bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of herpes simplex virus infection in the etiology of head and neck cancer–a Mendelian randomization study
Authors: Yan Ming , Xiao Li-yuan , Gosau Martin , Smeets Ralf , Feng Hong-chao , Burg Simon , Fu Ling-ling , Friedrich Reinhard E.
Published: August 2024

Introduction

Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear.

Methods

This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR‐Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses.

Results

Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003–1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004–1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.

Conclusion

Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.
Longitudinal transcriptomic analysis reveals persistent enrichment of iron homeostasis and erythrocyte function pathways in severe COVID-19 ARDS
Authors: Eltobgy Moemen , Johns Finny , Farkas Daniela , Leuenberger Laura , Cohen Sarah P. , Ho Kevin , Karow Sarah , Swoope Gabrielle , Pannu Sonal , Horowitz Jeffrey C. , Mallampalli Rama K. , Englert Joshua A. , Bednash Joseph S.
Published: August 2024

Introduction

The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS.

Methods

We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing.

Results

We first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 (HBA1, HBA2), hemoglobin subunit beta (HBB), von Willebrand factor C and EGF domains (VWCE), and carbonic anhydrase 1 (CA1), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport.

Discussion

These findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution.
The relationship between influenza vaccine hesitancy and vaccine literacy among youth and adults in China
Authors: Wang Li , Guo Mengjie , Wang Yan , Chen Ren , Wei Xiaolin
Published: August 2024

Objectives

The present study aimed to assess influenza vaccine hesitancy and vaccine literacy levels among youth and adults in China, as well as the association between them.

Methods

An online cross-sectional survey was conducted in Mainland China. Participants’ total vaccine literacy and three sub-dimension vaccine literacy (knowledge literacy, competence literacy, and decision-making literacy) were assessed by a validated vaccine literacy scale. Having received influenza vaccination in the past three years or intending to accept it in next influenza season indicates less influenza vaccine hesitancy.

Results

Among 997 participants, a sub-optimal vaccine literacy was observed, with a mean score of 66.83 ± 10.27. Regression models 1–4 revealed that participants with middle (aOR: 1.431, P=0.039, 95% CI: 1.018~2.010) or high (aOR: 1.651, P=0.006, 95% CI: 1.157~2.354) total vaccine literacy, as well as those with high competence literacy (aOR: 1.533, P=0.017, 95% CI: 1.079~2.180), or high decision-making literacy (aOR: 1.822, P=0.001, 95% CI: 1.261~2.632) were more likely to have been vaccinated against influenza at least once in past three years. However, those with a high knowledge literacy were associated with a lower influenza vaccine rate (aOR: 0.676, P=0.046, 95% CI: 0.460~0.994). Regression models 5–8 revealed that participants with middle (aOR: 1.661, P=0.008, 95% CI: 1.142~2.414) or high total vaccine literacy (aOR: 2.645, P=0.000, 95% CI: 1.774~3.942), as well as those with middle (aOR: 1.703, P=0.005, 95% CI: 1.177~2.464) or high competence literacy (aOR: 2.346, P=0.000, 95% CI: 1.159~3.461), or high decision-making literacy (aOR: 2.294, P=0.000, 95% CI: 1.531~3.436) were more likely to express the willingness to receive the influenza vaccine in the next influenza season.

Conclusion

The participants’ influenza vaccine hesitancy was negatively associated with their total vaccine literacy levels and two of the three sub-dimensions: competence literacy and decision-making literacy. Knowledge literacy suggested a positive or no relationship with influenza vaccine hesitancy.
Analysis of microbial communities in wheat, alfalfa, and oat crops after Tilletia laevis Kühn infection
Authors: Shen Yuyang , Delai Chen , Liu Taiguo , Chen Wanquan , Li Guangkuo , Gao Haifeng , Gao Li
Published: August 2024

