bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 mitigates the response to TKIs in patients with CML via the inhibition of T-cell immunity
Authors: He Na , Li Guosheng , Liu Jinting , Liu Wancheng , Tian Ruifeng , Ma Daoxin
Published: November 2024

Introduction

Chronic myeloid leukemia (CML) is a severe hematological malignancy characterized by BCR-ABL fusion gene. The advent of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL has improved the landscape of CML treatment dramatically. The occurrence of coronavirus disease 2019 (COVID-19) has challenged many cancers. However, its effect on TKI therapy of CML remains unknown.

Methods

In this study, we collected peripheral blood from chronic phase CML patients treated with TKIs at low-level BCR-ABL P210 during COVID-19 pandemic, and determined the alterations of BCR-ABL P210 by applying the well-established BCR-ABL P210 detection system.

Results

Our results showed that the level of BCR-ABL P210 of CML patients was significantly elevated shortly after contracting COVID-19, and then recovered to pre-infection level within one month. The elevated degree of P210 was positively correlated with the duration of COVID-19. And the level of P210 was elevated in CML patients that took COVID-19 vaccination. Furthermore, lymphocyte subsets and cytokine detections were performed by flow cytometry to analyze the alteration of immune responses. Our results showed that effector CD8+ T (Teff) cells were significantly downregulated while naïve CD8+ T cells or Treg cells were obviously upregulated in P210-elevated CML patients after contracting COVID-19 compared to that in P210-unchanged or decreased CML patients. Moreover, the SARS-CoV-2 pseudovirus was constructed to further determine its effects. The results showed that the level of BCR-ABL P210 was upregulated upon transfection of SARS-CoV-2 pseudovirus into blood samples of CML patients.

Discussion

Our results demonstrate that COVID-19 suppresses the immune activity and consequentially elevates the level of BCR-ABL P210 of CML patients.
Integrated single-cell and bulk RNA sequencing reveals immune-related SPP1+ macrophages as a potential strategy for predicting the prognosis and treatment of liver fibrosis and hepatocellular carcinoma
Authors: Li Bangjie , Hu Jialiang , Xu Hanmei
Published: November 2024

Background

Liver fibrosis is a pathological response to liver damage induced by multiple etiologies including NASH and CCl4, which may further lead to cirrhosis and hepatocellular carcinoma (HCC). Despite the increasing understanding of liver fibrosis and HCC, clinical prognosis and targeted therapy remain challenging.

Methods

This study integrated single-cell sequencing analysis, bulk sequencing analysis, and mouse models to identify highly expressed genes, cell subsets, and signaling pathways associated with liver fibrosis and HCC. Clinical prediction models and prognostic genes were established and verified through machine learning, survival analysis, as well as the utilization of clinical data and tissue samples from HCC patients. The expression heterogeneity of the core prognostic gene, along with its correlation with the tumor microenvironment and prognostic outcomes, was analyzed through single-cell analysis and immune infiltration analysis. In addition, the cAMP database and molecular docking techniques were employed to screen potential small molecule drugs for the treatment of liver fibrosis and HCC.

Result

We identified 40 pathogenic genes, 15 critical cell subsets (especially Macrophages), and regulatory signaling pathways related to cell adhesion and the actin cytoskeleton that promote the development of liver fibrosis and HCC. In addition, 7 specific prognostic genes (CCR7, COL3A1, FMNL2, HP, PFN1, SPP1 and TENM4) were identified and evaluated, and expression heterogeneity of core gene SPP1 and its positive correlation with immune infiltration and prognostic development were interpreted. Moreover, 6 potential small molecule drugs for the treatment of liver fibrosis and HCC were provided.

Conclusion

The comprehensive investigation, based on a bioinformatics and mouse model strategy, may identify pathogenic genes, cell subsets, regulatory mechanisms, prognostic genes, and potential small molecule drugs, thereby providing valuable insights into the clinical prognosis and targeted treatment of liver fibrosis and HCC.
Associations between human milk EV-miRNAs and oligosaccharide concentrations in human milk
Authors: Holzhausen Elizabeth A. , Patterson William B. , Wong Benjamin H. , Kim Sewan , Kupsco Allison , Howe Caitlin G. , Bode Lars , Goran Michael I. , Alderete Tanya L.
Published: November 2024

Introduction

Human milk contains human milk oligosaccharides (HMOs) and microRNAs (miRNAs), which are key bioactive components. HMOs are indigestible carbohydrates that impact infant growth and development. miRNAs are small, non-coding RNAs that regulate post-transcriptional gene expression. miRNAs are abundant in human milk and can be contained in extracellular vesicles (EVs). There is evidence that miRNAs are synthesized in the mammary epithelium and may influence mammary gland development and milk synthesis. However, the relationships between miRNAs and HMOs have yet to be fully characterized.

Methods

This study examined the associations between 210 human milk EV-miRNAs and 19 HMOs in a cohort of 98 Latina mothers. HMO measures included summary measures and concentrations of 19 HMOs. Relationships between EV-miRNAs and HMOs were examined using principal components analysis and associations between individual EV-miRNAs and HMOs were assessed.

