bluuebunny/crossref_metadata_2025 huggingface dataset:
The level of highly sensitive C-reactive protein and mortality within a year after discharge from the hospital in patients with chronic heart failure with preserved ejection fraction
Authors: Belozerskikh Yu. S. , Kochetkov A. I. , Dashabylova V. B. , Lepekhin G. V. , Puhaeva A. A. , Ostroumova O. D.
Published: May 2024

Background. In recent years, there has been a steady trend in the form of an increase in the number of polymorbid patients with chronic heart failure with preserved ejection fraction (CHFpEF) and an increase in the frequency of its decompensation, which leads to an increased risk of adverse outcomes and increased mortality rates.

Objective: to study the mortality structure in patients with CHFpEF within 1 year from the moment of discharge after initial hospitalization for decompensation of heart failure, as well as the level of highly sensitive C-reactive protein (hs-CRP) and clinical and laboratory characteristics of patients depending on the outcome.

Methods. The data of patients with CHFpEF were retrospectively analyzed within 1 year from the moment of discharge after hospitalization due to decompensation of heart failure (n=372; median age 72.6 [63.3; 82.8] years, women – 44.4 %, NYHA class III and IV chronic heart failure, respectively, had 79.3 % and 15.9 % of patients). The concentration of hs-CRP in serum was determined in all patients during the first 24 hours after admission to the hospital.

Results. During the follow-up, 65 deaths were registered (17.5 % of the included patients), of which 56 (86.2 % of all deaths) were caused by cardiovascular and cerebrovascular events – acute myocardial infarction (30 cases, 46.2 %), postinfarction cardiosclerosis (11 cases, 16.9 %), ischemic stroke (10 cases, 15.4 %), and rupture of an aortic aneurysm (1 case, 1.5 %). The level of hs-CRP compared with the surviving patients (4.84 [3.78; 5.88] mg/l) was statistically significantly higher both in the group of deaths from cardiovascular causes (5.22 [4.53; 6.21] mg/l, p=0.029) and in the group of deaths from all causes (5.33[4.49; 6.19] mg/l, p=0.020). A comparative analysis of patient characteristics revealed that patients who died from cardiovascular causes, compared with survivors, had a statistically significantly lower body mass index (p=0.046), higher total cholesterol (p=0.002), and aspartate aminotransferase (p=0.025). When comparing patients who died from all causes with patients without a fatal outcome, statistically significant differences in similar indicators were obtained.

Conclusion. In patients with CHFpEF, both cardiovascular mortality and all-cause mortality within 1 year after hospitalization for decompensation of heart failure may be associated with sluggish inflammation, as well as an initially lower body mass index, higher total cholesterol and indirect signs of more pronounced myocardial damage.
Anticholinergic burden and the cognitive functions in elderly and senile patients with arterial hypertension
Authors: Ostroumova O. D. , Dzamikhov K. K. , Kochetkov A. I. , Ostroumova Т. M. , Ebzeyeva E. Yu. , Andrianov А. I. , Dashabylova V. B.
Published: May 2024

The aim of the study was to evaluate the effect of anticholinergic load (AHN) on cognitive functions (CF) in elderly and senile multimorbid patients with arterial hypertension (AH).

Materials and methods. 330 patients aged 60 years and older with essential AH were included in the study (median age 79 [72; 84] years, 158 (51 %) of women). All the patients were underwent the assesment of CF using the Montreal Cognitive Assessment Scale (MoCA), Mini-Mental Status Scale (MMS), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog), Trial Making Test (TMT), Digit Symbol Substitution Test (DSST), Verbal Association Test (literal (letter) and categorical (animal) associations), Boston Naming Test (BNT), Word-Color Interference Test, Stroop colorword conflict test. The anticholinergic load was determined using the anticholinergic load scale (Anticholinergic Cognitive Burden Scale, ACB).

Results. Compared with patients who do not take anticholinergic drugs, multimorbid elderly and senile hypertensive patients with 2 or more points on the ACB scale had significantly lower final scores on the MoCA test (23 [21; 24.3] versus 24 [22; 25] points, respectively, p=0.042) and on MMSE (26 [24; 29] vs. 27.5 [25; 29] points, respectively, p=0.015), they spent statistically more time completing part B of the TMT test (217.5 [187.3; 246.3] vs. 204 [166.8; 247.3] seconds, respectively, p=0.038). The difference between the execution time of part B and part A of the TMT test in patients with 2 or more points on the ACB scale was statistically significantly greater than in patients with 0 points on this scale (141 [103.8; 168.5] versus 124 [83.8; 162] sec, respectively, p=0.034). Age, gender, education, and the structure of concomitant diseases did not differ between the groups.

