bluuebunny/crossref_metadata_2025 huggingface dataset:
The epigenetic modification of DNA methylation in neurological diseases
Authors: Li Linke , Chen Rui , Zhang Hui , Li Jinsheng , Huang Hao , Weng Jie , Tan Huan , Guo Tailin , Wang Mengyuan , Xie Jiang
Published: September 2024

Methylation, a key epigenetic modification, is essential for regulating gene expression and protein function without altering the DNA sequence, contributing to various biological processes, including gene transcription, embryonic development, and cellular functions. Methylation encompasses DNA methylation, RNA methylation and histone modification. Recent research indicates that DNA methylation is vital for establishing and maintaining normal brain functions by modulating the high-order structure of DNA. Alterations in the patterns of DNA methylation can exert significant impacts on both gene expression and cellular function, playing a role in the development of numerous diseases, such as neurological disorders, cardiovascular diseases as well as cancer. Our current understanding of the etiology of neurological diseases emphasizes a multifaceted process that includes neurodegenerative, neuroinflammatory, and neurovascular events. Epigenetic modifications, especially DNA methylation, are fundamental in the control of gene expression and are critical in the onset and progression of neurological disorders. Furthermore, we comprehensively overview the role and mechanism of DNA methylation in in various biological processes and gene regulation in neurological diseases. Understanding the mechanisms and dynamics of DNA methylation in neural development can provide valuable insights into human biology and potentially lead to novel therapies for various neurological diseases.
Fibrinogen induces inflammatory responses via the immune activating receptor LILRA2
Authors: Li Yifan , Hirayasu Kouyuki , Hasegawa Gen , Tomita Yosei , Hashikawa Yuko , Hiwa Ryosuke , Arase Hisashi , Hanayama Rikinari
Published: September 2024

The leukocyte immunoglobulin-like receptor (LILR) family, a group of primate-specific immunoreceptors, is widely expressed on most immune cells and regulates immune responses through interactions with various ligands. The inhibitory type, LILRB, has been extensively studied, and many ligands, such as HLA class I, have been identified. However, the activating type, LILRA, is less understood. We have previously identified microbially cleaved immunoglobulin as a non-self-ligand for LILRA2. In this study, we identified fibrinogen as an endogenous ligand for LILRA2 using mass spectrometry. Although human plasma contains fibrinogen in abundance in its soluble form, LILRA2 only recognizes solid-phase fibrinogen. In addition to the activating LILRA2, fibrinogen was also recognized by the inhibitory LILRB2 and by soluble LILRA3. In contrast, fibrin was recognized by LILRB2 and LILRA3, but not by LILRA2. Moreover, LILRA3 bound more strongly to fibrin than to fibrinogen and blocked the LILRB2-fibrinogen/fibrin interaction. These results suggest that morphological changes in fibrinogen determine whether activating or inhibitory immune responses are induced. Upon recognizing solid-phase fibrinogen, LILRA2 activated human primary monocytes and promoted the expression of various inflammation-related genes, such as chemokines, as revealed by RNA-seq analysis. A blocking antibody against LILRA2 inhibited the fibrinogen-induced inflammatory responses, indicating that LILRA2 is the primary receptor of fibrinogen. Taken together, our findings suggest that solid-phase fibrinogen is an inflammation-inducing endogenous ligand for LILRA2, and this interaction may represent a novel therapeutic target for inflammatory diseases.
Distinct soluble immune checkpoint profiles characterize COVID-19 severity, mortality and SARS-CoV-2 variant infections
Authors: Paranga Tudorita Gabriela , Pavel-Tanasa Mariana , Constantinescu Daniela , Iftimi Elena , Plesca Claudia Elena , Miftode Ionela-Larisa , Cianga Petru , Miftode Egidia
Published: September 2024

Introduction

Over the past four years, the COVID-19 pandemic has posed serious global health challenges. The severe form of disease and death resulted from the failure of immune regulatory mechanisms, closely highlighted by the dual proinflammatory cytokine and soluble immune checkpoint (sICP) storm. Identifying the individual factors impacting on disease severity, evolution and outcome, as well as any additional interconnections, have become of high scientific interest.

Methods

In this study, we evaluated a novel panel composed of ten sICPs for the predictive values of COVID-19 disease severity, mortality and Delta vs. Omicron variant infections in relation to hyperinflammatory biomarkers. The serum levels of sICPs from confirmed SARS-CoV-2 infected patients at hospital admission were determined by Luminex, and artificial neural network analysis was applied for defining the distinct patterns of molecular associations with each form of disease: mild, moderate, and severe.

Results

Notably, distinct sICP profiles characterized various stages of disease and Delta infections: while sCD40 played a central role in all defined diagrams, the differences emerged from the distribution levels of four molecules recently found and relatively less investigated (sCD30, s4-1BB, sTIM-1, sB7-H3), and their associations with various hematological and biochemical inflammatory biomarkers. The artificial neural network analysis revealed the prominent role of serum sTIM-1 and Galectin-9 levels at hospital admission in discriminating between survivors and non-survivors, as well as the role of specific anti-interleukin therapy (Tocilizumab, Anakinra) in improving survival for patients with initially high sTIM-1 levels. Furthermore, strong associations between sCD40 and Galectin-9 with suPAR defined the Omicron variant infections, while the positive match of sCD40 with sTREM-1 serum levels characterized the Delta-infected patients.

