bluuebunny/crossref_metadata_2025 huggingface dataset:
General aspects, host interaction, and application of Metarhizium sp. in arthropod pest and vector control
Authors: de Miranda Rodrigo Prado Rodrigues , Soares Talita Kellen dos Anjos , Castro Daniele Pereira , Genta Fernando Ariel
Published: November 2024

The application of microorganisms as bio-control agents against arthropod populations is a need in many countries, especially in tropical, subtropical, and neotropical endemic areas. Several arthropod species became agricultural pests of paramount economic significance, and many methods have been developed for field and urban applications to prevent their, the most common being the application of chemical insecticides. However, the indiscriminate treatment based upon those substances acted as a selective pressure for upcoming resistant phenotype populations. As alternative tools, microorganisms have been prospected as complementary tools for pest and vectorial control, once they act in a more specific pattern against target organisms than chemicals. They are considered environmentally friendly since they have considerably less off-target effects. Entomopathogenic fungi are organisms capable of exerting pathogenesis in many vector species, thus becoming potential tools for biological management. The entomopathogenic fungi Metarhizium sp. have been investigated as a microbiological agent for the control of populations of insects in tropical regions. However, the development of entomopathogenic fungi as control tools depends on physiological studies regarding aspects such as mechanisms of pathogenicity, secreted enzymes, viability, and host-pathogen aspects. The following review briefly narrates current aspects of entomopathogenic fungi, such as physiology, cellular characteristics, host-pathogen interactions, and its previous applications against different insect orders with medical and economic importance. Approaches integrating new isolation, prospection, characterization, delivery strategies, formulations, and molecular and genetic tools will be decisive to elucidate the molecular mechanisms of EPFs and to develop more sustainable alternative pesticides.
Genome-wide identification and expression analysis of phosphate-sensing SPX proteins in oats
Authors: Du Yinke , Gong Jie , Dou Ziyi , Zheng Wei , Sun Renwei , Gao Shiqing
Published: November 2024

Phosphorus is indispensable to plant growth and development. Soil phosphorus deficiency poses a substantial constraint on crop yield. SPXs play pivotal roles in phosphate transport and absorption in plants. Yet, the functions of SPXs of oat (Avena sativa L.) under abiotic stresses remain unclear. In this study, we conducted a genome-wide analysis of 169 SPXs from hexaploid oat and five closely related plant species. All homologous AsSPXs were found to arise from duplication events and depict a strong purifying selection. Subcellular localization prediction revealed that AsSPXs were mainly located on the plasma membrane. Seventeen cis-acting elements, predominantly comprising light-, low temperature-, abscisic acid-, and drought-responsive elements, were dispersed in the promoter regions of AsSPXs. Analysis of cis-regulatory elements, protein-protein interaction networks, and qRT-PCR showed that AsSPXs are not solely involved in phosphorus starvation response but also in various stress responses. Notably, AsSPX18-5D (AVESA.00001b.r3.5Dg0002895) exerted pivotal roles in conferring resistance against low phosphorus, salt, and ABA treatments. Our study aimed to explore important stress-resistant genes in oat. Our results could provide a basis for future studies on the evolution and functions of the AsSPX gene family and a crucial foundation for comprehending how oat responds to environmental stresses.
The FGFR inhibitor Rogaratinib reduces microglia reactivity and synaptic loss in TBI
Authors: Rehman Rida , Froehlich Albrecht , olde Heuvel Florian , Elsayed Lobna , Boeckers Tobias , Huber-Lang Markus , Morganti-Kossmann Cristina , Roselli Francesco
Published: November 2024

Background

Traumatic brain injury (TBI) induces an acute reactive state of microglia, which contribute to secondary injury processes through phagocytic activity and release of cytokines. Several receptor tyrosine kinases (RTK) are activated in microglia upon TBI, and their blockade may reduce the acute inflammation and decrease the secondary loss of neurons; thus, RTKs are potential therapeutic targets. We have previously demonstrated that several members of the Fibroblast Growth Factor Receptor (FGFR) family are transiently phosporylated upon TBI; the availability for drug repurposing of FGFR inhibitors makes worthwhile the elucidation of the role of FGFR in the acute phases of the response to TBI and the effect of FGFR inhibition.

Methods

A closed, blunt, weight-drop mild TBI protocol was employed. The pan-FGFR inhibitor Rogaratinib was administered to mice 30min after the TBI and daily up to 7 days post injury. Phosphor-RTK Arrays and proteomic antibody arrays were used to determine target engagement and large-scale impact of the FGFR inhibitor. pFGFR1 and pFGFR3 immunostaining were employed for validation. As outcome parameters of the TBI injury immunostainings for NeuN, VGLUT1, VGAT at 7dpi were considered.

Results

Inhibition of FGFR during TBI restricted phosphorylation of FGFR1, FGFR3, FGFR4 and ErbB4. Phosphorylation of FGFR1 and FGFR3 during TBI was traced back to Iba1+ microglia. Rogaratinib substantially dowregulated the proteomic signature of the neuroimmunological response to trauma, including the expression of CD40L, CXCR3, CCL4, CCR4, ILR6, MMP3 and OPG. Prolonged Rogaratinib treatment reduced neuronal loss upon TBI and prevented the loss of excitatory (vGLUT+) synapses.