Results

Overall patterns of EV-miRNA levels, summarized using principal components, were associated with HMO summary measures and concentrations. Levels of individual EV-miRNAs were associated with HMO summary measures and individual concentrations of 2’FL, 3FL, 3’SL, 6’SL, FLNH, LNFP I, and LNH.

Discussion

Results from this study suggest that human milk EV-miRNAs are associated with the concentration of HMOs, which may have important effects on infant growth and development.
Case report: Modified transplantation for pediatric patients with pyruvate kinase deficiency
Authors: Pang Yuhui , Qi Xiaoyu , Qin Jiayue , Zhai Xiaoran , Wang Rongxiao , Cao Jianzhu , Zhang Na , Liu Jinxia , Li Jianying , Wu Weihai , Wei Shanshan , Zhang Jingjing , Zhang Shaofei , Zhang Yaochen , Yue Yan
Published: November 2024

Pyruvate kinase deficiency (PKD) is an autosomal recessive genetic disease caused by mutations in the PKLR gene. To date, the clinical manifestations of PKD are heterogeneous, ranging from fetal anemia, neonatal jaundice, and severe chronic hemolytic anemia to fully compensated hemolytic anemia. Successful cases of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for PKD have been reported, however, the number of cases is very small, and experiences are very limited. Here, we report two successful cases involving our modified conditioning regimen. This approach is suitable for patients with severe transfusion dependence. In conclusion, for PKD patients with severe transfusion dependence, allo-HSCT is an option and is currently a safe and effective way to completely eliminate the need for transfusions of drugs, such as Mitapivat, or genetic therapies and allow the patient to return to normal life.
Single-cell RNA sequencing reveals key molecular drivers and immune landscape in uveal melanoma: implications for targeted therapy and prognostic modeling
Authors: Song Zeyu , Shao Wenwen , Xiahou Zhikai , Xu Yue , Zhang Xiaofeng
Published: November 2024

Background

Uveal melanoma (UM), arising from melanocytes in the choroid, accounts for 3% to 5% of all melanocytic tumors and over 70% of intraocular malignancies. Despite effective local treatments, metastasis remains a significant challenge, with more than half of patients developing metastatic disease within ten years. Conventional therapies often yield poor outcomes, highlighting the urgent need for novel therapeutic strategies to enhance survival and prognosis for UM patients.

Methods

We conducted a detailed analysis of the GSE139829 dataset, focusing on scRNA-seq data from eight primary UM patients and three with metastatic disease. Through clustering and marker gene expression analyses, we identified distinct subtypes of UM tumor cells and examined their transcriptional, metabolic, and intercellular communication profiles. We developed a novel prognostic model, PCOLCE TCs Risk Score (PTRS), centered on the C5 PCOLCE+ tumor cells, which was validated through in vitro functional assays. Additionally, we performed immune infiltration and metabolic pathway analyses to elucidate tumor-immune interactions and their clinical significance.

Results

We identified eight distinct cell types in UM and classified tumor subpopulations into six subgroups. The C5 PCOLCE+ TCs subpopulation was highlighted as crucial in UM malignancy, demonstrating high differentiation potential and a significant role in tumor progression. CellChat analysis revealed substantial communication between C5 PCOLCE+ TCs and fibroblasts, suggesting their involvement in tumor growth and extracellular matrix remodeling. Metabolic pathway analysis indicated enhanced oxidative phosphorylation and glutathione metabolism in this subpopulation. Additionally, we developed a PTRS model based on C5 PCOLCE+ TCs, identifying CITED1 as a high-risk gene that promotes UM cell proliferation, invasion, and migration in vitro.

Conclusion

This study provides insights into UM metastasis via single-cell analysis, identifying C5 PCOLCE+ TCs as key malignancy drivers associated with oxidative phosphorylation and immune interactions. Our PTRS model highlights CITED1 as a high-risk gene that promotes UM cell proliferation, paving the way for new prognostic models and therapeutic targets to enhance patient outcomes.
Near-inertial ocean response to a typhoon on a continental slope in the Northern South China Sea
Authors: Zhang Han , Wu Renhao , Liu Fu , Ni Xiaobo , Tian Di
Published: November 2024

Typhoons are strong natural events that significantly influence the marine environment. In 2018, Typhoon Mangkhut traveled over a moored station with a depth ~1900 m on continental slope in the northern South China Sea, the near-inertial oceanic responses are studied based on the Regional Ocean Modeling System (ROMS) model simulation combined with observation data. Near-inertial currents after Mangkhut can be divided into three layers: near-circular polarized in upper ocean, across-slope polarized in deep ocean and along-slope polarized near the bottom, thickness of the three layers depend on the slope steepness. According to across-slope and along-slope intensified currents, the near-bottom vertical velocities and near-inertial energy were intensified at the moored station. The across-slope forth/back near-inertial flows brought cold/warm and salty/fresh water from deeper/shallower depth, increased vertical excursions of near-bottom temperature/salinity isolines and near-inertial available potential energy. The near-inertial barotropic across-slope currents were much greater than along-slope currents, with net cooling and salinity increase of the whole water column at the moored station. The core responses to Mangkhut were within 100 km around the station. The near-inertial kinetic energy generated both at sea surface and bottom slope, then propagated vertically into ocean interior and horizontally into the South China Sea basin as well as some topography-trapped waves propagated along the slope. This work enriches the understanding of air–sea interactions in coastal regions and the effect of ocean topography, especially after a typhoon.
Spatio-temporal patterns of fish acoustic communities in Western Mediterranean coralligenous reefs: optimizing monitoring through recording duration
Authors: La Manna Gabriella , Moro Merella Mariangela , Vargiu Riccardo , Morello Giuseppe , Sarà Gianluca , Ceccherelli Giulia
Published: November 2024

