bluuebunny/crossref_metadata_2025 huggingface dataset:
S-CDK-regulated bipartite interaction of Mcm10 with MCM is essential for DNA replication
Authors: Wang Xueting , Liu Lu , Chen Mengke , Quan Yun , Zhang Jiaxin , Lou Huiqiang , Xia Yisui , Chen Hongxiang , Hou Wenya
Published: September 2024

Mcm10 plays an essential role in the activation of replicative helicase CMG through the cell cycle-regulated interaction with the prototype MCM double hexamer in Saccharomyces cerevisiae. In this study, we reported that Mcm10 is phosphorylated by S-phase cyclin-dependent kinases (S-CDKs) at S66, which enhances Mcm10–-MCM association during the S phase. S66A single mutation or even deletion of whole N-terminus (a.a. 1–128) only causes mild growth defects. Nevertheless, S66 becomes indispensable in the absence of the Mcm10 C-terminus ((a.a. 463–571), the major MCM-binding domain. Using a two-degron strategy to efficiently deplete Mcm10, we show that mcm10-S66AΔC has a severe defect in proceeding into the S phase. Notably, both lethality and S-phase deficiency can be rescued by artificially tethering mcm10-S66AΔC to MCM. These findings illustrate how the Mcm10–MCM association is regulated as a crucial event in DNA replication initiation.
Alteration of cardiac structure and function and its prognostic value in patients with Takayasu arteritis: a cardiac magnetic resonance study
Authors: Tang Zehui , Wei Chuangwei , Zhao Wenjing , Liu Dongting , Liu Jiayi , Qin Huai , Pan Lili , Zhang Nan , Wen Zhaoying
Published: September 2024

Purpose

To investigate the prevalence and characteristics of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) and its prognostic value in patients with Takayasu arteritis (TA).

Materials and methods

Sixty TA patients with a CMR examination were retrospectively included. All TA patients were divided into with LGE-positive and LGE-negative groups. Bi-ventricular function and location, distribution, and pattern of left ventricular (LV) LGE were evaluated in both LGE-positive and LGE-negative groups. Primary outcome was defined as a composite of cardiovascular death, hospitalization for heart failure, coronary artery revascularization, and stroke. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between variables and primary outcomes.

Results

Sixty consecutive TA patients were enrolled in this study. The mean age was 38.2 ± 13.8 years and 54 patients (54/60, 90.0%) were female. LGE-positive was observed in twenty-one (21/60, 35%) patients in the total patients with TA. LGE was predominantly distributed in the middle wall and subendocardial. The patchy and infarcted LGE patterns were the most common. Compared with the LGE-negative group, the LGE-positive group had reduced LV ejection fraction (P = 0.033), elevated LV end-diastolic volume index (P = 0.008), LV end-systolic volume index (P = 0.012), and LV mass (P = 0.008). During a median follow-up period of 1,892 days (interquartile range: 1,764–1,988 days), the primary outcomes occurred in thirteen patients. In the univariate analysis, LGE-positive (hazard ratio [HR] = 4.478, 95% confidence interval [CI]: 1.376–14.570; P = 0.013) were independently associated with the primary outcomes. However, LGE-positive did not retain its value as an independent predictor of primary outcomes in the multivariate analysis. Instead, LVMI (HR = 1.030, 95%CI: 1.013–1.048; P = 0.001) was the strongest independent predictor of primary outcomes in patients with TA. The Kaplan-Meier plot revealed that patients with LVMI ≥ 57.5 g/m2 have a worse prognosis.

Conclusion

LGE-positive detected by CMR was observed in 35% of total TA patients with different distributions and patterns. LGE is associated with adverse LV remodeling and worsen cardiac function. However, LVMI rather than LGE can provide independent prognostic information in patients with TA.
Cooperative energy interaction for neighboring multiple distribution substation areas considering demand response
Authors: Wang Feng , Wen Xiangyu , Li Jianxiu , Liu Yang , Yu Haidong
Published: September 2024

With the growing integration of renewable energy into medium- and low-voltage distribution networks, the distribution substation area (DSA) has emerged, encompassing energy storage and loads. This paper introduces an energy interaction framework for multiple DSAs aimed at enhancing local renewable energy consumption. The energy interaction issue among various DSAs is modeled as a Nash bargaining problem to encourage energy exchanges. However, the variability in pricing and internal demand response may influence scheduling decisions, necessitating further investigation. To address price forecast errors, scenarios are developed using a stochastic programming approach to represent price uncertainties while adjusting the DSA’s load accordingly. Optimal power flow constraints are integrated into the model to bolster power system operation security. Additionally, the transmission capacity can impact scheduling outcomes and operational costs. The influence of transmission limitations on operational strategies is examined within the allowable capacity. To solve this issue, the bargaining model is divided into two subproblems, and an enhanced alternating direction multiplier method (ADMM) is used to maintain the privacy of DSAs. The simulation results obtained using the IEEE-33 bus system indicate that energy interaction among multiple DSAs significantly lowers operating costs and facilitates the integration of renewable energy.
Multi-objective parameter design and economic analysis of VSG-controlled hybrid energy systems in islanded grids
Authors: Wu Yi-Syuan , Liao Jian-Tang , Yang Hong-Tzer
Published: September 2024

