhibited remarkably for PEF-treated samples. Transcriptome sequencing results showed that differentially expressed genes (DEGs) related to the biosynthesis of the cell membrane, DNA replication and repair, energy metabolism, and mobility were significantly affected. In conclusion, membrane damage, energy metabolism disruption, and other pathways are important mechanisms of PEF’s inhibitory effect on E. coli.
Heterologous Expression and Biochemical Characterization of a Novel Lytic Polysaccharide Monooxygenase from Chitinilyticum aquatile CSC-1
Authors: Shao Xuezhi , Fang Hongliang , Li Tao , Yang Liyan , Yang Dengfeng , Pan Lixia
Published: July 2024

Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that catalyze the oxidative cleavage of recalcitrant polysaccharides. There are limited reports on LPMOs capable of concurrently catalyzing the oxidative cleavage of both cellulose and chitin. In this study, we identified and cloned a novel LPMO from the newly isolated bacterium Chitinilyticum aquatile CSC-1, designated as CaLPMO10. When using 2, 6-dimethylphenol (2, 6-DMP) as the substrate, CaLPMO10 exhibited optimal activity at 50 °C and pH 8, demonstrating good temperature stability at 30 °C. Even after a 6 h incubation at pH 8 and 30 °C, CaLPMO10 retained approximately 83.03 ± 1.25% residual enzyme activity. Most metal ions were found to enhance the enzyme activity of CaLPMO10, with ascorbic acid identified as the optimal reducing agent. Mass spectrometry analysis indicated that CaLPMO10 displayed oxidative activity towards both chitin and cellulose, identifying it as a C1/C4-oxidized LPMO. CaLPMO10 shows promise as a key enzyme for the efficient utilization of biomass resources in future applications.
The Impact of Culture Negativity on the Outcomes of Revision Total Knee Arthroplasty for Chronic PJI
Authors: Ronan Emily M. , Ruff Garrett , Ashkenazi Itay , Raymond Hayley , Cardillo Casey , Villa Jordan C. , Schwarzkopf Ran , Aggarwal Vinay K.
Published: July 2024

Culture-positive (CP) and culture-negative (CN) periprosthetic joint infections (PJI) remain a crucial area of research; however, current studies comparing these infections rely on unstandardized outcome reporting tools. Our study aimed to compare the outcomes of two-stage revision of CP and CN PJI using the standardized Musculoskeletal Infection Society (MSIS) outcome reporting tool. We retrospectively reviewed 138 patients who were diagnosed with PJI and indicated for two-stage revision total knee arthroplasty (rTKA). The majority of patients in both CP and CN cohorts achieved infection control without the need for reoperation (54.1% and 62.5%, respectively). There was a significant difference in the overall distribution of MSIS outcomes (p = 0.043), with a significantly greater rate of CN patients falling into Tier 1 (infection control without the use of suppressive antibiotics) (52.5% versus 29.6%, p = 0.011). There was also a significant difference in the distribution of septic versus aseptic reoperations after 2nd stage (p = 0.013), with more CP reoperations being septic and more CN reoperations being aseptic. The duration from first to second stage was significantly shorter in the CN cohort (p = 0.002). While overall infection control was similar between cohorts, these data suggest that the outcomes of two-stage rTKA are favorable in cases of CN PJI.
Effects of Lipoproteins on Metabolic Health
Authors: Albitar Obaida , D’Souza Crystal M. , Adeghate Ernest A.
Published: July 2024