Conclusion

The FGFR family is involved in the early induction of reactive microglia in TBI. FGFR inhibition selectively prevented FGFR phosphorylation in the microglia, dampened the overall neuroimmunological response and enhanced the preservation of neuronal and synaptic integrity. Thus, FGFR inhibitors may be relevant targets for drug repurposing aimed at modulating microglial reactivity in TBI.
A comprehensive nomogram for assessing the prognosis of non-small cell lung cancer patients receiving immunotherapy: a prospective cohort study in China
Authors: Li Hongmei , Yuan Yuliang , Xu Qianjie , Liang Guangzhong , Hu Zuhai , Li Xiaosheng , Zhang Wei , Lei Haike
Published: November 2024

Objective

In China, lung cancer ranks first in both incidence and mortality among all malignant tumors. Non-small cell lung cancer (NSCLC) constitutes the vast majority of cases, accounting for 80% to 85% of cases. Immune checkpoint inhibitors (ICIs), either as monotherapies or combined with other treatments, have become the standard first-line therapy for NSCLC patients. This study aimed to establish a nomogram model for NSCLC patients receiving immunotherapy incorporating demographic information, clinical characteristics, and laboratory indicators.

Methods

From January 1, 2019, to December 31, 2022, a prospective longitudinal cohort study involving 1321 patients with NSCLC undergoing immunotherapy was conducted at Chongqing University Cancer Hospital. Clinical and pathological characteristics, as well as follow-up data, were collected and analyzed. To explore prognostic factors affecting overall survival (OS), a Cox regression model was used to test the significance of various variables. Independent prognostic indicators were identified through multivariate analysis and then used to construct a nomogram prediction model. To validate the accuracy and practicality of this model, the concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.

Result

In the final model, 11 variables from the training cohort were identified as independent risk factors for patients with NSCLC: age, KPS score, BMI, diabetes, targeted therapy, Hb, WBC, LDH, CRP, PLR, and LMR. The C-index for OS in the training cohort was 0.717 (95% CI, 0.689–0.745) and 0.704 (95% CI, 0.660–0.750) in the validation cohort. Calibration curves for survival probability showed good concordance between the nomogram predictions and actual observations. The AUCs for 1-year, 2-year, and 3-year OS in the training cohort were 0.724, 0.764, and 0.79, respectively, and 0.725, 0.736, and 0.818 in the validation cohort. DCA demonstrated that the nomogram model had a greater overall net benefit.

Conclusion

A prognostic model for OS in NSCLC patients receiving immunotherapy was established, providing a simple and reliable tool for predicting patient survival (https://icisnsclc.shinyapps.io/DynNomapp/). This model offers valuable guidance for clinicians in making treatment decisions and recommendations.
HLA class, calcineurin inhibitor levels, and the risk of graft failure in kidney recipients with de novo donor-specific antibodies
Authors: Béland Marc-Antoine , Lapointe Isabelle , Côté Isabelle , Lesage Julie , Houde Isabelle , Wagner Eric , Riopel Julie , Latulippe Eva , Désy Olivier , De Serres Sacha A.
Published: November 2024

Introduction

De novo donor-specific HLA antibody (dnDSA) are associated with poor outcomes. Whether this observation applies to both HLA class I and II dnDSA remains unclear.

Methods

We studied 1236 consecutive kidney recipients who had routine anti-HLA antibody surveillance post-transplant.

Results

During the screening period, 55/1236 (4.4%) patients developed dnDSA: 18 (33%) HLA-I only, 33 (60%) HLA-II only, and 4 (7%) both classes. Thirty patients experienced graft loss at a median of 39 months after dnDSA detection: 9/18 (50%) HLA-I only, 17/33 (52%) HLA-II only, and 4/4 (100%) both classes. A control group was created by matching patients with dnDSA to patients who did not develop DSA and had a functioning graft at the time of dnDSA detection in their respective cases. Compared with these controls, the risk estimates of graft loss were similar between patients with HLA-I only and HLA-II only dnDSA (aHR [95% CI] 2.7 [1.1-6.6], p=0.04 and 3.1 [1.5-6.6], p<0.01 respectively). Additionally, the risk of graft loss decreased with increasing CNI trough levels following dnDSA detection (aHR 0.7 [0.6-0.9] for each increase in 1 ng/mL, p=0.02).

Conclusions

The prognosis of patients with dnDSA is similar regardless of the HLA class specificity. Lower calcineurin inhibitor levels predict graft loss in such patients.
The role of macrophages in liver fibrosis: composition, heterogeneity, and therapeutic strategies
Authors: Ma Xiaocao , Qiu Jia , Zou Shubiao , Tan Liling , Miao Tingting
Published: November 2024

