bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive analysis of molecular mechanisms underlying kidney stones: gene expression profiles and potential diagnostic markers
Authors: Aji Kaisaier , Aikebaier Aierken , Abula Asimujiang , Song Guang Lu
Published: November 2024

Background

The study aimed to investigate the molecular mechanisms underlying kidney stones by analyzing gene expression profiles. They focused on identifying differentially expressed genes (DEGs), performing gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and screening optimal feature genes using various machine learning algorithms.

Methods

Data from the GSE73680 dataset, comprising normal renal papillary tissues and Randall’s Plaque (RP) tissues, were downloaded from the GEO database. DEGs were identified using the limma R package, followed by GSEA and WGCNA to explore functional modules. Functional enrichment analysis was conducted using KEGG and Disease Ontology. Various machine learning algorithms were used for screening the most suitable feature genes, which were then assessed for their expression and diagnostic significance through Wilcoxon rank-sum tests and ROC curves. GSEA and correlation analysis were performed on optimal feature genes, and immune cell infiltration was assessed using the CIBERSORT algorithm.

Results

412 DEGs were identified, with 194 downregulated and 218 upregulated genes in kidney stone samples. GSEA revealed enriched pathways related to metabolic processes, immune response, and disease states. WGCNA identified modules correlated with kidney stones, particularly the yellow module. Functional enrichment analysis highlighted pathways involved in metabolism, immune response, and disease pathology. Through machine learning algorithms, KLK1 and MMP10 were identified as optimal feature genes, significantly upregulated in kidney stone samples, with high diagnostic value. GSEA further elucidated their biological functions and pathway associations.

Conclusion

The study comprehensively analyzed gene expression profiles to uncover molecular mechanisms underlying kidney stones. KLK1 and MMP10 were identified as potential diagnostic markers and key players in kidney stone progression. Functional enrichment analysis provided insights into their roles in metabolic processes, immune response, and disease pathology. These results contribute significantly to a better understanding of kidney stone pathogenesis and may inform future diagnostic and therapeutic strategies.
What are microsatellites and how to choose the best tool: a user-friendly review of SSR and 74 SSR mining tools
Authors: Alves Sandy Ingrid Aguiar , Dantas Carlos Willian Dias , Macedo Daralyns Borges , Ramos Rommel Thiago Jucá
Published: November 2024

Microsatellites, also known as SSR or STR, are essential molecular markers in genomic research, playing crucial roles in genetic mapping, population genetics, and evolutionary studies. Their applications range from plant breeding to forensics, highlighting their diverse utility across disciplines. Despite their widespread use, traditional methods for SSR analysis are often laborious and time-consuming, requiring significant resources and expertise. To address these challenges, a variety of computational tools for SSR analysis have been developed, offering faster and more efficient alternatives to traditional methods. However, selecting the most appropriate tool can be daunting due to rapid technological advancements and the sheer number of options available. This study presents a comprehensive review and analysis of 74 SSR tools, aiming to provide researchers with a valuable resource for SSR analysis tool selection. The methodology employed includes thorough literature reviews, detailed tool comparisons, and in-depth analyses of tool functionality. By compiling and analyzing these tools, this study not only advances the field of genomic research but also contributes to the broader scientific community by facilitating informed decision-making in the selection of SSR analysis tools. Researchers seeking to understand SSRs and select the most appropriate tools for their projects will benefit from this comprehensive guide. Overall, this study enhances our understanding of SSR analysis tools, paving the way for more efficient and effective SSR research in various fields of study.
Tumor-associated macrophages in bladder cancer: roles and targeted therapeutic strategies
Authors: Ma Yuanchun , Sun Ying , Guo Hongqian , Yang Rong
Published: November 2024

Bladder cancer (BC) is the ninth most common and “expensive” cancer in the world. Despite the availability of various treatment modalities such as chemotherapy, immunotherapy and surgery, the overall survival rate of patients with advanced bladder cancer remains low. As one of the most abundant infiltrating immune cells in bladder cancer, tumor-associated macrophages (TAMs) play an important role in the development of BC and in the standard regimen of intravesical BCG therapy. Targeting TAMs have achieved excellent results in clinical trials for a variety of other cancers, but few studies have been conducted for bladder cancer. Further exploration is still needed to develop TAM-related therapeutic strategies for BC treatment, which are expected to improve the therapeutic efficacy and life quality of patients. This review summarizes the relationship between TAMs in bladder cancer and disease staging, evolution, patient prognosis, and treatment outcome. Several potential TAM targets in BC are also pointed, which may help to inhibit tumor-promoting TAMs and provide new therapeutic approaches for advanced BC.
Small-molecule inhibitors of the CD40–CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models
Authors: Chuang Sung-Ting , Alcazar Oscar , Watts Brandon , Abdulreda Midhat H. , Buchwald Peter
Published: November 2024