Lipids are primarily transported in the bloodstream by lipoproteins, which are macromolecules of lipids and conjugated proteins also known as apolipoproteins. The processes of lipoprotein assembly, secretion, transportation, modification, and clearance are crucial components of maintaining a healthy lipid metabolism. Disruption in any of these steps results in pathophysiological abnormalities such as dyslipidemia, obesity, insulin resistance, inflammation, atherosclerosis, peripheral artery disease, and cardiovascular diseases. By studying these genetic mutations, researchers can gain valuable insights into the underlying mechanisms that govern the relationship between protein structure and its physiological role. These lipoproteins, including HDL, LDL, lipoprotein(a), and VLDL, mainly serve the purpose of transporting lipids between tissues and organs. However, studies have provided evidence that apo(a) also possesses protective properties against pathogens. In the future, the field of study will be significantly influenced by the integration of recombinant DNA technology and human site-specific mutagenesis for treating hereditary disorders. Several medications are available for the treatment of dyslipoproteinemia. These include statins, fibrates, ezetimibe, niacin, PCSK9 inhibitors, evinacumab, DPP 4 inhibitors, glucagon-like peptide-1 receptor agonists GLP1RAs, GLP-1, and GIP dual receptor agonists, in addition to SGLT2 inhibitors. This current review article exhibits, for the first time, a comprehensive reflection of the available body of publications concerning the impact of lipoproteins on metabolic well-being across various pathological states.
Exploring the Association between Mediterranean Diet Adherence and Arterial Stiffness in Healthy Adults: Findings from the EvasCu Study
Authors: Otero-Luis Iris , Saz-Lara Alicia , Moreno-Herráiz Nerea , Lever-Megina Carla Geovanna , Bizzozero-Peroni Bruno , Martínez-Ortega Isabel Antonia , Varga-Cirila Rebeca , Cavero-Redondo Iván
Published: July 2024

(1) Background: Previous evidence has indicated a connection between a Mediterranean diet and cardiovascular disease. However, evidence for subclinical markers of cardiovascular disease, such as arterial stiffness, is limited. Therefore, the aim of this study was to assess the associations between adherence to the Mediterranean diet (MD), as assessed by the MEDAS-14 questionnaire, and arterial stiffness, as assessed by aortic pulse wave velocity, in healthy adults and according to sex. (2) A cross-sectional study including 386 healthy participants was performed in the EVasCu study. Adjusted and unadjusted differences in adherence to the MD and arterial stiffness were determined using Student’s t test and ANCOVA for the total sample and according to sex. (3) Results: Our results showed that individuals with a high adherence to the MD had a greater arterial stiffness, both in the total sample and in females, although this difference was not significant after adjusting for possible confounding variables, such as age. (4) Conclusions: Our findings indicated that, in the unadjusted analyses, healthy subjects with a high adherence to the MD showed a greater arterial stiffness. When these analyses were adjusted, no significant differences were shown in a-PWv according to the categories of MD adherence.
Poor Adherence to the Mediterranean Diet and Sleep Disturbances Are Associated with Migraine Chronification and Disability among an Adult Population in the Lazio Region, Italy
Authors: Bovenzi Roberta , Noce Annalisa , Conti Matteo , Di Lauro Manuela , Chiaramonte Barbara , Della Morte David , Stefani Alessandro , De Lorenzo Antonino , Mercuri Nicola Biagio , Albanese Maria
Published: July 2024

Lifestyle factors, such as diet and sleep quality, are receiving increasing interest as accessible therapeutic approaches to migraine. The Mediterranean diet (MD) has shown clear benefits in cardiovascular and metabolic diseases, as well as in sleep patterns. Here, our objective was to identify the impact of adherence to the MD and other lifestyle factors on the clinical burden of migraine. For this purpose, we enrolled 170 migraine patients and 100 controls, assessing the clinical disability of headache using standardized clinical scales (HIT-6 and MIDAS) in the migraineur cohort and lifestyle patterns in both groups through the PREDIMED score for MD adherence, the IPAQ scale for physical activity, and BMI. Subjects were also screened for sleep–wake disturbances based on the Pittsburgh Sleep Quality Index (PSQI). We found that migraine patients had lower adherence to the MD compared to the controls and that the HIT-6 scale had a significant negative relationship with MD adherence in patients with high-frequency episodic and chronic migraine. Additionally, in the same migraine patients, the presence of sleep–wake disturbances was correlated with greater migraine disability as assessed by the MIDAS score. In conclusion, this study found that among different lifestyle factors, poor adherence to the MD and the presence of sleep–wake disturbances were closely associated with migraine disability and chronification.
Leukotoxin A Production and Release by JP2 and Non-JP2 Genotype Aggregatibacter actinomycetemcomitans in Relation to Culture Conditions
Authors: Kalfas Sotirios , Pour Zahra Khayyat , Claesson Rolf , Johansson Anders
Published: July 2024

