bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrospun bioresorbable polymer membranes for coronary artery stents
Authors: Rezvova Maria A. , Ovcharenko Evgeny A. , Klyshnikov Kirill Yu , Glushkova Tatiana V. , Kostyunin Alexander E. , Shishkova Daria K. , Matveeva Vera G. , Velikanova Elena A. , Shabaev Amin R. , Kudryavtseva Yulia A.
Published: August 2024

Percutaneous coronary intervention, a common treatment for atherosclerotic coronary artery lesions, occasionally results in perforations associated with increased mortality rates. Stents coated with a bioresorbable polymer membrane may offer an effective solution for sealing coronary artery perforations. Additionally, such coatings could be effective in mitigating neointimal hyperplasia within the vascular lumen and correcting symptomatic aneurysms. This study examines polymer membranes fabricated by electrospinning of polycaprolactone, polydioxanone, polylactide-co-caprolactone, and polylactide-co-glycolide. In uniaxial tensile tests, all the materials appear to surpass theoretically derived elongation thresholds necessary for stent deployment, albeit polydioxanone membranes are found to disintegrate during the experimental balloon expansion. As revealed by in vitro hemocompatibility testing, polylactide-co-caprolactone membranes exhibit higher thrombogenicity compared to other evaluated polymers, while polylactide-co-glycolide samples fail within the first day post-implantation into the abdominal aorta in rats. The PCL membrane exhibited significant water leakage in the permeability test. Comprehensive evaluation of mechanical testing, bio- and hemocompatibility, as well as biodegradation dynamics shows the advantage of membranes based on and the mixture of polylactide-co-caprolactone and polydioxanone over other polymer groups. These findings lay a foundational framework for conducting preclinical studies on stent configurations in large laboratory animals, emphasizing that further investigations under conditions closely mimicking clinical use are imperative for making definitive conclusions.
Understanding public perspectives on genetically engineered Brinjal and the adoption of modern biotechnology in Bangladesh
Authors: Ahmed Sium , Shohael Abdullah Mohammad , Ahamed Tanvir , Ahmed Razu , Ahmed Shawon , Hassan H. M. Shahid
Published: August 2024

The agricultural sector in Bangladesh is currently facing numerous challenges. The country is currently endeavoring to adopt modern biotechnological tools, such as genetic engineering, to modify crops with the aim of ensuring food security. Notably, Bt Brinjal represents a significant milestone as the first genetically engineered (GE) food crop commercially cultivated in South Asia. Public perception and awareness are crucial steps forward for accepting and commercializing GE crops within society. The study discussed here aims to assess public perception and awareness regarding modern biotechnology and GE crops, focusing mainly on Bt Brinjal in Bangladesh. A random survey considered demographic factors such as age, gender, hometown, educational qualification, and occupation to explore the public attitudes towards Bt Brinjal and modern biotechnology. Approximately one-third of those surveyed considered Bt Brinjal safe for consumption, and a third expressed a willingness to buy Bt Brinjal, while nearly two-thirds believed it would gain popularity in the market alongside other crops. Most respondents recognized the necessity of utilizing modern biotechnology for crop improvement beyond Bt Brinjal, and respondents with science backgrounds displayed higher awareness and a more positive attitude than those with limited education or non-science backgrounds. This study explores the public perceptions of Bt Brinjal and the adoption of modern biotechnology in Bangladesh by examining factors such as knowledge dissemination, acceptance levels, and concerns related to GE crops, and offers a meaningful perspective that can shape decision-making processes to promote agricultural sustainability and achieve relevant sustainable development goals in Bangladesh.
Full-scale trial embankment and numerical analysis of mortar column inclusion and high-strength geotextile-reinforced load transfer platform on peat
Authors: Himawan Agus , Sahadewa Andhika , Irsyam Masyhur , Mikhail Reguel , Suhendra Idwan , Rifai Muchamad , Beckhaus Karsten , Widodo Yasin , Moormann Christian , Schweiger Helmut F. , Hakim Abi Maulana , Nawir Hasbullah , Aldiamar Fahmi
Published: August 2024

Pile-supported embankments have been recognized as long-standing solutions for construction in compressible soft soils. Instead of improving the physical and mechanical properties of the soft soil, this method emphasizes efforts to transfer the embankment load to a competent layer below the compressible layer. Mortar column inclusion (inklusi kolom mortar or IKM) is recognized as one of the rigid inclusions in a pile-supported embankment. The IKM combined with a load transfer platform (LTP) has been widely utilized to support embankments. Studies on pile-supported embankments have generally focused on the arching mechanisms and geotextile tensile force evaluations; however, most of these investigations were conducted on soft cohesive soils. The application of pile-supported embankment on peat has rarely been studied comprehensively. This study presents a full-scale trial embankment on peat in West Sumatra, Indonesia. The 8-m-high trial embankment was supported by a series of IKM piles and a geotextile-reinforced LTP layer; instruments were then installed in the embankment, ground, LTP, geotextile, and IKM. These instruments included a series of vibrating wire earth pressure cells, vibrating wire strain gages, fiber optic sensors, vibrating wire piezometers, settlement profilers, settlement plates, and inclinometers. The instruments provided observations on the ground movements, IKM displacements, and stresses in the materials. Comprehensive evaluations from field monitoring allowed study of load transfer via the arching mechanism, deformation pattern, and IKM performance in peat. Finite element analyses (FEAs) were also conducted for comparison and verification. The field monitoring results and FEAs showed good agreement, thereby demonstrating the potential of the proposed ground improvement method for embankment construction on peat.
Molecular insights into kaempferol derivatives as potential inhibitors for CDK2 in colon cancer: pharmacophore modeling, docking, and dynamic analysis
Authors: Xing Fei , Wang Zhicheng , Bahadar Noor , Wang Can , Wang Xu-Dong
Published: August 2024