As part of our work to develop small-molecule inhibitors (SMIs) of the CD40-CD40L(CD154) costimulatory protein-protein interaction, here, we describe the ability of two of our most promising SMIs, DRI-C21041 and DRI-C21095, to prolong the survival and function of islet allografts in two murine models of islet transplantation (under the kidney capsule and in the anterior chamber of the eye) and to prevent autoimmune type 1 diabetes (T1D) onset in NOD mice. In both transplant models, a significant portion of islet allografts (50%-80%) remained intact and functional long after terminating treatment, suggesting the possibility of inducing operational immune tolerance via inhibition of the CD40-CD40L axis. SMI-treated mice maintained the structural integrity and function of their islet allografts with concomitant reduction in immune cell infiltration as evidenced by direct longitudinal imaging in situ. Furthermore, in female NODs, three-month SMI treatment reduced the incidence of diabetes from 80% to 60% (DRI-C21041) and 25% (DRI-C21095). These results (i) demonstrate the susceptibility of this TNF superfamily protein-protein interaction to small-molecule inhibition, (ii) confirm the in vivo therapeutic potential of these SMIs of a critical immune checkpoint, and (iii) reaffirm the therapeutic promise of CD40-CD40L blockade in islet transplantation and T1D prevention. Thus, CD40L-targeting SMIs could ultimately lead to alternative immunomodulatory therapeutics for transplant recipients and prevention of autoimmune diseases that are safer, less immunogenic, more controllable (shorter half-lives), and more patient-friendly (i.e., suitable for oral administration, which makes them easier to administer) than corresponding antibody-based interventions.
Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies
Authors: Nolan-Stevaux Olivier , Smith Richard
Published: November 2024

CAR-T cell and T cell engager therapies have demonstrated transformational efficacy against hematological malignancies, but achieving efficacy in solid tumors has been more challenging, in large part because of on-target/off-tumor toxicities and sub-optimal T cell anti-tumor cytotoxic functions. Here, we discuss engineering solutions that exploit biological properties of solid tumors to overcome these challenges. Using logic gates as a framework, we categorize the numerous approaches that leverage two inputs instead of one to achieve better cancer selectivity or efficacy in solid tumors with dual-input CAR-Ts or multi-specific TCEs. In addition to the “OR gate” and “AND gate” approaches that leverage dual tumor antigen targeting, we also review “contextual AND gate” technologies whereby continuous cancer-selective inputs such a pH, hypoxia, target density, tumor proteases, and immune-suppressive cytokine gradients can be creatively incorporated in therapy designs. We also introduce the notion of “output directionality” to distinguish dual-input strategies that mechanistically impact cancer cell killing or T cell fitness. Finally, we contrast the feasibility and potential benefits of the various approaches using CAR-T and TCE therapeutics and discuss why the promising “IF/THEN” and “NOT” gate types pertain more specifically to CAR-T therapies, but can also succeed by integrating both technologies.
Effect of recycled molybdenum tailings on mechanical properties of ultra-high-performance concrete
Authors: Li Xin , Liu Cun-Xiang , Zhao Xin-Yu , Kang Shao-Bo
Published: November 2024

This paper presents experimental studies on mechanical properties and micro-structures of ultra-high performance concrete (UHPC) made of recycled molybdenum tailings. The particle size distribution and chemical compositions of recycled molybdenum tailings were analysed at first. Then, compressive and flexural tests were conducted on UHPC in which different volume fractions of recycled molybdenum tailings were used to replace silica sand. The effects of recycled molybdenum tailings replacement ratio on the compressive and flexural strengths were determined through comparisons. Besides, X-ray diffraction tests and backscattered electron tests were carried out to analyse the effect of molybdenum tailings on the micro-structure of UHPC. Based on test data, an optimal replacement ratio of molybdenum tailings was determined which could significantly reduce the cost of UHPC but maintain the mechanical properties in compression. A molybdenum tailings replacement ratio of 30% was recommended to maximise the economic effect and to reduce the carbon emission.
Prevalence of paucibacillary cases of leprosy in Brazil: a 20-year systematic review and meta-analysis
Authors: Brito Gonçalves Bruna Eduarda , Raiol André Matheus Porto , Brito Ana Vitória Cruz , Silva Marcos Jessé Abrahão , Sardinha Daniele Melo , Lima Karla Valéria Batista , Lima Luana Nepomuceno Gondim Costa
Published: November 2024

Introduction

Leprosy is a chronic infectious disease caused by the agent Mycobacterium leprae, characterized by its high disabling power. Data points to Brazil being the second country with the highest number of cases in the world, behind only India, representing a major challenge for public health. This work aims to determine the prevalence of paucibacillary (PB) cases in relation to leprosy cases in Brazil, using data published in the literature.

Methods

This is a systematic review and meta-analysis carried out with studies from the last 20 years, being developed based on the Preferred Reporting Items for Systematic Review and Meta-analyzes (PRISMA).The search was carried out in the databases: PUBMED, SciELO, LILACS (via VHL)and Science Direct in October 2023, using the following descriptors (((“Brazil” [Mesh]) AND (“Leprosy, paucibacillary” [Mesh])) AND “Epidemiology” [Mesh]), in English, Portuguese and Spanish. Original studies of the analytical case–control, cohort, cross-sectional, epidemiological types were selected, as well as articles with satisfactory information for numerical extraction with separate data on the paucibacillary and multibacillary clinical forms. The methodological quality assessment followed the JBI critical appraisal checklist. Statistical analysis was performed using the Comprehensive Meta-Analyses-CMA software, version 3.0 (Biostat, Engewood, NJ, United States).