Photovoltaic (PV) systems offer cost-effective power solutions for outlying islands but often compromise system stability due to reduced inertia. This study introduces a Virtual Synchronous Generator (VSG) control strategy, integrated with Energy Storage Systems (ESS) and PV, to enhance system inertia. By optimizing coordination between these energy sources, the proposed method mitigates oscillations and improves grid stability. However, PV-VSG systems are generally not favored by energy providers due to the requirement for pre-curtailment of power output. To address this, the paper proposes a parameter design method for VSG control of ESS and PV, utilizing multi-objective genetic algorithm (MOGA) optimization to simultaneously increase the frequency nadir and minimize the settling time after disturbances. Additionally, an adaptive curtailment decision and parameter design method based on artificial neural networks is introduced to enhance the feasibility of PV-VSG systems by reducing PV pre-curtailment and prioritizing PV power release and ESS charging during frequency oscillations. Real data from the Penghu Archipelago in Taiwan are used to build a dynamic model in DIgSILENT, enabling interaction with MOGA. The Value at Risk (VaR) method with dual stochastic variables is employed to assess the allowable PV installed capacity. The results show that when VaR is set at 1%, the proposed PV-VSG method can increase PV penetration by 57.5% compared to scenarios without VSG. Furthermore, compared to traditional PV-VSG methods, the proposed approach achieves a 16.8% increase in PV penetration and reduces annual PV curtailment by 25 MWh. This study also evaluates the economic impact of planners choosing different risk levels, offering valuable insights for grid development in remote or island regions.
The impact of XLPE surface defects on electric field and breakdown voltage
Authors: He Guanghua , Zhang Wei , Sun Ke , Qi Jinlong , Zhao Jiahao , Han Jiayi , Zhu Xiaoshuai
Published: September 2024

During the construction of cable joints, three common defects may occur on the XLPE surface: scratches, moisture exposure, and adhered contaminated particles. To evaluate the impact of these defects on joint performance, this paper establishes a sheet model of XLPE insulation in cable joints to analyze the changes in the electric field under different defects and explore the influence of different defects on the electric field and breakdown voltage. Results of the study reveal that the electric field at the scratch site on XLPE produces severe distortion, being 1.6 times that of non-scratch areas. When exposed to moisture, the more conductive impurities present in the adhered contaminated water on the XLPE surface, the higher the conductivity of the contaminated water, thereby increasing its conductive performance and the electric field strength, which is 1.22–1.4 times that of the non-moist interface. When particles adhere to the XLPE surface, severe distortion occurs at the particle-interface electric field, approximately 1.5 times that of the defect-free interface. Scratches have the most significant impact on the electric field of XLPE insulation. Experimental results also demonstrate that the breakdown voltage without defects is 129.6 kV, while the breakdown voltage with scratch defects is 59.1 kV, moisture defects is 69.7 kV, and particle contamination defects is 59.2 kV, with scratches having the most significant impact on the breakdown voltage of XLPE insulation. These findings provide important insights into the influence of different defects on the insulation performance of cable joints.
Traditional Chinese herbal medicine: harnessing dendritic cells for anti-tumor benefits
Authors: Shen Mengyi , Li Zhen , Wang Jing , Xiang Hongjie , Xie Qi
Published: September 2024

Chinese Herbal Medicine (CHM) is being more and more used in cancer treatment because of its ability to regulate the immune system. Chinese Herbal Medicine has several advantages over other treatment options, including being multi-component, multi-target, and having fewer side effects. Dendritic cells (DCs) are specialized antigen presenting cells that play a vital part in connecting the innate and adaptive immune systems. They are also important in immunotherapy. Recent evidence suggests that Chinese Herbal Medicine and its components can positively impact the immune response by targeting key functions of dendritic cells. In this review, we have summarized the influences of Chinese Herbal Medicine on the immunobiological feature of dendritic cells, emphasized an anti-tumor effect of CHM-treated DCs, and also pointed out deficiencies in the regulation of DC function by Chinese Herbal Medicine and outlined future research directions.
TET proteins regulate Drosha expression and impact microRNAs in iNKT cells
Authors: Gioulbasani Marianthi , Äijö Tarmo , Valenzuela Jair E. , Bettes Julia Buquera , Tsagaratou Ageliki
Published: September 2024