Common bunt caused by Tilletia laevis Kühn is one of the most serious fungal diseases of wheat. The root–microbial associations play key roles in protecting plants against biotic and abiotic factors. Managing these associations offers a platform for improving the sustainability and efficiency of agriculture production. Here, by using high throughput sequencing, we aimed to identify the bacterial and fungal associations in wheat, alfalfa, and oat crops cultivated in different years in the Gansu province of China. Soil samples (0–6 cm below the surface) from infected wheat by T. laevis had significantly more bacterial and fungal richness than control samples as per the Chao1 analysis. We found some dominant fungi and bacterial phyla in infected wheat by T. laevis, such as Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Ascomycota, Basidiomycota, and Mortierello mycota. We also analyzed the chemical and enzymatic properties of soil samples after T. laevis inoculation. The total nitrogen, total kalium (TK), ammonium nitrogen, available kalium, organic carbon, invertase, phosphatase, and catalase were more in T. laevis-infected samples as compared to the control samples, while pH, total phosphorus, nitrate nitrogen, available phosphorus, and urease were more in control samples compared to T. laevis-infected samples. The results of this study will contribute to the control of wheat common bunt by candidate antagonistic microorganisms and adverse properties of soil.
Impact of the chemical modification of tRNAs anticodon loop on the variability and evolution of codon usage in proteobacteria
Authors: Delgado Sebastián , Armijo Álvaro , Bravo Verónica , Orellana Omar , Salazar Juan Carlos , Katz Assaf
Published: August 2024

Despite the highly conserved nature of the genetic code, the frequency of usage of each codon can vary significantly. The evolution of codon usage is shaped by two main evolutionary forces: mutational bias and selection pressures. These pressures can be driven by environmental factors, but also by the need for efficient translation, which depends heavily on the concentration of transfer RNAs (tRNAs) within the cell. The data presented here supports the proposal that tRNA modifications play a key role in shaping the overall preference of codon usage in proteobacteria. Interestingly, some codons, such as CGA and AGG (encoding arginine), exhibit a surprisingly low level of variation in their frequency of usage, even across genomes with differing GC content. These findings suggest that the evolution of GC content in proteobacterial genomes might be primarily driven by changes in the usage of a specific subset of codons, whose usage is itself influenced by tRNA modifications.
Nitrogen limitation-induced adaptive response and lipogenesis in the Antarctic yeast Rhodotorula mucilaginosa M94C9
Authors: Rosas-Paz Miguel , Zamora-Bello Alberto , Torres-Ramírez Nayeli , Villarreal-Huerta Diana , Romero-Aguilar Lucero , Pardo Juan Pablo , El Hafidi Mohammed , Sandoval Georgina , Segal-Kischinevzky Claudia , González James
Published: August 2024

The extremotolerant red yeast Rhodotorula mucilaginosa displays resilience to diverse environmental stressors, including cold, osmolarity, salinity, and oligotrophic conditions. Particularly, this yeast exhibits a remarkable ability to accumulate lipids and carotenoids in response to stress conditions. However, research into lipid biosynthesis has been hampered by limited genetic tools and a scarcity of studies on adaptive responses to nutrient stressors stimulating lipogenesis. This study investigated the impact of nitrogen stress on the adaptive response in Antarctic yeast R. mucilaginosa M94C9. Varied nitrogen availability reveals a nitrogen-dependent modulation of biomass and lipid droplet production, accompanied by significant ultrastructural changes to withstand nitrogen starvation. In silico analysis identifies open reading frames of genes encoding key lipogenesis enzymes, including acetyl-CoA carboxylase (Acc1), fatty acid synthases 1 and 2 (Fas1/Fas2), and acyl-CoA diacylglycerol O-acyltransferase 1 (Dga1). Further investigation into the expression profiles of RmACC1, RmFAS1, RmFAS2, and RmDGA1 genes under nitrogen stress revealed that the prolonged up-regulation of the RmDGA1 gene is a molecular indicator of lipogenesis. Subsequent fatty acid profiling unveiled an accumulation of oleic and palmitic acids under nitrogen limitation during the stationary phase. This investigation enhances our understanding of nitrogen stress adaptation and lipid biosynthesis, offering valuable insights into R. mucilaginosa M94C9 for potential industrial applications in the future.
LC–MS metabolomics and lipidomics in cerebrospinal fluid from viral and bacterial CNS infections: a review
Authors: Plaatjie Ontefetse Neo , van Furth A. Marceline Tutu , van der Kuip Martijn , Mason Shayne
Published: August 2024