Results

The meta-analysis of the 48 studies obtained a paucibacillary prevalence rate in Brazil of 50.5% or 0.505 (95% CI = 0.502–0.509).The differences in the analyzes were statistically significant (Q-value 4302.681;df 47; I 98.905), with a high heterogeneity value evidenced by I2 (98.905). This analysis demonstrated that the frequency in the Midwest region was the highest and the South region was the lowest (21.4%). Begg’s (Kendall Tau p = 0.35) and Egger’s tests (p = 0.20) were performed, in which no high publication bias was noted. Subgroup analysis indicated that paucibacillary cases varied from region to region, with the Midwest region having the highest prevalence and the South region having the lowest.

Conclusion

The results stand out significantly for the research gaps that investigate PB cases, requiring more research aimed at investigating the paucibacillary clinical form that can contribute to the early diagnosis of leprosy.

Systematic review registration

PROSPERO code: CRD42024514106.
Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis
Authors: Zhang Zhengyi , Yang Meijie , Zhou Tong , Chen Yingjie , Zhou Xiujuan , Long Kunlan
Published: November 2024

Background

The association between the gut microbiota and sepsis has garnered attention in the field of intestinal research in sepsis. This study utilizes bibliometric methods to visualize and analyze the literature on gut microbiota research in sepsis from 2011 to 2024, providing a scientific foundation for research directions and key issues in this domain.

Methods

Original articles and reviews of gut microbiota research in sepsis, which published in English between 2011 and 2024, were obtained from the Web of Science Core Collection on June 21, 2024. Python, VOSviewer, and CiteSpace software were used for the visual analysis of the retrieved data.

Results

A total of 1,031 articles were analyzed, originating from 72 countries or regions, 1,614 research institutions, and 6,541 authors. The articles were published in 434 different journals, covering 89 different research fields. The number of publications and citations in this research area showed a significant growth trend from 2011 to 2024, with China, the United States, and the United Kingdom being the main research forces. Asada Leelahavanichkul from Thailand was identified as the most prolific author, making him the most authoritative expert in this field. “Nutrients” had the highest number of publications, while “Frontiers in Cellular and Infection Microbiology,” “Frontiers in Immunology” and “the International Journal of Molecular Sciences” have shown increasing attention to this field in the past 2 years. Author keywords appearing more than 100 times included “gut microbiota (GM),” “sepsis” and “microbiota.” Finally, this study identified “lipopolysaccharides (LPS),” “short-chain fatty acids (SCFAs),” “probiotics,” “fecal microbiota transplantation (FMT)” and “gut-liver axis” as the research hotspots and potential frontier directions in this field.

Conclusion

This bibliometric study summarizes current important perspectives and offers comprehensive guidance between sepsis and intestinal microbiota, which may help researchers choose the most appropriate research directions.
Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation
Authors: Han Xing , Zhang Bo-Wen , Zeng Wei , Ma Meng-Lin , Wang Ke-Xin , Yuan Bao-Juan , Xu Dan-Qi , Geng Jia-Xin , Fan Chao-Yuan , Gao Zhan-Kui , Arshad Muhammad , Gao Shan , Zhao Liangliang , Liu Shu-Lin , Mu Xiao-Qin
Published: November 2024

Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.
Identification of IspD as a novel target for tuberculosis treatment using compound M6
Authors: Dong Lijun , Qi Hui , Zhu Yue , Yang Yuma , Zhao Yue , Zhang Sihan , Su Yongqiang , Yue Taiyun , Du Xiancai , Lei Hetian , Yang Yanhui
Published: November 2024

Introduction

Tuberculosis (TB) is a serious infectious disease that endangers human health, and TB becomes more difficult in eradiation due to its multidrug resistance (MDR). The objective of this research was to identify novel targets for treating TB.

Methods

A 2-fold serial dilution method was used to determine minimal inhibitory concentrations (MIC) of compound M6 against Mycobacterium smegmatis (M. smegmatis). Compound M6 was subjected to reverse molecular docking with seven Mycobacterium tuberculosis proteins, and the best binding protein with the highest LibDock score was evaluated. The target protein with the highest score was purified through prokaryotic expression. Isolated target proteins were investigated for the enzyme activities and for the kinetic effect of compound M6 by absorbance detection. Subsequently, the CRISPR/Cas9 technology was employed to inhibit target gene expression for detecting MIC changes. Finally, potential targets were evaluated for the effect of the compound M6 in bacteria.

Results

The MIC values of compound M6 against M. smegmatis were 32 μg/mL. The results from reverse molecular docking show that IspD has the highest LibDock score of 142.50, followed by Rv0674, IspF, and Dxr, with docking scores of 110.762, 71.6955, and 57.7446, respectively. IspD is a key enzyme in the 2-C-methyl-D-erythritol 4-phosphate pathway of MTB. The aKi and Ki values of M6 for the substrate MEP are 609.58 μM and 81.33 μM. For CTP, the aKi and Ki values are 657.89 μM and 40.07 μM. With tetracycline inducing CRISPR/Cas9 to suppress the expression of IspD, the MIC value of M6 against IspD went down significantly from 32 μg/mL to 4 μg/mL.

