bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between serum methylmalonic acid and chronic kidney disease in adults: a cross-sectional study from NHANES 2013-2014
Authors: Zhang Zufa , Lv Long , Guan Sheng , Jiang Fengze , He Danni , Song Hongxuan , Sun Weibing , Jiang Sixiong , Tian Feng
Published: August 2024

Introduction

Chronic kidney disease(CKD) is a global medical problem. Serum methylmalonic acid(MMA) is a serum marker associated with many diseases. This study aimed to investigate the association between MMA and CKD.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were downloaded and analyzed. The association between MMA and CKD was confirmed by using multiple logistic regression modeling. The smooth curve fitting method was used to investigate the nonlinear relationship between them. Subgroup analyses and interaction tests were used to verify the stability of the association between different subgroups. Threshold effect analysis was used to determine the optimal control point for MMA.

Results

There was a unique W-shaped nonlinear relationship between MMA and the risk of CKD, with a positive correlation between them (OR=1.66,95% CI:1.27, 2.17; P=0.0002). As the stage of CKD progressed, MMA levels increased. Age, hypertension, and serum vitamin B12 had significant influences on the association between MMA and the risk of CKD.

Conclusion

Our findings revealed that serum MMA accumulation was positively associated with the risk of CKD. Serum MMA level may be a novel index to predict the development and course of CKD. This study may help in the early identification of people at risk for chronic kidney disease and provide new ideas and approaches for prevention and treatment.
Small-disturbance stability analysis and control-parameter optimization of grid-connected virtual synchronous generator
Authors: Sun Xianshan , Cai Jinming , Wang Dongsheng , Lin Jinwei , Li Kai
Published: August 2024

The virtual synchronous generator (VSG) has been widely used to improve the system inertia and damping in the renewable energy generation system. However, the in-depth understanding of VSG’s stability under disturbances on different control parameters is lacked. In order to solve the problem, the small-signal model of single-VSG is established at first. The influences of key control parameters on the stability of system are analyzed by using the eigenvalue analysis method in detail. On this basis, a novel optimization strategy for control parameters is proposed based on the Particle Swarm Optimization (PSO) algorithm. The control parameters are optimized to realize excellent damping and stability of VSG system. Finally, the simulation and experimental results verify the effectiveness of stability analysis and parameter optimization strategy.
Proteomic changes of the bovine blood plasma in response to heat stress in a tropically adapted cattle breed
Authors: Reolon Henrique Goncalves , Abduch Natalya Gardezani , Freitas Ana Claudia de , Silva Rafael Medeiros de Oliveira , Fragomeni Breno de Oliveira , Lourenco Daniela , Baldi Fernando , Paz Claudia Cristina Paro de , Stafuzza Nedenia Bonvino
Published: August 2024

Background

Identifying molecular mechanisms responsible for the response to heat stress is essential to increase production, reproduction, health, and welfare. This study aimed to identify early biological responses and potential biomarkers involved in the response to heat stress and animal’s recovery in tropically adapted beef cattle through proteomic analysis of blood plasma.

Methods

Blood samples were collected from 14 Caracu males during the heat stress peak (HSP) and 16 h after it (heat stress recovery—HSR) assessed based on wet bulb globe temperature index and rectal temperature. Proteome was investigated by liquid chromatography-tandem mass spectrometry from plasma samples, and the differentially regulated proteins were evaluated by functional enrichment analysis using DAVID tool. The protein-protein interaction network was evaluated by STRING tool.

Results

A total of 1,550 proteins were detected in both time points, of which 84 and 65 were downregulated and upregulated during HSR, respectively. Among the differentially regulated proteins with the highest absolute log-fold change values, those encoded by the GABBR1, EPHA2, DUSP5, MUC2, DGCR8, MAP2K7, ADRA1A, CXADR, TOPBP1, and NEB genes were highlighted as potential biomarkers because of their roles in response to heat stress. The functional enrichment analysis revealed that 65 Gene Ontology terms and 34 pathways were significant (P < 0.05). We highlighted those that could be associated with the response to heat stress, such as those related to the immune system, complement system, hemostasis, calcium, ECM-receptor interaction, and PI3K-Akt and MAPK signaling pathways. In addition, the protein–protein interaction network analysis revealed several complement and coagulation proteins and acute-phase proteins as important nodes based on their centrality and edges.