There is compelling evidence that a dysregulated immune inflammatory response in neuroinfectious diseases results in modifications in metabolic processes and altered metabolites, directly or indirectly influencing lipid metabolism within the central nervous system (CNS). The challenges in differential diagnosis and the provision of effective treatment in many neuroinfectious diseases are, in part, due to limited understanding of the pathophysiology underlying the disease. Although there are numerous metabolomics studies, there remains a deficit in neurolipidomics research to provide a comprehensive understanding of the connection between altered metabolites and changes in lipid metabolism. The brain is an inherently high-lipid organ; hence, understanding neurolipidomics is the key to future breakthroughs. This review aims to provide an integrative summary of altered cerebrospinal fluid (CSF) metabolites associated with neurolipid metabolism in bacterial and viral CNS infections, with a particular focus on studies that used liquid chromatography-mass spectrometry (LC–MS). Lipid components (phospholipids) and metabolites (carnitine and tryptophan) appear to be the most significant indicators in both bacterial and viral infections. On the basis of our analysis of the literature, we recommend employing neurolipidomics in conjunction with existing neurometabolomics data as a prospective method to enhance our understanding of the cross link between dysregulated metabolites and lipid metabolism in neuroinfectious diseases.
The association between energy-adjusted dietary inflammatory index and metabolic syndrome and its mediatory role for cardiometabolic diseases: a prospective cohort study
Authors: Pourmontaseri Hossein , Sepehrinia Matin , Kuchay Mohammad Shafi , Farjam Mojtaba , Vahid Farhad , Dehghan Azizallah , Homayounfar Reza , Naghizadeh Mohammad Mehdi , Hebert James R.
Published: August 2024

Background

Metabolic syndrome (MetS) is a collection of medical conditions that elevate the chance of cardiovascular disease. An unhealthy diet is a major risk factors for MetS through different mechanisms, especially systemic chronic inflammation.

Objective

This study aimed to investigate the effect of dietary inflammatory potential on MetS incidence and the role of MetS in the association between Energy-adjusted dietary inflammatory index (E-DII) and cardiometabolic diseases.

Methods

In this prospective cohort study, 10,138 participants were recruited. All participants were divided into MetS or non-MetS groups based on the Adult Treatment Panel III criteria. The E-DII was used to assess the inflammatory potential of diet. After excluding the participants with MetS at baseline, 2252 individuals were followed for 5 years (longitudinal phase), and the effect of E-DII on MetS incidence was investigated using logistic regression models (p-value <0.05).

Results

The cohort’s mean age (45.1% men) was 48.6 ± 10.0 years. E-DII ranged from −6.5 to 5.6 (mean: −0.278 ± 2.07). Higher E-DII score had a 29% (95%CI: 1.22–1.36) increased risk for incidence of MetS and its components during five-year follow-up. Also, E-DII was significantly associated with the prevalence of MetS (OR = 1.55, 95%CI: 1.51–1.59). Among MetS components, E-DII had the strongest association with waist circumference in the cross-sectional study (OR = 2.17, 95%CI: 2.08–2.25) and triglyceride in the longitudinal study (OR = 1.19, 95%CI: 1.13–1.25). The association between E-DII and MetS was consistent in both obese (OR = 1.13, 95%CI:1.05–1.21) and non-obese (OR = 1.42, 95%CI: 1.27–1.60) individuals and stronger among non-obese participants. Additionally, MetS mediated the association between E-DII and hypertension, diabetes, and myocardial infarction.

Conclusion

In conclusion, a pro-inflammatory diet consumption is associated with a higher risk of MetS and its components. Furthermore, a pro-inflammatory diet increases the risk of cardiometabolic diseases. The higher E-DII had a stronger association with MetS, even among normal-weight individuals.
Spatiotemporal correlation enhanced real-time 4D-CBCT imaging using convolutional LSTM networks
Authors: Zhang Hua , Chen Kai , Xu Xiaotong , You Tao , Sun Wenzheng , Dang Jun
Published: August 2024

Purpose

To enhance the accuracy of real-time four-dimensional cone beam CT (4D-CBCT) imaging by incorporating spatiotemporal correlation from the sequential projection image into the single projection-based 4D-CBCT estimation process.