Conclusion

IspD is a novel target of the compound M6 for treating TB.
Mature compost enhanced the harmlessness level in co-composting swine manure and carcasses in large-scale silo reactors
Authors: Jiao Ziwei , Zhang Liping , Zhang Ake , Li Ruoqi , Zhang Kui , Wu Zhen , Kang Zitong , Wei Yuquan , Zhang Longli , Wang Yue , Shi Xiong , Li Ji
Published: November 2024

This study aimed to investigate the impact of incorporating mature compost on the harmlessness and maturity level of composting from swine manure and carcasses from industrialized pig farms in continuously running large-scale silo reactor systems. The potential human or animal bacterial pathogens and core bacterial community in composting were analyzed by high-throughput sequencing of 16S rRNA gene amplicons. The results showed that the addition of mature compost in the GD group significantly increased the temperature of all depths, the accumulated temperature of compost, and the germination index (75.43%) compared to that in the HN group without mature compost. High-throughput sequencing revealed that the dominated genera in GD were Ureibacillus, Lactobacillus, Corynebacterium, Staphylococcus, and Jeotgalicoccus, and the addition of mature compost could significantly increase the relative abundance of Ureibacillus (16.82%) that was associated with the biodegradation of organics. A total of 421 potential bacterial pathogens were detected, and the dominated genera of pathogens were Streptococcus, Staphylococcus, and Anaerococcus. The potential pathogen in the GD group with mature compost was reduced from 7.16 to 0.77%, which was significantly lower than that (2.97%) in the HN group. Together, these findings revealed that mature compost addition in large-scale reactor composting could accelerate the harmless and humification process, providing an effective and environmentally friendly scheme to deal with the main organic wastes in intensive pig farms.
Nephrology intervention to avoid acute kidney injury in patients awaiting cardiac surgery: randomized clinical trial
Authors: Codina Sergi , Oliveras Laia , Ferreiro Eva , Rovira Aroa , Coloma Ana , Lloberas Nuria , Melilli Edoardo , Hueso Miguel , Sbraga Fabrizio , Boza Enric , Vazquez José M. , Pérez-Fernández José L. , Sabater Joan , Cruzado Josep M. , Montero Nuria
Published: November 2024

Introduction

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-known complication that increases morbidity and mortality rates. The objective of this study was to reduce CSA-AKI through nephrologist intervention in patients awaiting cardiac surgery.

Methods

We performed a single center, open-label, randomized clinical trial including 380 patients who underwent scheduled cardiac surgery at the Hospital de Bellvitge between July 2015 and October 2019. A total of 184 patients were evaluated by the same Nephrologist one month before the surgery to minimize the risk factors for AKI. In addition to assessments at the outpatient clinic, we also collected clinical data during hospitalization and during the first year.

Results

Despite the intervention, no differences were observed between the groups in the incidence of CSA-AKI (intervention group 26.37% vs. standard of care 25.13%, p=0.874), mortality (3.91% vs. 3.59%, p=0.999), length of Intensive Care Unit (ICU) stay (10 days [7.00;15.0] for both groups, p=0.347), or renal function after one year of follow-up (estimated glomerular filtration rate (eGFR) by CKD-EPI: 74.5 ml/min (standard deviation 20.6) vs 76.7 (20.8) ml/min, respectively, p=0.364). A reduction in the need for blood transfusion was observed in the intervention group, although the difference was not statistically significant (37.22% vs. 45.03%, p =0.155).

Conclusion

In this clinical trial, nephrologist intervention in the entire population on the cardiac surgery waiting list did not show a nephroprotective benefit.

Clinical trial registration

ClinicalTrials.gov, identifier (NCT02643745).
Hemodynamic assessment of intracranial atherosclerotic stenosis: comparison between invasive non-hyperemic pressure ratio and angiography-derived quantitative flow ratio
Authors: Wang Xiaohui , Bian Yang , Zhang Rongju , Zhu Haojing , Yang Junjie , Wang Ruiling , Liu Xinfeng , Lv Bin , Cao Xiangyu , Dai Wei , Sun Zhibin , Jing Jing , Du Zhihua , Yu Shengyuan , Wang Jun
Published: November 2024

Objectives

To evaluate the diagnostic accuracy of the quantitative flow ratio (QFR) for hemodynamic exploration of intracranial atherosclerotic stenosis, using the invasive cerebrovascular pressure ratio (CVPR) and resting full-cycle ratio (RFR) as reference standards.

Materials and methods

Patients with symptomatic unifocal intracranial atherosclerotic stenosis were included. The CVPR was defined as the ratio of the proximal and distal pressures. All patients underwent angioplasty under general anesthesia. The QFR was calculated based on digital subtraction angiography. Using the CVPR as a reference, we compared its correlation with the QFR across different degrees and locations of stenosis.