Conclusions

Of importance, this study provides a comprehensive analysis of circulatory immune factors governing the COVID-19 pathology, and identifies key roles of sCD40, sTIM-1, and Galectin-9 in predicting mortality.
Characteristics, efficacy, and prognosis analysis of newly diagnosed marginal zone lymphoma
Authors: Wang Haotian , Zhang Ying , Li Zhaoxia , Bai Ou
Published: September 2024

Objective

To retrospectively analyze the characteristics of newly diagnosed marginal zone lymphoma (MZL) patients, evaluate the efficacy of different treatment regimens, and explore prognostic factors in the era of immunotherapy.

Methods

We reviewed the clinical data of newly diagnosed MZL patients treated at the Department of Hematology, The First Hospital of Jilin University, from October 2013 to October 2023. Survival differences between groups were analyzed using the log-rank test, and prognostic factors were identified.

Results

A total of 265 newly diagnosed MZL patients were included, with a median age of 59 years (range 22-90). The most common pathological type was mucosa-associated lymphoid tissue (MALT) lymphoma, accounting for 66.0% of cases. Among the 147 MZL patients included in the efficacy analysis, the median follow-up was 43.4 months. Both the median progression-free survival (PFS) and overall survival (OS) were not reached. The 5-year PFS and OS rates were 76.0% and 86.6%, respectively. Patients who achieved complete response (CR) after induction therapy had significantly better PFS (P=0.0045), OS (P<0.001), and time to next treatment (TTNT) (P=0.0045) compared to those who did not achieve CR. A subgroup analysis was conducted on 51 MZL patients with high tumor burden who received ≥4 cycles of treatment. It was found that the CR rate (CRR) in patients receiving obinutuzumab (G) ± chemotherapy was significantly higher than in those receiving rituximab (R) ± chemotherapy (93.8% vs. 48.6%, P=0.002). Multivariate analysis revealed that disease progression or death within 24 months of initial treatment (POD24) was an independent risk factor affecting OS (P<0.001). Patients who experienced POD24 had a median survival of only 19.7 months, with a 3-year OS rate of just 37.6%, whereas those without POD24 had a 3-year OS rate of 97.3%.

Conclusion

MZL is predominantly seen in middle-aged and elderly patients and is a specific indolent B-cell lymphoma, with MALT lymphoma being the most common subtype. Achieving CR after induction therapy significantly prolongs survival in MZL patients. Compared to R ± chemotherapy, G ± chemotherapy achieves a higher CRR in high tumor burden MZL patients. In the era of immunotherapy, POD24 is an independent prognostic factor for MZL.
Social network analysis of intergovernmental relations and policy tools in China’s coastal reclamation management
Authors: Gong Hongbo , He Xiangmei , Li Jialin , Tian Peng , Ai Shunyi , Liu Yongchao
Published: September 2024

As an effective means of sea development and utilization, high-intensity coastal reclamation activities lead to increasingly prominent ecological problems. The accurate implementation of policies is paramount in managing and controlling coastal reclamation. We reviewed China’s coastal reclamation management and control policies from 1978 to 2022. Utilizing content analysis and social network analysis, we constructed a policy network to explore the evolution of intergovernmental relations and the habitual combination of policy tools in coastal reclamation management and control. The study shows that (1) The intergovernmental relations of reclamation management and control agencies have evolved from simple to complex, with key departments becoming increasingly prominent; (2) Environmental considerations form the mainstay of policy tools for reclamation control, highlighting an imbalance between supply-side and demand-side approaches; (3) Since 1999, the interactive network between intergovernmental relations and policy tools has begun to exhibit a distinct core-periphery structure, and the social circle has gradually expanded to form a social circle consisting of 23 administrative departments and most departmental policy tools, while there are also some independent working factions at different stages; (4) Policy sustainability is currently inadequate, and in the later stages of management and control, there is a noticeable conflict within the policy texts. The study shows that, China’s coastal reclamation management and controlstill faces challenges, It is necessary to continue to explore the policy visualization methods used in coastal reclamation to help balance policy tools and build efficient intergovernmental relations.
Research on the antibacterial properties of nanoscale zinc oxide particles comprehensive review
Authors: Nan Jiahe , Chu Yanhui , Guo Ran , Chen Peijian
Published: September 2024

Bacteria are present in the environment around us, including in the air, water, and soil. Moreover, infection-causing bacteria are transmitted indirectly through the air, food, and water, as well as through direct contact. Upon entering the human body, they multiply and cause various discomforts or diseases. To combat such diseases, antibiotics are the current choice of the primary treatment. However, their overuse has led to a major issue referred to as bacterial resistance. Metal NPs possess great potential in microbial detection along with disease diagnosis and treatment. Zinc is an essential trace element crucial for human growth and development, and zinc oxide (ZnO) nanoparticles (NPs) are an inorganic material with broad-spectrum antibacterial activity. Therefore, in this review article, we provide a detailed overview of the antibacterial mechanisms of ZnONPs, thereby providing theoretical support for their application.
Study on microstructure and mechanical properties of steel corrosion products in marine environment
Authors: Tang Bowen , Wang Wei , Yang Haicheng , Zhu Haiwei
Published: September 2024