Conclusion. The results obtained indicate the adverse effect of аnticholinergic вurden on CF of multimorbid elderly and senile hypertensive patients and dictate the need to optimize pharmacotherapy in this category of patients.
Effectiveness and safety of PCSK9 inhibitors in children with family hypercholesterolemia
Authors: Khachaturyan R. A. , Khidirova L. D. , Karavozova A. E.
Published: May 2024

Familial hypercholesterolemia (CGHS) is a monogenic disease with a predominantly autosomal dominant type of inheritance, accompanied by a significant increase in the level of low-density lipoprotein cholesterol in the blood, and as a result, premature development and progressive course of atherosclerosis, usually at a young age. One of the common causes of the disease is a mutation in the PCSK9 gene. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the main link in the regulation of blood lipid metabolism due to its direct participation in the degradation of LDL receptors. Currently, only evolocumab is used as PCSK9 inhibitors in children over 12 years of age in the Russian Federation, which has proven the safety and steady reduction of LDL cholesterol in pediatric patients with HES. Another representative of this pharmacological group is alirocumab, which is currently indicated only for people over the age of 18, due to the lack of evidence in children.
Genetic engineering of a thermophilic acetogen, Moorella thermoacetica Y72, to enable acetoin production
Authors: Kato Junya , Fujii Tatsuya , Kato Setsu , Wada Keisuke , Watanabe Masahiro , Nakamichi Yusuke , Aoi Yoshiteru , Morita Tomotake , Murakami Katsuji , Nakashimada Yutaka
Published: May 2024

Acetogens are among the key microorganisms involved in the bioproduction of commodity chemicals from diverse carbon resources, such as biomass and waste gas. Thermophilic acetogens are particularly attractive because fermentation at higher temperatures offers multiple advantages. However, the main target product is acetic acid. Therefore, it is necessary to reshape metabolism using genetic engineering to produce the desired chemicals with varied carbon lengths. Although such metabolic engineering has been hampered by the difficulty involved in genetic modification, a model thermophilic acetogen, M. thermoacetica ATCC 39073, is the case with a few successful cases of C2 and C3 compound production, other than acetate. This brief report attempts to expand the product spectrum to include C4 compounds by using strain Y72 of Moorella thermoacetica. Strain Y72 is a strain related to the type strain ATCC 39073 and has been reported to have a less stringent restriction-modification system, which could alleviate the cumbersome transformation process. A simplified procedure successfully introduced a key enzyme for acetoin (a C4 chemical) production, and the resulting strains produced acetoin from sugars and gaseous substrates. The culture profile revealed varied acetoin yields depending on the type of substrate and culture conditions, implying the need for further engineering in the future. Thus, the use of a user-friendly chassis could benefit the genetic engineering of M. thermoacetica.
Economic evaluation of decarbonizing the electricity sector in the Dominican Republic
Authors: Victor-Gallardo Luis , Solórzano-Jiménez Susana , Rodríguez-Delgado Lucía , Roccard Jessica , Quirós-Tortós Jairo , Gómez Rafael , Dionicio Maribel , Baldivieso Hector , Lefevre Benoit
Published: May 2024

This paper presents an in-depth analysis of decarbonizing the electricity sector in the Dominican Republic, pivotal for addressing climate change and fostering economic growth. Employing the robust-decision making methodology, we studied multiple scenarios via computational models, capturing inputs from stakeholders and evaluating each scenario across 1,000 futures to capture deep uncertainty. Four scenarios were examined: baseline, reference, natural gas, and renewable. The renewable scenario emerged as the most advantageous, proposing the replacement of coal-fired power generation with renewable sources, primarily solar and wind, coupled with batteries. A significant investment, averaging US$3.3 billion, is necessary for this shift toward renewable energy; however, these investments are overcompensated by savings in operational costs. Crucially, this transition promises substantial benefits by 2050: an estimated cumulative average net economic gain of US$2.7 billion, an 8% reduction in average generation costs in 2050, the creation of 160,000 direct jobs, and the avoidance of circa 140 million tons of CO2. The findings underscore the feasibility and economic viability of transitioning to a 55% renewable energy generation by 2050. The study offers a critical roadmap for policymakers, highlighting renewable energy expansion, transmission grid strengthening, and strategic coal generation replacement, thus offering a comprehensive blueprint for the nation's energy transition.
Non-neuronal cell-derived acetylcholine, a key modulator of the vascular endothelial function in health and disease
Authors: Sonobe Takashi , Kakinuma Yoshihiko
Published: May 2024