Results

The CVPR and QFR were measured in 34 vessels of 32 patients. The QFR demonstrated a high correlation and excellent agreement(r = 0.8227, p < 0.001) with the CVPR in distal stenosis before intervention. In the subgroup with diameter stenosis >80%, the QFR showed a high correlation (r = 0.8812, p < 0.001) with the CVPR. In the anterior circulation subgroup, the QFR showed an excellent correlation (r = 0.9066, p < 0.001) with the CVPR. In the posterior circulation subgroup, the QFR showed a high correlation with the CVPR (r = 0.7706, p < 0.001). Diameter stenosis rates showed a moderate negative correlation with the CVPR.

Conclusion

There was a strong correlation between the QFR and wire-based CVPR, especially for anterior circulation lesions before intervention. The QFR may serve as a predictive factor for evaluating hemodynamic changes in intracranial atherosclerotic stenosis.
Biopsychosocial rehabilitation therapy in small fiber neuropathy: research protocol to study the effect of rehabilitation treatment
Authors: Damci Aysun , den Hollander Marlies , Hoeijmakers Janneke G. J. , Faber Catharina G. , Goossens Mariëlle E. J. B. , Verbunt Jeanine A. M. C. F.
Published: November 2024

Background

Small fiber neuropathy (SFN) is a chronic neuropathic pain condition that can lead to a decreased quality of life (QOL) and disability. Current pain treatment is mainly symptomatic, consisting of analgesics, with often disappointing results. There is a need for new, more effective treatment modality. Treatment based on a biopsychosocial approach on SFN-related pain may be a promising alternative. A rehabilitation treatment study protocol is presented with the following main objective: to test the effect of a tailored interdisciplinary rehabilitation treatment targeting both cognitive and psychological factors related to pain, in decreasing disability, and improving QOL in SFN.

Methods

Single-case experimental design. Ten participants with SFN will be included. Every patient will be offered a personalized program based on one of three rehabilitation treatment modules (graded activity, exposure in vivo or acceptance and commitment therapy) depending on the most prominent factor maintaining disability. Treatment will be provided for at least 8 weeks with 2 sessions a week.

Discussion/conclusion

This is the first study investigating personalized rehabilitation treatment in patients with idiopathic SFN. The findings are expected to result in an effective treatment for SFN with an increase in QOL and a decrease in disability.

Clinical trial registration

ClinicalTrials.gov, identifier NCT05798949.
Examining how topicality impacts pronoun resolution in second language processing
Authors: Wang Tingting , Minai Utako , Gabriele Alison
Published: November 2024

In research on second language (L2) processing, the processing of reference has been highlighted as a domain of particular difficulty, but the source of the difficulty is not well understood. The present study examines whether differences in the pronominal systems of the first language (L1) and L2 impact processing. We take a novel approach, testing a group of intermediate-advanced L2 learners in both their L1 (Mandarin Chinese) and L2 (English), allowing us to directly examine whether L2 learners show similar or different patterns when processing the L1 and L2. We also test a group of L1 English speakers. The study focused on two topicality-related factors, subjecthood and pronominalization, that have been shown to increase the prominence of an entity in the discourse, making it more likely that an entity in subject position (subjecthood) or an entity that has been referred to with a pronoun (pronominalization) will be considered as an antecedent for a subsequent pronoun. We developed a picture verification task with visual-world eye-tracking in both English and Chinese. This task provides a measure of both pronoun interpretation and online processing. Results showed subtle differences in how subjecthood and pronominalization are weighted in English and Chinese as L1s: pronominalization played a stronger role in L1 Chinese than in L1 English both in the interpretation measure and in the eye-movement data. The results for the L2 English learners showed an interesting pattern in which their results were more similar to the L1 English results on the measure of pronoun interpretation, but were more similar to the L1 Chinese results in the eye-movement data. These results show successful use of discourse cues in L2 pronoun interpretation but differences between L1 and L2 speakers during processing. It is proposed that decreased sensitivity to morphosyntactic information that is not present in the L1 (case on pronouns) leads to differences in L2 referential processing, in line with proposals that L2 learners face challenges with integrating different kinds of linguistic information online, particularly morphosyntactic information.
Beta-gamma phase-amplitude coupling of scalp electroencephalography during walking preparation in Parkinson’s disease differs depending on the freezing of gait
Authors: Kimoto Yuki , Tani Naoki , Emura Takuto , Matsuhashi Takahiro , Yamamoto Takuto , Fujita Yuya , Oshino Satoru , Hosomi Koichi , Khoo Hui Ming , Miura Shimpei , Fujinaga Takahiro , Yanagisawa Takufumi , Kishima Haruhiko
Published: November 2024

Introduction

Despite using beta oscillations within the subthalamic nucleus as a biomarker of akinesia or rigidity in Parkinson’s disease, a specific biomarker for freezing of gait (FOG) remains unclear. Recently, scalp phase-amplitude coupling (PAC) measured through scalp electroencephalography (EEG) has emerged as a promising tool for analyzing brain function. In this study, we examined whether PAC could be a biomarker for FOG.