Macrophages, the predominant immune cells in the liver, are essential for maintaining hepatic homeostasis and responding to liver injury caused by external stressors. The hepatic macrophage population is highly heterogeneous and plastic, mainly comprised of hepatic resident kuffer cells (KCs), monocyte-derived macrophages (MoMφs), lipid-associated macrophages (LAMs), and liver capsular macrophages (LCMs). KCs, a population of resident macrophages, are localized in the liver and can self-renew through in situ proliferation. However, MoMφs in the liver are recruited from the periphery circulation. LAMs are a self-renewing subgroup of liver macrophages near the bile duct. While LCMs are located in the liver capsule and derived from peripheral monocytes. LAMs and LCMs are also involved in liver damage induced by various factors. Hepatic macrophages exhibit distinct phenotypes and functions depending on the specific microenvironment in the liver. KCs are critical for initiating inflammatory responses after sensing tissue damage, while the MoMφs infiltrated in the liver are implicated in both the progression and resolution of chronic hepatic inflammation and fibrosis. The regulatory function of liver macrophages in hepatic fibrosis has attracted significant interest in current research. Numerous literatures have documented that the MoMφs in the liver have a dual impact on the progression and resolution of liver fibrosis. The MoMφs in the liver can be categorized into two subtypes based on their Ly-6C expression level: inflammatory macrophages with high Ly-6C expression (referred to as Ly-6Chi subgroup macrophages) and reparative macrophages with low Ly-6C expression (referred to as Ly-6Clo subgroup macrophages). Ly-6Chi subgroup macrophages are conducive to the occurrence and progression of liver fibrosis, while Ly-6Clo subgroup macrophages are associated with the degradation of extracellular matrix (ECM) and regression of liver fibrosis. Given this, liver macrophages play a pivotal role in the occurrence, progression, and regression of liver fibrosis. Based on these studies, treatment therapies targeting liver macrophages are also being studied gradually. This review aims to summarize researches on the composition and origin of liver macrophages, the macrophage heterogeneity in the progression and regression of liver fibrosis, and anti-fibrosis therapeutic strategies targeting macrophages in the liver.
Exploring the dynamic mechanical response and mesoscopic characteristics of typical frozen rock in Yulong Copper Mine
Authors: Shoudong Xie , Chengjie Li , Ying Xu , Zhongyi Zhang , Mengqi Wang , Qi An
Published: November 2024

Dynamic mechanical characteristic testing at low temperatures was conducted for the typical porphyry and sandstone specimens of Yulong Copper Mine in Tibet, China. The stress and strain characteristics of the specimens at different temperatures were analyzed. A dynamic constitutive model was developed by considering the initial damage. Furthermore, microscopic damage characteristics during the water-saturated rock freezing process were investigated using the PFC3D software, revealing the mechanisms of frost heave damage to rocks. The results indicated that the water-ice phase transition either enhanced or deteriorated the specimen strength at low temperatures. Specifically, freezing at −10°C and −20°C enhanced the strength of sandstone. However, freezing at −10°C enhanced the porphyry specimens, and freezing at −20°C caused significant frost swelling injury. The new constitutive equation effectively fitted the dynamic stress and strain curves for both specimens, highlighting their differences. The maximum contact force and particle contact in the frozen rock PFC3D model were affected by rock and water particle deformations. The frost swelling deformation of water particles had a more pronounced impact on specimen damage and was related to the temperature. A specific freezing temperature existed at which the increase in saturated rock strength corresponded to the maximum specimen strength at that temperature.
Development of the interpretable typing prediction model for osteosarcoma and chondrosarcoma based on machine learning and radiomics: a multicenter retrospective study
Authors: Long Qing-Yuan , Wang Feng-Yan , Hu Yue , Gao Bo , Zhang Chuan , Ban Bo-Heng , Tian Xiao-Bin
Published: November 2024

Background

Osteosarcoma and chondrosarcoma are common malignant bone tumors, and accurate differentiation between these two tumors is crucial for treatment strategies and prognosis assessment. However, traditional radiological methods face diagnostic challenges due to the similarity in imaging between the two.

Methods

Clinical CT images and pathological data of 76 patients confirmed by pathology from January 2018 to January 2024 were retrospectively collected from Guizhou Medical University Affiliated Hospital and Guizhou Medical University Second Affiliated Hospital. A total of 788 radiomic features, including shape, texture, and first-order statistics, were extracted in this study. Six machine learning models, including Random Forest (RF), Extra Trees (ET), AdaBoost, Gradient Boosting Tree (GB), Linear Discriminant Analysis (LDA), and XGBoost (XGB), were trained and validated. Additionally, the importance of features and the interpretability of the models were evaluated through SHAP value analysis.

Results

The RF model performed best in distinguishing between these two tumor types, with an AUC value close to perfect at 1.00. The ET and AdaBoost models also demonstrated high performance, with AUC values of 0.98 and 0.93, respectively. SHAP value analysis revealed significant influences of wavelet-transformed GLCM and First Order features on model predictions, further enhancing diagnostic interpretability.

Conclusion

This study confirms the effectiveness of combining machine learning with radiomic features in improving the accuracy and interpretability of osteosarcoma and chondrosarcoma diagnosis. The excellent performance of the RF model is particularly suitable for complex imaging data processing, providing valuable insights for the future.
Visualized trends and bibliometric analysis in ankle cartilage repair from 2004 to 2024
Authors: Fu Xuefei , Zhang Zhixing , Wang Yingxiang , Lu Lin , Chen Tao , Deng Haobin , Li Hao , Yu Defu
Published: November 2024