DNA demethylases TET2 and TET3 play a fundamental role in thymic invariant natural killer T (iNKT) cell differentiation by mediating DNA demethylation of genes encoding for lineage specifying factors. Paradoxically, differential gene expression analysis revealed that significant number of genes were upregulated upon TET2 and TET3 loss in iNKT cells. This unexpected finding could be potentially explained if loss of TET proteins was reducing the expression of proteins that suppress gene expression. In this study, we discover that TET2 and TET3 synergistically regulate Drosha expression, by generating 5hmC across the gene body and by impacting chromatin accessibility. As DROSHA is involved in microRNA biogenesis, we proceed to investigate the impact of TET2/3 loss on microRNAs in iNKT cells. We report that among the downregulated microRNAs are members of the Let-7 family that downregulate in vivo the expression of the iNKT cell lineage specifying factor PLZF. Our data link TET proteins with microRNA expression and reveal an additional layer of TET mediated regulation of gene expression.
Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma
Authors: Wu Sixuan , Pan Junfan , Pan Qihong , Zeng Lijun , Liang Renji , Li Yuehua
Published: September 2024

Lung adenocarcinoma (LUAD), characterized by a low 5-year survival rate, is the most common and aggressive type of lung cancer. Recent studies have shown that tertiary lymphoid structures (TLS), which resemble lymphoid structures, are closely linked to the immune response and tumor prognosis. The functions of the tertiary lymphoid structure-related genes (TLS-RGs) in the tumor microenvironment (TME) are poorly understood. Based on publicly available data, we conducted a comprehensive study of the function of TLS-RGs in LUAD. Initially, we categorized LUAD patients into two TLS and two gene subtypes. Subsequently, risk scores were calculated, and prognostic models were constructed using seven genes (CIITA, FCRL2, GBP1, BIRC3, SCGB1A1, CLDN18, and S100P). To enhance the clinical application of TLS scores, we have developed a precise nomogram. Furthermore, drug sensitivity, tumor mutational burden (TMB), and the cancer stem cell (CSC) index were found to be substantially correlated with the TLS scores. Single-cell sequencing results reflected the distribution of TLS-RGs in cells. Finally, we took the intersection of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) prognosis-related genes and then further validated the expression of these genes by qRT-PCR. Our in-depth investigation of TLS-RGs in LUAD revealed their possible contributions to the clinicopathological features, prognosis, and characteristics of TME. These findings underscore the potential of TLS-RGs as prognostic biomarkers and therapeutic targets for LUAD, thereby paving the way for personalized treatment strategies.
Enhancing typhoon wave hindcasting with random forests and BP neural networks in the SWAN model
Authors: Chen Cheng , Lin Hongkun , Guan Dawei , Cai Feng , Wang Qiaoyi , Liu Qingchun
Published: September 2024

Forecasting typhoon waves during typhoons is crucial. In this paper, the numerical wave model SWAN was enhanced through integration with two machine learning methods: the Back Propagation Neural Network and Random Forest. This integration facilitated the development of two distinct models, namely SWAN-BP and SWAN-Tree. Through correlation analysis, key input features were identified for the machine learning models. The forecasts from the SWAN model were subsequently utilized as inputs to enhance further wave prediction. These hybrid models were validated using data from Typhoon Doksuri (2023) and Typhoon Nesat (2017). The results indicated significant improvements in predicting typhoon-induced wave heights with both the SWAN-BP and SWAN-Tree models compared to the original SWAN model. Specifically, the SWAN-BP model demonstrated a 33% improvement in accuracy for the Typhoon Doksuri, whereas the SWAN-Tree model exhibited a 24% improvement. For Typhoon Nesat, the accuracy improvements were 23% for the SWAN-BP model and 21% for the SWAN-Tree model. These findings demonstrate that integrating wave numerical models with machine learning techniques can significantly enhance the predictive accuracy of numerical models. This approach offers a cost-effective means to improve the existing wave forecasting database. Traditionally, the direct use of meteorological and oceanographic data for typhoon wave prediction might be compromised by biases inherent in the numerical wave models. However, the SWAN-BP and SWAN-Tree models effectively reduce these biases, thereby providing more accurate and robust predictions. In conclusion, this paper enhances the predictive accuracy of the SWAN model and establishes a crucial foundation for more precise typhoon wave forecasting through the application of machine learning techniques.
Adult diffuse hepatic hemangiomatosis lesion occupying the entire abdominal and pelvic cavities: a case report
Authors: Ge Ya-Nan , Shao Yan , Dong Shu-Chen , Ma Xing-Bin , Wang Wei
Published: September 2024

Introduction

Adult diffuse hepatic hemangiomatosis (DHH) is an extremely rare disease. Consequently, its characteristics are poorly understood. Herein, we report a case of adult DHH involving both liver lobes but without extrahepatic involvement. To the best of our knowledge, this the largest reported adult DHH to date.

Case presentation

A 51-year-old man was admitted due to abdominal distension and dyspnea. Physical examination revealed marked liver enlargement. Color Doppler, plain and contrast-enhanced computed tomography, and contrast-enhanced magnetic resonance imaging revealed a hepatic lesion sized 35.1 × 32.1 × 14.1 cm occupying nearly the entire abdominal and pelvic cavities. Diagnosis was established by liver puncture biopsy. The patient exhibited clinical signs of portal hypertension and hypersplenism, but remains free of serious DHH-related complications. He is followed up regularly, with proactive evaluation for future liver transplantation.