In this study, we explored the fish acoustic community at two coralligenous sites in Sardinia (Tavolara and Santa Teresa, western Mediterranean Sea) during the summer 2023. Our goal was to understand spatial and temporal patterns of fish acoustic activity on different temporal scales to offer insights for optimizing acoustic monitoring of this crucial ecosystem. We identified seventeen distinct sound types, revealing a diverse acoustic community. Tavolara had higher acoustic richness and abundance compared to Santa Teresa, which may be attributed to site-specific factors such as habitat structure, species composition, or levels of protection. Temporal analysis revealed clear diel patterns, with certain sounds associated with nocturnal or diurnal periods, reflecting the daily rhythms of different species. The study also examined how recording duration influenced acoustic richness, finding that longer recordings (15 minutes per hour and 15 minutes per hour at night) provided a more comprehensive detection of acoustic activity. Additionally, the number of recording days required to detect species richness varied depending on the site. While extended recordings improve the likelihood of detecting rare or sporadic sounds, they also present challenges in data management and equipment maintenance. The study underscores the importance of carefully planning sampling strategies to optimize acoustic monitoring and ensure effective and sustainable ecological research in coralligenous ecosystems.
Tracheobronchopathia osteoplastica: a clinical case report of a 63-year-old man
Authors: Lai Jing , Deng Yingli , He Qingmin
Published: November 2024

Tracheobronchopathia osteoplastica (TO) is a rare benign lesion of the airways, characterized by multiple nodular proliferations of bone and/or cartilaginous tissue in the submucosa of the trachea and bronchi. In this paper, we present a case of a 63-year-old male patient who was admitted to the hospital due to cough and blood in his sputum. The patient was diagnosed with TO through examination and pathological biopsy. The exact pathogenesis of this disease remains unclear, but it may be related to multiple factors such as chronic infection and inflammation. The clinical manifestations are diverse, with no symptoms or only mild cough in the early stage, and persistent cough, dyspnea, and other symptoms may appear as the disease progresses. Diagnosis mainly relies on pathological biopsy, while treatment is mainly symptomatic, including inhalation of glucocorticoids, airway interventional therapy, and stent placement. Overall, TO progresses slowly and has a good prognosis, but early diagnosis and elimination of predisposing factors are crucial for treatment.
Self-directed teaching: a holistic framework for educator autonomy
Authors: Mohiyeddini Changiz
Published: November 2024

Over recent decades, the complexity of higher education in general, and teaching specifically, has increased significantly, resulting in a myriad of challenges for educators. Traditional approaches to teaching often rely on standardized curricula and top-down instructional methods. Therefore, they are critically scrutinized for their lack of adaptability and limitations in addressing the diverse needs of contemporary educators and learners. The purpose of this paper is to introduce the concept of self-directed teaching (SDT) as a response to the contemporary challenges in education and explore its relevance and potential impact on educators and learners. SDT is proposed as a holistic, theory-based, proactive approach that integrates multiple core aspects of the teaching process into a cohesive framework. It aims to empower educators to embrace their autonomy, control their professional development, and adapt their teaching strategies, much like the concept of self-directed learning (SDL) applies to students. SDT has the potential to promote educator autonomy, provide strategies to address burnout, and offer adaptable approaches to meet diverse educational contexts. It encourages educators to tailor their teaching strategies and engage in continuous professional development, positioning them to respond flexibly to changing educational demands. Furthermore, this article outlines the theoretical foundations of SDT, grounded in theories such as self-directed learning, self-determination theory, and constructivist theory. Key components of SDT including autonomy awareness, teaching needs diagnosis, goal setting, resource identification, and continuous evaluation and reflection are discussed including strategies for successful implementation of SDT.
Diagnostic test accuracy of cellular analysis of bronchoalveolar lavage fluid in distinguishing pulmonary infectious and non-infectious diseases in patients with pulmonary shadow
Authors: Li Jiyang , Wang Ting , Liu Faming , Wang Juan , Qiu Xiaojian , Zhang Jie
Published: November 2024

Purpose

This study aims to assess the diagnostic accuracy of cellular analysis of bronchoalveolar lavage fluid (BALF) in distinguishing between pulmonary infectious and non-infectious diseases in patients with pulmonary shadows. Additionally, it will develop and validate a novel scoring system based on a nomogram for the purpose of differential diagnosis.

Methods

A retrospective analysis was conducted involving data from 222 patients with pulmonary shadows, whose etiological factors were determined at our institution. The cohort was randomly allocated into a training set comprising 155 patients and a validation set of 67 patients, (ratio of 7:3), the least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. The receiver operating characteristic curve (ROC) and calibration curve were utilized to assess the prediction accuracy of the model. Decision curve analysis (DCA) and clinical impact curve (CIC) were employed to evaluate the clinical applicability of the model. Moreover, model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the risk factors.