Conclusion

Identifying differentially regulated proteins and their relationship, as well as their roles in key pathways contribute to improve the knowledge of the mechanisms behind the response to heat stress in naturally adapted cattle breeds. In addition, proteins highlighted herein are potential biomarkers involved in the early response and recovery from heat stress in tropically adapted beef cattle.
Immunological characterization and comparison of children with COVID-19 from their adult counterparts at single-cell resolution
Authors: Jia Ran , Li Zifeng , Hu Shiwen , Chang Hailing , Zeng Mei , Liu Pengcheng , Lu Lijuan , Xu Menghua , Zhai Xiaowen , Qian Maoxiang , Xu Jin
Published: August 2024

Introduction

The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.

Methods

Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).

Results

The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.

Conclusion

Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.
Efgartigimod-associated Kaposi’s varicelliform eruption and herpetic conjunctivitis in a patient with seropositive ocular myasthenia gravis: a case report and review
Authors: Ge Lingzhi , Li Yanyan , Sun Ying , Chen Wenfang , Ni Xiaoli , Wei Fangli , Mu Zhen
Published: August 2024

Background

Efgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi’s varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG).

Case description

A 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications.

Conclusions

This case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod.
Early lymphocyte levels and low doses radiation exposure of lung predict lymphopenia in radiotherapy for lung cancer
Authors: Kuncman Łukasz , Pajdziński Matusz , Smółka Krzysztof , Bilski Mateusz , Socha Joanna , Stando Rafał , Peszyńska-Piorun Magdalena , Korab Katarzyna , Jereczek-Fossa Barbara Alicja , Fijuth Jacek
Published: August 2024

Introduction

Radiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians.

Methods

We conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, eXtreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir).

Results

Two hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV-3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm3. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm³). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 ≤ 2.005K/mm3, median alc_nadir predictions were 0.54K/mm3 for lung_v05p > 51.8% and 0.76K/mm3 for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm3.

Discussion

RIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs.
Integrated bioinformatics analysis of nucleotide metabolism based molecular subtyping and biomarkers in lung adenocarcinoma
Authors: Luo Dayuan , Wang Haohui , Zeng Zhen , Chen Jiajing , Wang Haiqin
Published: August 2024

Background

Lung adenocarcinoma (LUAD), a predominant subtype of non-small cell lung cancers, continues to challenge treatment outcomes due to its heterogeneity and complex tumor microenvironment (TME). Dysregulation in nucleotide metabolism has been identified as a significant factor in tumorigenesis, suggesting its potential as a therapeutic target.

Methods

This study analyzed LUAD samples from The Cancer Genome Atlas (TCGA) using Non-negative Matrix Factorization (NMF) clustering, Weighted Correlation Network Analysis (WGCNA), and various machine learning techniques. We investigated the role of nucleotide metabolism in relation to clinical features and immune microenvironment through large-scale data analysis and single-cell sequencing. Using in vivo and in vitro experiments such as RT-qPCR, Western Blot, immunohistochemistry, and subcutaneous tumor formation in mice, we further validated the functions of key nucleotide metabolism genes in cell lines and animals.

Results

Nucleotide metabolism genes classified LUAD patients into two distinct subtypes with significant prognostic differences. The ‘C1’ subtype associated with active nucleotide metabolism pathways showed poorer prognosis and a more aggressive tumor phenotype. Furthermore, a nucleotide metabolism-related score (NMRS) calculated from the expression of 28 key genes effectively differentiated between patient outcomes and predicted associations with oncogenic pathways and immune responses. By integrating various immune infiltration algorithms, we delineated the associations between nucleotide metabolism signature genes and the tumor microenvironment, and characterized their distribution differences at the cellular level by analyzing single-cell sequencing dataset related to immunochemotherapy. Finally, we demonstrated the differential expression of the key nucleotide metabolism gene AUNIP acts as an oncogene to promote LUAD cell proliferation and is associated with tumor immune infiltration.

Conclusion

The study underscores the pivotal role of nucleotide metabolism in LUAD progression and prognosis, highlighting the NMRS as a valuable biomarker for clinical outcomes and therapeutic responses. Specifically, AUNIP functions as a critical oncogene, offering a promising target for novel treatment strategies in LUAD.
Genomic hotspots: localized chromosome gene expansions identify lineage-specific innovations as targets for functional biodiversity and predictions of stress resilience
Authors: Edsinger Eric , Moroz Leonid L.
Published: August 2024