The microstructure and mechanical properties of steel corrosion products in marine environment are key parameters for developing the concrete corrosion-induced model. In this study, steel corrosion products from steel plates, concrete specimens with 10 mm and 20 mm covers, and cracked beams in Zhejiang province were sampled and analyzed. Initially, the microstructure of the steel corrosion products were determined by X-ray diffractometry (XRD), thermogravimetric analysis (TG), scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS). Subsequently, the mechanical properties of steel corrosion products including nanoindentation elastic modulus, hardness and instantaneous elastic modulus were measured by nanoindentation and consolidation experiments. This study holds potential for establishing the concrete corrosion-induced model and assessment of the concrete structure durability in marine environment.
Medical residents’ knowledge, attitudes and practices regarding antibiotics, antimicrobial stewardship and multidrug-resistant bacteria: a cross-sectional study in a major university in Iran
Authors: Kiani Fatemeh , Sajadi Ghazaleh , Motamedi Narges , Salmasi Mehrzad , Solgi Hamid
Published: September 2024

Background

Antimicrobial resistance (AMR) is one of the biggest threats to global public health systems. This study aimed to assess the knowledge, attitudes and practice about AMR, antimicrobial stewardship programs (ASPs) and multidrug-resistant (MDR) bacteria.

Methods

A web-based questionnaire survey was conducted among the residents of Isfahan University of Medical Sciences from May to November 2023. Data analysis was done using SPSS version 24.0 software.

Results

Overall, 400 out of 450 medical residents responded to the questionnaire, giving a response rate of 88.9%. The participants’ ages ranged from 26 to 54 years, and the majority were female (227/400 56.8%). Average scores for knowledge, attitudes, and practices were 53.70 ± 15.88, 36.97 ± 5.89 and 24.69 ± 4.24, respectively. In terms of knowledge, only 26.8% had heard the term “ASPs” and knew what it was. Most incorrect answers appeared to the treatment of infection caused by MDR bacteria including ESBL-producing Escherichia coli (27.8%) and carbapenem-resistant Klebsiella pneumoniae (30.8%), as well as the atypical bacteria (45.5%). Approximately, 50 and 71.7% said they had received no specific training in the fields of microbiological sampling methods and the appropriate time to prescribe antibiotics, respectively. Surprisingly, regarding practice, 81.8% of the respondents stated that antibiotics are used to treat flu or the common cold.

Conclusion

Residents considered their training on important issues including ASPs, MDR bacteria and the spectrum of antibiotics insufficient. This result highlights the need for targeted training interventions about antibiotic prescription in the curriculum at the university with more emphasis on ASPs to limit the development of resistance.
The involvement of aquaporin 5 in the inflammatory response of primary Sjogren’s syndrome dry eye: potential therapeutic targets exploration
Authors: Fu Lijuan , Zhao Zihang , Zhao Shuang , Zhang Meiying , Teng Xiaoming , Wang Liyuan , Yang Tiansong
Published: September 2024

Sjogren’s syndrome (SS) is a chronic autoimmune disease. Mainly due to the infiltration of lymphoplasmic cells into the exocrine glands, especially the salivary glands and lacrimal glands, resulting in reduced tear and saliva secretion. Reduced tear flow can trigger Sjogren’s syndrome dry eye (SSDE). Although the pathophysiology of SSDE xerosis remains incompletely understood, recent advances have identified aquaporin-5 (AQP5) as a critical factor in dysregulation of the exocrine gland and epithelium, influencing the clinical presentation of SSDE through modulation of inflammatory microenvironment and tear secretion processes. This review aims to explore AQP5 regulatory mechanisms in SSDE and analyze its potential as a therapeutic target, providing new directions for SSDE treatment.
Sex differences in pathogenesis and treatment of dyslipidemia in patients with type 2 diabetes and steatotic liver disease
Authors: Ábel Tatjana , Benczúr Béla , Csobod Éva Csajbókné
Published: September 2024

Previously published studies have shown that women with type 2 diabetes have a higher risk of atherosclerotic cardiovascular disease than men with type 2 diabetes. The exact reason for this is not yet known. The association between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes appears to be bidirectional, meaning that the onset of one may increase the risk of the onset and progression of the other. Dyslipidemia is common in both diseases. Our aim was therefore to investigate whether there is a sex difference in the pathogenesis and management of dyslipidemia in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction. While the majority of published studies to date have found no difference between men and women in statin treatment, some studies have shown reduced effectiveness in women compared to men. Statin treatment is under-prescribed for both type 2 diabetics and patients with dysfunction-associated steatotic liver disease. No sex differences were found for ezetimibe treatment. However, to the best of our knowledge, no such study was found for fibrate treatment. Conflicting results on the efficacy of newer cholesterol-lowering PCSK9 inhibitors have been reported in women and men. Results from two real-world studies suggest that up-titration of statin dose improves the efficacy of PCSK9 inhibitors in women. Bempedoic acid treatment has been shown to be effective and safe in patients with type 2 diabetes and more effective in lipid lowering in women compared to men, based on phase 3 results published to date. Further research is needed to clarify whether the sex difference in dyslipidemia management shown in some studies plays a role in the risk of ASCVD in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction.
Bacterial microbiota from the gut of Rhodnius ecuadoriensis, a vector of Chagas disease in Ecuador's Central Coast and Southern Andes
Authors: Villacís Juan F. , López-Rosero Andrea , Bustillos Juan José , Cadena Matías , Yumiseva César A. , Grijalva Mario J. , Villacís Anita G.
Published: September 2024