Cyclin-dependent kinase 2 (CDK2) has been recognized as one of the crucial factors in cell cycle regulation and has been proposed as a potential target for cancer therapies, particularly for colorectal cancer (CRC). Due to the increased incidence rate of CRC and challenges associated with existing treatment options, there is a need for efficient and selective anti-cancer compounds. The current work aims to explore the ability of novel kaempferol derivatives as CDK2 inhibitors by performing conceptual pharmacophore modeling, molecular docking, and molecular dynamic analysis. Kaempferol and its derivatives were obtained from PubChem, and the optimized 3D structures of the compounds were generated using Maestro Ligprep. Subsequently, a pharmacophore model was developed to identify compounds with high fitness values, resulting in the selection of several kaempferol derivatives for further study. We evaluated the ADMET properties of these compounds to assess their therapeutic potential. Molecular docking was conducted using Maestro and BIOVIA Discovery Studio version 4.0 to predict the binding affinities of the compounds to CDK2. The top candidates were subjected to MM-GBSA analysis to predict their binding free energies. Molecular dynamics simulations using GROMACS were performed to assess the thermodynamic stability of the ligand-protein complexes. The results revealed several kaempferol derivatives with high predicted binding affinities to CDK2 and favorable ADMET properties. Specifically, compounds 5281642, 5318980, and 14427423 demonstrated binding free energies of −30.26, −38.66, and −34.2 kcal/mol, respectively. Molecular dynamics simulations indicated that these ligand-protein complexes remained stable throughout the simulation period, with RMSD values remaining below 2 Å. In conclusion, the identified kaempferol derivatives show potential as CDK2 inhibitors based on computational predictions and demonstrate stability in molecular dynamics simulations, suggesting their future application in CRC treatment by targeting CDK2. These computational findings encourage further experimental validation and development of kaempferol derivatives as anti-cancer agents.
Lung microbiota: implications and interactions in chronic pulmonary diseases
Authors: Zhou Jing , Hou Wang , Zhong Huilin , Liu Dan
Published: August 2024

The lungs, as vital organs in the human body, continuously engage in gas exchange with the external environment. The lung microbiota, a critical component in maintaining internal homeostasis, significantly influences the onset and progression of diseases. Beneficial interactions between the host and its microbial community are essential for preserving the host’s health, whereas disease development is often linked to dysbiosis or alterations in the microbial community. Evidence has demonstrated that changes in lung microbiota contribute to the development of major chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung cancer. However, in-depth mechanistic studies are constrained by the small scale of the lung microbiota and its susceptibility to environmental pollutants and other factors, leaving many questions unanswered. This review examines recent research on the lung microbiota and lung diseases, as well as methodological advancements in studying lung microbiota, summarizing the ways in which lung microbiota impacts lung diseases and introducing research methods for investigating lung microbiota.
Comparative gene expression responses to Babesia infection and oil contamination in a seabird
Authors: Esperanza Carlos W. , Quock Rachel C. , Duerr Rebecca S. , Roy Scott W. , Sehgal Ravinder N. M.
Published: August 2024

The common murre (Uria aalge) is a species of seabird particularly vulnerable to several environmental stressors, including parasitic infection and oil contamination. However, the molecular response to these stressors is severely understudied. This study investigated the common murre’s transcriptomic responses to these stressors. Blood samples were collected from common murres undergoing rehabilitation at International Bird Rescue in Fairfield, CA. Total RNA was extracted from these samples, followed by library preparation and Illumina sequencing to generate whole transcriptome data. Differential gene expression analysis was conducted using DeSeq2 to identify genes significantly altered in response to oil contamination and parasitic infection. Differential gene expression analysis revealed 194 genes shared between oil-contaminated and infected birds, including key immune-related genes, such as ANXA2, LY96, and LY86. These genes play vital roles in mediating the production of pro-inflammatory cytokines. Gene Set Enrichment Analysis indicated significant alterations in stress, immune, and inflammatory responses, with additional lipid metabolism changes in contaminated birds. Our findings highlight the detrimental effects that these stressors have on wild birds. These findings suggest a generalized stress response and specific metabolic adaptations to oil exposure, providing insights for seabird conservation.
The central mechanisms of electroacupuncture at LR3 in the treatment of spontaneous hypertension: a PET and mRNA transcriptome study
Authors: Li Jing , Peng Chong , He Kejie , Wang Yumei , Lai Xinsheng
Published: August 2024

Objective

To reveal the efficacy and potential mechanisms of electroacupuncture (EA) in treating hypertension.