Functional and biodiversity genomics is essential for assessment and monitoring of planetary health and species-specific management in changing ecosystems. However, experimental knowledge of gene functions is limited to a few species, and dependencies on distantly related models. Combined with unrecognized degrees of lineage-specific gene family expansion, this means that traditional comparative methods are insufficient. Here, we introduce the concept of a hotspot, defined as innovations underlying the evolution of lineage-specific biology. We illustrate hotspots using molluscs having chromosome-scale genome assemblies and focus on heat-sensing TRPM channels and species living in environments of extreme heat stress (e.g., high intertidal and hydrothermal vent gastropods and bivalves). Integrating gene family, orthogroup, and domain-based methods with genomic hotspots (local homolog expansions on chromosomes), we show that conventional approaches overlook substantial amounts of species-specific gene family diversity due to limitations of distant homology detection. In contrast, local segmental duplications are often recent, lineage-specific genetic innovations reflecting emerging adaptions and can be identified for any genome. Revealed TRPM gene family diversification highlights unique neural and behavioral mechanisms that could be beneficial in predicting species’ resilience to heat stress. In summary, the identification of hotspots and their integration with other types of analyses illuminate evolutionary (neuro)genomic strategies that do not depend on knowledge from model organisms and unbiasedly reveal evolutionarily recent lineage-specific adaptations. This strategy enables discoveries of biological innovations across species as prospective targets for modeling, management, and biodiversity conservation.
Nontuberculosis mycobacteria (NTM) infections in patients with leukemia: a single center case series
Authors: Marvin-Peek Jennifer , Sasaki Koji , Kontoyiannis Dimitrios P. , Adachi Javier , Ohanian Maro , Takahashi Koichi , Issa Ghayas C. , Kornblau Steven , Abbas Hussein A.
Published: August 2024

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with leukemia. Sending AFB cultures early is important to direct appropriate antimicrobial therapy and allow for future leukemia-directed therapy.
Generation of secondary microbial methane of high-rank coals: insights from the microbial community and carbon isotope
Authors: Nai Hui , Xu Sheng , Chen Biying , Zhong Jun , Fang Lujia , Qin Sirou , Sano Yuji
Published: August 2024

Secondary microbial methane could provide a valuable energy source if it were better understood. Although coal seam is an ideal environment for investigating secondary microbial methane, there are few studies to trace the secondary microbial methane of high-rank coals. Here, we collected co-produced water samples from coalbeds in the Qinshui Basin (China) and analyzed the microbial community structure by 16S ribosomal RNA (16S rRNA) amplicon sequencing analysis. 16S rRNA sequencing demonstrated abundant methanogens in coalbeds including 6 orders (Methanobacteriales, Methanococcales, Methanofastidiosales, Methanomassiliicoccale, Methanomicrobiales, and Methanosarciniales) and 22 genera of methanogens. Superheavy DIC (δ13CDIC ranging from −4.2‰ to 34.8‰) and abundance of methanogenic microbes in co-produced water revealed the generation of secondary biogenic methane in high-rank coal seams in the Qingshui Basin. Hydrogenotrophic methanogenesis is the main pathway for secondary biogenic methane production. In deeply buried coal seams, biogenic methane is dominated by CO2 and H2 reduction methanogenesis, and in shallow buried coal seams, it may be produced synergistically by hydrocarbon degradation and hydrogenotrophic methanogenic microbes. The study discussed here is important for a better understanding of the generation of secondary microbial methane in high-rank coal.
Alteration of cGAS-STING signaling pathway components in the mouse cortex and hippocampus during healthy brain aging
Authors: Passarella Sergio , Kethiswaran Shananthan , Brandes Karina , Tsai I-Chin , Cebulski Kristin , Kröger Andrea , Dieterich Daniela C. , Landgraf Peter
Published: August 2024

The cGAS-STING pathway is a pivotal element of the innate immune system, recognizing cytosolic DNA to initiate the production of type I interferons and pro-inflammatory cytokines. This study investigates the alterations of the cGAS-STING signaling components in the cortex and hippocampus of mice aged 24 and 108 weeks. In the cortex of old mice, an increase in the dsDNA sensor protein cGAS and its product 2′3′-cGAMP was observed, without corresponding activation of downstream signaling, suggesting an uncoupling of cGAS activity from STING activation. This phenomenon may be attributed to increased dsDNA concentrations in the EC neurons, potentially arising from nuclear DNA damage. Contrastingly, the hippocampus did not exhibit increased cGAS activity with aging, but there was a notable elevation in STING levels, particularly in microglia, neurons and astrocytes. This increase in STING did not correlate with enhanced IRF3 activation, indicating that brain inflammation induced by the cGAS-STING pathway may manifest extremely late in the aging process. Furthermore, we highlight the role of autophagy and its interplay with the cGAS-STING pathway, with evidence of autophagy dysfunction in aged hippocampal neurons leading to STING accumulation. These findings underscore the complexity of the cGAS-STING pathway’s involvement in brain aging, with regional variations in activity and potential implications for neurodegenerative diseases.
Comprehensive ethological analysis of fear expression in rats using DeepLabCut and SimBA machine learning model
Authors: Chanthongdee Kanat , Fuentealba Yerko , Wahlestedt Thor , Foulhac Lou , Kardash Tetiana , Coppola Andrea , Heilig Markus , Barbier Estelle
Published: August 2024