Aggressive forms of periodontitis, especially in young patients, are often associated with an increased proportion of the Gram-negative bacterium Aggregatibacter actinomycetemcomitans of the microbiota of the affected periodontal sites. One of the virulence factors of A. actinomycetemcomitans is a leukotoxin (LtxA) that induces a pro-inflammatory cell death process in leukocytes. A. actinomycetemcomitans exhibits a large genetic diversity and different genotypes vary in LtxA production capacity. The genotype JP2 is a heavy LtxA producer due to a 530-base pair deletion in the promoter for the toxin genes, and this trait has been associated with an increased pathogenic potential. The present study focused on the production and release of LtxA by different A. actinomycetemcomitans genotypes and serotypes under various growth conditions. Four different strains of this bacterium were cultured in two different culture broths, and the amount of LtxA bound to the bacterial surface or released into the broths was determined. The cultures were examined during the logarithmic and the early stationary phases of growth. The JP2 genotype exhibited the highest LtxA production among the strains tested, and production was not affected by the growth phase. The opposite was observed with the other strains. The composition of the culture broth had no effect on the growth pattern of the tested strains. However, the abundant release of LtxA from the bacterial surface into the culture broth was found in the presence of horse serum. Besides confirming the enhanced leucotoxicity of the JP2 genotype, the study provides new data on LtxA production in the logarithmic and stationary phases of growth and the effect of media composition on the release of the toxin from the bacterial membrane.
2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation
Authors: Lorca Marcos , Muscia Gisela C. , Pérez-Benavente Susana , Bautista José M. , Acosta Alison , González Cesar , Sabadini Gianfranco , Mella Jaime , Asís Silvia E. , Mellado Marco
Published: July 2024

Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.
Metformin-Associated Gastrointestinal Adverse Events Are Reduced by Probiotics: A Meta-Analysis
Authors: Szymczak-Pajor Izabela , Drzewoski Józef , Wenclewska Sylwia , Śliwińska Agnieszka
Published: July 2024

Metformin, one of the most frequently used oral glucose-lowering drugs (GLDs), is associated with the occurrence of gastrointestinal (GI) adverse events in approximately 20% of users. These unwanted actions result in non-compliance or even discontinuation of metformin therapy. The aim of the presented meta-analysis was to determine whether adding a drug from the group of sulfonylureas, glitazones, DPP-IV inhibitors, or probiotics to metformin monotherapy may affect the risk of GI side effects. The material for this meta-analysis comprised data from 26 randomized controlled clinical trials (RCTs) published in English. This meta-analysis included 41,048 patients. The PubMed, Cochrane Library, and Clinical Trials databases were thoroughly searched to find relevant RCTs. The Population, Intervention, Comparison, Outcomes, and Study Type (PICOT) structure was used to formulate study selection criteria and the research question. Cochrane Review Manager Software 5.4 was used to carry out analysis of collected data. The results were presented as relative risk (RR) and 95% confidence interval (95% CI) for each group, and p < 0.05 was considered as statistically significant. As expected from clinical practice, metformin was associated with a markedly increased risk of abdominal pain, nausea, and vomiting compared to placebo. In comparison to other GLDs, taking metformin was related to an elevated risk of diarrhea and abdominal pain and to a lowered risk of vomiting and bloating. In turn, adding other GLDs to metformin treatment was associated with an elevated risk of nausea and vomiting than treatment with metformin in monotherapy. However, adding probiotics to metformin therapy was related to a decreased risk of diarrhea, bloating, and constipation. The obtained results demonstrate that the combination of metformin with other GLDs may elevate the risk of nausea and vomiting, whereas combination with probiotics decreases the risk of diarrhea, bloating, and constipation. Thus, the results of our meta-analysis suggest that probiotics may reduce the risk of some GI side effects in people with type 2 diabetes mellitus (T2DM) who started treatment with metformin.
Full-Spectrum Surveillance of Pre-Treatment HIV Drug Resistance in Southeastern China
Authors: Zhang Jiafeng , Sun Baochang , Sheng Zihang , Ding Xiaobei , Fan Qin , Huang Gang , Guo Zhihong , Zhong Ping , Liao Lingjie , Xing Hui , Xia Yan , Chai Chengliang , Jiang Jianmin
Published: July 2024

HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease–reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4–9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3–2.3] for NRTIs, 4.1% [95% CI: 2.5–6.5] for NNRTIs, 1.8% [95% CI: 0.8–3.6] for PIs and 0.5% [95% CI: 0.1–1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.
Risk-Based Approach for Defining Retest Dates for Active Pharmaceutical Ingredients and Excipients
Authors: Charoo Naseem A. , Akanji Omotayo , Rahman Ziyaur , Khan Aqeel A. , Badshah Aqal
Published: July 2024

Drug substances and excipients must be stored in recommended storage conditions and should comply with their specifications during the retest period for their use in the manufacture of drug products. The ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) and WHO (World Health Organization) regulatory guidelines mandate that after the retest period, the drug substances must be retested for compliance with the specification and then used immediately in the manufacture of the finished product. Although these substances can be retested multiple times, an emphasis is placed on immediate use following a retest and compliance with standards. The phrase “used immediately” is ambiguous and is left for interpretation. In this article, we will look at the various processes that must be completed to determine the retest date. In addition, we present a risk-based method for establishing retest dates and the time during which material can be used.
Medicinal Orchids of Mexico: A Review
Authors: Castillo-Pérez Luis J. , Ponce-Hernández Amauri , Alonso-Castro Angel Josabad , Solano Rodolfo , Fortanelli-Martínez Javier , Lagunez-Rivera Luicita , Carranza-Álvarez Candy
Published: July 2024

Some species of the Orchidaceae family are used in Mexican traditional medicine. However, there are no current and critical compilations of the medicinal uses and pharmacological effects of the members of the Orchidaceae family. This review provides a current, critical, and comprehensive analysis of the traditional medicinal uses, pharmacological reports, and active compounds isolated from Mexican orchids. A total of 62 Mexican orchids with medicinal potential have been recorded, of which 14 have scientific evidence. The remaining 48 plant species have ethnomedicinal information but have not been validated with scientific studies. These orchids are distributed in 14 states of the Mexican Republic, mainly in the southern region of Mexico. The most common pharmacological activities reported are anti-inflammatory, vasorelaxant, antinociceptive, antioxidant, spasmolytic, antihypertensive, and hallucinogenic activities. It is necessary to increase the number of pharmacological, phytochemical, and toxicological studies with medicinal orchids from Mexico because there are scientific studies on only 22.5% of these species. In further studies, it will be possible to evaluate the pharmacological effects of Mexican orchids in clinical trials. In addition, the mechanisms of action by which plant extracts and their active compounds exert medicinal effects remain to be studied. Plant extracts from orchids and their active compounds show promising antinociceptive and spasmolytic effects, respectively.
Synthesis and Characterization of Chemically and Green-Synthesized Silver Oxide Particles for Evaluation of Antiviral and Anticancer Activity
Authors: Asif Muhammad , Iqbal Wajeeha , Fakhar-e-Alam Muhammad , Hussain Zahid , Saadullah Malik , Hassan Mudassir , Rehman Javed , Dahlous Kholood A. , Al-Qahtani Noora H.
Published: July 2024