Results

Among the relevant predictors, the percentage of neutrophils in BALF (BALF NP) exhibited the most substantial differentiation, as evidenced by the largest area under the ROC curve (AUC = 0.783, 95% CI: 0.713–0.854). A BALF NP threshold of ≥16% yielded a sensitivity of 72%, specificity of 70%, a positive likelihood ratio of 2.07, and a negative likelihood ratio of 0.38. LASSO and multivariate regression analyses indicated that BALF NP (p < 0.001, OR = 1.04, 95% CI: 1.02–1.06) and procalcitonin (p < 0.021, OR = 52.60, 95% CI: 1.83–1510.06) serve as independent predictors of pulmonary infection. The AUCs for the training and validation sets were determined to be 0.853 (95% CI: 0.806–0.918) and 0.801 (95% CI: 0.697–0.904), respectively, with calibration curves demonstrating strong concordance. The DCA and CIC analyses indicated that the nomogram model possesses commendable clinical applicability. In models comparison, ROC analyses revealed that the nomogram exhibited superior discriminatory accuracy compared to alternative models, with DCA further identifying the nomogram as offering the highest net benefits across a broad spectrum of threshold probabilities.

Conclusion

BALF NP ≥16% serves as an effective discriminator between pulmonary infectious and non-infectious diseases in patients with pulmonary shadows. We have developed a nomogram model incorporating BALF NP and procalcitonin (PCT), which has proven to be a valuable tool for predicting the risk of pulmonary infections. This model holds significant potential to assist clinicians in making informed treatment decisions.
Metagenomic insights into microbial community, functional annotation, and antibiotic resistance genes in Himalayan Brahmaputra River sediment, India
Authors: Sharma Niti , Das Basanta Kumar , Bhattacharjya Birendra Kumar , Chaudhari Aparna , Behera Bijay Kumar , Kumar Annam Pavan , Chakraborty Hirak Jyoti
Published: November 2024

Introduction

The Brahmaputra, a major transboundary river of the Himalayas flowing predominantly through Northeast India, particularly Assam, is increasingly endangered by contamination due to rapid urbanization and anthropogenic pressures. These environmental changes pose significant risks at the microbial level, affecting nutrient cycling and productivity, and thereby impacting river ecosystem health. The next-generation sequencing technology using a metagenomics approach has revolutionized our understanding of the microbiome and its critical role in various aquatic environments.

Methods

The present study aimed to investigate the structure of the bacterial community and its functional potentials within the sediments of the Brahmaputra River, India, using high-throughput shotgun metagenomics. Additionally, this study sought to explore the presence of antimicrobial resistance genes in the river’s sediment.

Results and discussion

Shotgun metagenomics revealed a diverse bacterial community comprising 31 phyla, 52 classes, 291 families, 1,016 genera, and 3,630 species. Dominant phyla included Pseudomonadota (62.47–83.48%), Actinobacteria (11.10–24.89%), Bacteroidetes (0.97–3.82%), Firmicutes (0.54–3.94%), Cyanobacteria (0.14–1.70%), and Planctomycetes (0.30–0.78%). Functional profiling highlighted significant involvement in energy metabolism, amino acid and central carbon metabolism, stress response, and degradation pathways, emphasizing the microbial community’s role in ecosystem functioning and resilience. Notably, 50 types of antibiotic resistance genes (ARGs) were detected, with resistance profiles spanning multidrug, aminoglycoside, β-lactam, fluoroquinolone, rifampicin, sulfonamide, and tetracycline classes. Network analysis underscored the intricate relationships among ARG subtypes, suggesting potential mechanisms of resistance propagation. Furthermore, plasmid-related genes and 185 virulence factor genes (VFGs) were identified, indicating additional layers of microbial adaptation and potential pathogenicity within the river sediments. This comprehensive microbial and functional profiling of the Brahmaputra’s sediment metagenome provides crucial insights into microbial diversity, resistance potential, and ecological functions, offering a foundation for informed management and mitigation strategies to preserve river health and mitigate pollution impacts.
Patterns of antibiotic resistance genes and virulence factor genes in the gut microbiome of patients with osteoarthritis and rheumatoid arthritis
Authors: Guo Yaqi , Feng Hang , Du Lin , Yu Zhenghong
Published: November 2024

Background

The gut microbiome compositions of osteoarthritis (OA) and rheumatoid arthritis (RA) patients have been revealed; however, the functional genomics, particularly antibiotic resistance genes (ARGs) and virulence factor genes (VFGs), have not yet been explored.

Methods

We used gut metagenomic data to elucidate the distribution of ARGs and VFGs. Building on these differences in gut microbiome, we developed a diagnostic model using a random forest classifier based on ARG and VFG abundances.