Introduction

Defensive responses to threat-associated cues are commonly evaluated using conditioned freezing or suppression of operant responding. However, rats display a broad range of behaviors and shift their defensive behaviors based on immediacy of threats and context. This study aimed to systematically quantify the defensive behaviors that are triggered in response to threat-associated cues and assess whether they can accurately be identified using DeepLabCut in conjunction with SimBA.

Methods

We evaluated behavioral responses to fear using the auditory fear conditioning paradigm. Observable behaviors triggered by threat-associated cues were manually scored using Ethovision XT. Subsequently, we investigated the effects of diazepam (0, 0.3, or 1 mg/kg), administered intraperitoneally before fear memory testing, to assess its anxiolytic impact on these behaviors. We then developed a DeepLabCut + SimBA workflow for ethological analysis employing a series of machine learning models. The accuracy of behavior classifications generated by this pipeline was evaluated by comparing its output scores to the manually annotated scores.

Results

Our findings show that, besides conditioned suppression and freezing, rats exhibit heightened risk assessment behaviors, including sniffing, rearing, free-air whisking, and head scanning. We observed that diazepam dose-dependently mitigates these risk-assessment behaviors in both sexes, suggesting a good predictive validity of our readouts. With adequate amount of training data (approximately > 30,000 frames containing such behavior), DeepLabCut + SimBA workflow yields high accuracy with a reasonable transferability to classify well-represented behaviors in a different experimental condition. We also found that maintaining the same condition between training and evaluation data sets is recommended while developing DeepLabCut + SimBA workflow to achieve the highest accuracy.

Discussion

Our findings suggest that an ethological analysis can be used to assess fear learning. With the application of DeepLabCut and SimBA, this approach provides an alternative method to decode ongoing defensive behaviors in both male and female rats for further investigation of fear-related neurobiological underpinnings.
Modeling Alzheimer’s disease using human cell derived brain organoids and 3D models
Authors: Fernandes Sarah , Revanna Jasmin , Pratt Joshua , Hayes Nicholas , Marchetto Maria C. , Gage Fred H.
Published: August 2024

Age-related neurodegenerative diseases, like Alzheimer’s disease (AD), are challenging diseases for those affected with no cure and limited treatment options. Functional, human derived brain tissues that represent the diverse genetic background and cellular subtypes contributing to sporadic AD (sAD) are limited. Human stem cell derived brain organoids recapitulate some features of human brain cytoarchitecture and AD-like pathology, providing a tool for illuminating the relationship between AD pathology and neural cell dysregulation leading to cognitive decline. In this review, we explore current strategies for implementing brain organoids in the study of AD as well as the challenges associated with investigating age-related brain diseases using organoid models.
A study on the reasonable dietary trajectory of elderly people in the community and its correlation with body mass index
Authors: Liu Mengya , Chang Yuqing , Guo Wenjing , Zhao Siyi , Zhang Meng , Ma Xiaoyan , Ji Xiaomei , Liu Youran , Zhang Li
Published: August 2024

Objective

To explore the reasonable dietary trajectory of elderly people in the community and to test the correlation between different dietary trajectories and body mass index (BMI) of the elderly people in the community to provide a reference for these individuals to formulate scientific interventions and cultivate healthy living habits.

Methods

The data of The Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018 were used to evaluate the dietary status of elderly people in the community according to their diet, and body mass index was calculated according to height and weight. The latent variable growth mixed (LGMM) model was used to analyze the development trajectory of diet in elderly people, and the multivariate logistic regression model was used to test the relationship between different dietary development trajectories and BMI changes as well as to test the correlation between different dietary trajectories and BMI of the elderly people in the community.