Vascular endothelial cells play an important role in regulating peripheral circulation by modulating arterial tone in the microvasculature. Elevated intracellular Ca2+ levels are required in endothelial cells to induce smooth muscle relaxation via endothelium-dependent mechanisms such as nitric oxide production, prostacyclin, and endothelial cell hyperpolarization. It is well established that exogenous administration of acetylcholine can increase intracellular Ca2+ concentrations, followed by endothelium-dependent vasodilation. Although endogenous acetylcholine's regulation of vascular tone remains debatable, recent studies have reported that endogenously derived acetylcholine, but not neuronal cell-derived acetylcholine, is a key modulator of endothelial cell function. In this minireview, we summarize the current knowledge of the non-neuronal cholinergic system (NNCS) in vascular function, particularly vascular endothelial cell function, which contributes to blood pressure regulation. We also discuss the possible pathophysiological impact of endothelial NNCS, which may induce the development of vascular diseases due to endothelial dysfunction, and the potential of endothelial NNCS as a novel therapeutic target for endothelial dysfunction in the early stages of metabolic syndrome, diabetes, and hypertension.
Analyzing the efficacy of comprehensive testing: a comprehensive evaluation
Authors: Alolaywi Yasamiyan , Alkhalaf Shatha , Almuhilib Badar
Published: May 2024

This study aimed to examine the variations in comprehensive exam results in the English department at Qassim University in Saudi Arabia across six semesters, focusing on average score, range, and standard deviation, as well as overall student achievements. Additionally, it sought to assess the performance levels of male and female students in comprehensive tests and determine how they differ over the past six semesters. The research design utilized both analytical and descriptive approaches, with quantitative analysis of the data using frequency statistics such as mean, standard deviation, and range. The data consisted of scores from six consecutive exit exams. The findings reveal that male students scored slightly higher on average than female students, with minimal difference (p = 0.07). Moreover, male scores exhibited more variability and spread, indicating varying performance levels. These results suggest the need for further investigation into the factors that contribute to gender-based differences in test performance. Furthermore, longitudinal studies tracking individual student performance over multiple semesters could offer a more in-depth understanding of academic progress and the efficacy of comprehensive exam practices.
Exploring the perceived knowledge of teacher educators and pre-service teachers on the differentiated instruction practices of teacher educators
Authors: Nketsia William , Opoku Maxwell P. , Amponteng Michael , Mprah Wisdom Kwadwo
Published: May 2024

Inclusive education involves creating effective learning environments that welcome and meet the diverse needs of all students. Differentiated instruction (DI) has been identified as a key instructional approach to addressing the diverse needs of all students in regular classrooms. While there is a large body of literature on DI, that relating to the non-Western context is sparse. Using comprehensive model of DI as a conceptual framework, this study examined teacher educators’ perceived usage of DI practices in teacher training institutions in Ghana. It used a questionnaire design based on the tenets of model for data collection. A total of 1,002 participants (199 teacher educators and 883 pre-service teachers) were recruited from four teacher training institutions in Ghana. The data were analyzed using confirmatory factor analysis, t-tests, and Hayes’s model for performing moderation analysis. The results show differences between pre-service teachers and teacher educators, with the former rating the latter lower on the perceived usage of DI. The study concludes with a discussion on the training needs of teacher educators in the usage of DI and enabling them to effectively model appropriate differentiated teaching experiences to beginning teachers.
Heutagogy as an alternative in teacher education: conceptions of lecturers and pre-service teachers of school of education and life-long learning, SDD-UBIDS
Authors: Mwinkaar Linus , Lonibe Jane-Frances Yirdong
Published: May 2024

Introduction

The needs of today’s higher education have changed and higher education does not need a one-way communication from teacher to student but rather learn to appreciate the new role of the teacher as a facilitator with mutual responsibilities toward the creation of knowledge. Heutagogy, which emphasizes learner autonomy and the creation of self-determined learners, has garnered attention as a potential solution to address the evolving needs of teacher preparation. However, empirical research on the beliefs and attitudes of Heutagogy within the teacher education context remains limited. This study aimed to fill this gap by exploring the beliefs and attitudes of lecturers and pre-service teachers of the School of Education and Life-Long Learning (SoELL) at SDD-UBIDS.