Results

Our results indicated that both OA and RA patients exhibit significantly higher alpha diversity in ARGs, as measured by observed genes, the Shannon index, and the Simpson index, compared to healthy controls. However, this increased diversity is not significantly different between OA and RA patients. In contrast, VFGs showed higher diversity in RA patients than in healthy individuals, which was not as pronounced in OA patients. An analysis of the top 20 ARGs and VFGs revealed a largely similar composition between the three groups, with notable exceptions of certain genes that were uniquely enriched in either OA or RA patients. This suggests unique microbial patterns associated with each condition. Our beta diversity analysis further demonstrated distinct distributions of ARG and VFG profiles across the three groups, with several genes significantly enriched in both OA and RA patients, indicating potential markers for these diseases. The model achieved high accuracy (74.7–83.6%) when distinguishing both OA and RA from healthy controls using ARG profiles and substantial accuracy using VFG profiles.

Conclusion

These results support the potential of ARGs and VFGs as reliable biomarkers for diagnosing OA and RA.
Expression and functional study of DNA polymerases from Psychrobacillus sp. BL-248-WT-3 and FJAT-21963
Authors: Sun Yaping , Ko Danny Hsu , Gao Jie , Fu Kang , Mao Yuanchen , He Yun , Tian Hui
Published: November 2024

The properties of DNA polymerases isolated from thermophilic and mesophilic microorganisms, such as the thermophilic Geobacillus stearothermophilus (Bst) and mesophilic Bacillus subtilis phage (Phi29), have been widely researched. However, DNA polymerases in psychrophilic microorganisms remain poorly understood. In this study, we present for the first time the expression and functional characterization of DNA polymerases PWT-WT and FWT-WT from Psychrobacillus sp. BL-248-WT-3 and FJAT-21963. Enzymatic activity assays revealed that FWT-WT possessed strand displacement but lacked exonuclease activity and high ionic strength tolerance, whereas PWT-WT lacked all these properties. Further protein engineering and biochemical analysis identified D423 and S490 as critical mutation sites for improving strand displacement and tolerance to high ionic strength, specifically in the presence of 0–0.3 M potassium chloride (KCl), sodium chloride (NaCl), and potassium acetate (KAc). Three-dimensional structural analysis demonstrated that the size and the electric charge of the single-stranded DNA (ssDNA) encapsulation entrance were pivotal factors in the binding of the ssDNA template.
Grape seed proanthocyanidins improves growth performance, antioxidative capacity, and intestinal microbiota in growing pigs
Authors: Zheng Yuyang , Li Yan , Yu Bing , Huang Zhiqing , Luo Yuheng , Zheng Ping , Mao Xiangbing , Yu Jie , Tan Huize , Luo Junqiu , Yan Hui , He Jun
Published: November 2024

Grape seed proanthocyanidin (GSP) is a kind of plant polyphenols with a wide variety of biological activities. In this study, we explored the effect of dietary GSP supplementation on growth performance, nutrient digestibility, and intestinal microbiota in growing pigs. A total of 180 growing pigs (30.37 ± 0.31 kg) were randomly assigned to five treatment groups, each consisting of six replicate pens with six pigs per pen. The pigs received either a basal diet (control) or a basal diet supplemented with GSP at 15, 30, 60, or 120 mg/kg. The trial lasted for 33 days, and blood and fecal samples were collected for biochemical measurements. GSP supplementation at a dose from 30 to 120 mg/kg decreased the ratio of feed intake to gain (F:G) (p < 0.05). GSP also increased the digestibility of dry matter, crude protein, ether extract, and gross energy (p < 0.05). GSP supplementation at 30 mg/kg increased the serum concentrations of immunoglobulin (Ig) A (p < 0.05). Interestingly, GSP supplementation at 60 mg/kg decreased the serum concentrations of urea and malondialdehyde (p < 0.05). However, the serum concentrations of glutathione peroxidase and total superoxide dismutase were significantly increased upon GSP supplementation (p < 0.05). Importantly, GSP supplementation at 120 mg/kg significantly increased the abundance of the phylum Firmicutes, but decreased the abundance of phylum Bacteroidetes and Epsilonbacteraeota in the feces (p < 0.05). Moreover, GSP supplementation significantly elevated the abundance of genus Lactobacillus, but decreased the abundance of genus Prevotellaceae NK3B31 (p < 0.05). Dietary GSP supplementation improves the growth performance and nutrient digestibility in growing pigs, which may be associated with enhancement of the antioxidative capacity, as well as improvement in gut microbiota. This study may promote the use of GSP in animal nutrition and the feed industry.
Keeping toxigenic Aspergillus section Flavi and aflatoxin contamination at bay by deploying atoxigenic-based biocontrol products during production of groundnut and maize in Mozambique
Authors: Augusto Joao , Atehnkeng Joseph , Ortega-Beltran Alejandro , Cotty Peter J. , Bandyopadhyay Ranajit
Published: November 2024