Methods

We first derived 4D deformation vector fields (DVFs) from patient 4D-CT. Principal component analysis (PCA) was then employed to extract distinctive feature labels for each DVF, focusing on the first three PCA coefficients. To simulate a wide range of respiratory motion, we expanded the motion amplitude and used random sampling to generate approximately 900 sets of PCA labels. These labels were used to produce 900 simulated 4D-DVFs, which in turn deformed the 0% phase 4D-CT to obtain 900 CBCT volumes with continuous motion amplitudes. Following this, the forward projection was performed at one angle to get all of the digital reconstructed radiographs (DRRs). These DRRs and the PCA labels were used as the training data set. To capture the spatiotemporal correlation in the projections, we propose to use the convolutional LSTM (ConvLSTM) network for PCA coefficient estimation. For network testing, when several online CBCT projections (with different motion amplitudes that cover the full respiration range) are acquired and sent into the network, the corresponding 4D-PCA coefficients will be obtained and finally lead to a full online 4D-CBCT prediction. A phantom experiment is first performed with the XCAT phantom; then, a pilot clinical evaluation is further conducted.

Results

Results on the XCAT phantom and the patient data show that the proposed approach outperformed other networks in terms of visual inspection and quantitative metrics. For the XCAT phantom experiment, ConvLSTM achieves the highest quantification accuracy with MAPE(Mean Absolute Percentage Error), PSNR (Peak Signal-to-Noise Ratio), and RMSE(Root Mean Squared Error) of 0.0459, 64.6742, and 0.0011, respectively. For the patient pilot clinical experiment, ConvLSTM also achieves the best quantification accuracy with that of 0.0934, 63.7294, and 0.0019, respectively. The quantification evaluation labels that we used are 1) the Mean Absolute Error (MAE), 2) the Normalized Cross Correlation (NCC), 3)the Structural Similarity Index Measurement(SSIM), 4)the Peak Signal-to-Noise Ratio (PSNR), 5)the Root Mean Squared Error(RMSE), and 6) the Absolute Percentage Error (MAPE).

Conclusion

The spatiotemporal correlation-based respiration motion modeling supplied a potential solution for accurate real-time 4D-CBCT reconstruction.
Insights into uveitis from Brentuximab vedotin in refractory Hodgkin’s lymphoma: a case report and brief review
Authors: Liu Mengyuan , Ren Kexing , Ai Ping , Zou Liqun
Published: August 2024

This case report describes a 16-year-old patient with refractory Hodgkin’s lymphoma who developed bilateral anterior and intermediate uveitis as an adverse reaction to Brentuximab vedotin (BV). This is a rare case of an ocular adverse reaction potentially related to BV, with symptoms like blurred vision, decreased visual acuity, photophobia, and redness. Potential mechanisms include BV targeting CD30+ T cells in the uveal tissue or an immune response triggered by the microtubule-disrupting agent MMAE within BV. This highlights the need for vigilant monitoring of ocular adverse events in BV-treated patients and further research into their mechanisms and management.
Risk prediction model for postoperative pneumonia in esophageal cancer patients: A systematic review
Authors: Jiang Yaxin , Li Zimeng , Jiang Weiting , Wei Tingyu , Chen Bizhen
Published: August 2024

Background

Numerous studies have developed or validated prediction models to estimate the likelihood of postoperative pneumonia (POP) in esophageal cancer (EC) patients. The quality of these models and the evaluation of their applicability to clinical practice and future research remains unknown. This study systematically evaluated the risk of bias and applicability of risk prediction models for developing POP in patients undergoing esophageal cancer surgery.

Methods

PubMed, Embase, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), WanFang Database and Chinese Biomedical Literature Database were searched from inception to March 12, 2024. Two investigators independently screened the literature and extracted data. The Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist was employed to evaluate both the risk of bias and applicability.

Result

A total of 14 studies involving 23 models were included. These studies were mainly published between 2014 and 2023. The applicability of all studies was good. However, all studies exhibited a high risk of bias, primarily attributed to inappropriate data sources, insufficient sample size, irrational treatment of variables and missing data, and lack of model validation. The incidence of POP in patients undergoing esophageal cancer surgery ranged from 14.60% to 39.26%. The most frequently used predictors were smoking, age, chronic obstructive pulmonary disease(COPD), diabetes mellitus, and methods of thoracotomy. Inter-model discrimination ranged from 0.627 to 0.850, sensitivity ranged between 60.7% and 84.0%, and specificity ranged from 59.1% to 83.9%.