Conclusion

This case will contribute to the current knowledge on the clinical and imaging features of this rare entity.
GWAS and polygenic risk score of severe COVID-19 in Eastern Europe
Authors: Kovalenko Elena , Shaheen Layal , Vergasova Ekaterina , Kamelin Alexey , Rubinova Valerya , Kharitonov Dmitry , Kim Anna , Plotnikov Nikolay , Elmuratov Artem , Borovkova Natalia , Storozheva Maya , Solonin Sergey , Gilyazova Irina , Mironov Petr , Khusnutdinova Elza , Petrikov Sergey , Ilinskaya Anna , Ilinsky Valery , Rakitko Alexander
Published: September 2024

Background

COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.

Methods

We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk.

Results

We identified two genome-wide significant loci (P-value <5 × 10−8) and one locus with approximately genome-wide significance (P-value = 5.92 × 10−8-6.15 × 10−8). The most genome-wide significant variants were located in the leucine zipper transcription factor like 1 (LZTFL1) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), P-value = 8.9 × 10−9].

Conclusion

We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.
Transcriptomic insights into pseudorabies virus suppressed cell death pathways in neuroblastoma cells
Authors: Cao Shinuo , Zhang Li , Zhou Mo , Zhu Shanyuan
Published: September 2024

Pseudorabies virus (PRV) exhibits a complex interplay of host-pathogen interactions, primarily by modulating host cell death pathways to optimize its replication and spread in Neuro-2a cells. Using high-throughput RNA sequencing, we identified 2,382 upregulated differentially expressed genes (DEGs) and 3,998 downregulated DEGs, indicating a intricate interaction between viral pathogenesis and host cellular responses. This research offers valuable insights into the molecular processes involved in PRV infection, highlighting the substantial inhibition of crucial cell death pathways in Neuro-2a cells, including necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis. Cells infected with PRV exhibit decreased expression of genes critical in these pathways, potentially as a mechanism to avoid host immune reactions and ensure cell survival to support ongoing viral replication. This extensive inhibition of apoptosis and metabolic alterations highlights the sophisticated tactics utilized by PRV, enhancing our comprehension of herpesvirus biology and the feasibility of creating specific antiviral treatments. This research contributes to our understanding of how viruses manipulate host cell death and presents potential opportunities for therapeutic interventions to disrupt the virus’s lifecycle.
Clinical characteristics and predictive factors of recurrent idiopathic transverse myelitis
Authors: Lee Eun Kyoung , Kim Sooyoung , Sohn Eunhee
Published: September 2024

Background

Idiopathic transverse myelitis (iTM) is defined as an inflammatory myelopathy of undetermined etiology, even after a comprehensive workup to identify other possible causes. Generally, the characteristics of recurrent iTM are not clearly defined. This study aimed to identify the clinical characteristics and predictive factors of recurrence in patients with iTM.

Methods

We retrospectively recruited patients with transverse myelitis (TM) who visited Chungnam National University Hospital between January 2011 and December 2021. We included patients who were followed up for at least 2 years and excluded those diagnosed with multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD) during the initial episode or follow-up period. Patients with iTM were categorized into two groups: monophasic idiopathic TM (mTM) and recurrent idiopathic TM (rTM). We compared the clinical characteristics and spinal magnetic resonance imaging findings between the two groups.

Results

In total, 167 patients were reviewed, of whom 112 were excluded. Finally, we included 55 patients with iTM. In 55 patients, 11 (20.0%) and 44 (80%) were classified into the rTM and mTM groups, respectively. Male predominance was observed in the iTM, rTM, and mTM groups. The percentage of patients with low vitamin D levels was significantly higher in the rTM group (100.0%) compared with the mTM group (70%) (p = 0.049). In addition, longitudinally extensive transverse myelitis (LETM) was observed more frequently in the rTM group, in 8 of 11 (72.7%) patients, compared with 15 of 44 (34.1%) patients in the mTM group, with the difference being statistically significant (p = 0.020). In multivariate regression analysis, female sex, younger age at onset, low serum vitamin D level (<30 ng/mL), and LETM were risk factors for recurrence. LETM was a significant predictor of relapse in iTM (p = 0.043, odds ratio = 13.408).

Conclusion

In this study, the clinical features of mTM and rTM are nearly indistinguishable. In conclusion, >20% of the patients with iTM experience recurrence, and LETM is the most significant risk factor for recurrence. In cases of recurrence, there is a favorable response to immunotherapy, and the prognosis is generally good. Although LETM may be the initial symptom of NMOSD, it may be manifestation of iTM, and in cases of idiopathic LETM, it is important to be mindful of the elevated risk of recurrence. Based on these results, idiopathic rTM has good clinical prognosis and response to immunosuppressive treatment.
Psychosocial profiles influencing healthy dietary behaviors among adolescents in Shandong Province, China: a cross-sectional study
Authors: Shi Ya , Fu Lin , Li Shengping , Jiang Ke , Shi Zumin , Sharma Manoj , Zhao Yong
Published: September 2024

Objectives

We aimed to assess the influence of psychosocial profiles on dietary behaviors among school-aged adolescents in China.