Results

The LGMM fit four dietary trajectories of elderly individuals: the continuous reasonable diet group (37.81%), the dietary behavior decline group (28.84%), the continuous unreasonable diet group (20.16%), and the dietary behavior improvement group (13.19%). The results showed that factors including male sex, rural setting, being spouseless, nonformal education status, not being wealthy, living alone, and having tooth loss were more likely to be classified as the “persistently unreasonable diet group” (p < 0.05). The logistic regression results showed that the “continuous reasonable diet group” and the “dietary behavior improvement group” were significantly correlated with the development of obesity to a normal BMI.

Conclusion

The dietary behavior of the elderly was significantly correlated with BMI value, and improving the reasonable dietary behavior of the elderly could reduce the high BMI to the normal range, but could not restore the low BMI to the normal range, indicating that reasonable dietary behavior is an important measure to prevent and improve overweight or obesity in the elderly. There is significant heterogeneity in the dietary behavior of the elderly, and community medical staff should identify the risk factors of various dietary behaviors of other groups as soon as possible, and provide corresponding intervention strategies to help them change their poor dietary behaviors and improve their nutritional status.
Comparative study: how dry heating treatment and annealing influence the multi-structure, physicochemical properties and in vitro digestibility of black highland barley starch
Authors: Liu Hang , Gao Shanshan , Tian Ge , Zhang Si , Liu Shuang
Published: August 2024

In this study, comparative investigation on the effect of dry heating treatment (DHT) and annealing (ANN) on multi-structure, physicochemical properties and in vitro digestibility of black highland barley (BHB) starch was done. Results revealed that both DHT and ANN did not affect the “A”-type crystalline pattern and FT-IR spectroscopy of BHB starch, but changed the morphology, raised water absorption capacity and lowered viscosities. Compared to native starch, DHT- and ANN-modified samples had totally opposite alteration trends in amylose content, color characteristics, oil absorption capacity, gelatinization parameters and pasting temperature. These changes were positively related to treatment temperature and time for DHT-modified starches, while which were dependant on treatment duration for ANN-modified starches. Total in vitro hydrolysis rate and rapidly digestive starch content in starch markedly raised after DHT, whereas slowly digestive starch and RS levels decreased. Nevertheless, ANN significantly improved the hydrolyzation stability with treatment time prolonging, especially increased RS content and lowered RDS level. Therefore, this study identified both DHT and ANN were effective methods to alter the properties of BHB starch, and more importantly, they had distinguishing influence by different mechanisms, which would remind user to select appropriate means for physical starch modification based on different application purposes.
Thoracic radiation in combination with erlotinib—results from a phase 2 randomized trial
Authors: Nymoen Hanne Marte , Alver Tine Norman , Horndalsveen Henrik , Eide Hanne Astrid , Bjaanæs Maria Moksnes , Brustugun Odd Terje , Grønberg Bjørn Henning , Haakensen Vilde Drageset , Helland Åslaug
Published: August 2024

Background

Radiotherapy (RT) can be used to reduce symptoms and maintain open airways for patients with non-small cell lung cancer when systemic treatment is not sufficient. For some patients, tumor control is not achieved due to radioresistance. Concurrent inhibition of epidermal growth factor receptors has been proposed as a strategy to overcome radioresistance but may increase toxicity. We performed a randomized trial to assess the efficacy, tolerance, and quality of life of concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer.

Methods

Patients were randomized 1:1 to RT alone (arm A) or in combination with erlotinib (arm B). A computed tomography (CT) scan at baseline and one at 4–12 weeks after inclusion was used to evaluate treatment response. Adverse events were registered during treatment and the subsequent 30 days. Health-related quality-of-life questionnaires were completed by the patients at baseline, weeks 2, 6, and 20.

Results

A total of 114 patients were included. Of the 74 patients with CT scans available for evaluation of treatment effect, there were no significant differences in tumor size reduction between the two groups: median 14.5% reduction in the control arm A and 17.0% in the erlotinib arm B (p = 0.68). Overall survival was not significantly different between the two treatment arms: 7.0 and 7.8 months in arm A and arm B, respectively (log-rank p = 0.32). There was no significant increase in adverse events in the experimental arm, other than what is expected from erlotinib treatment alone. Overall, patients reported similar quality of life in both treatment arms.

Conclusion

Concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer was well tolerated but did not improve the efficacy of the RT.