Silver oxide (Ag2O) particles are wonderful candidates due to their unique properties, and their use in a wide range of research, industrial and biomedical applications is rapidly increasing. This makes it fundamental to develop simple, environmentally friendly methods with possible scaling. Herein, sodium borohydride and Datura innoxia leaf extract were applied as chemical and biological stabilizing and reducing agents to develop Ag2O particles. The primary aim was to evaluate the anticancer and antiviral activity of Ag2O particles prepared via two methods. XRD, UV-visible and SEM analyses were used to examine the crystallite structure, optical properties and morphology, respectively. The resulting green-synthesized Ag2O particles exhibited small size, spherically agglomerated shape, and high anticancer and antiviral activities compared to chemically synthesized Ag2O particles. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium-bromide) assay of green-synthesized Ag2O particles showed high anticancer activity against MCF-7 cells with IC50 = 17.908 µg/mL compared to chemically synthesized Ag2O particles with IC50 = 23.856 µg/mL. The antiviral activity of green-synthesized Ag2O particles and chemically synthesized Ag2O particles was also evaluated by a plaque-forming assay, and green-synthesized Ag2O particles showed higher antiviral ability with IC50 = 0.618 µg/mL as compared to chemically synthesized Ag2O particles with IC50 = 6.129 µg/mL. We propose the use of green-synthesized Ag2O particles in cancer treatment and drug delivery.
Enrofloxacin Pharmaceutical Formulations through the Polymer-Free Electrospinning of β-Cyclodextrin–oligolactide Derivatives
Authors: Blaj Diana-Andreea , Peptu Cătălina Anișoara , Danu Maricel , Harabagiu Valeria , Peptu Cristian , Bujor Alexandra , Ochiuz Lăcrămioara , Tuchiluș Cristina Gabriela
Published: July 2024

Enrofloxacin (ENR), a member of the fluoroquinolone class of antibiotics, is widely used in veterinary medicine to treat bacterial infections. Like many antibiotics, ENR has limited water solubility and low bioavailability. To address these challenges, drug formulations using solid dispersions, nanosuspensions, surfactants, cocrystal/salt formation, and inclusion complexes with cyclodextrins may be employed. The approach described herein proposes the development of ENR formulations by co-electrospinning ENR with custom-prepared cyclodextrin–oligolactide (CDLA) derivatives. This method benefits from the high solubility of these derivatives, enabling polymer-free electrospinning. The electrospinning parameters were optimized to incorporate significant amounts of ENR into the CDLA nanofibrous webs, reaching up to 15.6% by weight. The obtained formulations were characterized by FTIR and NMR spectroscopy methods and evaluated for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This study indicates that the presence of CDLA derivative does not inhibit the antibacterial activity of ENR, recommending these formulations for further development.
Casgevy: Innovative Medicinal Products Require Innovative Approaches to Regulatory Assessment
Authors: Kerwash Essam , Johnston John D.
Published: July 2024

Casgevy (exa-cel) is an autologous cellular therapy modified ex vivo by a CRISPR-Cas9-mediated gene-editing technology. For Casgevy to be granted the indication in transfusion-dependent β-thalassemia, one single-arm trial was submitted which was not amenable to conventional statistical analysis of ‘effect of cause’. Therefore, an analysis was conducted on the basis of ‘cause of effect’ making use of the scheme described by Toulmin coupled to an analysis of causal inference. Based on the current data within the submitted study: subjects with transfusion-dependent β-thalassemia no longer needed a red blood cell transfusion with a 93-percent probability if and only if administered Casgevy; PNS = 93%. It is acknowledged that unknown elements of safety may yet be revealed by long-term follow-up of recipients of Casgevy. Its durability of efficacy is, at present, also an unknown that may also be ascertained by long-term follow-up of recipients. The limitations of a causal analysis are related to assumptions of the proposed causal structure which may not capture the complexity of the real world. Overall, the claim that Casgevy is indicated to treat people with transfusion-dependent β-thalassemia is considered to be supported by the results of the submitted study; the benefit–risk evaluation of Casgevy is found to be positive.
The Absurdity of Rational Choice: Time Travel, Foreknowledge, and the Aesthetic Dimension of Newcomb Problems
Authors: Bourne Craig , Caddick Bourne Emily
Published: July 2024

Nikk Effingham and Huw Price argue that in certain cases of Newcomb problems involving time travel and foreknowledge, being given information about the future makes it rational to choose as an evidential decision theorist would choose. Although the cases they consider have some intuitive pull, and so appear to aid in answering the question of what it is rational to do, we argue that their respective positions are not compelling. Newcomb problems are structured such that whichever way one chooses, one might be led by one’s preferred decision theory to miss out on some riches (riches which others obtain whilst employing their preferred decision theory). According to the novel aesthetic diagnosis we shall offer of the Newcomb dialectic, missing out in this way does not render one irrational but, rather, subject to being seen as absurd. This is a different kind of cost but not one that undermines one’s rationality.