Methods

A cross-sectional study was conducted involving 7,862 adolescents from 100 schools in Shandong, China. Psychosocial profiles and dietary behaviors were assessed using the Junior High School Students’ Psychosocial Profiles Questionnaire (JPPQ) and the Chinese Diet Quality Questionnaire (DQQ), respectively. Linear regression models were used to investigate the association between adolescents’ psychosocial profiles and dietary behaviors.

Results

The mean age of the participants was 13.18 ± 1.15 years; 48.5% of them were boys. The majority of participants (97.90%) were Han Chinese, and approximately half of the participants (50.90%) resided in rural areas. After adjusting for sociodemographic characteristics and family computer and Internet ownership and usage, healthy dietary behavior was positively correlated with higher psychosocial profile scores (p < 0.05). The stratified analysis results revealed that the group with the highest psychosocial profile score was associated with an increased overall global dietary reference (GDR) score in “households without a family computer and Internet” (β: 5.357, 95% Cl: 4.931–5.784, p < 0.05).

Conclusion

Good psychosocial profiles exhibit a positive influence on healthy dietary behaviors. Therefore, policymakers should focus on Internet usage to maximize the positive effects on global youth health behaviors.
The influence of salt reduction with encapsulated oleoresins on the quality of mayonnaise, mustard, and ketchup
Authors: Serrano Carmo , Sapata Margarida , Castelo-Branco Diogo , Tasso Ana , Marques António , Viegas Cláudia , Figueira Diogo , Komora Norton
Published: September 2024

Introduction

Mayonnaise, mustard, and ketchup are table sauces enjoyed worldwide, adding flavour and texture to many dishes. However, these products often contain high sodium content, which contributes to health issues such as high blood pressure and cardiovascular disease. To address these concerns, reducing salt content in the sauces has become a significant goal for both manufacturers and consumers.

Objectives

This study investigates the effects of three formulations of microencapsulated (ME) oleoresins (F1, F2, and F3), derived from aromatic plants and spices, on the mineral content, physical–chemical properties, colour, and sensory profiles of mayonnaise, mustard, and ketchup.

Results

The addition of ME ingredients resulted in significant reductions in salt content across all sauces, with reductions up to 50% in mayonnaise, 45% in mustard, and 52% in ketchup, aligning with EU sodium guidelines and allowing for a “reduced Na/NaCl content” nutrition claim. Potassium levels in mustard and ketchup were sufficient to support health claims related to blood pressure maintenance, while chloride content was reduced in ME formulations, better aligning with dietary reference values. Physical–chemical analysis revealed that ME ingredients had minimal impact on parameters like pH, lipid oxidation, and viscosity, although significant differences were observed in specific areas, such as the consistency of ketchup and chloride content in mustard and ketchup. The use of inulin, as a carrier agent, helped maintain the sauces rheological properties. Mustard showed the most similarity to the control in terms of physical–chemical parameters. Colour analysis indicated minimal changes in mayonnaise, moderate changes in mustard, and significant differences in ketchup, particularly with the ME-F3 formulation, where the light-yellow ME ingredients had a pronounced effect on the darker sauce. Despite these differences, the sensory analysis demonstrated that the overall sensory profiles of the ME formulations were similar the like control for all sauces. Mayonnaise showed the closest resemblance, while mustard had slightly lower scores in flavour and saltiness. Ketchup followed the same trend as mayonnaise, with no significant sensory differences compared to the control.

Conclusion

These findings suggest that ME ingredients can be effectively used in condiment reformulation to achieve significant salt reduction without compromising sensory qualities, while also supporting health-related claims. By incorporating ME-based salt reduction strategies and exploring low-sodium alternatives, consumers can continue to enjoy their favourite sauces while minimising sodium intake. Embracing these changes not only benefits personal health but also aligns with the industry’s commitment to offering more nutritious options.
Guiding the starting dose of the once-daily formulation of tacrolimus in “de novo” adult renal transplant patients: a population approach
Authors: Fernández-Alarcón Beatriz , Nolberger Oscar , Vidal-Alabró Anna , Rigo-Bonnin Raul , Grinyó Josep M. , Melilli Edoardo , Montero Nuria , Manonelles Anna , Coloma Ana , Favà Alex , Codina Sergi , Cruzado Josep M. , Colom Helena , Lloberas Nuria
Published: September 2024

Aims

The once-daily extended-release tacrolimus formulation (ER-Tac) has demonstrated similar efficacy and safety to the twice-daily immediate-release formulation (IR-Tac), but few population-based pharmacokinetic models have been developed in de novo kidney transplant patients to optimize doses. Therefore, this study aimed i) at developing a population pharmacokinetic model for ER-Tac in de novo adult kidney transplant patients ii) and identifying genetic factors and time-varying covariates predictive of pharmacokinetic variability to guide tacrolimus dosage during the early post-transplant period.