Methods

Convergent mixed method design with both quantitative and qualitative data analysis, the study collected both quantitative and qualitative data on 513 Pre-service teachers and 30 Lecturers from SoELL, SDD-UBIDS using a four-point Likert scale questionnaire and interview.

Results

The findings revealed diverse perspectives among Lecturers and Pre-service Teachers regarding Heutagogy, with varying levels of understanding, acceptance, and readiness for implementation. Lecturers expressed enthusiasm for Heutagogy’s potential to foster learner autonomy and critical thinking skills, while pre-service teachers demonstrated varying levels of readiness and comfort with self-directed learning approaches.

Discussion

Lecturers and Pre-service teachers expressed willingness to embrace a self-determined approach in which the learner reflects on what is learned and how it is learned and where the Lecturers teach the learners how to learn by themselves. The cognitive conflict and the inadequacy of pre-service teachers’ preparedness will necessitate a shift in their attitudes toward developing autonomy skills to effectively navigate the challenges of the 21st-century knowledge economy.
Education 4.0 framework for sustainable entrepreneurship through transdisciplinary and abductive thinking: a case study
Authors: Torres-Sánchez Patricia , Juárez Antonio Marcelo , Miranda Jhonattan
Published: May 2024

The global challenges and problems that threaten sustainability and human well-being demand the provision of creative, innovative, and affordable solutions so that they are within the reach of different levels of society. From the point of view of Higher Education, this is a major challenge since it is responsible for training new generations with the competencies and knowledge that allow them to respond to contemporary challenges and problems. This study provides a framework to promote sustainable entrepreneurship through transdisciplinary and abductive thinking. This combination of approaches will allow students to identify, analyze, and understand contemporary problems and, through a systematized process based on the “design thinking” design model, propose creative, innovative, and affordable solutions that can be implemented through entrepreneurship mechanisms. The identified findings that will be presented in this work are (i) the relevance of the Education 4.0 model as a reference to promote transdisciplinarity in a current teaching-learning context, (ii) The relevance of “design for sustainable development” as a trigger for sustainable entrepreneurship, (iii) The formation of desirable competencies in the profile of the higher education student based on transdisciplinarity and abductive thinking within the active learning process, and (iv) quantitative and qualitative measurement that allows measuring acceptance and evaluation of the long-term sustainability of the solutions obtained. This work will present the implementation of the proposed framework through a case study. This case study allowed us to identify elements of the proposed reference framework. The case study will address the problem of water scarcity and pollution, describing initiatives to achieve ODS 6, where it explains how sustainable and visionary solutions can be forged through transdisciplinary collaboration and abductive thinking. The project named “STEAM-mural fountain” done by a transdisciplinary working team between academia-society-industry is described, which aims to make technological advances in water treatment and monitoring visible to society.
Physical and mental wellbeing, teaching efficacy and school connectedness—A study with preschool teachers in Portugal
Authors: Ferreira Marco , Barqueira Ana , Reis-Jorge José , Pacheco Patrícia , Brito Rita , Baltazar Isabel
Published: May 2024

This article aims to investigate correlations between physical and mental wellbeing, teaching efficacy and school connectedness and to explore the relationship between those dimensions and sociodemographic variables such as age, teaching experience, academic qualifications, education sector, and geographical regions. For this purpose, an online questionnaire was applied to 450 preschool teachers. To assess physical and mental wellbeing the PISA 2020 teacher questionnaire was used, and to evaluate teaching efficacy and school connectedness the Subjective Teacher Wellbeing Questionnaire was applied. Descriptive statistics were calculated for all variables. The reliability, internal consistency and suitability of the data for factor analysis. were assessed for each of the questionnaires. The ANOVA test and Kruskal–Wallis’s test were used to identify significant differences between the dimensions under analysis and sociodemographic variables. The results show that school connectedness is positively related to teaching efficacy and the same positive association occurs between physical and mental wellbeing. A negative association is observed between school connectedness and physical and mental wellbeing and teaching efficacy and physical wellbeing and mental wellbeing. The results also indicate that older preschool teachers and those with more years of experience had a significantly higher score in teaching efficacy than their younger and less experienced counterparts. The preschool teachers from the Porto and North Regions of Portugal had significantly higher scores in the mental wellbeing dimension when compared with their colleagues from other regions of the country.
Cardiorespiratory fitness attenuates the association between fatness and cardiometabolic risk in Chinese children
Authors: Zhang Ping-Ping , Wang You-Xin , Gu Jia-Yin , Xu Miao , Zhou Ye , Wang Hai-Jun , Lau Patrick W C. , Wang Hui , Li Li
Published: May 2024