Methods

Male spontaneously hypertensive rats (SHRs) were randomly assigned to the SHR group, EA group, and Sham-EA group, with Wistar-Kyoto rats (WKY) as the normal control group. SHRs in the EA group received electroacupuncture at the bilateral Taichong (LR3) acupoints for 7 consecutive days. Evaluation of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) was conducted. Positron emission tomography-computed tomography (PET-CT) was employed to explore the active brain regions associated with acupuncture-induced blood pressure reduction. Furthermore, mRNA expression profiling was analyzed in the active brain regions to identify differentially expressed genes, and quantitative polymerase chain reaction (qPCR) was used to validate the mRNA expression of differentially expressed genes in the active brain region.

Results

EA reduced elevated SBP, DBP, MAP and HR in SHR. PET-CT revealed that EA decreased glucose metabolism in the hypothalamus. Genomic analysis suggested that, compared to the SHR group, the differentially expressed genes in the hypothalamus of the EA group included Nr4a1, Sirt1, Trh, GPR88, Cck, and Th. EA downregulated the mRNA expression of Th, Trh, Gpr88, and Nr4a1, while upregulating the expression of Sirt1 and Cck at the mRNA level.

Conclusion

EA may exert a unique antihypertensive effect in the hypothalamus of SHR, involving the modulation of sympathetic nerve activity, neuroinflammation, and oxidative stress response.
Delta-wave automatic mapping of the manifest accessory pathway
Authors: Iacopino Saverio , Fabiano Gennaro , Sorrenti Paolo , Petretta Andrea , Colella Jacopo , Vilio Alessandro Di , Statuto Giovanni , Diomede Nicolangelo , Artale Paolo , Filannino Pasquale , Pardeo Antonino , Placentino Filippo , Campagna Giuseppe , Peluso Gianluca , Cecchini Edoardo , Cecchini Federico , Speziale Giuseppe , Gaita Fiorenzo
Published: August 2024

Background

Despite the high success rate of radiofrequency catheter ablation (RFCA) in Wolff-Parkinson-White Syndrome (WPW), localizing the successful ablation site can be challenging and may require multiple radiofrequency (RF) applications.

Objective

This study aims to evaluate the efficacy of a novel workflow for the automatic and precise identification of accessory pathway ablation site, named Delta Wave Automatic Mapping.

Methods

Patients undergoing a first procedure for RF ablation of a manifest accessory pathway were included. Electro-Anatomical Mapping (EAM) was performed with the CARTO 3 system (Biosense Webster, Johnson & Johnson Medical S.p.a., Irvine, CA) leveraging auto-acquisition algorithms already present in the CARTO 3 software. Mapping and ablation were performed with an irrigated tip catheter with contact force sensor. Procedure success was defined as loss of pathway function after ablation. The number of RF applications required and time to effect were measured for each patient. Recurrences were evaluated during follow-up visits. Additionally, at the end of each procedure, historical predictors of ablation success were measured offline to evaluate their relationship with the successful ablation site found with the novel workflow.

Results

A total of 50 patients were analysed (62% APs right and 38% APs left). All 50 APs were successfully eliminated in each procedure with a median Time-to-effect (TTE) of 2.0 (IQR 1.2–3.5) seconds. No AP recurrences during a median follow-up of 10 (IQR 6–13) months were recorded. Offline analysis of successful ablation site revealed a pre-ablation delta/ventricular interval of ≤−10 msec in 52% of the patients and in 100% of the patients the signal related to the Kent bundle was identified.

Conclusions

The novel workflow efficiently localizes APs without requiring manual annotations. Historical endocardial parameters predicting success were measured offline for each case and they corresponded to the ablation target automatically annotated by the proposed workflow. This novel mapping workflow holds promise in enhancing the efficacy of RFCA in the presence of manifest APs.
Lithofacies identification of deep coalbed methane reservoir based on high-resolution seismic inversion
Authors: Qi Yu , Wu Kui , Wang Bo , Zheng Xiaowen , Li Wenlan , Li Dan
Published: August 2024

During the exploration and development of deep coalbed methane (CBM), delineating the thickness of coal seam and lithofacies of the roof and floor is one of the major challenging tasks. In past attempts, the prediction methods of these parameters have been limited to the conventional inversion. However, the effect of coal shielding on adjacent reflecting layers restricts the identification of underlying sand effectively by conventional inversion. Also, the depth at which the deep CBM zone is located (1,500–2000 m) produces a significant overlap of P-wave impedance and Vp/Vs of sands and shale which increases classification uncertainty between these two lithofacies. We proposed a new workflow for high-precision quantitative seismic interpretation of deep CBM reservoir. Not only P-wave impedance but also GR is selected as the optimized attributes for lithofacies classification. To reduce the effect of strong reflection of coal seam and identifying thin coal layers, the seismic waveform indication inversion method is used to obtain high-resolution results of P-wave impedance and GR. It uses horizontal changes in seismic waveforms to reflect lithological assemblage characteristics for facies-controlled constraints. Then, Bayesian classification theory is used to achieve three-dimensional lithofacies classification with multi-source data. To improve the continuity and accuracy of the interpreted results, a Markov chain is applied in the Bayesian rule as the spatial prior constraint. A well-associated synthetic test and field data application in Ordos Basin demonstrates the accuracy of the proposed workflow. Compared with conventional inversion, the results of proposed workflow showed higher resolution and accuracy. By providing a new solution for the identification of roof and floor lithofacies of deep CBM reservoir, this workflow aims to contribute to the better exploration and development of deep CBM.
Urban-rural gap in education performance in Peruvian public institutions during 2018: an analysis using the Oaxaca-Blinder decomposition
Authors: Rojas Apaza Raúl , Paredes Rene Paz , Arpi Roberto , Quispe Lino Carmen Nievez , Chura-Zea Efrain
Published: August 2024