Ankle cartilage injuries are a common sports-related condition that significantly impairs patients’ daily activities and imposes substantial economic burdens on both families and society. Effective cartilage repair strategies are crucial to addressing this pathological condition. Current conservative treatments include muscle strengthening, use of ankle braces, physical therapy, and the administration of NSAIDs. In cases of severe injury, surgical interventions such as osteophyte resection and cartilage transplantation may be necessary. However, the inherent regenerative capacity of articular cartilage is limited, and conventional treatments are insufficient to promote cartilage regeneration and repair. Consequently, innovative therapies such as stem cell therapy, exosome therapy, and cartilage regeneration scaffolds are prioritized for future development. In recent years, significant progress has been made in ankle cartilage repair. While bibliometric studies on cartilage repair exist, specific analyses focused on ankle cartilage repair are lacking. This study aims to address this gap by conducting a bibliometric analysis of 131 articles published over the past two decades, highlighting development trajectories, research hotspots, and evolutionary trends through knowledge mapping. Our findings indicate growing global interest, with the United States leading in international collaboration, funding, publication output, and citation frequency. Foot & Ankle International emerges as the leading journal for publication and dissemination in this field, with Kerkhoffs GMMJ identified as the most influential author. Notable hotspot keywords include “osteochondral lesions” and “platelet-rich plasma.” By highlighting critical research hotspots and collaboration patterns, this study not only enriches the existing literature on ankle cartilage repair but also serves as a foundational resource for clinicians and researchers aiming to develop innovative strategies for improving patient outcomes. Furthermore, our findings underscore the necessity of interdisciplinary collaboration in advancing the understanding and treatment of ankle cartilage injuries. Ultimately, the visual characterization of these trends provides valuable insights into the field’s evolutionary trajectory, offering guidelines for future research directions and encouraging further exploration of this promising area.
Serum beta2-microglobulin and peripheral blood eosinophils for the assessment of severity and prognosis with omicron variant COVID-19 infection
Authors: Tan Jie , Fang Hanxi , Hu Xiao , Yue Ming , Yang Junling
Published: November 2024

Background

The Omicron variant’s high transmissibility has made it the most widespread novel coronavirus variant. Elevated serum β2-MG levels from viral infections and EOS’ role in viral clearance have garnered attention. However, their predictive value for Omicron’s severity and prognosis needs further exploration.

Methods

This retrospective study included 424 patients with confirmed COVID-19 Omicron variant admitted to the Second Hospital of Jilin University in Changchun, China, of whom 128 experienced in-hospital mortality. Patients were divided into high and low groups according to β2-MG and EOS levels; the relationship between disease severity and patient prognosis was analyzed.

Results

Our findings showed that severe-to-critical Omicron patients had higher β2-MG levels than mild-normal patients. Conversely, EOS levels were higher in mild-moderate cases. Both β2-MG and EOS levels normalized when Omicron patients tested negative for nucleic acid. Deceased Omicron patients had significantly lower pre-mortem EOS levels. Elevated β2-MG and lower EOS levels correlated with reduced overall survival. Multivariate COX regression analysis indicated that elevated β2-MG was an independent adverse prognostic factor for Omicron patients.

Conclusion

High serum β2-MG levels and low eosinophil levels upon admission correlate with omicron variant severity and prognosis. β2-MG is an independent risk factor for poor outcomes in omicron patients.
Identification of key genes to predict response to chemoradiotherapy and prognosis in esophageal squamous cell carcinoma
Authors: Cui Yingying , Wen Jing , Fu Jianhua , Leng Changsen
Published: November 2024

Background

Chemoradiotherapy is a crucial treatment modality for esophageal squamous cell carcinoma (ESCC). This study aimed to identify chemoradiotherapy sensitivity-related genes and analyze their prognostic value and potential associations with the tumor microenvironment in ESCC.

Methods

Utilizing the Gene Expression Omnibus database, we identified differentially expressed genes between ESCC patients who achieved complete and incomplete pathological responses following chemoradiotherapy. Prognostic genes were then screened, and key genes associated with chemoradiotherapy sensitivity were determined using random survival forest analysis. We examined the relationships between key genes, infiltrating immune cells, and immunoregulatory genes. Additionally, drug sensitivity and enrichment analyses were conducted to assess the impact of key genes on chemotherapy responses and signaling pathways. A prognostic nomogram for ESCC was developed incorporating key genes, and its effectiveness was evaluated. Genome-wide association study data were employed to investigate chromosomal pathogenic regions associated with key genes.

Results

Three key genes including ATF2, SLC27A5, and ALOXE3 were identified. These genes can predict the sensitivity of ESCC patients to neoadjuvant chemoradiotherapy and hold significant clinical relevance in prognostication. These genes were also found to be significantly correlated with certain immune cells and immunoregulatory genes within the tumor microenvironment and were involved in critical tumor-related signaling pathways, including the epithelial-mesenchymal transition and P53 pathways. A nomogram was established to predict the prognosis of ESCC by integrating key genes with clinical stages, demonstrating favorable predictability and reliability.

Conclusion

This study identified three key genes that predict chemoradiotherapy sensitivity and prognosis and are involved in multiple tumor-related biological processes in ESCC. These findings provide predictive biomarkers for chemoradiotherapy response and support the development of individualized treatment strategies for ESCC patients.
ISFM-SLAM: dynamic visual SLAM with instance segmentation and feature matching
Authors: Li Chao , Hu Yang , Liu Jianqiang , Jin Jianhai , Sun Jun
Published: November 2024

Introduction

Simultaneous Localization and Mapping (SLAM) is a technology used in intelligent systems such as robots and autonomous vehicles. Visual SLAM has become a more popular type of SLAM due to its acceptable cost and good scalability when applied in robot positioning, navigation and other functions. However, most of the visual SLAM algorithms assume a static environment, so when they are implemented in highly dynamic scenes, problems such as tracking failure and overlapped mapping are prone to occur.