Background

Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences.

Methods

We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF.

Results

Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What’s more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001).

Conclusion

In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.
Terminal strip detection and recognition based on improved YOLOv7-tiny and MAH-CRNN+CTC models
Authors: Zhijun Guo , Weiming Luo , Qiujie Chen , Hongbo Zou
Published: May 2024

For substation secondary circuit terminal strip wiring, low efficiency, less easy fault detection and inspection, and a variety of other issues, this study proposes a text detection and identification model based on improved YOLOv7-tiny and MAH-CRNN+CTC terminal lines. First, the YOLOv7-tiny target detection model is improved by the introduction of the spatially invariant multi-attention mechanism (SimAM) and the weighted bidirectional feature pyramid network (BiFPN). This also improves the feature enhancements and feature fusion ability of the model, balances various scales of characteristic information, and increases the positioning accuracy of the text test box. Then, a multi-head attention hybrid (MAH) mechanism is implemented to optimize the convolutional recurrent neural network with connectionist temporal classification (CRNN+CTC) so that the model could learn data features with larger weights and increase the recognition accuracy of the model. The findings indicate that the enhanced YOLOv7-tiny model achieves 97.39%, 98.62%, and 95.07% of precision, recall, and mean average precision (mAP), respectively, on the detection dataset. The improved MAH-CRNN+CTC model achieves 91.2% character recognition accuracy in the recognition dataset.
Development and calibration of a bio-geo-reactive transport model for UHS
Authors: Hogeweg Sebastian , Hagemann Birger , Bobrov Vadim , Ganzer Leonhard
Published: May 2024

The increased share of renewable energy sources will lead to large fluctuations in energy availability and increases energy storage’s significance. Large-scale hydrogen storage in the subsurface may become a vital element of a future sustainable energy system because stored hydrogen becomes an energy carrier available on demand. Large hydrogen amounts can be stored in porous formations such as former gas fields or gas storages, while caverns can contribute with high deliverability. However, the storage of hydrogen induces unique processes in fluid-fluid and rock-fluid interactions (for example, bio- and geochemical reactions), which may affect the efficiency of the storage. In the present study, a mathematical model describing the two-phase multicomponent flow in porous media, including bio- and geochemical reactions, is developed to predict these hydrogen-related processes. The proposed model extends an existing model in the open source simulator DuMux describing the bio-reactive transport process considering methanation and sulfate-reduction by geochemical reactions. Significant attention is placed on the reduction from pyrite-to-pyrrhotite coming with the generation of harmful hydrogen sulfide. This reaction is calibrated by developing a kinetic model in DuMux that mimics the observations of reactor experiments from literature. The developed and calibrated model is afterwards used for simulation runs on field scale to assess the impact on Underground Hydrogen Storage (UHS) operations. The developed kinetic model describes the reduction from pyrite-to-pyrrhotite in agreement with the observations in the literature, whereby particular focus was placed on the hydrogen sulfide production rate. The consecutive implementation of the transport model in DuMux on field scale, including the bio- and geochemical reactions, shows the potential permanent hydrogen losses caused by reactions and temporary ones induced by gas-gas mixing with the initial and cushion gas.
Examining performance calibration in smart power system electricity metering based on environmental perception attention LSTM-network
Authors: Zhang Bo , Xia Xin , He Chuanliang , Kang Wei , Zhang Jinxia
Published: May 2024