The research aimed to assess the urban-rural gap in mathematics achievement among secondary education students in Peru using the ECE 2018 evaluation and the Oaxaca-Blinder method. Employing a retrospective observational design, the study analyzed data from the ECE to understand this disparity. It revealed a significant gap favoring urban areas, even after adjusting for socioeconomic factors and school contributions, with a difference of 63.28 points. Decomposition analysis showed that 82.58% of this gap is explained by differences in observable attributes (endowments), primarily socioeconomic variables and school inputs. These findings underscore the importance of public policies targeting improvements in both school resources and the living standards of impoverished populations to address educational disparities effectively.
T-cell exhaustion-related genes in Graves’ disease: a comprehensive genome mapping analysis
Authors: Jiang Zhengrong , Cai Huiyao , Lin Yizhao , Lin Ruhai , Chen Lijun , Huang Huibin
Published: August 2024

Background

T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves’ disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation.

Methods

Through gene landscape analysis, a protein–protein interaction network of 40 Tex-related genes was constructed. mRNA expression levels were compared between GD patients and healthy control (HCs). Unsupervised clustering categorized GD cases into subtypes, revealing distinctions in gene expression, immune cell infiltration, and immune responses. Weighted gene co-expression network analysis and differential gene expression profiling identified potential therapeutic targets. RT-qPCR validation of candidate gene expression was performed using blood samples from 112 GD patients. Correlations between Tex-related gene expression and clinical indicators were analyzed.

Results

Extensive Tex-related gene interactions were observed, with six genes displaying aberrant expression in GD patients. This was associated with atypical immune cell infiltration and regulation. Cluster analysis delineated two GD subtypes, revealing notable variations in gene expression and immune responses. Screening efforts identified diverse drug candidates for GD treatment. The Tex-related gene CBL was identified for further validation and showed reduced mRNA expression in GD patients, especially in cases of relapse. CBL mRNA expression was significantly lower in patients with moderate-to-severe thyroid enlargement than in those without such enlargement. Additionally, CBL mRNA expression was negatively correlated with the disease-specific indicator thyrotropin receptor antibodies.

Conclusion

Tex-related genes modulate GD pathogenesis, and their grouping aids subtype differentiation and exploration of therapeutic targets. CBL represents a potential marker for GD recurrence.
Bisphosphonate- and disumab-related gingival disorders: case analysis from the U.S. Food and Drug Administration Adverse Event Reporting System
Authors: Wang Lei , Zhang Wei , Zhao Cheng-long , Fu Zhong-hua
Published: August 2024

Prior research has indicated that bisphosphonates (BPs) can improve periodontal disease because of their anti-osteoporosis properties. In vitro studies have shown that BPs induce cytotoxicity, inhibit wound healing, and thus affect periodontal disease. Denosumab and BPs have alternative indications. BP and denosumab are not known to correlate with gingival disorders. We assessed such a relationship by applying Bayesian and nonproportional analyses to data in the US FDA Adverse Event Reporting System (FAERS) database. The study analyzed BPs and denosumab-reported incidents with preferred terms found in the narrow Standardized MedDRA Queries for gingival disorders. A total of 5863 reported cases of gingival disorders were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, and zoledronate) and denosumab. More than 15% of patients with gingival disorders related to BPs and denosumab other than denosumab were hospitalized over short- or long-term periods. Our findings indicated BPs and denosumab had significant reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) with respect to gingival disorders. Pamidronate had the highest association (ROR = 64.58, PRR = 57.99, IC = 5.71), while the weakest association was found with denosumab (ROR = 3.61, PRR = 3.60, IC = 1.77). Significant associations were found between the six drugs and gingival pain, gingival recession, gingivitis, periodontal disease, and periodontitis. In conclusion, our comprehensive overview of the correlations, clinical characteristics, and prognoses of BPs and denosumab-related gingival disorders suggests that these issues deserve continued surveillance and appropriate management.
Research progress on the role of mindfulness in intervention for adolescent obesity
Authors: Shao Shuming , Li Linda , Zhang Yimin , Liu Zheng , Zhang Xiaorui
Published: August 2024

In the face of the increasingly serious background of overweight and obesity rates among adolescents in China, mindfulness, as an emerging therapeutic approach, has shown its unique effectiveness. This article reviewed the research progress of mindfulness in the intervention of adolescent obesity, summarized its effects on improving physiological and psychological indicators, and listed the different options for implementing mindfulness therapy. These studies supported the preliminary effectiveness of mindfulness in the intervention of adolescent obesity, providing a basis for mindfulness to become a new approach for obesity intervention in the future.
Accurate parameters identification of proton exchange membrane fuel cell using Young’s double-slit experiment optimizer
Authors: Tummala Ayyarao S. L. V. , Polumahanthi Nishanth , Khan Baseem , Ali Ahmed
Published: August 2024

Introduction

Fuel cell technology is a harbinger of the future for generating electricity due to their high efficiency and low emissions achieved through the direct conversion of chemical energy into electrical energy without combustion.