Methods

To deal with this issue, we propose ISFM-SLAM, a dynamic visual SLAM built upon the classic ORB-SLAM2, incorporating an improved instance segmentation network and enhanced feature matching. Based on YOLACT, the improved instance segmentation network applies the multi-scale residual network Res2Net as its backbone, and utilizes CIoU_Loss in the bounding box loss function, to enhance the detection accuracy of the segmentation network. To improve the matching rate and calculation efficiency of the internal feature points, we fuse ORB key points with an efficient image descriptor to replace traditional ORB feature matching of ORB-SLAM2. Moreover, the motion consistency detection algorithm based on external variance values is proposed and integrated into ISFM-SLAM, to assist the proposed SLAM systems in culling dynamic feature points more effectively.

Results and discussion

Simulation results on the TUM dataset show that the overall pose estimation accuracy of the ISFM-SLAM is 97% better than the ORB-SLAM2, and is superior to other mainstream and state-of-the-art dynamic SLAM systems. Further real-world experiments validate the feasibility of the proposed SLAM system in practical applications.
Multimodal robot-assisted English writing guidance and error correction with reinforcement learning
Authors: Wang Ni
Published: November 2024

Introduction

With the development of globalization and the increasing importance of English in international communication, effectively improving English writing skills has become a key focus in language learning. Traditional methods for English writing guidance and error correction have predominantly relied on rule-based approaches or statistical models, such as conventional language models and basic machine learning algorithms. While these methods can aid learners in improving their writing quality to some extent, they often suffer from limitations such as inflexibility, insufficient contextual understanding, and an inability to handle multimodal information. These shortcomings restrict their effectiveness in more complex linguistic environments.

Methods

To address these challenges, this study introduces ETG-ALtrans, a multimodal robot-assisted English writing guidance and error correction technology based on an improved ALBEF model and VGG19 architecture, enhanced by reinforcement learning. The approach leverages VGG19 to extract visual features and integrates them with the ALBEF model, achieving precise alignment and fusion of images and text. This enhances the model's ability to comprehend context. Furthermore, by incorporating reinforcement learning, the model can adaptively refine its correction strategies, thereby optimizing the effectiveness of writing guidance.

Results and discussion

Experimental results demonstrate that the proposed ETG-ALtrans method significantly improves the accuracy of English writing error correction and the intelligence level of writing guidance in multimodal data scenarios. Compared to traditional methods, this approach not only enhances the precision of writing suggestions but also better caters to the personalized needs of learners, thereby effectively improving their writing skills. This research is of significant importance in the field of language learning technology and offers new perspectives and methodologies for the development of future English writing assistance tools.
Elevated systemic inflammation response index is associated with poor outcomes in minor ischemic stroke
Authors: Li Jie , Zhang Ping , Chen Hong , Wang Yanfen , Han Yangyun , Wang Chun , Yi Xingyang
Published: November 2024

Objectives

Patients with minor ischemic stroke (MIS) have substantial disability rates at 90 days. Our study aimed to explore the association between the systemic inflammation response index (SIRI) and 3-month functional outcomes in patients with MIS.

Methods

We conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score of 0–3] admitted within 24 h from symptoms onset. Blood samples for the SIRI measurement were collected on admission. The primary outcome measure was poor outcomes at 90 days (defined as a modified Rankin Scale score of 2–6). Univariate and multivariate logistic analyses were performed to assess the association between the SIRI and the risk of 3-month poor outcomes.

Results

A total of 152 patients with MIS were enrolled, of which 24 cases (15.8%) had poor outcomes at 90 days. The median SIRI level was 1.27 [interquartile range (IQR), 0.77–1.92, ×10^9 /L] on admission. MIS patients with poor outcomes had higher levels of the SIRI than patients with good outcomes (poor outcomes: median, 1.93, IQR: 1.17–3.28, ×10^9 /L; good outcomes: median, 1.21, IQR: 0.71–1.80, ×10^9 /L; p = 0.003). The high SIRI level group (SIRI >1.27 × 10^9 /L) had significantly higher rates of poor outcomes at 90 days (22.4% vs. 9.2%, p = 0.026). After adjusting for age, baseline NIHSS score, prehospital delay, Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification, and other confounders in multivariate analyses, an elevated SIRI level remained independently associated with an increased risk of poor outcomes in patients with MIS [odds ratio (OR): 1.57, 95% confidence interval (CI): 1.12–2.20; p = 0.010]. Meanwhile, a high level of the SIRI (>1.27 × 10^9/L) was still an independent risk factor for 3-month poor outcomes (OR: 4.80, 95%CI: 1.51–15.29; p = 0.008) in MIS patients.

Conclusion

Disability at 90 days was common in patients with MIS. An elevated SIRI was associated with poor outcomes in MIS patients. The SIRI might be a promising biomarker candidate that can help identify high-risk MIS patients with poor outcomes for reaching individual therapeutic decisions in clinical trials.
Enhancing early Alzheimer's disease classification accuracy through the fusion of sMRI and rsMEG data: a deep learning approach
Authors: Liu Yuchen , Wang Ling , Ning Xiaolin , Gao Yang , Wang Defeng
Published: November 2024

Objective

Early detection and prediction of Alzheimer's Disease are paramount for elucidating neurodegenerative processes and enhancing cognitive resilience. Structural Magnetic Resonance Imaging (sMRI) provides insights into brain morphology, while resting-state Magnetoencephalography (rsMEG) elucidates functional aspects. However, inherent disparities between these multimodal neuroimaging modalities pose challenges to the effective integration of multimodal features.