Methods

A total of 1,067 blood tacrolimus concentrations from 138 kidney transplant patients were analyzed. A total of 29 out of 138 patients were intensively sampled for 24 h on the day 5 post-transplantation; meanwhile, for the remaining patients, concentrations were collected on days 5, 10, and 15 after transplantation. Tacrolimus daily doses and genetic and demographic characteristics were retrieved from the medical files. Biochemistry time-varying covariates were obtained on different days over the pharmacokinetic (PK) study. A simultaneous PK analysis of all concentrations was carried out using the non-linear mixed-effects approach with NONMEM 7.5.

Results

A two-compartment model with linear elimination and delayed absorption best described the tacrolimus pharmacokinetics. Between-patient variability was associated with oral blood clearance (CL/F) and the central compartment distribution volume (Vc/F). Tacrolimus concentrations standardized to a hematocrit value of 45% significantly improved the model (p < 0.001). This method outperformed the standard covariate modeling of the hematocrit–blood clearance relationship. The effect of the CYP3A5 genotype was statistically (p < 0.001) and clinically significant on CL/F. The CL/F of patients who were CYP3A5*1 carriers was 51% higher than that of CYP3A5*1 non-carriers. Age also influenced CL/F variability (p < 0.001). Specifically, CL/F declined by 0.0562 units per each increased year from the value estimated in patients who were 60 years and younger.

Conclusion

The 36% between-patient variability in CL/F was explained by CYP3A5 genotype, age, and hematocrit. Hematocrit standardization to 45% explained the variability of tacrolimus whole-blood concentrations, and this was of utmost importance in order to better interpret whole-blood tacrolimus concentrations during therapeutic drug monitoring. The dose requirements of CYP3A5*/1 carriers in patients aged 60 years or younger would be highest, while CYP3A5*/1 non-carriers older than 60 years would require the lowest doses.
Extensive transcriptome data providing great efficacy in genetic research and adaptive gene discovery: a case study of Elymus sibiricus L. (Poaceae, Triticeae)
Authors: Xiong Yanli , Li Daxu , Liu Tianqi , Xiong Yi , Yu Qingqing , Lei Xiong , Zhao Junming , Yan Lijun , Ma Xiao
Published: September 2024

Genetic markers play a central role in understanding genetic diversity, speciation, evolutionary processes, and how species respond to environmental stresses. However, conventional molecular markers are less effective when studying polyploid species with large genomes. In this study, we compared gene expression levels in 101 accessions of Elymus sibiricus, a widely distributed allotetraploid forage species across the Eurasian continent. A total of 20,273 high quality transcriptomic SNPs were identified. In addition, 72,344 evolutionary information loci of these accessions of E. sibiricus were identified using genome skimming data in conjunction with the assembled composite genome. The population structure results suggest that transcriptome SNPs were more effective than SNPs derived from genome skimming data in revealing the population structure of E. sibiricus from different locations, and also outperformed gene expression levels. Compared with transcriptome SNPs, the investigation of population-specifically-expressed genes (PSEGs) using expression levels revealed a larger number of locally adapted genes mainly involved in the ion response process in the Sichuan, Inner Mongolia, and Xizang geographical groups. Furthermore, we performed the weighted gene co-expression network analysis (WGCNA) and successfully identified potential regulators of PSEGs. Therefore, for species lacking genomic information, the use of transcriptome SNPs is an efficient approach to perform population structure analysis. In addition, analyzing genes under selection through nucleotide diversity and genetic differentiation index analysis based on transcriptome SNPs, and exploring PSEG through expression levels is an effective method for analyzing locally adaptive genes.
Social health markers in the context of cognitive decline and dementia: an international qualitative study
Authors: Kristanti Martina S. , Vernooij-Dassen Myrra , Jeon Yun-Hee , Verspoor Eline , Samtani Suraj , Ottoboni Giovanni , Chattat Rabih , Brodaty Henry , Lenart-Bugla Marta , Kowalski Krzysztof , Rymaszewska Joanna , Szczesniak Dorota M. , Gerhardus Ansgar , Seifert Imke , A’la Muhamad Zulvatul , Effendy Christantie , Perry Marieke
Published: September 2024

Background

Social health in the context of dementia has recently gained interest. The development of a social health conceptual framework at the individual and social environmental levels, has revealed a critical need for a further exploration of social health markers that can be used in the development of dementia intervention and to construct social health measures.

Objective

To identify social health markers in the context of dementia.

Method

This international qualitative study included six countries: Australia, Germany, Indonesia, Italy, Poland, and the Netherlands. Using purposive sampling, three to five cases per country were recruited to the study, with each case consisting of a person living with dementia, a primary informal caregiver, an active network member, and a health care professional involved in the care of the person with dementia. In-depth interviews, using an agreed topic guide, and content analysis were conducted to identify known and new social health markers. The codes were then categorized against our conceptual framework of social health.