Methods

To optimize the design and performance, a fuel cell model is essential to predict its behaviour in different conditions. This technical note presents a novel physics-based approach, the Young’s Double-slit Experiment Optimizer (YDEO), for identifying parameters in Proton Exchange Membrane Fuel Cells. A performance metric is established by formulating an objective function that relies on the summation of squared errors between experimental and estimated values.

Results and discussion

The effectiveness of this approach is evaluated through the analysis of four benchmark test cases: Horizon 500 W, BCS500 W, NedstackPS6, and 250 W. The corresponding objective function values for these test cases are 0.011243, 2.065557, 0.011698, and 5.250849, respectively. The simulation results demonstrate the efficacy of the proposed YDEO algorithm when compared with other existing popular and contemporary algorithms in the literature.
Enhanced photochemical formation of active nitrogen species from aqueous nitrate in the presence of halide ions
Authors: Zhao Yilong , Liu Chengwei , Tu Xiang , Huang Wenkai , Liu Yu , Fu Hongbo
Published: August 2024

Field observations have confirmed that halide ions are widely distributed among aerosols from the marine boundary layer and on the surfaces of ice and snow in polar regions. Consequently, the coexistence of halide ions may play a more significant role in nitrate photolysis than previously thought. In this study, we simultaneously measured HONO, NO2, and NO2−in situ to gain a deeper understanding of the coexisting system, including the photogenerated nitrogen products and the effects on nitrate photolysis rates due to enhanced aqueous nitrite and HONO transfer rates by halides. The presence of halides significantly increased the photogenerated nitrogen products across various molar ratios ([X–]/[NO3−]) at pH 3.5. By eliminating oxygen flux, the transformation of the primary photogenerated products was affected, resulting in higher concentrations of N(III) as both HONO and NO2−. Experiments involving OH scavengers indicated that the attack from·OH initiated by halides leads to side reactions that enhance nitrate photolysis. Both theoretical calculations and nitrate actinometry were used to determine the photolysis rate of nitrate solutions, which together indicated that the presence of halides enhances nitrate photolysis. A newly developed model was used to determine the HONO transfer rate, finding that the presence of halides ([X–]/[NO3−] = 0.2) enhanced the evaporation of N(III) in solution by factors of 0.68, 0.95, and 1.27 for Cl−, Br−, and I−, respectively. To our knowledge, this is the first determination of halide effects on the mass transfer of HONO. The enhanced nitrate photolysis rate can be attributed to the differential surface effects of halides and parallel reactions initiated via ·OH stemming from nitrate photolysis, with varying rates leading to different quantities of nitrogenous products. Additionally, simultaneous measurements of photoproducts in both gas and condensed phases are recommended to better constrain the rate constants of NO3− photolysis.
In planta evaluation of different bacterial consortia for the protection of tomato plants against Alternaria spp. infection and Alternaria toxins presence in fruits
Authors: Giorni Paola , Bulla Giulia , Bellotti Gabriele , Antinori Maria Elena , Guerrieri Maria Chiara , Fiorini Andrea , Bertuzzi Terenzio , Puglisi Edoardo
Published: August 2024

Four Plant Growth-Promoting Rhizobacteria (PGPR) consortia were assembled based on their plant growth-promoting (PGP) traits and biocontrol properties, previously characterized in vitro, and tested to protect tomato plants against Alternaria spp. infections. Results indicated that PGPR consortia significantly reduced Alternaria disease severity on tomato plants. Consortia C2 and C3 were particularly effective, demonstrating disease control rates similar to or exceeding those achieved with full-dose chemical fungicides. Furthermore, PGPR treatments markedly decreased fungal colonization in both leaves and fruits, with the best performing consortia reducing fungal presence by up to 98% shortly after inoculation in the short term. Only tenuazonic acid (TeA) was detected among the tested mycotoxins, and its levels were significantly lower in fruits from PGPR-treated plants. The combination of PGPR consortia with a reduced dose of fungicide also showed promising results, indicating a synergistic effect in controlling both fungal spread and mycotoxin production in the long run. Findings support the potential of PGPR as sustainable alternative to chemical fungicides, enhancing plant health while reducing environmental impact, aligning with current agricultural policies.
Risk factors and prediction model for osteonecrosis of the femoral head in female systemic lupus erythematosus
Authors: Xu Wenbo , Wang Lihe , Shi Pengbo , Liu Linfeng , Zhang Wenxin
Published: August 2024

Background

Osteonecrosis of the femoral head (ONFH) is a severe complication of systemic lupus erythematosus (SLE) and occurs more frequently in SLE patients than in other autoimmune diseases, which can influence patients’ life quality. The objective of this research was to analyze risk factors for the occurrence of ONFH in female SLE patients, construct and validate a risk nomogram model.