The operating environment greatly influences the accuracy of power metering devices, resulting in variations and inconsistencies in measurement results across different working situations. A calibration model for power metering devices is proposed in this study, considering a range of environmental circumstances. The first step involves investigating the environmental conditions that impact the accuracy of power metering devices. The mutual information approach is utilized to identify environmental disturbances affecting device accuracy. A machine learning-driven symmetry attention Long Short-Term Memory (LSTM) network addresses measurement errors, capitalizing on the network’s symmetry data knowledge. Ultimately, the efficacy of the suggested approach is substantiated through the utilization of performance indicators, namely, Mean Absolute Percentage Error (MAPE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE). The results show that the proposed method can effectively reduce the errors of the power measurement device in all quarters, and the error reduction effect is over 10% in the spring, which is better than other models, demonstrating exemplary performance in correcting the calibration errors of the power measurement device.
Digital transformation, green innovation, and audit fees
Authors: Lou Pengzhen , Zhou Xiaohui
Published: May 2024

Under the trend of synergistic development of digitalization and greening, this paper investigates the impact of enterprise digital transformation on audit fees and its mechanism, by using textual analysis and performing empirical tests on the data of Chinese listed companies from 2007 to 2021. It is found that enterprise digital transformation significantly increases audit fees, and green innovation partially mediates this process. The study results are robust, even after a series of robustness tests. When financing constraints and environmental regulations are low, the mediating role of green innovation between digital transformation and audit fees is more significant. In addition, green innovation has a stronger mediating role between the use of underlying technology and audit fees, while green substantive innovation has a stronger mediating role between digital transformation and audit fees. This study investigates the effect of enterprise digital transformation on audit fees from the standpoint of green innovation. It offers a new perspective on how accounting firms make audit pricing decisions, provides guidance for enterprise digital transformation and green innovation, and gives an opportunity for China to promote the synergistic transformation and development of digitalization and greening to achieve the dual-carbon goal.
Identifying potential drug targets for varicose veins through integration of GWAS and eQTL summary data
Authors: Cui Yu , Hu Mengting , Zhou He , Guo Jiarui , Wang Qijia , Xu Zaihua , Chen Liyun , Zhang Wancong , Tang Shijie
Published: May 2024

Background

Varicose veins (VV) are a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment.

Methods

This study conducted Summary-data-based Mendelian Randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies and cis-expression quantitative trait loci databases. Only genes with PP.H4 > 0.7 in colocalization were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization (MR) analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies and The Drug-Gene Interaction Database data to identify and screen the remaining genes and identified four drug targets for the treatment of VV.

Results

We identified four genes significantly associated with VV, namely, KRTAP5-AS1 [Odds ratio (OR) = 1.08, 95% Confidence interval (CI): 1.05–1.11, p = 1.42e-10] and PLEKHA5 (OR = 1.13, 95% CI: 1.06–1.20, p = 6.90e-5), CBWD1 (OR = 1.05, 95% CI: 1.01–1.11, p = 1.42e-2) and CRIM1 (OR = 0.87, 95% CI: 0.81–0.95, p = 3.67e-3). Increased expression of three genes, namely, KRTAP5-AS1, PLEKHA5, and CBWD1, was associated with increased risk of the disease, and increased expression of CRIM1 was associated with decreased risk of the disease. These four genes could be targeted for VV therapy.

Conclusion

We identified four potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that KRTAP5-AS1, PLEKHA5, CBWD1, and CRIM1 might be potential drug targets for varicose veins.
Climate change and liver disease: a mini review
Authors: Ribeiro Tiago , Macedo Guilherme
Published: May 2024

Climate change poses a growing threat to human health and well-being, with emerging evidence pointing to its intricate relationship with liver diseases. Indeed, climate change influences liver diseases through various direct and indirect mechanisms. Alcohol-related liver disease, Metabolic dysfunction-associated liver disease (MASLD), and viral hepatitis are the three most common causes of liver disease, and all are susceptible to the effects of climate change. Shifts in dietary habits driven by altered food availability, substance abuse exacerbated by social instability, extreme weather events affecting healthcare access, and the emergence of waterborne infections are among the factors exacerbating liver disease incidence and severity. On the flip side, healthcare systems, including liver units, significantly contribute to climate change through energy consumption, medical waste, and transportation emissions. The need for sustainable healthcare practices, telemedicine, and waste reduction strategies is becoming increasingly evident. Recognizing this intricate interplay and addressing the dual interaction between climate change and liver disease is imperative for safeguarding human health and reducing the environmental footprint of healthcare facilities. As climate change continues to unfold, understanding its implications for liver disease is critical for public health and environmental sustainability.
Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents
Authors: Rivera-Pérez Daniela , Méndez Constanza , Diethelm-Varela Benjamín , Melo-González Felipe , Vázquez Yaneisi , Meng Xing , Xin Qianqian , Fasce Rodrigo A. , Fernández Jorge , Mora Judith , Ramirez Eugenio , Acevedo Mónica L. , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Astudillo Patricio , Le Corre Nicole , Abarca Katia , Perret Cecilia , González Pablo A. , Soto Jorge A. , Bueno Susan M. , Kalergis Alexis M.
Published: May 2024

Background

Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus.