Methods

We enrolled 11 patients with Parkinson’s disease and recorded scalp EEG in preparation for and during gait while simultaneously assessing motor function, including FOG. We investigated changes in cortical PAC during walking with and without FOG and examined its correlation with the postural instability and gait difficulty (PIGD) score.

Results

Patient characteristics were as follows: mean age 59.1 ± 6.9 years, disease duration 13.9 ± 4.1 years, and seven men. Four trials were excluded from the analysis owing to artifacts. In the trials without FOG (n = 18), beta-gamma PAC in the sensorimotor area decreased during gait preparation (p = 0.011; linear mixed-effects model), which was not the case in trials with FOG (n = 6) (p = 0.64; linear mixed-effects model). Using a support vector machine, machine learning of PAC during preparation for walking predicted the presence of FOG with an accuracy of 71.2%. Conversely, PAC increased during walking in trials with FOG (p = 0.0042; linear mixed-effects model), and PAC 20 s after the start of walking was positively correlated with the PIGD score (correlation coefficient = 0.406, p = 0.032; Pearson’s rank correlation).

Conclusion

Beta-gamma PAC in the sensorimotor area during preparation for walking differs depending on the emergence of FOG. As gait symptoms worsened, beta-gamma PAC in the sensorimotor area during walking gradually increased. Cortical PAC may be a biomarker for FOG in Parkinson’s disease and may lead to the development of strategies to prevent falls in the future.
Non-invasive vagus nerve stimulation in anti-inflammatory therapy: mechanistic insights and future perspectives
Authors: Liu Fu-Jun , Wu Jing , Gong Li-Jun , Yang Hong-Shuai , Chen Huan
Published: November 2024

Non-invasive vagus nerve stimulation (VNS) represents a transformative approach for managing a broad spectrum of inflammatory and autoimmune conditions, including rheumatoid arthritis and inflammatory bowel disease. This comprehensive review delineates the mechanisms underlying VNS, emphasizing the cholinergic anti-inflammatory pathway, and explores interactions within the neuro-immune and vagus-gut axes based on both clinical outcomes and pre-clinical models. Clinical applications have confirmed the efficacy of VNS in managing specific autoimmune diseases, such as rheumatoid arthritis, and chronic inflammatory conditions like inflammatory bowel disease, showcasing the variability in stimulation parameters and patient responses. Concurrently, pre-clinical studies have provided insights into the potential of VNS in modulating cardiovascular and broader inflammatory responses, paving the way for its translational application in clinical settings. Innovations in non-invasive VNS technology and precision neuromodulation are enhancing its therapeutic potential, making it a viable option for patients who are unresponsive to conventional treatments. Nonetheless, the widespread adoption of this promising therapy is impeded by regulatory challenges, patient compliance issues, and the need for extensive studies on long-term efficacy and safety. Future research directions will focus on refining VNS technology, optimizing treatment parameters, and exploring synergistic effects with other therapeutic modalities, which could revolutionize the management of chronic inflammatory and autoimmune disorders.
Effects of time-of-day resistance training on muscle strength, hormonal adaptations, and sleep quality during Ramadan fasting
Authors: Triki Raoua , Ben Abderrahman Abderraouf , Salhi Iyed , Rhibi Fatma , Saeidi Ayoub , Almaqhawi Abdullah , Hackney Anthony C. , Laher Ismail , Granacher Urs , Zouhal Hassane
Published: November 2024

Objectives

We investigated the timing of resistance training (RT) during Ramadan fasting (RF) on muscle strength, hormonal adaptations, and sleep quality.

Methods

Forty healthy and physically active male Muslims (age = 25.7 ± 5.6 years, body mass = 85.1 ± 17.5 kg, height = 175 ± 9 cm, BMI = 28.3 ± 5.7 kg/m2) were enrolled in this study and 37 completed pre and post-tests. Subjects were randomly allocated into two experimental groups. Group 1 (FAST, n = 20) completed an 8-week whole-body RT in the late afternoon (between 16 h and 18 h) while fasting. Group 2 (FED, n = 20) completed the similar RT protocol compared with FAST at night (between 20 h and 22 h). The following parameters were analyzed at various time-points: 2 weeks before the start of RF (T0), on the 15th day of Ramadan (T1), on the 29th day of Ramadan (T2), and 21 days after the last day of RF (T3) where both groups were in a fed state. One-repetition maximum tests (1-RM) were conducted for the squats (1-RMSQ), the deadlift (1-RMDL) and the bench press (1-RMBP). Sleep quality was assessed using the full Pittsburgh Sleep Quality Index (PSQI). Blood samples were taken to determine cortisol, testosterone and IGF-1 levels. Additionally, acute hormonal responses were evaluated before (BF), immediately after (AF), and 30 min after a RT session (AF-30 min) at T0, T1, T2, and T3.