Conclusion

In all included studies, good discrimination was reported for risk prediction models for POP in patients undergoing esophageal cancer surgery, indicating stable model performance. However, according to the PROBAST checklist, all studies had a high risk of bias. Future studies should use the predictive model assessment tool to improve study design and develop new models with larger samples and multicenter external validation.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42024527085.
Assessing how individuals conceptualize numeric pain ratings: validity and reliability of the Pain Schema Inventory (PSI–6) Short Form
Authors: Wiederien Robert C. , Wang Dan , Frey-Law Laura A.
Published: August 2024

Background

While numeric scales to represent pain intensity have been well validated, individuals use various conceptualizations when assigning a number to pain intensity, referred to as pain rating schema. The 18-item Pain Schema Inventory (PSI-18) quantifies pain rating schema by asking for numeric values for multiple mild, moderate or severe pain conditions. This study aimed to assess the validity and reliability of a shortened form of the PSI, using only 6 items (PSI-6).

Methods

A secondary analysis was performed on two existing datasets. The first (n = 641) involved a community-based population that completed the PSI-18. The second (n = 182) included participants with chronic pain who completed the PSI-6 twice, one week apart. We assessed face validity, convergent validity, offset biases, test-retest reliability, and internal consistency of the PSI-6 compared to the PSI-18.

Results

Both the PSI-18 and PSI-6 demonstrated excellent face validity. The PSI-6 demonstrated excellent convergent validity relative to the PSI-18, with correlations from r = 0.88 to 0.92. Bland-Altman plots revealed offset biases near zero (< 0.22 on 0–10 scale) across all categories of mild, moderate, severe and average pain. Internal consistency was excellent, with Cronbach's Alpha = 0.91 and 0.80, for PSI-18 and PSI-6 respectively. Test-retest reliability of the PSI-6 was high with correlations from r = 0.70–0.76.

Conclusion

The PSI-6 is a valid and reliable tool to assess pain rating schema with reduced subject burden, to better interpret individuals’ pain ratings and adjust for inter-individual variability.
Distinguishing types and severity of pediatric pneumonia using modified lung ultrasound score
Authors: Xie Wen , Ruan Junxian , Jiang Qiuxia , Zheng Jingyang , Lin Weiru , Lyu Guorong
Published: August 2024

Objective

This study aimed to investigate the diagnostic utility of the modified lung ultrasound score (MLUS) in distinguishing between Mycoplasma pneumonia and viral pneumonia in children and evaluate their severity.

Methods

A prospective collection of 137 suspected cases of community-acquired pneumonia in children admitted to the Quanzhou Maternity and Children's Hospital in Quanzhou City, Fujian Province, from January 2023 to December 2023 constituted the study cohort. All patients underwent lung ultrasound examinations, and MLUS scores were assigned based on ultrasound findings, including pleural lines, A-lines, B-lines, and lung consolidations. Based on the pathogenic results, the patients were categorized into the Mycoplasma pneumonia (74 cases) and viral pneumonia (63 cases) groups. The severity was classified as mild (110 cases) or severe (27 cases). The diagnostic value of MLUS for Mycoplasma pneumonia and viral pneumonia in children was analyzed.

Results

(1) MLUS scores were significantly different between the Mycoplasma pneumonia (15, 10–21) and viral pneumonia (8, 5–16) groups (P = 0.002). ROC curve analysis indicated that using a cut-off value of 11, MLUS exhibited a sensitivity of 70.3%, specificity of 58.7%, and an area under curve (AUC) of 0.653 for diagnosing Mycoplasma pneumonia. Furthermore, large-area lung consolidation on ultrasound images demonstrated good diagnostic performance for predicting Mycoplasma pneumonia, with an AUC of 0.763, a sensitivity of 71.6%, and a specificity of 81.0%. (2) MLUS scores were significantly different between the mild pneumonia (10.5, 5–17) and severe pneumonia (21, 16–29) groups (P < 0.001). ROC curve analysis using a cut-off value of 16 showed a sensitivity of 77.8%, specificity of 73.6%, and AUC of 0.818 for diagnosing severe pneumonia. Multivariate regression analysis revealed that both MLUS and white blood cell count were independent factors influencing the severity. The constructed nomogram model demonstrated robust stability with a sensitivity of 85.2%, a specificity of 74.5%, and an AUC of 0.858 for predicting severe childhood pneumonia.