Approach

To address these challenges, we propose a deep learning-based multimodal classification framework for Alzheimer's disease, which harnesses the fusion of pivotal features from sMRI and rsMEG to augment classification precision. Utilizing the BioFIND dataset, classification trials were conducted on 163 Mild Cognitive Impairment cases and 144 cognitively Healthy Controls.

Results

The study findings demonstrate that the InterFusion method, combining sMRI and rsMEG data, achieved a classification accuracy of 0.827. This accuracy significantly surpassed the accuracies obtained by rsMEG only at 0.710 and sMRI only at 0.749. Moreover, the evaluation of different fusion techniques revealed that InterFusion outperformed both EarlyFusion with an accuracy of 0.756 and LateFusion with an accuracy of 0.801. Additionally, the study delved deeper into the role of different frequency band features of rsMEG in fusion by analyzing six frequency bands, thus expanding the diagnostic scope.

Discussion

These results highlight the value of integrating resting-state rsMEG and sMRI data in the early diagnosis of Alzheimer's disease, demonstrating significant potential in the field of neuroscience diagnostics.
The nitrone compound OKN-007 delays motor neuron loss and disease progression in the G93A mouse model of amyotrophic lateral sclerosis
Authors: Bhaskaran Shylesh , Piekarz Katarzyna M. , Brown Jacob , Yang Brian , Ocañas Sarah R. , Wren Jonathan D. , Georgescu Constantin , Bottoms Christopher , Murphy Ashley , Thomason Jessica , Saunders Debra , Smith Nataliya , Towner Rheal , Van Remmen Holly
Published: November 2024

Our study investigated the therapeutic potential of OKN-007 in the SOD1 G93A mouse model of amyotrophic lateral sclerosis (ALS). The impact of OKN-007, known for its antioxidant, anti-inflammatory, and neuroprotective properties, was tested at two doses (150 mg/kg and 300 mg/kg) at onset and late-stage disease. Results demonstrated a significant delay in disease progression at both doses, with treated mice showing a slower advance to early disease stages compared to untreated controls. Motor neuron counts in the lumbar spinal cord were notably higher in OKN-007 treated mice at the time of disease onset, suggesting neuroprotection. Additionally, OKN-007 reduced microglial activation and preserved reduced neuromuscular junction fragmentation, although it did not significantly alter the increase in astrocyte number or the decline in hindlimb muscle mass. MR spectroscopy (MRS) revealed improved spinal cord perfusion and normalized myo-inositol levels in treated mice, supporting reduced neuroinflammation. While the expression of several proteins associated with inflammation is increased in spinal cord extracts from G93A mice, OKN-007 dampened the expression of IL-1β, IL-1ra and IL-1α. Despite its promising effects on early-stage disease progression, in general, the beneficial effects of OKN-007 diminished over longer treatment durations. Further, we found no improvement in muscle atrophy or weakness phenotypes in OKN-007 treated G93A mice, and no effect on mitochondrial function or lifespan. Overall, our findings suggest that OKN-007 holds potential as a disease-modifying treatment for ALS, although further research is needed to optimize dosing regimens and understand its long-term effects.
Improvement effect of insulin resistance in one-day outpatient service by reducing stress adaptation disorders in patients with gestational diabetes mellitus
Authors: Feng Yan , Yu Quan , Gu Fuqian , Feng Qi , Zhang Yinghong
Published: November 2024

Aim

Conducted a one-day outpatient service for GDM patients, analyzed the relationship between stress adaptation disorder and insulin resistance in GDM patients after intervention, and tried to provide some new clues for the prevention and treatment of GDM, provide some theoretical basis for the multidisciplinary diagnosis and treatment model of GDM patients.

Methods

240 GDM women were included in this study, 120 women were included in one-day diabetes clinic management for GDM women as GDM Intervention Group, and 120 GDM women receiving regular dietary education as GDM Control Group. One-day diabetes clinic management including disease knowledge and dietary education, sports education and blood sugar monitoring and personalized issues and follow-up visits, and intervention time lasting for 1 month.

Results

After intervention, the concentration of 2-h postprandial blood glucose, and HOMA-IR were decreased in GDM Intervention Group, while weekly weight gain rate and insulin application rate were significantly lower than GDM Control Group (all p < 0.05). Cortisol and MDA in GDM Intervention Group were significantly lower than GDM Control Group (both p < 0.01). HOMA-IR was positively correlated with weight gain, E, NE and cortisol (r = 0.249, 0.242, 0.663, 0.313, all p < 0.01), E and HOMA-IR were negatively correlated with SOD in GDM Intervention Group (r = −0.306, −0.213, both p < 0.01).