Clinical trial registration

ClinicalTrials.gov, identifier NCT02714530.
Association between PCSK9 inhibitors and acute kidney injury: a pharmacovigilance study
Authors: Liu Hailing
Published: August 2024

Background

PCSK9 inhibitors are a novel class of lipid-lowering medications, and numerous clinical studies have confirmed their significant role in improving the progression of chronic kidney disease. However, recent case reports have indicated new evidence regarding their association with acute kidney injury (AKI), with some patients experiencing acute tubular injury after PCSK9 inhibitors use.

Objectives

To clarify the relationship between PCSK9 inhibitors and AKI, we conducted a pharmacovigilance study.

Methods

Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2015 to the fourth quarter of 2022, a disproportionality analysis was employed to identify adverse events suggestive of AKI after PCSK9 inhibitors use. The drugs of interest included evolocumab and alirocumab.

Results

A total of 144,341 adverse event reports related to PCSK9 inhibitors were analyzed, among which 444 cases were suspected of AKI for evolocumab, and 172 cases for alirocumab. Evolocumab had a greater impact on AKI in males (ROR 1.4, 95% CI 1.54–1.69). The ROR and 95% CI for evolocumab and Alirocumab were 0.13 (0.12–0.14) and 0.26 (0.23–0.30) respectively. Further analysis of AKI associated with the concomitant use of PCSK9 inhibitors with cephalosporins, furosemide, torsemide, pantoprazole, omeprazole, and esomeprazole revealed ROR and 95% CI of 0.38 (0.23–0.62), 0.38 (0.31–0.48), 0.18 (0.08–0.38), 0.23 (0.17–0.29), 0.20 (0.16–0.26), and 0.14 (0.10–0.20) respectively.

Conclusion

Through the FAERS database, we analyzed the clinical characteristics of AKI associated with PCSK9 inhibitors, exploring its risks. Our findings suggest that PCSK9 inhibitors might have a potential protective effect against AKI and exhibit similar effects when co-administered with other nephrotoxic drugs.
Angong Niuhuang Wan ameliorates LPS-induced cerebrovascular edema by inhibiting blood‒brain barrier leakage and promoting the membrane expression of AQP4
Authors: Liu Bo-Tong , Li Quan , Sun Kai , Pan Chun-Shui , Huo Xin-Mei , Huang Ping , Yan Li , He Qi-Hua , Zhong Li-Jun , Wang Yuan , Hu Meng-Lei , Li An-Qing , Jiao Ying-Qian , Zhang Shuang , Wang Xiao-Yi , Liu Jian , Han Jing-Yan
Published: August 2024

Introduction

Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms.

Methods

A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed.

Results

AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1.

Conclusion

AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.
Exploiting the anti-fibrotic effects of statins on thoracic aortic aneurysm progression: results from a meta-analysis and experimental data
Authors: Myasoedova Veronika A. , Rega Sara , Valerio Vincenza , Moschetta Donato , Massaiu Ilaria , Bonalumi Giorgia , Esposito Giampiero , Rusconi Valentina , Bertolini Francesca , Perrucci Gianluca Lorenzo , Poggio Paolo
Published: August 2024

Aims

Thoracic aortic aneurysm (TAA) that progress to acute aortic dissection is often fatal and there is no pharmacological treatment that can reduce TAA progression. We aim to evaluate statins’ effects on TAA growth rate and outcomes using a meta-analysis approach.

Methods and results

A detailed search related to the effects of statins on TAA was conducted according to PRISMA guidelines. The analyses of statins’ effects on TAA growth rate were performed on 4 studies (n = 1850), while the impact on outcomes was evaluated on 3 studies (n = 2,867). Patients under statin treatment showed a reduced TAA growth rate (difference in means = −0.36 cm/year; 95%CI: −0.64, −0.08; p = 0.013) when compared to controls, patients not taking statins. Regarding the outcomes (death, dissection, or rupture of the aorta, and the need for operative repair), statins exhibited a protective effect reducing the number of events (log odds ratio = −0.56; 95%CI: −1.06, −0.05; p = 0.030). In vitro, the anti-fibrotic effect of atorvastatin was tested on vascular smooth muscle cells (VMSC) isolated from patients with TAA. Our results highlighted that, in transforming growth factor beta 1 (TGF-β1) pro-fibrotic condition, VSMC expressed a significant lower amount of collagen type I alpha 1 chain (COL1A1) when treated with atorvastatin (untreated = +2.66 ± 0.23 fold-change vs. treated = +1.63 ± 0.09 fold-change; p = 0.014).