Methods

Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay.

Results

2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects.

Conclusion

SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease.

Clinical Trial Registration

clinicaltrials.gov #NCT04992260
MCP-3 as a prognostic biomarker for severe fever with thrombocytopenia syndrome: a longitudinal cytokine profile study
Authors: Liu Zishuai , Zhao Chenxi , Yu Hong , Zhang Rongling , Xue Xiaoyu , Jiang Zhouling , Ge Ziruo , Xu Yanli , Zhang Wei , Lin Ling , Chen Zhihai
Published: May 2024

Introduction

Severe fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients.

Methods

The prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis.

Results

The levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P <0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load (P<0.01).

Discussion

For the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects.
Preliminary evidence of localizing CD8+ T-cell responses in COVID-19 patients with PET imaging
Authors: Koenen Hans J. P. M. , Kouijzer Ilse J. E. , de Groot Michel , Peters Steffie , Lobeek Daphne , van Genugten Evelien A. J. , Diavatopoulos Dimitri A. , van Oosten Nienke , Gianotten Sanne , Prokop Mathias M. , Netea Mihai G. , van de Veerdonk Frank L. , Aarntzen Erik H. J. G.
Published: May 2024

The upper respiratory tract (URT) is the entry site for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), from where it further disseminates. Early and effective adaptive immune responses are crucial to restrict viral replication and limit symptom development and transmission. Current vaccines increasingly incorporate strategies to boost mucosal immunity in the respiratory tract. Positron emission tomography (PET) is a non-invasive technology that measures cellular responses at a whole-body level. In this case series, we explored the feasibility of [89Zr]Zr-crefmirlimab berdoxam PET to assess CD8+ T-cell localization during active COVID-19. Our results suggest that CD8+ T-cell distributions assessed by PET imaging reflect their differentiation and functional state in blood. Therefore, PET imaging may represent a novel tool to visualize and quantify cellular immune responses during infections at a whole-body level.
Influence of sports on cortical excitability in patients with spinal cord injury: a TMS study
Authors: Frey Vanessa N. , Langthaler Patrick B. , Renz Nora , Zimmermann Georg , Höhn Christopher , Schwenker Kerstin , Thomschewski Aljoscha , Kunz Alexander B. , Höller Yvonne , Nardone Raffaele , Trinka Eugen
Published: May 2024

Background

Patients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI.

Methods

We used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24).

Results

There were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability.

Conclusion

The small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.
Characterization and evaluation of actinomycete from the Protaetia brevitarsis Larva Frass
Authors: Zhang Lida , Zhao Tianxin , Geng Lili , Zhang Chao , Xiang Wensheng , Zhang Jie , Wang Xiangjing , Shu Changlong
Published: May 2024

Protaetia brevitarsis larvae (PBL) are soil insects important for the soil organic carbon cycle, and PBL frass not only contains a large amount of humic acid but also affects the diversity, novelty, and potential functions of actinomycetes. Here, we characterized and assessed the actinomycete. The operational taxonomic unit (OTU) data showed that 90% of the actinomycetes cannot be annotated to species, and pure culture and genome analysis showed that 35% of the strains had the potential to be new species, indicating the novelty of PBL frass actinomycetes. Additionally, genome annotation showed that many gene clusters related to antifungal, antibacterial and insecticidal compound synthesis were identified, and confrontation culture confirmed the antifungal activities of the actinomycetes against soil-borne plant pathogenic fungi. The incubation experiment results showed that all isolates were able to thrive on media composed of straw powder and alkaline lignin. These results indicated that PBL hindgut-enriched actinomycetes could survive in soil by using the residual lignocellulose organic matter from plant residues, and the antibiotics produced not only give them a competitive advantage among soil microflora but also have a certain inhibitory effect on plant diseases and pests. This study suggests that the application of PBL frass can not only supplement soil humic acid but also potentially affect the soil microbiota of cultivated land, which is beneficial for the healthy growth of crops.
Establishment of a reverse transcription–recombinase polymerase amplification–lateral flow dipstick method for the dual detection of Israeli acute paralysis virus and chronic bee paralysis virus
Authors: Sun Li , Cheng Yu , Fei Dongliang , Ma Yueyu , Ma Mingxiao , Li Ming
Published: May 2024