Conclusion

The intervention model in our study was based on the one-day outpatient comprehensive management model of diabetes, which improved the insulin resistance of GDM patients. The possible mechanism was related to the implementation of one-day outpatient intervention measures, which reduced the stress adaptation disorder and oxidative stress injury of GDM patients. At the same time, the implementation of intervention measures reduced the rate of weight gain, which can also alleviate insulin resistance to a certain extent. One-day outpatient treatment has a positive effect on improving insulin resistance in GDM women, which can reduce the risk of maternal and fetal complications.
Acer tegmentosum Maxim and Bacillus subtilis-fermented products inhibit TNF-α-induced endothelial inflammation and vascular dysfunction of the retina: the role of tyrosol moiety in active compounds targeting Glu230 in SIRT1
Authors: Nguyen Phuc Anh , Won Jong Soon , Cho Min Kyung
Published: November 2024

Acer tegmentosum Maxim (AT) is a medicinal plant used to treat hepatic, neurological diseases, and cancer. However, the beneficial effects of AT on endothelial dysfunction have not been reported yet. In this study, we evaluated the effects of AT and the main compounds against TNF-α-mediated inflammatory responses and their possible mechanism of action. The anti-inflammatory effect and its molecular mechanism were analyzed by adhesion assay, immunoblotting, promoter-luciferase assay, ELISA, RT-PCR, immunocytochemistry, immunoprecipitation, siRNA gene knockdown, docking, and molecular dynamics simulation. AT and its compounds salidroside and tyrosol reduced TNF-α-induced adhesion between monocytes and endothelial cells. Fermentation of AT with Bacillus subtilis converted salidroside to tyrosol, which is salidroside’s aglycone. The fermented AT product (ATF) potently inhibited TNF-α-mediated monocyte adhesion with higher potency than AT. AT or ATF abrogated TNF-α-induced expression of adhesion molecules (VCAM-1 and ICAM-1) and production of MCP-1 with the inhibition of phosphorylated MAP kinases. TNF-α-mediated NF-κB transactivation and RelA/p65 acetylation were suppressed by AT and ATF through the interaction of NF-κB with sirtuin-1 (SIRT1), an NAD+-dependent histone deacetylase. Sirt1 gene knockdown diminished the protective effects of AT and ATF against TNF-α-mediated signaling and inflammatory response. Interestingly, SIRT1 protein expression was significantly increased by ATF and tyrosol rather than by AT and salidroside, respectively. Molecular docking showed that the tyrosol moiety is critical for the interaction with Glu230 of SIRT1 (PDB ID: 4ZZH and 4ZZJ) for the deacetylase activity. Molecular dynamics revealed that tyrosol can induce the movement of the N-terminal domain toward the catalytic domain of SIRT1. This study demonstrates the potential of AT and ATF to prevent endothelial inflammation and vascular dysfunction of the retina by the MAPK/NF-κB/SIRT1 signaling pathways and targeting of the tyrosol moiety to Glu230 in SIRT1.
Astragaloside IV alleviates inflammation and improves myocardial metabolism in heart failure mice with preserved ejection fraction
Authors: Wang Xiao , Chen Xinting , Wang Yuting , He Xinyu , Li Lan , Wang Xiaodan , Huang Yuting , Fan Guanwei , Ni Jingyu
Published: November 2024

Background

Heart failure with preserved ejection fraction (HFpEF) has grown to become the dominant form of heart failure worldwide. However, no unequivocally effective treatment for HFpEF has been identified in clinical trials. In this study, we report that Astragaloside IV (AS-IV) can be used to treat HFpEF.

Methods

Mice were fed on a high-fat diet and given 0.5 g/L L-NAME (in drinking water) for 10 weeks to establish the HFpEF model. After 10th weeks, the HFpEF mice were given 10 mg/kg empagliflozin, 10 mg/kg AS-IV, or 20 mg/kg AS-IV for 4 weeks. The echocardiography, blood pressure, hemodynamics, heart failure biomarkers, collagen deposition and fibrosis, histopathology, and inflammation in HFpEF mice were evaluated. Metabolic profiling based on NMR measurements was also performed. Myocardial glucose and fatty acid metabolism were evaluated.

Results

AS-IV improves cardiac function and myocardial remodeling in HFpEF mice. AS-IV attenuates systemic inflammatory infiltration and myocardial inflammation levels in HFpEF mice by decreasing the expression of plasma inflammatory markers GDF15, CRP, IL1RL1, and MCP-1, NLRP3, IL-1β, Caspase-1, and IL-6 in the myocardium of HFpEF mice. Metabolomic analysis suggested that AS-IV improved cardiac glucose and fatty acid metabolism in HFpEF mice. Further studies showed that AS-IV significantly improved Complex I activity, increased ATP production, and elevated plasma NAD + levels; AS-IV also significantly improved pyruvate dehydrogenase activity and decreased pyruvate and lactate accumulation, thereby improving glucose metabolism in the hearts of HFpEF mice.

Conclusion

These results provide novel evidence that Astragaloside IV alleviates inflammation and improves myocardial metabolism in HFpEF mice.
A real-world pharmacovigilance analysis of adverse events associated with irbesartan using the FAERS and JADER databases
Authors: Liu Qian , Cui Zhiwei , Deng Chao , Yang Chao , Shi Tao
Published: November 2024

Objective

Hypertension is a leading global risk factor for disability and death. Irbesartan, a potent angiotensin II receptor blocker, requires continuous safety monitoring. We conducted a disproportionality analysis of irbesartan-related adverse drug events (ADEs) using the FDA’s FAERS and Japan’s JADER databases.

Methods

We extracted irbesartan-related ADE reports from FAERS (Q1 2004 to Q1 2024) and JADER (Q2 2008 to Q4 2023). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) for signal detection. Sensitivity analyses were conducted to exclude comorbid medications, and subgroup analyses by age and gender were performed to explore ADE occurrence in specific populations. Th time to onset (TTO) of ADEs was assessed using Weibull distribution test and Kaplan-Meier curves.