Introduction

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi that is transmitted mainly by the feces of infected Triatomines. In Ecuador the main vector is Rhodnius ecuadoriensis which is distributed in several provinces of the country. More than 40% of these insects in the wild have T. cruzi as part of their intestinal microbiota. For this reason, the objective of this research was to characterize the intestinal bacterial microbiota of R. ecuadoriensis.

Methods

The methodology used was based on the DNA extraction of the intestinal contents from the wild collected insects (adults and nymphs V), as well as the insects maintained at the insectary of the CISeAL. Finally, the samples were analyzed by metagenomics extensions based on the different selected criteria.

Results

The intestinal microbiota of R. ecuadoriensis presented a marked divergence between laboratory-raised and wild collected insects. This difference was observed in all stages and was similar between insects from Loja and Manabí. A large loss of microbial symbionts was observed in laboratory-raised insects.

Discussion

This study is a crucial first step in investigating microbiota interactions and advancing new methodologies.
DNA methylation-mediated FGFR1 silencing enhances NF-κB signaling: implications for asthma pathogenesis
Authors: Meng Minglu , Ma Yingjiao , Xu Jianguo , Chen Gao , Mahato Roshan Kumar
Published: September 2024

Background

Fibroblast growth factor receptor 1 (FGFR1) is known to play a crucial role in the pathogenesis of asthma, although the precise mechanism remains unclear. This study aims to investigate how DNA methylation-mediated silencing of FGFR1 contributes to the enhancement of NF-κB signaling, thereby influencing the progression of asthma.

Methods

RT-qPCR was utilized to assess FGFR1 mRNA levels in the serum of asthma patients and BEAS-2B, HBEpiC, and PCS-301-011 cells. CCK8 assays were conducted to evaluate the impact of FGFR1 overexpression on the proliferation of BEAS-2B, PCS-301-011, and HBEpiC cells. Dual-luciferase and DNA methylation inhibition assays were performed to elucidate the underlying mechanism of FGFR1 gene in asthma. The MassARRAY technique was employed to measure the methylation levels of the FGFR1 DNA.

Results

Elevated FGFR1 mRNA levels were observed in the serum of asthma patients compared to healthy controls. Overexpression of FGFR1 in BEAS-2B cells significantly enhanced cell proliferation and stimulated NF-ĸB transcriptional activity in HERK-293T cells. Furthermore, treatment with 5-Aza-CdR, a DNA demethylating agent, markedly increased the expression of FGFR1 mRNA in BEAS-2B, PCS-301-011, and HBEpiC cells. Luciferase activity analysis confirmed heightened NF-ĸB transcriptional activity in FGFR1-overexpressing BEAS-2B cells and BEAS-2B cells treated with 5-Aza-CdR. Additionally, a decrease in methylation levels in the FGFR1 DNA promoter was detected in the serum of asthma patients using the MassARRAY technique.

Conclusion

Our findings reveal a potential mechanism involving FGFR1 in the progression of asthma. DNA methylation of FGFR1 inactivates the NF-ĸB signaling pathway, suggesting a promising avenue for developing effective therapeutic strategies for asthma.
A meta-analysis of the effects of transcranial direct current stimulation combined with cognitive training on working memory in healthy older adults
Authors: Lv Yanxin , Wu Shuo , Nitsche Michael A. , Yue Tian , Zschorlich Volker R. , Qi Fengxue
Published: September 2024

Background

Working memory (WM) loss, which can lead to a loss of independence, and declines in the quality of life of older adults, is becoming an increasingly prominent issue affecting the ageing population. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, is emerging as a potential alternative to pharmacological treatments that shows promise for enhancing WM capacity and May enhance the effects of cognitive training (CT) interventions.

Objective

The purpose of this meta-analysis was to explore how different tDCS protocols in combination with CT enhanced WM in healthy older adults.

Methods

Randomized controlled trials (RCTs) exploring the effects of tDCS combined with CT on WM in healthy older adults were retrieved from the Web of Science, PubMed, Embase, Scopus and the Cochrane Library databases. The search time period ranged from database inception to January 15, 2024. Methodological quality of the trials was assessed using the risk-of-bias criteria for RCTs from the Cochrane Collaboration Network, and RevMan 5.3 (Cochrane, London, United Kingdom) was used for the meta-analysis of the final literature outcomes.