Conclusion

Statins show a protective effect on TAA growth rate and adverse outcomes in patients with TAA, possibly via their anti-fibrotic properties on VSMC. Given the current lack of effective drug treatments for TAA, we believe our findings highlight the need for more in-depth research to explore the potential benefits of statins in this context.
The relationship of redox signaling with the risk for atherosclerosis
Authors: Lei Sujuan , Liu Chen , Zheng Tian-xiang , Fu Wenguang , Huang Mei-zhou
Published: August 2024

Oxidative balance plays a pivotal role in physiological homeostasis, and many diseases, particularly age-related conditions, are closely associated with oxidative imbalance. While the strategic role of oxidative regulation in various diseases is well-established, the specific involvement of oxidative stress in atherosclerosis remains elusive. Atherosclerosis is a chronic inflammatory disorder characterized by plaque formation within the arteries. Alterations in the oxidative status of vascular tissues are linked to the onset, progression, and outcome of atherosclerosis. This review examines the role of redox signaling in atherosclerosis, including its impact on risk factors such as dyslipidemia, hyperglycemia, inflammation, and unhealthy lifestyle, along with dysregulation, vascular homeostasis, immune system interaction, and therapeutic considerations. Understanding redox signal transduction and the regulation of redox signaling will offer valuable insights into the pathogenesis of atherosclerosis and guide the development of novel therapeutic strategies.
Research trends and hotspot evolution of exercise-regulated myokines: a bibliometric analysis from 2003 to 2023
Authors: Sun Zhiyuan , Wu Zekai , Zhu Lei , Li Xinhe , Xu Dongdong , Tian Xuewen , Mao Dewei
Published: August 2024

Background

The lack of physical activity is a common issue in modern society and is considered a major risk factor for various chronic non-communicable diseases. Bioactive factors secreted by skeletal muscle during exercise play a crucial role in inter-organ interactions. Since the concept of “myokines” was proposed in 2004, hundreds of regulatory myokines have been identified. Visual analysis of research on exercise-regulated myokines is significant to explore research hotspots and frontiers in this field.

Methods

Research literature on exercise-regulated myokines from 2003 to 2023 in the “Web of Science” database was used as the data source. Knowledge maps were drawn using “VOS Viewer, CiteSpace, and R-bibliometrix” software.

Results

A total of 1,405 papers were included, showing a fluctuating yet slow growth in annual publications. The United States and China led in the number of publications and collaboration networks. Harvard University ranked first with 120 publications. CIBER (centrality 0.16) and the University of California System (centrality 0.16) were pivotal in advancing this field. PEDERSEN BK led author rankings with 41 publications and 1,952 citations. FRONTIERS IN PHYSIOLOGY ranked first among journals with 64 publications and the highest g-index (39), while PLoS One had the highest h-index (25) and most citations (2,599). Key co-cited reference clusters included #1 skeletal muscle dysfunction, #2 obesity, #6 ASCs, and #7 adaptive immunocytes. Pontus Boström’s paper had a notable citation burst intensity of 77.37. High-frequency keywords were “exercise” (509), “skeletal muscle” (452), and “expression” (293), with long-term keywords such as #0 irisin, #2 insulin resistance, #3 transcription, and #6 physical activity. Recently, keywords like “physical exercise,” “resistance exercise,” “aerobic exercise,” “insulin,” and “oxidative stress” have emerged.

Conclusion

Research in the field of exercise-regulated myokines shows an overall upward trend. The focus areas include myokines mediated by different types of exercise, the interaction of irisin-mediated muscle with other organs, and the important role of myokine-mediated oxidative stress in exercise simulation.
Interlinking FinTech and eHealth: a qualitative study
Authors: Al-Anezi Fahad
Published: August 2024

Introduction

This study investigates the integration of financial technology (FinTech) and electronic health (eHealth) to explore the opportunities, challenges, and implications arising from their interlinkage in Saudi Arabia.

Methods

Utilizing qualitative semi-structured interviews with 26 participants—including physicians, patients, technical and administrative managers, and FinTech consultants—the research adopts an inductive approach to understand diverse perspectives.

Results

Key findings reveal significant benefits such as improved efficiency in administrative processes, enhanced access to healthcare services, increased financial inclusion, better decision-making, improved patient experience, and the promotion of innovation and sustainability. However, barriers including regulatory challenges, data privacy and security concerns, interoperability issues, the digital divide, resistance to change, and cost implications were also identified.