Results

Sixty-seven participants were interviewed. We identified various social health markers, ranging from those that are commonly used in epidemiological studies such as loneliness to novel markers of social health at the individual and the social environmental level. Examples of novel individual-level markers were efforts to comply with social norms and making own choices in, for example, keeping contact or refusing support. At a social environmental level, examples of novel markers were proximity (physical distance) and the function of the social network of helping the person maintaining dignity.

Conclusions

The current study identified both well-known and novel social health markers in the context of dementia, mapped to the social health framework we developed. Future research should focus on translating these markers into validated measures and on developing social health focused interventions for persons with dementia.
Vaccine hesitancy among parents of children in their first two years of life
Authors: Magyar Ruth , Voitl Peter K. , Voitl Julian J. M. , Diesner-Treiber Susanne C.
Published: September 2024

Background

Vaccine hesitancy is considered a primary cause of outbreaks of vaccine-preventable infectious diseases. The Austrian vaccination plan includes 24 vaccinations in the first 2 years of life, 12 for free and 12 subject to a fee. Since preterm babies are more susceptible to severe infections, immunization is a vital protection strategy. This study examines the routine immunization schedule recommended for children in Austria, the number of timely vaccinations, and the number of delayed and rejected vaccinations. Possible reasons for vaccination delays and rejection and potential influencing factors (preterm birth, COVID-19 pandemic, information sources) are also analyzed.

Methods

We included children aged 2 to 5 years who presented to Vienna's largest pediatric center with an Austrian mother-child pass and spent the first 2 years of their lives in Austria. Data was collected using questionnaires about the vaccination status, parents' reasons for any rejections or delays in the recommended vaccination regimen, the impact of the COVID-19 pandemic on individuals' vaccination behavior, and child-specific influencing factors such as preterm birth and socioeconomic factors.

Results

90% of the 150 study subjects follow the recommendations on routine vaccinations, while 40–62% accept vaccinations subject to a fee. Preterm infants received less fee-based (53%) as well as gratuitous (88%) vaccinations. While free vaccinations tend to be delayed, more fee based vaccinations are rejected. With free vaccinations, delays and refusals occur due to illness or missed appointments. In the case of fee- required vaccinations, however, fears of side effects are also one of the main reasons. Due to the COVID-19 pandemic, about a quarter of parents have become more skeptical about vaccines. However, the vaccination rate of premature babies is usually just below that of full-term babies. Physicians remain the most trustworthy source of information about vaccinations.

Conclusion

Free vaccinations are more accepted by parents than fee based vaccinations. Preterm babies, which are a high risk group for vaccination preventable diseases, show a lower or delayed vaccination rate, which must be prevented through intensive doctor education. In addition, vaccination hesitancy changed during the COVID-19 pandemic, which needs to be addressed during the medical consultation.
Breaking chains of tobacco: empowering African American churches in West Virginia for a healthier future
Authors: Reed Donald , Dangerfield Truman , Robinson Rhonda , Ray Kenneth , Danberry Kathy , Tieman Kim
Published: September 2024

Across West Virginia, tobacco use continues to be a significant public health challenge. Specifically, tobacco use is linked to high poverty across the state and disproportionately affects African Americans. A faith-based tobacco prevention network was formed to address these concerns and increase education and cessation. The West Virginia African American Tobacco Prevention Network (WVAATPN) was formed in 2021 and since then has expanded its reach across the state, involving 22 congregations. The Network’s model includes annual training for lay leaders on various tobacco-related topics, tailored educational curriculum for congregations, and collaboration with national experts to enhance program efficacy. The Network has run educational and cessation workshops and promoted events such as No Menthol Sunday. Workshops have yielded positive outcomes among participants, including increased awareness of tobacco marketing tactics, higher cessation rates, and improved understanding of the health impacts of tobacco. The WVAATPN continues to expand its reach and effectiveness by advocating for policy change, enhancing community engagement, and fostering partnerships to combat tobacco-related disparities in West Virginia’s African American communities.
Vulnerability Analysis of a Multilayer Logistics Network against Cascading Failure
Authors: Wu Tongyu , Li Minjie , Lin Shuangjiao
Published: September 2024

One of the most challenging issues in contemporary complex network research is to understand the structure and vulnerability of multilayer networks, even though cascading failures in single networks have been widely studied in recent years. The goal of this work is to compare the similarities and differences between four single layers and understand the implications of interdependencies among cities on the overall vulnerability of a multilayer global logistics network. In this paper, a global logistics network model set as a multilayer network considering cascading failures is proposed in different disruption scenarios. Two types of attack strategies—a highest load attack and a lowest load attack—are used to evaluate the vulnerability of the global logistics network and to further analyze the changes in the topology properties. For a multilayer network, the vulnerability of single layers is compared as well. The results suggest that compared with the results of a single global logistics network, a multilayer network has a higher vulnerability. In addition, the heterogeneity of networks plays an important role in the vulnerability of a multilayer network against targeted attacks. Protecting the most important nodes is critical to safeguard the potential “vulnerability” in the development of the global logistics network. The three-step response strategy of “Prewarning–Response–Postrepair” is the main pathway to improving the adjustment ability and adaptability of logistics hub cities in response to external shocks. These findings supplement and extend the previous attack results on nodes and can thus help us better explain the vulnerability of different networks and provide insight into more tolerant, real, complex system designs.
Rapid SLAM Method for Star Surface Rover in Unstructured Space Environments
Authors: Zhang Zhengpeng , Cheng Yan , Bu Lijing , Ye Jiayan
Published: September 2024