Results

Six RCTs with a total of 323 participants were ultimately included. The results of the meta-analysis show that tDCS combined with CT statistically significantly improves WM performance compared to the control sham stimulation group in healthy older adults [standard mean difference (SMD) = 0.35, 95% CI: 0.11–0.59, I2 = 0%, Z = 2.86, p = 0.004]. The first subgroup analysis indicated that, when the stimulus intensity was 2 mA, a statistically significant improvement in WM performance in healthy older adults was achieved (SMD = 0.39, 95% CI: 0.08–0.70, I2 = 6%, Z = 2.46, p = 0.01). The second subgroup analysis showed that long-term intervention (≥ 10 sessions) with tDCS combined with CT statistically significantly improved WM compared to the control group in healthy older adults (SMD = 0.72, 95% CI: 0.22–1.21, I2 = 0%, Z = 2.85, p = 0.004).

Conclusion

tDCS combined with CT statistically significantly improves WM in healthy older adults. For the stimulus parameters, long-term interventions (≥ 10 sessions) with a stimulation intensity of 2 mA are the most effective.
The function of Mef2c toward the development of excitatory and inhibitory cortical neurons
Authors: Ward Claire , Sjulson Lucas , Batista-Brito Renata
Published: September 2024

Neurodevelopmental disorders (NDDs) are caused by abnormal brain development, leading to altered brain function and affecting cognition, learning, self-control, memory, and emotion. NDDs are often demarcated as discrete entities for diagnosis, but empirical evidence indicates that NDDs share a great deal of overlap, including genetics, core symptoms, and biomarkers. Many NDDs also share a primary sensitive period for disease, specifically the last trimester of pregnancy in humans, which corresponds to the neonatal period in mice. This period is notable for cortical circuit assembly, suggesting that deficits in the establishment of brain connectivity are likely a leading cause of brain dysfunction across different NDDs. Regulators of gene programs that underlie neurodevelopment represent a point of convergence for NDDs. Here, we review how the transcription factor MEF2C, a risk factor for various NDDs, impacts cortical development. Cortical activity requires a precise balance of various types of excitatory and inhibitory neuron types. We use MEF2C loss-of-function as a study case to illustrate how brain dysfunction and altered behavior may derive from the dysfunction of specific cortical circuits at specific developmental times.
Multi-level exploration of auricular acupuncture: from traditional Chinese medicine theory to modern medical application
Authors: Guo Kaixin , Lu Yan , Wang Xiuping , Duan Yunfeng , Li Hui , Gao Fengxiao , Wang Jian
Published: September 2024

As medical research advances and technology rapidly develops, auricular acupuncture has emerged as a point of growing interest. This paper delves into the intricate anatomy of auricular points, their significance and therapeutic principles in traditional Chinese medicine (TCM), and the underlying mechanisms of auricular acupuncture in contemporary medicine. The aim is to delve deeply into this ancient and mysterious medical tradition, unveiling its multi-layered mysteries in the field of neurostimulation. The anatomical structure of auricular points is complex and delicate, and their unique neurovascular network grants them a special status in neurostimulation therapy. Through exploration of these anatomical features, we not only comprehend the position of auricular points in TCM theory but also provide a profound foundation for their modern medical applications. Through systematic review, we synthesize insights from traditional Chinese medical theory for modern medical research. Building upon anatomical and classical theoretical foundations, we focus on the mechanisms of auricular acupuncture as a unique neurostimulation therapy. This field encompasses neuroregulation, pain management, psychological wellbeing, metabolic disorders, and immune modulation. The latest clinical research not only confirms the efficacy of auricular stimulation in alleviating pain symptoms and modulating metabolic diseases at the endocrine level but also underscores its potential role in regulating patients’ psychological wellbeing. This article aims to promote a comprehensive understanding of auricular acupuncture by demonstrating its diverse applications and providing substantial evidence to support its broader adoption in clinical practice.
Toward standardized brain tumor tissue processing protocols in neuro-oncology: a perspective for gliomas and beyond
Authors: Rodriguez Analiz , Ahluwalia Manmeet S. , Bettegowda Chetan , Brem Henry , Carter Bob S. , Chang Susan , Das Sunit , Eberhart Charles , Garzon-Muvdi Tomas , Hadjipanayis Costas G. , Hawkins Cynthia , Jacques Thomas S. , Khalessi Alexander A. , McDermott Michael W. , Mikkelsen Tom , Orr Brent A. , Phillips Joanna J. , Rosenblum Mark , Shelton William J. , Solomon David A. , von Deimling Andreas , Woodworth Graeme F. , Rutka James T.
Published: September 2024

Implementation of standardized protocols in neurooncology during the surgical resection of brain tumors is needed to advance the clinical treatment paradigms that use tissue for diagnosis, prognosis, bio-banking, and treatment. Currently recommendations on intraoperative tissue procurement only exist for diffuse gliomas but management of other brain tumor subtypes can also benefit from these protocols. Fresh tissue from surgical resection can now be used for intraoperative diagnostics and functional precision medicine assays. A multidisciplinary neuro-oncology perspective is critical to develop the best avenues for practical standardization. This perspective from the multidisciplinary Oncology Tissue Advisory Board (OTAB) discusses current advances, future directions, and the imperative of adopting standardized protocols for diverse brain tumor entities. There is a growing need for consistent operating room practices to enhance patient care, streamline research efforts, and optimize outcomes.
Cost-effectiveness analysis of direct oral anticoagulants versus low-molecular-weight heparin and no thromboprophylaxis in primary prevention of cancer-associated venous thromboembolism in China
Authors: Wu Yue , Yin TianChen , Jian GuiLin , Wan Tao , Zhou Benhong
Published: September 2024

Background and objective

Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China.