Results

A total of 5,816 (FAERS) and 366 (JADER) reports were analyzed, with irbesartan-related preferred terms (PTs) involving 27 System Organ Classes (SOCs) in FAERS and 22 in JADER. Three SOCs met detection thresholds in both databases: “metabolism and nutrition disorders,” “cardiac disorders,” and “renal and urinary disorders.” We identified 219 positive signals in FAERS and 20 in JADER, including known signals like hyperkalemia, hypotension, and acute kidney injury. Notably, newly identified signals such as acute pancreatitis (n = 50, ROR: 7.76 [5.88–10.25]) and rhabdomyolysis (n = 50, ROR: 7.76 [5.88–10.25]) in FAERS and respiratory failure (n = 7, ROR: 6.76 [3.20–14.26]) in JADER could have significant clinical implications, as they may lead to severe outcomes if not recognized and managed promptly. Subgroup analyses revealed both similarities and differences in signal detection across gender and age groups. Sensitivity analyses, excluding concomitant medications, confirmed the persistence of key positive signals, including hyperkalemia, angioedema, acute pancreatitis, and agranulocytosis. ADEs mainly occurred within 1 month (34.14%) and after 1 year (32.32%) after dosing, with a median onset of 107 days.

Conclusion

This study provides valuable real-world evidence on the safety profile of irbesartan. The identification of new safety signals underscores the necessity of updating drug labels, particularly for assessing and managing high-risk patients. Additionally, the TTO analysis emphasizes the importance of sustained vigilance for adverse events over time. In conclusion, our findings contribute to a more comprehensive understanding of irbesartan’s safety, aiding healthcare professionals in optimizing its use in clinical practice.
Evaluation of pharmacokinetics and relative bioavailability of pentoxifylline and its metabolite in beagle dogs following different formulations
Authors: Xu Yuxiang , Qie Hongxin , Zhao Haopeng , Gong Wenlin , Wang Peiyuan , Gao Xiaonan , Gao Jinglin , Feng Zhangying , Wang Mingxia
Published: November 2024

A single-oral-dose, two-period cross-over study with a 5-day washout period under fed condition was conducted in six beagle dogs to explore the pharmacokinetic characteristics and relative bioavailability between sustained-release (SR) tablets and enteric-coated (EC) tablets of pentoxifylline (PTX) and its metabolite. The results showed that M5 exhibited the highest exposure level, while M1 demonstrated the lowest in both the SR and EC tablet groups. For PTX and M1, T1/2 were 0.42 and 0.55 h, with tmax of 1.83 and 1.83 h, respectively, in the SR tablet group; in the EC tablet group, T1/2 were 0.38 and 0.47 h, respectively. However, a significantly prolonged absorption process was noted, with tmax values of 5.06 and 5.78 h. In contrast, M5 exhibited distinct pharmacokinetic differences compared to PTX and M1. For the SR tablet group, T1/2 and tmax were recorded at 2.03 and 3.08 h, respectively. In the EC tablet group, T1/2 and tmax were 1.67 and 5.78 h, respectively. With regard to the geometric least squares mean (LSM) of AUC and Cmax for SR tablets and EC tablets, the ratios of SR/EC of PTX, M1 and M5 were 67.62% (90% CI, 50.49%–90.55%), 78.18% (90% CI, 54.15%–112.88%), and 119.11% (90% CI, 99.62%–142.41%), respectively, for AUC(0-t). The ratios were 67.62% (90% CI, 50.50%–90.55%), 78.36% (90% CI, 54.48%–112.72%), and 119.39% (90% CI, 100.03%–142.50%) for AUC(0−∞) and 54.36% (90% CI, 36.63%–80.67%), 58.80% (90% CI, 40.84%–84.66%), and 100.51% (90% CI, 89.50%–112.88%) for Cmax, respectively. The AUC ratio predictions of bioconversion results indicated that there was no significant difference in the bioconversion of M1 between the SR tablets and EC tablets, with conversion rates of 0.37 and 0.36, respectively. In contrast, the conversion rate of M5 demonstrated a significant difference (p < 0.05) between the SR tablets and EC tablets, with the ratio of 3.09 and 1.91, respectively. Furthermore, the EC tablet group demonstrated notable inter-individual differences and irregular drug absorption, following meals. Consequently, the SR tablets appeared to provide a more stable and controllable therapeutic effect in beagle dogs.
Optimization of initial dosage of quetiapine in schizophrenic patients: effects of fluvoxamine or duloxetine coadministration
Authors: Chen Xiao , Zhang Yue , Yin Di , Jin Ying-Wei , He Su-Mei , Liu Chen-Xu , Zhang Cun , Wang Dong-Dong
Published: November 2024

Objective

Although quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug–drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK).

Methods

Ninety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs.

Results

It was found that the patient weights and fluvoxamine or duloxetine coadministration affected quetiapine clearance in schizophrenic patients. Without fluvoxamine or duloxetine coadministration, 16 and 12 mg/kg/day of quetiapine were recommended to schizophrenic patients whose weights were in the ranges of 40–50 and 50–120 kg, respectively. With fluvoxamine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the range of 40–120 kg. With duloxetine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the 40–120 kg range. With simultaneous coadministration of fluvoxamine and duloxetine, 4 mg/kg/day of quetiapine was recommended to patients with weights in the 40–120 kg range.

Conclusion

The present study was a pilot effort at investigating the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on PPK. The initial dosages of quetiapine administered to the patients were optimized according to the coadministration of fluvoxamine or duloxetine.