Aflatoxins, produced by aflatoxigenic Aspergillus section Flavi fungi, commonly occur in groundnut and maize grown in Mozambique and have long been associated with high prevalence of liver cancer, stunting, and restricted access to lucrative international markets. Effective aflatoxin control options in the country are limited and not adequately explored. Biocontrol products based on atoxigenic strains of A. flavus provide viable aflatoxin mitigation measures but require development for Mozambique. Four hundred and sixty-eight (468) and 558 groundnut and maize farmers, respectively, voluntarily evaluated the effectiveness of two biocontrol products (Aflasafe MWMZ01 and Aflasafe MZ02), each containing as active ingredients four distinct atoxigenic isolates of A. flavus belonging to native vegetative compatibility groups (VCGs), at preventing aflatoxin contamination and displacement of aflatoxigenic fungi for 2 years in various agro-ecologies. Most groundnut and maize treated with the biocontrol products were below maximum levels for food in the European Union (EU; 85%; p < 0.01) and the United States (US; 99%; p < 0.01). In contrast, most non-treated maize and groundnut (ranging from 38 to 70%; p = 0.05) were above the EU and US maximum allowable levels for food. Aflatoxin reductions ranged from 78 to 98% (p < 0.01) in treated groundnut, and from 61 to 93% (p < 0.01) in treated maize. Toxigenic fungi were almost completely displaced from soils and crops by the applied atoxigenic active ingredients. This study revealed that the atoxigenic based biocontrol technology is effective in Mozambique at displacing aflatoxigenic fungi and reducing aflatoxin accumulation in both groundnut and maize but a combination with other management tools is encouraged for better retention of crop quality along the value chain.
Secretase promotes AD progression: simultaneously cleave Notch and APP
Authors: Yang Ke-Fan , Zhang Jing-Yi , Feng Mei , Yao Kuo , Liu Yue-Yang , Zhou Ming-Sheng , Jia Hui
Published: November 2024

Alzheimer’s disease (AD) involves complex pathological mechanisms. Secretases include membrane protein extracellular structural domain proteases and intramembrane proteases that cleave the topology to type I or type II. Secretases can effectively regulate the activation of Notch and amyloid precursor protein (APP), key factors in the progression of AD and cancer. This article systematically summarizes the intracellular localization, cleavage sites and products, and biological functions of six subtypes of secretases (α-secretase, β-secretase, γ-secretase, δ-secretase, ε-secretase, and η-secretase), and for the first time, elucidates the commonalities and differences between these subtypes of secretases. We found that each subtype of secretase primarily cleaves APP and Notch as substrates, regulating Aβ levels through APP cleavage to impact the progression of AD, while also cleaving Notch receptors to affect cancer progression. Finally, we review the chemical structures, indications, and research stages of various secretase inhibitors, emphasizing the promising development of secretase inhibitors in the fields of cancer and AD.
Body roundness index and cognitive function in older adults: a nationwide perspective
Authors: Zhang Feng , Ning Zhongxing , Wang Can
Published: November 2024

Background

Obesity negatively impacts cognitive function. However, the correlation between the body roundness index (BRI) and cognitive performance remains inadequately explored.

Methods

This study used data from the National Health and Nutrition Examination Survey (NHANES) collected from 2011 to 2014 to examine the correlation between BRI and cognitive function in individuals aged 65 and older. Models of multiple linear regression were used to investigate the relationship between BRI and cognitive performance. Additionally, smoothed curve fittings explored potential non-linear associations. Interaction tests and subgroup analyses were also performed.

Results

One thousand eight hundred seventy participants were taken into account, revealing an important negative relationship between BRI levels and cognitive performance. In the fully adjusted model, elevated BRI was substantially correlated with lower Digit Symbol Substitution Test (DSST) scores (β = −0.34, 95% CI = −0.64 to −0.05, p = 0.023), indicating that the higher BRI values are linked to worse cognitive performance. Sex differences were observed, with males showing a stronger negative association (p for interaction = 0.040).

Conclusion

Elevated BRI is related to worse cognitive function in the elderly population.
Skeletal muscle proteome differs between young APOE3 and APOE4 targeted replacement mice in a sex-dependent manner
Authors: Johnson Chelsea N. , Lysaker Colton R. , McCoin Colin S. , Evans Mara R. , Thyfault John P. , Wilkins Heather M. , Morris Jill K. , Geiger Paige C.
Published: November 2024

Introduction

Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD), yet it's unclear how this allele mediates risk. APOE4 carriers experience reduced mobility and faster decline in muscle strength, suggesting skeletal muscle involvement. Mitochondria are critical for muscle function and although we have reported defects in muscle mitochondrial respiration during early cognitive decline, APOE4-mediated effects on muscle mitochondria are unknown.

Methods

Here, we sought to determine the impact of APOE4 on skeletal muscle bioenergetics using young, male and female APOE3 (control) and APOE4 targeted replacement mice (n = 8 per genotype/sex combination). We examined the proteome, mitochondrial respiration, fiber size, and fiber-type distribution in skeletal muscle.

Results

We found that APOE4 alters mitochondrial pathway expression in young mouse muscle in a sex-dependent manner without affecting respiration and fiber size or composition relative to APOE3. In both sexes, the expression of mitochondrial pathways involved in electron transport, ATP synthesis, and heat production by uncoupling proteins and mitochondrial dysfunction significantly differed between APOE4 and APOE3 muscle. For pathways with predicted direction of activation, electron transport and oxidative phosphorylation were upregulated while mitochondrial dysfunction and sirtuin signaling were downregulated in female APOE4 vs. APOE3 muscle. In males, sulfur amino acid metabolism was upregulated in APOE4 vs. APOE3 muscle.