Results

Significant group-by-time interactions were identified for 1-RMSQ (p = 0.001; effect size [ES] = 0.43) and 1-RMDL (p = 0.001; ES = 0.36). Post-hoc tests indicated significant 1-RMSQ (p = 0.03; ES = 0.12) and 1-RMDL (p = 0.04; ES = 0.21) improvements from T0-T2 for FED. Additionally, significant group-by-time interactions were observed for the chronic effects on cortisol (p = 0.03; ES = 0.27) and testosterone levels (p = 0.01; ES = 0.32). Post-hoc tests indicated significant increases of cortisol levels among FAST at T1 and T2 compared to T0 (p = 0.05; ES = 0.41, p = 0.03; ES =  0.34) and a significant increase in cortisol levels in FED at T1 (p = 0.05; ES = 0.29) and T2 (p = 0.04; ES = 0.25). However, the observed increase was lower compared to FAST. Post-hoc tests also indicated significant increases of testosterone only among FED at T2 (p = 0.04; ES = 0.31). A significant group-by-time interaction was found for the acute effect of exercise on cortisol level (p = 0.04; ES = 0.34). The cortisol level immediately after RT was higher in FAST only at T1 (p = 0.03; ES = 0.39) and T2 (p = 0.05; ES = 0.22) compared with T0. No significant group-by-time interactions were identified for sleep quality (p = 0.07; ES = 0.43).

Conclusion

Muslims can safely practice RT during RF. However, training in a fed state during Ramadan might be more effective than during fasted state for the enhancement of maximal strength with better hormonal responses observed.
Transcriptomic era of cancers in females: new epigenetic perspectives and therapeutic prospects
Authors: Zhu Runhe , Ni Jiawei , Ren Jiayin , Li Dongye , Xu Jiawei , Yu Xinru , Ma Ying Jie , Kou Luan
Published: November 2024

In the era of transcriptomics, the role of epigenetics in the study of cancers in females has gained increasing recognition. This article explores the impact of epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNA, on cancers in females, including breast, cervical, and ovarian cancers (1). Our findings suggest that these epigenetic markers not only influence tumor onset, progression, and metastasis but also present novel targets for therapeutic intervention. Detailed analyses of DNA methylation patterns have revealed aberrant events in cancer cells, particularly promoter region hypermethylation, which may lead to silencing of tumor suppressor genes. Furthermore, we examined the complex roles of histone modifications and long non-coding RNAs in regulating the expression of cancer-related genes, thereby providing a scientific basis for developing targeted epigenetic therapies. Our research emphasizes the importance of understanding the functions and mechanisms of epigenetics in cancers in females to develop effective treatment strategies. Future therapeutic approaches may include drugs targeting specific epigenetic markers, which could not only improve therapeutic outcomes but also enhance patient survival and quality of life. Through these efforts, we aim to offer new perspectives and hope for the prevention, diagnosis, and treatment of cancers in females.
Nomogram for predicting testicular yolk sac tumor in children based on age, alpha-fetoprotein, and ultrasonography
Authors: Yu Huan , Wang Hui , Huang Yichen , Hu Huiyong , Zhang Yue , Wu Min , Lyu Yiqing , Chen Yan , Zhou Lijun , Liang Yan , Sun Huizhen , Lin Xiaoling , Xie Hua , Chen Fang
Published: November 2024

Objective

To establish a predictive model for distinguishing testicular benign or yolk sac tumors in children.

Methods

We retrospectively analyzed data for 119 consecutive patients with unilateral testicular tumors treated at a single institution from June 2014 to July 2020. The patients were divided into the benign (n = 90) and yolk sac (n = 29) tumor groups based on the pathological diagnosis. We recorded patient age, serum markers [serum alpha-fetoprotein (AFP), human chorionic gonadotropin], and tumor ultrasonic findings (maximum diameter, ultrasonic echo, blood flow signal). Predictive factors were identified using descriptive statistical methods. A nomogram was established for preoperative prediction. An additional 46 patients were used as a validation cohort to verify the model.

Results

Patients with testicular yolk sac tumors were younger (median age: 14.0 vs. 34.0 months, P = 0.001) and had a higher incidence of elevated AFP levels (93.1% vs. 2.2%, P < 0.001). Ultrasonography indicated that testicular yolk sac tumors tended to have larger maximum diameters (26.5 ± 11.3 vs. 16.6 ± 9.2 cm, P < 0.001), a higher proportion of hypoechoic masses (44.8% vs. 8.9%, P < 0.001), and a higher incidence of masses with strong blood flow signals (93.1% vs. 5.6%, P < 0.001). A nomogram based on age, AFP levels, and ultrasound blood flow signals effectively predicted the probability of yolk sac tumor in children, with an accuracy of 0.98 (95% confidence interval: 0.984–1.003). The Brier score of the nomogram was 0.0002.