The space environment is characterized by unstructured features, sparsity, and poor lighting conditions. The difficulty in extracting features from the visual frontend of traditional SLAM methods results in poor localization and time-consuming issues. This paper proposes a rapid and real-time localization and mapping method for star chart surveyors in unstructured space environments. Improved localization is achieved using multiple sensor fusion to sense the space environment. We replaced the traditional feature extraction module with an enhanced SuperPoint feature extraction network to tackle the challenge of challenging feature extraction in unstructured space environments. By dynamically adjusting detection thresholds, we achieved uniform detection and description of image keypoints, ultimately resulting in robust and accurate feature association information. Furthermore, we minimized redundant information to achieve precise positioning with high efficiency and low power consumption. We established a star surface rover simulation system and created simulated environments resembling Mars and the lunar surface. Compared to the LVI-SAM system, our method achieved a 20% improvement in localization accuracy for lunar scenarios. In Mars scenarios, our method achieved a positioning accuracy of 0.716 m and reduced runtime by 18.682 s for the same tasks. Our approach exhibits higher localization accuracy and lower power consumption in unstructured space environments.
Response of Bacterial Community Structure and Function in Rhizosphere Soil on the Photosynthesis of Selected Plant Types C3 and C4 under Bis(2,4,6-tribromophenoxy) Ethane Exposure
Authors: Chen Yixuan , Wang Sen , Li Yuru , Liu Wanyu , Niu Zhenchuan
Published: September 2024

This study investigated the response of a bacterial community’s structure and function in the rhizosphere soil of C3 and C4 plants under bis(2,4,6-tribromophenoxy) ethane (BTBPE) exposure. The bacterial community composition was determined using 16S rRNA sequencing, while FAPROTAX and PICRUSt 2 were employed for functional predictions. Results showed significant differences between C3 and C4 plants in terms of bacterial community structure. C3 plants exhibited higher abundances of Proteobacteria, Bacteroidetes at the phylum level and Sphingomicrobium at the genus level, compared to C4 plants. Conversely, C4 plants had higher abundances of Actinobacteria and Patescibacteria at the phylum level and Nocardioides at the genus level. LEfSe and function prediction analyses revealed that the rhizosphere soil bacteria in C3 plants exhibited significantly higher enrichment in nitrogen fixation functions (p < 0.05), whereas C4 plants showed a significantly higher relative abundance of bacteria and functions related to organic pollutant degradation (p < 0.05). These findings suggest that the rhizosphere soil bacteria of C3 plants exhibit a stronger response to BTBPE exposure in nitrogen metabolism-related processes, while C4 plants possess superior biodegradation ability compared to C3 plants.
Halving Environmental Impacts of Diverse Crop Production in Fujian, China through Optimized Nitrogen Management
Authors: Li Jun , Wang Minglei , Shi Wenjiao , Shi Xiaoli
Published: September 2024

Nitrogen (N) fertilizer is essential for agricultural production as it is the main nutrient driving crop growth. However, in China, only one-third of applied N fertilizer is effectively absorbed by crops, while the rest leads to significant environmental impacts. In this study, we introduced a nitrogen threshold boundary (NTB) approach to establish different thresholds for N use efficiency (NUE) and N surplus without affecting crop yield. We also developed an integrated assessment framework to systematically evaluate the potential for improving N utilization and reducing environmental impacts in the production of grain crops (rice, wheat, maize, and soybeans) and cash crops (tea, fruits, and vegetables) at the county level in Fujian Province. Three N management strategies were evaluated: a scenario with reduced N surplus (S1), a scenario with increased NUE (S2), and a combined scenario that simultaneously reduces N surplus and increases NUE (S3). The predictions indicate that, under the aforementioned scenarios, there will be a decrease of 66%, 58%, and 71% in N application without affecting crop yields, respectively. Correspondingly, N surplus will decrease by 65%, 56%, and 67%, while greenhouse gas (GHG) emissions will decrease by 54%, 48%, and 57%. In addition, NUE will increase by 23%, 17% and 25%, respectively. It is notable that scenario S3 demonstrated the greatest potential for improvement. For cash crops, N application will decrease by 65–78%, NUE will increase by 13–21%, N surplus will decrease by 63–74%, and GHG emissions will reduce by 66–78%. In contrast, for grain crops, N application will decrease by 27–38%, NUE will increase by 9–13%, N surplus will decrease by 26–37%, and GHG emissions will reduce by 24–28%. Overall, the potential for improvement is greater for cash crops compared to grain crops. The application of the assessment framework in this study demonstrates its effectiveness as a valuable tool for promoting green and sustainable development in conventional agricultural regions.