Introduction

As an important social insect, honey bees play crucial roles in agricultural production, sustainable development of agricultural production, and the balance of the natural environment. However, in recent years, Israeli acute paralysis virus (IAPV) and chronic bee paralysis virus (CBPV), the main pathogens of bee paralysis, have continuously harmed bee colonies and caused certain losses to the beekeeping industry. Some beekeeping farms are located in wild or remote mountainous areas, and samples from these farms cannot be sent to the laboratory for testing in a timely manner, thereby limiting the accurate and rapid diagnosis of the disease.

Methods and results

In this study, we used a reverse transcription–recombinase polymerase amplification–lateral flow dipstick (RT–RPA–LFD) method for the dual detection of IAPV and CBPV. RPA primers and LFD detection probes were designed separately for their conserved genes. Primers and probes were screened, and the forward and reverse primer ratios, reaction times, and temperatures were optimized. According to the results of the optimization tests, the optimal reaction temperature for RT–RPA is 37°C, and when combined with LFD, detection with the naked eye requires <20 min. The developed RPA–LFD method specifically targets IAPV and CBPV and has no cross-reactivity with other common bee viruses. In addition, the minimum detection limit of the RT–RPA–LFD method is 101 copies/μL.

Conclusion

Based this study, this method is suitable for the detection of clinical samples and can be used for field detection of IAPV and CBPV.
Genetic and virulence characteristics of hybrid Shiga toxin-producing and atypical enteropathogenic Escherichia coli strains isolated in South Korea
Authors: Lee Woojung , Ha Jina , Choi Jaehyun , Jung Yewon , Kim Eiseul , An Eun Sook , Kim Seung Hwan , Shin Hakdong , Ryu Sangryeol , Kim Soon Han , Kim Hae-Yeong
Published: May 2024

Introduction

The predominant hybrid pathogenic E. coli, enterohemorrhagic E. coli (EHEC), combines characteristics of Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC), contributing to global outbreaks with severe symptoms including fatal consequences. Since EHEC infection was designated as a notifiable disease in 2000 in South Korea, around 2000 cases have been reported, averaging approximately 90 cases annually.

Aim

In this work, genome-based characteristic analysis and cell-based assay of hybrid STEC/aEPEC strains isolated from livestock feces, animal source foods, and water in South Korea was performed.

Methods

To identify the virulence and antimicrobial resistance genes, determining the phylogenetic position of hybrid STEC/aEPEC strains isolated in South Korea, a combination of real-time PCR and whole-genome sequencing (WGS) was used. Additionally, to assess the virulence of the hybrid strains and compare them with genomic characterization, we performed a cell cytotoxicity and invasion assays.

Results

The hybrid STEC/aEPEC strains harbored stx and eae genes, encoding Shiga toxins and E. coli attachment/effacement related protein of STEC and EPEC, respectively. Furthermore, all hybrid strains harbored plasmid-carried enterohemolysin(ehxCABD), a key virulence factor in prevalent pathogenic E. coli infections, such as diarrheal disease and hemolytic-uremic syndrome (HUS). Genome-wide phylogenetic analysis revealed a close association between all hybrid strains and specific EPEC strains, suggesting the potential acquisition of Stx phages during STEC/aEPEC hybrid formation. Some hybrid strains showed cytotoxic activity against HeLa cells and invasive properties against epithelial cells. Notably, all STEC/aEPEC hybrids with sequence type (ST) 1,034 (n = 11) exhibited higher invasiveness than those with E2348/69. This highlights the importance of investigating potential correlations between STs and virulence characteristics of E. coli hybrid strains.

Conclusion

Through genome-based characterization, we confirmed that the hybrid STEC/aEPEC strains are likely EPEC strains that have acquired STEC virulence genes via phage. Furthermore, our results emphasize the potential increased danger to humans posed by hybrid STEC/aEPEC strains isolated in South Korea, containing both stx and eaeA, compared to STEC or EPEC alone.