Methods

Clinical records of SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were retrospectively analyzed. The Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to summarize the independent risk factors of ONFH in female SLE patients, which were used to develop a nomogram. The predictive performance of the nomogram was assessed using the receiver characteristic (ROC) curve, calibration curves and decision curve analysis (DCA).

Results

793 female SLE patients were ultimately included in this study, of which 87 patients (10.9%) developed ONFH. Ten independent risk factors including disease duration, respiratory involvement, menstrual abnormalities, Sjögren's syndrome, osteoporosis, anti-RNP, mycophenolate mofetil, cyclophosphamide, biologics, and the largest daily glucocorticoid (GC) were identified to construct the nomogram. The area under the ROC curve of the nomogram model was 0.826 (95% CI: 0.780–0.872) and its calibration for forecasting the occurrence of ONFH was good (χ2= 5.589, P = 0.693). DCA showed that the use of nomogram prediction model had certain application in clinical practice when the threshold was 0.05 to 0.95. In subgroup analysis, we found that the risk of ONFH was significantly increased in age at SLE onset of ≤ 50 years old, largest daily GC dose of ≥50 mg and the therapy of GC combined with immunosuppressant patients with menstrual abnormalities.

Conclusion

Menstrual abnormalities were the first time reported for the risk factors of ONFH in female SLE patients, which remind that clinicians should pay more attention on female SLE patients with menstrual abnormalities and take early interventions to prevent or slow the progression of ONFH. Besides, the nomogram prediction model could provide an insightful and applicable tool for physicians to predict the risk of ONFH.
Dynamics and implications of anti-drug antibodies against adalimumab using ultra-sensitive and highly drug-tolerant assays
Authors: Ding Xiaoliang , Xue Ling , Wang Mingjun , Zhu Shengxiong , Zhu Kouzhu , Jiang Sheng , Wu Jian , Miao Liyan
Published: August 2024

Background

Adalimumab induces the production of anti-drug antibodies (ADA) that may lead to reduced drug concentration and loss-of-response, posing significant clinical challenges. However, traditional immunoassays have limitations in terms of sensitivity and drug-tolerance, hindering the insights of ADA response.

Methods

Herein, we developed an integrated immunoassay platform combining the electrochemiluminescence immunoassay with immunomagnetic separation strategy. A longitudinal cohort study involving 49 patients with ankylosing spondylitis was carried out to analyze the dynamic profiles of ADA and to investigate the impact of ADA on adalimumab pharmacokinetics using a population pharmacokinetic model. Additionally, cross-sectional data from 12 patients were collected to validate the correlation between ADA levels and disease relapse.

Results

The ADA assay demonstrated high sensitivity (0.4 ng/mL) and drug-tolerance (100 μg/mL), while the neutralizing antibodies (NAB) assay showed a sensitivity of 100 ng/mL and drug-tolerance of 20 μg/mL. Analysis of the longitudinal cohort revealed that a majority of patients (44/49, 90%) developed persistent ADA within the first 24 weeks of treatment. ADA levels tended to plateau over time after an initial increase during the early immune response phase. Further, nearly all of the tested patients (26/27, 96%) were classified as NAB positive, with a strong correlation between ADA levels and neutralization capacity (R2 = 0.83, P < 0.001). Population pharmacokinetic modeling revealed a significant positive association between model-estimated individual clearance and observed ADA levels. Higher ADA levels were associated with adalimumab clearance and disease relapse in a cross-sectional cohort, suggesting a promising ADA threshold of 10 for potential clinical application. Moreover, the IgG class was the primary contributor to ADA against adalimumab and the apparent affinity exhibited an increasing trend over time, indicating a T-cell dependent mechanism for ADA elicitation by adalimumab.

Conclusion

In summary, this integrated immunoassay platform shows promise for in-depth analysis of ADA against biologics, offering fresh insights into immunogenicity and its clinical implications.
Circulating cell adhesion molecules in systemic sclerosis: a systematic review and meta-analysis
Authors: Mangoni Arduino A. , Zinellu Angelo
Published: August 2024

Introduction

Patients with systemic sclerosis (SSc) have an increased risk of endothelial dysfunction, atherosclerosis, and cardiovascular events compared to the general population. Therefore, the availability of robust circulating biomarkers of endothelial dysfunction and atherogenesis may facilitate early recognition and management of cardiovascular risk in SSc. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating various types of circulating cell adhesion molecules involved in endothelial dysfunction and atherogenesis (i.e., immunoglobulin-like vascular cell, VCAM-1, intercellular, ICAM-1, platelet endothelial cell, PECAM-1, neural cell, NCAM, Down syndrome cell, DSCAM, and endothelial cell-selective, ESAM, adhesion molecules, E-, L-, and P-selectin, integrins, and cadherins) in SSc patients and healthy controls.

Methods

We searched PubMed, Scopus, and Web of Science from inception to 1 May 2024. Risk of bias and certainty of evidence were assessed using validated tools.