Discussion

This work highlights early involvement of skeletal muscle in a mouse model of APOE4-linked AD, which may contribute to AD pathogenesis or serve as a biomarker for brain health.
Brain function assessment of acupuncture for chronic insomnia disorder with mild cognitive dysfunction based on fNIRS: protocol for a randomized controlled trial
Authors: Wang Tianyu , Li Zhi , Ma Tingting , Zhu Fengya , Yang Bin , Kim Sieun , Miao Runqing , Wu Jie
Published: November 2024

Background

Chronic Insomnia Disorder (CID) is highly prevalent among older adults and impairs cognitive function. Insomnia accelerates the progression of mild cognitive impairment (MCI) and increases the risk of developing dementia. Acupuncture has been demonstrated in improving sleep quality and cognitive function. This study aims to explore the functional brain characteristics of CID with MCI patients and to assess the effects of acupuncture therapy using functional near-infrared spectroscopy (fNIRS).

Methods and design

This study is a single-center randomized controlled trial. Participants will be randomly assigned to the manual acupuncture group or the placebo acupuncture group for an 8-week intervention period. fNIRS data will be collected during resting test and working memory test at baseline and at end of the intervention. The primary outcome is the change of the Montreal Cognitive Assessment (MoCA) score, secondary outcomes include the change of Mini-Mental State Examination (MMSE), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Apathy Evaluation Scale-Informant (AES-I).

Discussion

The results of the study will provide insights into the effects of acupuncture on sleep quality and cognitive performance in CID with MCI patients. By utilizing fNIRS technology, we will elucidate the neural functional characteristic underlying the therapeutic benefits of acupuncture.

Clinical trial registration

https://ClinicalTrials.gov, identifier ChiCTR2300076182.
Study protocol for a randomized trial comparing two electroacupuncture waveforms for different severity groups of Bell palsy
Authors: Bian Zhiyuan , Wang Jiawei , Fang Fei , Yu Binyan , Shi Yan , Wan Yijia , Hong Mei , Ji Conghua , Shao Xiaomei , Liang Yi , Fang Jianqiao , Sun Jing
Published: November 2024

Background

Bell palsy (BP) is the most common cause of acute peripheral facial palsy which leads to functional and esthetic disturbances in patients and has a negative influence on daily living. Electroacupuncture (EA) has been considered an alternative treatment for improving facial function in patients with BP. However, there is no agreement on the preferred waveform type of the EA for treating BP.

Methods

This is a study protocol for a pilot randomized, two-arm, three-center, clinical trial at the Third Affiliated hospital of Zhejiang Chinese Medical University, the First Affiliated hospital of Zhejiang Chinese Medical University, and the Hangzhou First People’s Hospital. The trial began in November 2023 and is expected to end in December 2025. Sixty patients with BP whose electroneurography (ENoG) value is at least 20% and 60 patients with BP whose ENoG value is less than 20% will be randomly assigned to the low frequency continuous waveform group or the intermittent waveform group in a 1:1 ratio. Participants will receive 4 weeks of EA treatment and clinical assessments. The primary outcome is the change from baseline score of the Facial Nerve Grading System 2.0. The secondary outcomes include the change from baseline score of the Sunnybrook grading scale and the change from baseline amplitude of the compound muscle action potential of the affected side in the ENoG tests.

Discussion

This is the first study protocol to compare the treatment effect and safety of EA with low frequency continuous waveform and intermittent waveform for different severity groups of BP. This study will contribute to subsequent studies for exploring optimal EA parameters for BP treatment.

Clinical trial registration

ClinicalTrials.gov, NCT06063954.
Embodied echoes: navigating the familiarity in continued intention to play VR game
Authors: Yang Ling , Xiao Daibo
Published: November 2024

Introduction

Virtual reality (VR) games, propelled by advancements in VR and artificial intelligence technologies, offer a level of realism and interactivity that traditional games cannot match. However, despite their immersive potential, VR games have not yet reached the widespread popularity of their conventional counterparts. While VR can craft the illusion of a parallel reality, users often remain cognizant of the delineation between the virtual and the real.

Methods

In this paper, we employ a blend of qualitative and quantitative research methods to explore the impact of familiarity with virtual environments and interactive elements on users sense of embodiment, flow experience, and their intention to continue playing VR games. Additionally, we examine the moderating influence of perceived cost within this framework.

Results and discussions

Our analysis of 307 collected responses, facilitated by PLS-SEM, reveals that familiarity with interactivity is positively associated with both sense of embodiment and flow experience, whereas familiarity with the virtual scene primarily influences sense of embodiment. Interestingly, perceived cost exerts a positive moderating effect on the relationship between flow experience and the intention to persist with VR gaming, while it negatively moderates the impact of sense of embodiment on this intention. This study offers theoretical insights that can guide future research in the domain of VR gaming, as well as practical takeaways for companies in the VR game industry, shedding light on how to enhance user engagement and sustain long-term interest in VR gaming experiences.
Enhancing human activity recognition for the elderly and individuals with disabilities through optimized Internet-of-Things and artificial intelligence integration with advanced neural networks
Authors: Deeptha R. , Ramkumar K. , Venkateswaran Sri , Hassan Mohammad Mehedi , Hassan Md. Rafiul , Noori Farzan M. , Uddin Md. Zia
Published: November 2024