Conclusion

Overall, the integration of FinTech and eHealth holds substantial promise for advancing healthcare delivery in Saudi Arabia. Future implications include the expansion of telehealth services, an increase in startups, the integration of wearable health devices, blockchain-based systems, evolving regulatory frameworks, and heightened collaborations. Addressing the identified challenges is crucial for realizing the full potential of this integration.
Associations of heavy metal exposure with diabetic retinopathy in the U.S. diabetic population: a cross-sectional study
Authors: Meng Chunren , Gu Chufeng , Cai Chunyang , He Shuai , Lai Dongwei , Qiu Qinghua
Published: August 2024

Background

Mounting evidence suggests a correlation between heavy metals exposure and diabetes. Diabetic retinopathy (DR) is a prevalent and irreversible complication of diabetes that can result in blindness. However, studies focusing on the effects of exposure to heavy metals on DR remain scarce. Thus, this study aimed to investigate the potential correlation between heavy metals exposure and DR.

Methods

A total of 1,146 diabetics from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were included in this study. Heavy metal levels were measured via urine testing. Weighted logistic regression, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) were utilized to investigate the potential relationships between exposure to 10 heavy metals and DR. Finally, subgroup analysis was conducted based on the glycemic control status.

Results

Among the 1,146 participants, 239 (20.86%) were diagnosed with DR. Those with DR had worse glycemic control and a higher prevalence of chronic kidney disease compared to those without DR. Moreover, both the WQS regression and BKMR models demonstrated a positive relationship between exposure to mixed heavy metals and the risk of DR. The results of weighted logistic regression revealed a positive correlation between cobalt (Co) and antimony (Sb) exposure and the risk of DR (OR = 1.489, 95%CI: 1.064–2.082, p = 0.021; OR = 1.475, 95% CI: 1.084–2.008, p = 0.014), while mercury (Hg) exposure was found to promote DR exclusively in the group with good glycemic control (OR = 1.509, 95% CI: 1.157–1.967, p = 0.003). These findings were corroborated by the results of the RCS analysis.

Conclusion

Heavy metal exposure is associated with an increased risk of DR, especially Sb, Co, and Hg exposure. Nevertheless, well-designed prospective studies are warranted to validate these findings.
Effects of different Chinese traditional exercises on mental health during the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Zhang Shiqing , Liu Min , Zhao Lijin
Published: August 2024

Introduction

As the COVID-19 outbreak escalated into a global pandemic, there was a significant surge in mental health issues worldwide. Over the past three decades, traditional Chinese exercises (TCEs) has gained increasing recognition for its ability to regulate mental well-being. The aim of this study (PROSPERO CRD42024516002) was to comprehensively assess and carry out a meta-analysis on the impact of traditional Chinese exercise on personal mental well-being amidst the COVID-19 pandemic.

Methods

Literature with publication dates from 2020 to 2023 was searched in four databases, including CNKI, Wanfang, Pubmed and Web of science. The literature was selected layer by layer according to the PRIMA guidelines, and then the quality of the included literature was assessed using the Cochrane Risk assessment tool.

Results

A total of 174 articles were screened, and 10 studies met the criteria and were included in the study. The results showed that TCEs had a positive effect on anxiety symptoms [SMD = −1.68, I2 = 98.40, 95%CI = (−2.80, −0.56), p = 0.00] and depressive symptoms [SMD = -1.23, I2 = 89.23, 95%CI = (−1.87, −0.58), p = 0.00]. The data of subgroup analysis showed that Baduanjin exercise had the best effect on reducing anxiety [SMD = −2.29, I2 = 98.3, 95%CI = (−3.69, −0.89), p < 0.000]. Individuals who practiced TCEs less than or equal to 30 min each time had the best effect on anxiety [SMD = −2.06, I2 = 96.2%, p < 0.000] and depression [SMD = −1.90, I2 = 68.4, 95%CI = (−2.25, −1.55), p = 0.042]. Individuals who trained TCEs more than 7 times a week were most likely to reduce symptoms of anxiety [SMD = −4.30, I2 = 92.6, 95%CI = (−6.78, −1.81), p < 0.000] and depression [SMD = −2.39, I2 = 0.0, 95%CI = (−2.91, −1.87), p = 0.625]. It is worth noting that TCEs had the most significant effect on the improvement of depression in people aged 30–50 years [SMD = −1.58, I2 = 89.0, 95%CI = (−3.05, −0.10), p = 0.003].

Conclusion

During the global pandemic, traditional Chinese sports have shown a positive and significant impact on reducing symptoms of anxiety and depression, and have played a significant role in improving mental health problems.

Systematic review registration:

PROSPERO, identifier CRD42024516002, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024516002.