Results

In 43 eligible studies, compared to controls, patients with SSc had significantly higher plasma or serum concentrations of ICAM-1 (standard mean difference, SMD=1.16, 95% CI 0.88 to 1.44, p<0.001; moderate certainty), VCAM-1 (SMD=1.09, 95% CI 0.72 to 1.46, p<0.001; moderate certainty), PECAM-1 (SMD=1.65, 95% CI 0.33 to 2.98, p=0.014; very low certainty), E-selectin (SMD=1.17, 95% CI 0.72 to 1.62, p<0.001; moderate certainty), and P-selectin (SMD=1.10, 95% CI 0.31 to 1.90, p=0.007; low certainty). There were no significant between-group differences in L-selectin concentrations (SMD=-0.35, 95% CI -1.03 to 0.32, p=0.31; very low certainty), whereas minimal/no evidence was available for cadherins, NCAM, DSCAM, ESAM, or integrins. Overall, no significant associations were observed between the effect size and various patient and study characteristics in meta-regression and subgroup analyses.

Discussion

The results of this systematic review and meta-analysis suggest that specific circulating cell adhesion molecules, i.e., ICAM-1, VCAM-1, PECAM-1, E-selectin, and P-selectin, can be helpful as biomarkers of endothelial dysfunction and atherogenesis in the assessment of cardiovascular risk in SSc patients.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024549710.
Dissociation of LAG-3 inhibitory cluster from TCR microcluster by immune checkpoint blockade
Authors: Hashimoto-Tane Akiko , Bowman Edward P. , Sakuma Machie , Yoneda Natsumi , Yugi Katsuyuki , de Waal Malefyt Rene , Saito Takashi
Published: August 2024

Lymphocyte activation gene (Lag)-3 is an inhibitory co-receptor and target of immune checkpoint inhibitor (ICI) therapy for cancer. The dynamic behavior of Lag-3 was analyzed at the immune synapse upon T-cell activation to elucidate the Lag-3 inhibitory mechanism. Lag-3 formed clusters and co-localized with T-cell receptor microcluster (TCR-MC) upon T-cell activation similar to PD-1. Lag-3 blocking antibodies (Abs) inhibited the co-localization between Lag-3 and TCR-MC without inhibiting Lag-3 cluster formation. Lag-3 also inhibited MHC-II-independent stimulation and Lag-3 Ab, which did not block MHC-II binding could still block Lag-3’s inhibitory function, suggesting that the Lag-3 Ab blocks the Lag-3 inhibitory signal by dissociating the co-assembly of TCR-MC and Lag-3 clusters. Consistent with the combination benefit of PD-1 and Lag-3 Abs to augment T-cell responses, bispecific Lag-3/PD-1 antagonists effectively inhibited both cluster formation and co-localization of PD-1 and Lag-3 with TCR-MC. Therefore, Lag-3 inhibits T-cell activation at TCR-MC, and the target of Lag-3 ICI is to dissociate the co-localization of Lag-3 with TCR-MC.
TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma
Authors: Chen Zilong , Cai Haoxi , Ye Weiwei , Wu Junming , Liu Jing , Xie Yun , Feng Shiqiang , Jin Yuanpei , Lv Yunxia , Ye Hui , Cai Chengfu , Cai Gengming
Published: August 2024

Background

Most head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at an advanced local stage. While immunotherapy has improved survival rates, only a minority of patients respond durably to targeted immunotherapies, posing substantial clinical challenges. We investigated the heterogeneity of the tumor microenvironment in HNSCC cohorts before and after immunotherapy by analyzing single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing datasets retrieved from public databases.

Methods

We constructed a single-cell transcriptome landscape of HNSCC patients before and after immunotherapy and analyzed the cellular composition, developmental trajectories, gene regulatory networks, and communication patterns of different cell type subpopulations. Additionally, we assessed the expression levels of relevant indicators in HNSCC cells via western blot, ELISA, and fluorescent probe techniques.

Results

At the single-cell level, we identified a subpopulation of TP63+ SLC7A5+ HNSCC that exhibited a ferroptosis-resistant phenotype. This subpopulation suppresses ferroptosis in malignant cells through the transcriptional upregulation of SLC7A5 mediated by high TP63 expression, thereby promoting tumor growth and resistance to immunotherapy. The experimental results demonstrated that the overexpression of TP63 upregulated the expression of SLC7A5 and suppressed the concentrations of Fe2+ and ROS in HNSCC cells. By integrating bulk transcriptome data, we developed a clinical scoring model based on TP63 and SLC7A5, which are closely associated with tumor stage, revealing the significant prognostic efficacy of the TP63+ SLC7A5+ HNSCC-mediated ferroptosis mechanism in HNSCC patients.

Conclusion

Our research elucidates the TME in HNSCC before and after immunotherapy, revealing a novel mechanism by which TP63+ SLC7A5+ HNSCC inhibits ferroptosis and enhances tumor resistance via TP63-induced SLC7A5 upregulation. These insights lay the foundation for the development of more effective treatments for HNSCC.
The landscape of miRNA-mRNA regulatory network and cellular sources in inflammatory bowel diseases: insights from text mining and single cell RNA sequencing analysis
Authors: Li Yuan , Wang Yao , Chen Simeng , Liu Lijia
Published: August 2024

Background

Inflammatory Bowel Diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn’s Disease (CD), are chronic, recurrent inflammatory conditions of the gastrointestinal tract. The microRNA (miRNA) -mRNA regulatory network is pivotal in the initiation and progression of IBDs. Although individual studies provide valuable insights into miRNA mechanisms in IBDs, they often have limited scope due to constraints in population diversity, sample size, sequencing platform variability, batch effects, and potential researcher bias. Our study aimed to construct comprehensive miRNA-mRNA regulatory networks and determine the cellular sources and functions of key miRNAs in IBD pathogenesis.