Conclusion

A nomogram based on age, AFP levels, and ultrasound blood flow signals can effectively predict the probability of testicular yolk sac tumor preoperatively, aiding in clinical decision-making and patient counseling.
A review on the treatment of hyperlipidemia with Erchen Decoction
Authors: Tian Xinyang , Liu Peiyu , Wang Ruolin , Hou Yawei , Zhou Ying , Wang Chunyan , Zhang Guiju
Published: November 2024

Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research.
Pyroptosis in asthma: inflammatory phenotypes, immune and non-immune cells, and novel treatment approaches
Authors: Hao Yuqiu , Wang Wenrui , Zhang Lin , Li Wei
Published: November 2024

Pyroptosis is a form of inflammatory programmed cell death, and is activated by pathogen infections or endogenous danger signals. The canonical pyroptosis process is characterized by the inflammasome (typically NLRP3)-mediated activation of caspase-1, which in turn cleaves and activates IL-1β and IL-18, as well as gasdermin D, which is a pore-forming executor protein, leading to cell membrane rupture, and the release of proinflammatory cytokines and damage-associated molecular pattern molecules. Pyroptosis is considered a part of the innate immune response. A certain level of pyroptosis can help eliminate pathogenic microorganisms, but excessive pyroptosis can lead to persistent inflammatory responses, and cause tissue damage. In recent years, pyroptosis has emerged as a crucial contributor to the development of chronic inflammatory respiratory diseases, such as asthma. The present study reviews the involvement of pyroptosis in the development of asthma, in terms of its role in different inflammatory phenotypes of the disease, and its influence on various immune and non-immune cells in the airway. In addition, the potential therapeutic value of targeting pyroptosis for the treatment of specific phenotypes of asthma is discussed.
Soil test crop response nutrient prescription equations for improving soil health and yield sustainability—a long-term study under Alfisols of southern India
Authors: Murthy R. Krishna , Nagaraju Bhavya , Govinda K. , Uday Kumar S. N. , Basavaraja P. K. , Saqeebulla H. M. , Gangamrutha G. V. , Srivastava Sanjay , Dey Pradip
Published: November 2024

Introduction

Enhancing soil health and nutrient levels through fertilizers boosts agricultural productivity and global food security. However, careful fertilizer use is essential to prevent environmental damage and improve crop yields. The soil test crop response (STCR) is a scientific approach to fertilizer recommendation that ensures efficient use, supporting higher crop production while protecting the environment and preserving resources.

Methodology

A long-term field experiment on the STCR approach was initiated in 2017 at the Zonal Agriculture Research Station, University of Agricultural Sciences, Bangalore, India. The experiment aimed to study the impact of STCR-based nutrient prescription along with farmyard manure (FYM) for a targeted yield of soybean (Glycine max), sunflower (Helianthus annuus), dry chili (Capsicum annuum), aerobic rice (Oryza sativa L.), foxtail millet (Setaria italica), okra (Abelmoschus esculentus), and kodo millet (Paspalum scrobiculatum) on yield and changes in soil health in comparison with other approaches of fertilizer recommendation.

Results

The results showed a significant and positive impact of the integrated use of fertilizer with FYM based on the STCR approach on the productivity of all the crops and soil fertility. Significantly higher yields of soybean (23.91 q ha−1), sunflower (27.13 q ha−1), dry chili (16.67 q ha−1), aerobic rice (65.46 q ha−1), foxtail millet (14.07 q ha−1), okra (26.82 t ha−1), and kodo millet (17.10 q ha−1) were observed in the STCR NPK + FYM approach at yield level 1 compared to the general recommended dose and soil fertility rating approach. This approach outperformed the standard recommendations, enhancing nutrient uptake and efficiency across various crops. Utilizing the principal component analysis, the soil quality index effectively reflected the impact of nutrient management on soil properties, with the STCR NPK + FYM treatment at yield level 1 showing the highest correlation with improved soil physical and chemical parameters.

Discussion

The STCR approach led to improved yield, nutrient uptake, utilization efficiency, and soil health, thanks to a balanced fertilization strategy. This strategy was informed by soil tests and included factors like crop-induced nutrient depletion, baseline soil fertility, the efficiency of inherent and added nutrients through fertilizers and farmyard manure, and the success of yield-targeting techniques in meeting the nutritional needs of crops.
Claroideglomus etunicatum enhances Pteris vittata L. arsenic resistance and accumulation by mediating the rapid reduction and transport of arsenic in roots
Authors: Pan Guofei , Xu YueZhen , Li WeiZhen , Zan Linyan , Wang Xueli
Published: November 2024

Arbuscular mycorrhizal fungi (AMF) have been widely shown to significantly promote the growth and recovery of Pteris vittata L. growth and repair under arsenic stress; however, little is known about the molecular mechanisms by which AMF mediate the efficient uptake of arsenic in this species. To understand how AMF mediate P. vittata arsenic metabolism under arsenic stress, we performed P. vittata root transcriptome analysis before and after Claroideglomus etunicatum (C. etunicatum) colonization. The results showed that after C. etunicatum colonization, P. vittata showed greater arsenic resistance and enrichment, and its dry weight and arsenic accumulation increased by 2.01–3.36 times. This response is attributed to the rapid reduction and upward translocation of arsenic. C. etunicatum enhances arsenic uptake by mediating the MIP, PHT, and NRT transporter families, while also increasing arsenic reduction (PvACR2 direct reduction and vesicular PvGSTF1 reduction). In addition, it downregulates the expression of ABC and P-type ATPase protein families, which inhibits the compartmentalization of arsenic in the roots and promotes its translocation to the leaves. This study revealed the mechanism of C. etunicatum-mediated arsenic hyperaccumulation in P. vittata, providing guidance for understanding the regulatory mechanism of P. vittata.