Elderly and individuals with disabilities can greatly benefit from human activity recognition (HAR) systems, which have recently advanced significantly due to the integration of the Internet of Things (IoT) and artificial intelligence (AI). The blending of IoT and AI methodologies into HAR systems has the potential to enable these populations to lead more autonomous and comfortable lives. HAR systems are equipped with various sensors, including motion capture sensors, microcontrollers, and transceivers, which supply data to assorted AI and machine learning (ML) algorithms for subsequent analyses. Despite the substantial advantages of this integration, current frameworks encounter significant challenges related to computational overhead, which arises from the complexity of AI and ML algorithms. This article introduces a novel ensemble of gated recurrent networks (GRN) and deep extreme feedforward neural networks (DEFNN), with hyperparameters optimized through the artificial water drop optimization (AWDO) algorithm. This framework leverages GRN for effective feature extraction, subsequently utilized by DEFNN for accurately classifying HAR data. Additionally, AWDO is employed within DEFNN to adjust hyperparameters, thereby mitigating computational overhead and enhancing detection efficiency. Extensive experiments were conducted to verify the proposed methodology using real-time datasets gathered from IoT testbeds, which employ NodeMCU units interfaced with Wi-Fi transceivers. The framework's efficiency was assessed using several metrics: accuracy at 99.5%, precision at 98%, recall at 97%, specificity at 98%, and F1-score of 98.2%. These results then were benchmarked against other contemporary deep learning (DL)-based HAR systems. The experimental outcomes indicate that our model achieves near-perfect accuracy, surpassing alternative learning-based HAR systems. Moreover, our model demonstrates reduced computational demands compared to preceding algorithms, suggesting that the proposed framework may offer superior efficacy and compatibility for deployment in HAR systems designed for elderly or individuals with disabilities.
Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
Authors: Presset Antoine , Bodard Sylvie , Lefèvre Antoine , Millet Anaïs , Oujagir Edward , Dupuy Camille , Iazourène Tarik , Bouakaz Ayache , Emond Patrick , Escoffre Jean-Michel , Nadal-Desbarats Lydie
Published: November 2024

Microbubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted, and efficient delivery of therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood–brain barrier opening (BBBO) induced by MB-assisted US. In the present study, the neurometabolic consequences of acoustically-mediated BBBO on cerebral tissue were investigated using multimodal metabolomics approaches. Sinusoid US waves (1 MHz, peak negative pressure 0.6 MPa, burst length 10 ms, total treatment time 30 s, MB bolus dose 0.7 × 105 MBs/g) were applied on the rats’ right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 h, 2 days, and 1 week after BBBO. After tissue preparation, the samples were analyzed using nuclear magnetic resonance spectrometry (NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Our findings showed a slight disruption of metabolic pathways in contralateral striata of animals. Analyses of metabolic pathways indicated changes in amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenine pathway (i.e., 3-hydroxy-kynurenine). In conclusion, the acoustically-mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.
Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding
Authors: Benita Benjamin A. , Koss Kyle M.
Published: November 2024

Uncontrolled and chronic inflammatory states in the Central Nervous System (CNS) are the hallmark of neurodegenerative pathology and every injury or stroke-related insult. The key mediators of these neuroinflammatory states are glial cells known as microglia, the resident immune cell at the core of the inflammatory event, and astroglia, which encapsulate inflammatory insults in proteoglycan-rich scar tissue. Since the majority of neuroinflammation is exclusively based on the responses of said glia, their phenotypes have been identified to be on an inflammatory spectrum encompassing developmental, homeostatic, and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation. Recently, research groups have focused on peptide discovery to identify these phenotypes, find novel mechanisms, and mediate or re-engineer their actions. Peptides retain the diverse function of proteins but significantly reduce the activity dependence on delicate 3D structures. Several peptides targeting unique phenotypes of microglia and astroglia have been identified, along with several capable of mediating deleterious behaviors or promoting beneficial outcomes in the context of neuroinflammation. A comprehensive review of the peptides unique to microglia and astroglia will be provided along with their primary discovery methodologies, including top-down approaches using known biomolecules and naïve strategies using peptide and phage libraries.
Experimental test of neutron intensity monitor with isomer production reaction for p-Li neutron source for boron neutron capture therapy
Authors: Tamaki Shingo , Ohtani Yuuki , Kusaka Sachie , Sato Fuminobu , Murata Isao
Published: November 2024

Introduction

Boron Neutron Capture Therapy (BNCT) is a promising cancer therapy. At present, development of accelerator based neutron source (ABNS) is underway to be utilized as a neutron source instead of nuclear reactor. However, it is known that the neutron field formed with accelerators have different characteristics depending on kinds of accelerators. We thus have to characterize the field before practical use.

Method

In the authors’ group, various neutronics characterization devices have been developed for our p-Li based BNCT machine named CSePT. In this paper, three neutron intensity monitor foils with an isomer production reaction for several tens to 800 keV of the p-Li neutrons were proposed, i.e., 107Ag, 115In and 189Os.

Result and Discussion

From the experimental test results, two activation foils of 107Ag and 115In were confirmed to be a possible candidate as the monitor. However, the isomer production cross sections of them should be examined for practical use.