Methods

To minimize potential bias from individual studies, we utilized a text mining-based approach on published scientific literature from PubMed and PMC databases to identify miRNAs and mRNAs associated with IBDs and their subtypes. We constructed miRNA-mRNA regulatory networks by integrating both predicted and experimentally validated results from DIANA, Targetscan, PicTar, Miranda, miRDB, and miRTarBase (all of which are databases for miRNA target annotation). The functions of miRNAs were determined through gene enrichment analysis of their target mRNAs. Additionally, we used two large-scale single-cell RNA sequencing datasets to identify the cellular sources of miRNAs and the association of their expression levels with clinical status, molecular and functional alternation in CD and UC.

Results

Our analysis systematically summarized IBD-related genes using text-mining methodologies. We constructed three comprehensive miRNA-mRNA regulatory networks specific to IBD, CD, and UC. Through cross-analysis with two large-scale scRNA-seq datasets, we determined the cellular sources of the identified miRNAs. Despite originating from different cell types, hsa-miR-142, hsa-miR-145, and hsa-miR-146a were common to both CD and UC. Notably, hsa-miR-145 was identified as myofibroblast-specific in both CD and UC. Furthermore, we found that higher tissue repair and enhanced glucose and lipid metabolism were associated with hsa-miR-145 in myofibroblasts in both CD and UC contexts.

Conclusion

This comprehensive approach revealed common and distinct miRNA-mRNA regulatory networks in CD and UC, identified cell-specific miRNA expressions (notably hsa-miR-145 in myofibroblasts), and linked miRNA expression to functional alterations in IBD. These findings not only enhance our understanding of IBD pathogenesis but also offer promising diagnostic biomarkers and therapeutic targets for clinical practice in managing IBDs.
Numerically efficient analysis of FRP confined CFST members under lateral low-velocity impact loading
Authors: Tang Jikai , Liu Bin , Kang Lijing , Fan Wei , Zhao Debo , Wang Tao , He Liang , Xie Jing
Published: August 2024

Fiber-reinforced polymer (FRP) confined concrete filled steel tube (CFST) structures effectively harness the advantages of FRP materials, improving the performance of CFST structures and overcoming durability issues of steel tubes. Three-dimensional detailed finite element (FE) models are usually employed to estimate the impact-resistant performance of FRP confined CFST members under impact loadings. However, detailed FE models are typically complex in modeling and low in calculation efficiency as well as require high performance in computer hardware. Hence, this paper aims to develop an alternative modeling method that can predict the impact behavior of FRP confined CFST members with high efficiency and low requirements in computer resources. The proposed method includes a contact model using mass-spring-damper elements to describe the contact behavior between the impactor and the impacted FRP confined CFST members and a nonlinear fiber-based beam-column element model to simulate the behavior of FRP-confined CFST members under impact loading. The accuracies of fiber-section beam-column elements are carefully examined for FRP confined CFST members based on quasi-static test data reported in the literature. It is found that the fiber-based elements considering confinement effects provided by FRP and steel tubes can accurately predict the force-deformation relationship of the FRP confined CFST members under monotonic loading. By incorporating the strain-rate effects of concrete, steel, and FRP materials, the validated fiber-section elements are employed to simulate eight impact tests on FRP confined CFST members. Good agreements are observed between the results obtained from the proposed models and the experimental data. The computational efficiency of the developed model is three orders of magnitude faster than that of the conventional detailed FE model.
A study on critical failure factors for implementation of sustainable Lean Six Sigma from Indian manufacturing industries perspective using BWM technique
Authors: Kumar Sandeep , Kumar Ravinder , Phanden Rakesh Kumar , Kumar Ajay , Bala Jagadeesh , Bharath Kumar S. , Giri Jayant , Sathish Rao U. , Agrawal Ashish , Vishwanatha H. M.
Published: August 2024

The adoption of Lean Six Sigma has become increasingly widespread in manufacturing industries worldwide. It is a powerful methodology for optimizing operational efficiency and quality, leading to increased productivity, reduced costs, and higher customer satisfaction. However, implementing LSS effectively, especially in Indian manufacturing sectors striving for sustainability, presents significant challenges. In this paper, the authors have presented the critical factors that impede the successful integration of sustainable Lean Six Sigma practices within the Indian manufacturing landscape. Through a systematic review of existing literature and empirical studies, authors have identified the eighteen failure factors. To prioritize these factors, authors have employed the Best Worst Method (BWM), a decision-making tool that aids in ranking factors based on their importance and impact. It is a multi-criterion decision-making (MCDM) methodology to solve different types of fact-based decision–making problems. This method involves initially identifying the best (most important) and worst (least important) factors, followed by pairwise comparisons to determine their relative significance. Results depict that “Failure of leadership to inspire and motivate”, “Lack of well-defined framework for executing initiatives”, and “High implementation cost and poor estimation of cost” are three top-level critical failure factors.