Methods

A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses.

Results

Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase.

Conclusion

Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.
Study of transport, tissue distribution, depletion, and hepatotoxicity of Cyadox, a quinoxaline-1,4-dioxide derivative
Authors: Tao Zhu , Li Changchun , Zhang Aiqun , Zhang Zhilin , Huang Jing , Harnud Sechenchogt
Published: September 2024

Background

Cyadox (CYA) is a derivative of quinoxaline 1,4-dioxide and a safe and effective synthetic antibacterial agent.

Objective

This study aimed to explore the drug transport in blood, distribution, depletion and hepatotoxicity of drugs in animals.

Methods

The transport of CYA in blood was studied using fluorescence, circular dichroism (CD) and molecular docking methods. Tissue distribution and depletion of CYA in rats were evaluated following oral administration of [3H]-CYA at different doses. Hepatotoxicity of drugs evaluated by transcriptomics.

Results

During transport in the bloodstream, the drug binds to bovine serum albumin (BSA) by hydrogen bonding and has only one binding site. Hydrogen bonds were formed between O (2) of CYA and ARG208, O (3) of CYA and LEU480, VAL481. The secondary protein conformation of BSA changed after binding with an increase in α-helix and a decrease in β-strand. After a single oral administration of [3H]-CYA, it was excreted rapidly within 7 days, with 34.81% from the urine and 60.25% from the feces. Higher and sustained levels of radioactivity were detected in the liver during the post-dose period, suggesting that the drug may concentrate in the liver. The transcriptomic data indicates that CYA exhibits low hepatotoxicity. However, there are indications that it may have an impact on steroid biosynthesis.

Conclusion

This study could serve as a basis for conducting further studies on the use of CYA in food animals and improving the pharmacologic, pharmacokinetic, and toxicologic effects of CYA on food animals.
Receptor activity-modifying protein modulation of parathyroid hormone-1 receptor function and signaling
Authors: Avgoustou Paris , Jailani Ameera B. A. , Desai Aditya J. , Roberts David J. , Lilley Ewan R. , Stothard Grant W. , Skerry Timothy M. , Richards Gareth O.
Published: September 2024

Introduction

Receptor activity-modifying proteins (RAMPs) are known to modulate the pharmacology and function of several G-protein-coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R). However, the precise effects of different RAMPs on PTH1R signalling and trafficking remain poorly understood. This study investigated the impact of RAMP2 and RAMP3 on PTH1R function using a range of PTH and PTH-related protein (PTHrP)-derived ligands.

Methods

We employed FRET imaging to assess PTH1R interactions with RAMPs. Cell surface expression of PTH1R was evaluated in the presence of RAMPs. PTH1R-mediated cAMP accumulation, β-arrestin recruitment, and calcium signalling were measured in response to various ligands. Antibody-capture scintillation proximity assays were used to examine G-protein activation patterns.

Results

PTH1R preferentially interacted with RAMP2 and, to a lesser extent, RAMP3, but not with RAMP1. RAMP3 co-expression reduced cell surface expression of PTH1R. RAMP2 significantly enhanced PTH1R-mediated signalling responses to PTH (1-34), PTHrP (1-34), PTH (1-84), and PTH (1-17) analogue ZP2307, while RAMP3 co-expression attenuated or abolished these responses. Full-length PTHrP analogues exhibited lower potency and efficacy than PTHrP (1-34) in activating PTH1R. RAMP2 increased the potency and/or efficacy of these analogues, whereas RAMP3 reduced these responses. RAMP2 differentially modulated G-protein activation by PTH1R in a ligand-dependent manner, with PTH (1-34) and PTHrP (1-34) inducing distinct patterns of G-protein subtype activation.

Discussion

These findings highlight the complex role of RAMPs in regulating PTH1R signalling and trafficking, revealing differential effects of RAMP2 and RAMP3 on receptor function. The data suggest that targeting the PTH1R/RAMP2 complex may be a promising strategy for developing novel bone anabolic therapies by leveraging biased agonism and functional selectivity. Further research using physiologically relevant models is needed to elucidate the therapeutic potential of this approach.
Organic fertilizer improved the lead and cadmium metal tolerance of Eucalyptus camaldulensis by enhancing the uptake of potassium, phosphorus, and calcium
Authors: Ouyang Linnan , Chen Shaoxiong , Yang Wentao , Zheng Jiaqi , Ye Lingshuai , Liu Qiang , Yang Jiaqi
Published: September 2024

Phytoremediation is a strategy for the amelioration of soil heavy metal contamination that aligns with ecological sustainability principles. Among the spectrum of phytoremediation candidates, woody plants are considered particularly adept for their substantial biomass, profound root systems, and non-participation in the food chain. This study used Eucalyptus camaldulensis—a tree species characterized for its high biomass and rapid growth rate—to assess its growth and metal uptake in mining tailings. The results were as follows: exposure to heavy metals reduced the E. camaldulensis uptake of potassium (K), phosphorus (P), and calcium (Ca). Heavy metal stress negatively affected the biomass of E. camaldulensis. Lead (Pb) primarily accumulated in the roots, while cadmium (Cd) predominantly accumulated in the stems. The application of organic fertilizers bolstered the stress tolerance of E. camaldulensis, mitigating the adverse impacts of heavy metal stress. A synergistic effect occurred when organic fertilizers were combined with bacterial fertilizers. The plant’s enrichment capacity for Cd and its tolerance to Pb was augmented through the concurrent application of bacterial and organic fertilizers. Collectively, the application of organic fertilizers improved the heavy metal tolerance of E. camaldulensis by enhancing the uptake of K, P, and Ca and elevating the content of glutathione peroxidase (GPX) and gibberellin acid (GA) in roots. These findings provided nascent groundwork for breeding E. camaldulensis with enhanced heavy metal tolerance. Moreover, this proved the potentiality of E. camaldulensis for the management of heavy metal-contaminated tailings and offers a promising avenue for future environmental restoration.
Research on the mechanism of Bacillus velezensis A-27 in enhancing the resistance of red kidney beans to soybean cyst nematode based on TMT proteomics analysis
Authors: Hu Yi , Ma Yibing , Wang Liyi , Luo Qingqing , Zhao Zengqi , Wang Jianming , Xu Yumei
Published: September 2024

Soybean cyst nematode (SCN) poses a significant challenge to red kidney beans cultivation, resulting in yield losses and quality deterioration. This study investigates the molecular mechanisms using Tandem Mass Tag (TMT) based proteomics technology to explore how the plant growth-promoting rhizobacterium (PGPR) Bacillus velezensis A-27 enhances the resistance of red kidney beans against SCN. The results revealed that out of 1,374 differentially expressed proteins (DEPs) in the red kidney beans roots, 734 DEPs were upregulated and 640 DEPs were downregulated in the A-27 + J2 vs J2 treatment group. KEGG analysis revealed that 14 DEPs were involved in the α-LeA metabolic pathway, crucial for the biosynthesis of jasmonic acid (JA) in plants. Quantitative real-time PCR (qRT-PCR) confirmed the upregulation of 4 key genes (PLA1, AOS, AOC, ACX) in the JA biosynthesis pathway, while enzyme-linked immunosorbent assay (ELISA) demonstrated a significant increase in JA content in the roots. The study demonstrates that B. velezensis A-27 stimulates induced systemic resistance (ISR) in red kidney beans, and induce JA biosynthesis by regulating the expression of key enzymes in the α-LeA metabolic pathway. This enhances the plant’s defense against SCN, providing a theoretical foundation for the potential use of B. velezensis A-27 as a biocontrol agent for managing SCN in leguminous crops.
Predicting candidate miRNAs for targeting begomovirus to induce sequence-specific gene silencing in chilli plants
Authors: Pandey Vineeta , Srivastava Aarshi , Ali Akhtar , Gupta Ramwant , Shahid Muhammad Shafiq , Gaur Rajarshi Kumar
Published: September 2024

The begomoviruses are the most economically damaging pathogens that pose a serious risk to India’s chilli crop and have been associated with the chilli leaf curl disease (ChiLCD). Chilli cultivars infected with begomovirus have suffered significant decreases in biomass output, negatively impacting their economic characteristics. We used the C-mii tool to predict twenty plant miRNA families from SRA chilli transcriptome data (retrieved from the NCBI and GenBank databases). Five target prediction algorithms, i.e., C-mii, miRanda, psRNATarget, RNAhybrid, and RNA22, were applied to identify and evaluate chilli miRNAs (microRNAs) as potential therapeutic targets against ten begomoviruses that cause ChiLCD. In this study, the top five chilli miRNAs which were identified by all five algorithms were thoroughly examined. Moreover, we also noted strong complementarities between these miRNAs and the AC1 (REP), AC2 (TrAP) and betaC1 genes. Three computational approaches (miRanda, RNA22, and psRNATarget) identified the consensus hybridization site for CA-miR838 at locus 2052. The top predicted targets within ORFs were indicated by CA-miR2673 (a and b). Through Circos algorithm, we identified novel targets and create the miRNA-mRNA interaction network using the R program. Furthermore, free energy calculation of the miRNA-target duplex revealed that thermodynamic stability was optimal for miR838 and miR2673 (a and b). To the best of our knowledge, this was the first instance of miRNA being predicted from chilli transcriptome information that had not been reported in miRbase previously. Consequently, the anticipated biological results substantially assist in developing chilli plants resistant to ChiLCD.
Example-based learning in heuristic domains: can using relevant content knowledge support the effective allocation of intrinsic, extraneous, and germane cognitive load?
Authors: Udvardi-Lakos Nina , Weirich Marlene , Asbrand Julia , Renkl Alexander
Published: September 2024

Introduction

Worked examples support initial skill acquisition. They often show skill application on content knowledge from another, “exemplifying” domain (e.g., argumentation skills have to be applied to some contents). Although learners’ focus should remain on the skill, learners need to understand the content knowledge to benefit from worked examples. Previous studies relied on exemplifying domains that are familiar and contain simple topics, to keep learners’ focus on skill acquisition.

Aim

We examined whether using a relevant exemplifying domain would allow learners to acquire both skills and content knowledge simultaneously, or whether relevant content distracts from the main learning goal of skill acquisition.

Methods and results

In a training study with 142 psychology students, we used example-based learning materials with an exemplifying domain that was either relevant or irrelevant for participants’ course outcomes. We assessed cognitive load, declarative knowledge about skills and course-related content knowledge, and argumentation quality. Incorporating relevant content knowledge in worked examples did not reduce learning outcomes compared to a condition using an irrelevant exemplifying domain.

Discussion

Contrary to previous research, the results suggest that worked examples with a relevant exemplifying domain could possibly be an efficient teaching method for fostering skills and content knowledge simultaneously.
A new neuropsychological tool for simultaneous reading and executive functions assessment: initial psychometric properties
Authors: de Oliveira Vinícius Figueiredo , Vial-Martins Jéssica , Pinto André Luiz de Carvalho Braule , Fonseca Rochele Paz , Malloy-Diniz Leandro Fernandes
Published: September 2024

Introduction

The development of reading and complex executive functions is fundamental for achieving social, academic, and professional success. So far, there is no single neuropsychological instrument that comprehensively assesses the domains of inhibitory control, cognitive flexibility, working memory, and reading comprehension. To assess executive functions related to reading, the “Assessment of Reading and Executive Functions” (AREF) was developed. In this study, we show initial evidence of validity and reliability for four subtests - Graphophonological-Semantic Flexibility, Inhibitory Control, Flexibility, and Working Memory.

Methods

A total of 93 students from 4th to 9th grade, aged 8-14, in public (n = 61) and private (n = 32) schools were evaluated. Tasks from the AREF instrument, as well as measures of reading comprehension, inhibitory control, cognitive flexibility, working memory, and intelligence, were administered. Correlations between AREF scores and the other measures were performed to assess external construct validity. Performance differences between school groups on AREF subtests were analyzed using ANOVA, t-test, and Mann-Whitney tests, and the internal consistency of the instrument’s tasks was evaluated using Cronbach’s alpha coefficient.

Results

The scores of the AREF subtests demonstrated significant positive correlations with reading measures (ranging from 0.339 to 0.367) and executive functions (ranging from 0.209 to 0.396). Significant differences were found in the performance of some AREF tasks when comparing individuals from public and private schools, as well as between 4th and 5th graders compared to students in higher grades. The internal consistency of the tasks was low for Graphophonological-Semantic Flexibility (Cronbach’s α = 0.566), moderate for Inhibitory Control and Flexibility (Cronbach’s α = 0.768), and high for Working Memory (Cronbach’s α = 0.881).

Discussion

The results provide initial evidence of construct validity and reliability for the AREF subtests. It is expected that this new neuropsychological test will contribute to the assessment of reading skills and executive functions, assisting in guiding clinical and educational interventions for individuals with and without neurodevelopmental disorders.
Neuropsychological impact of Sanda training on athlete attention performance
Authors: Teng Yuzhu , Wu Hailan , Zhou Xiaoyun , Li Feiyang , Dong Zhong , Wang Huafeng , Wang Kai , Yu Qianchun
Published: September 2024

Background

Sanda, a martial art that primarily involves punching, kicking, and throwing techniques, requires athletes to maintain high levels of concentration during combat. Sanda principally involves striking the opponent to secure victory, with trauma frequently occurring to the head; however, it remains unclear whether prolonged training enhances or impairs the athletes' attentional capacities. This study aimed to investigate the impact of Sanda training on athletes' attention by employing attention network tests.

Methods

A retrospective analysis was conducted on 37 professional Sanda athletes from a certain sports academy; 38 college students from the same institution majoring in physical education were recruited as the control group. Control participants had no prior experience in Sanda training, and the Sanda and control groups were matched in terms of sex, age, and education level. The Attention Network Test (ANT) was administered to both groups to compare differences in efficiency across the alerting, orienting, and executive control networks.

Results

Compared to the control group, the Sanda athletes exhibited significantly higher executive control network efficiency values and executive control network efficiency ratios (P < 0.05). There were no significant differences between the Sanda group and the control group regarding the efficiency values of the alerting and orienting networks (P > 0.05). Additionally, total accuracy and total reaction time between the Sanda athletes and control participants showed no statistically significant differences (P > 0.05).

Conclusion

Sanda practice has detrimental effects on attention, including a decrease in the efficiency of the executive control network and a prolongation of the total reaction time. Therefore, athletes should improve attention training and use head protection to prevent frequent head impacts during training.