Conclusion

MLUS, coupled with ultrasound signs of large-area lung consolidation, had reference significance for the differential diagnosis of Mycoplasma pneumonia and viral pneumonia in children and can be a preliminary assessment of the severity of viral pneumonia or mycoplasma pneumonia in children.
Pharmacological mechanisms of Ma Xing Shi Gan Decoction in treating influenza virus-induced pneumonia: intestinal microbiota and pulmonary glycolysis
Authors: Jiang Lin , Bai Chen , Zhu Jingru , Su Chen , Wang Yang , Liu Hui , Li Qianqian , Qin Xueying , Gu Xiaohong , Liu Tiegang
Published: August 2024

Background

Influenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in the intestine and glycolysis in the lung tissues. In the clinical guidelines for pneumonia treatment in China, Ma Xing Shi Gan Decoction (MXSG) is a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism of action is related to the regulation of intestinal microbiota structure and lung tissue glycolysis.

Objective

This study aimed to investigate the mechanism of action of MXSG in an animal model of influenza virus-induced pneumonia. Specifically, we aimed to elucidate how MXSG modulates intestinal microbiota structure and lung tissue glycolysis to exert its therapeutic effects on pneumonia.

Methods

We established a mouse model of influenza virus-induced pneumoni, and treated with MXSG. We observed changes in inflammatory cytokine levels and conducted 16S rRNA gene sequencing to assess the intestinal microbiota structure and function. Additionally, targeted metabolomics was performed to analyze lung tissue glycolytic metabolites, and Western blot and enzyme-linked immunosorbent assays were performed to assess glycolysis-related enzymes, lipopolysaccharides (LPSs), HIF-1a, and macrophage surface markers. Correlation analysis was conducted between the LPS and omics results to elucidate the relationship between intestinal microbiota and lung tissue glycolysis in pneumonia animals under the intervention of Ma Xing Shi Gan Decoction.

Results

MXSG reduced the abundance of Gram-negative bacteria in the intestines, such as Proteobacteria and Helicobacter, leading to reduced LPS content in the serum and lungs. This intervention also suppressed HIF-1a activity and lung tissue glycolysis metabolism, decreased the number of M1-type macrophages, and increased the number of M2-type macrophages, effectively alleviating lung damage caused by influenza virus-induced pneumonia.

Conclusion

MXSG can alleviate glycolysis in lung tissue, suppress M1-type macrophage activation, promote M2-type macrophage activation, and mitigate inflammation in lung tissue. This therapeutic effect appears to be mediated by modulating gut microbiota and reducing endogenous LPS production in the intestines. This study demonstrates the therapeutic effects of MXSG on pneumonia and explores its potential mechanism, thus providing data support for the use of traditional Chinese medicine in the treatment of respiratory infectious diseases.
Unveiling the multifaceted roles of microRNAs in extracellular vesicles derived from mesenchymal stem cells: implications in tumor progression and therapeutic interventions
Authors: Hu Sujia , Zhang Chang , Ma Qianhui , Li Minghe , Yu Xiao , Zhang Haiying , Lv Shuang , Shi Yingai , He Xu
Published: August 2024

Graphical Abstract

The multifaceted roles of EV-miRNAs derived from MSCs in tumor progression and therapeutic applications. MSC-EVs can transfer miRNAs into tumor cells to regulate cell proliferation, invasion and metastasis, immune response, angiogenesis, and chemosensitivity as well. One or more of MSCs, EVs and miRNAs can be modified to achieve the inhibitory effect on tumor progression, which provides the promising approaches for tumor clinical treatment. Besides, miRNAs in EVs can also mediate the interaction between MSCs and tumor cells in the TME (Created with Biorender.com).
Celastrus orbiculatus Thunb. extracts and celastrol alleviate NAFLD by preserving mitochondrial function through activating the FGF21/AMPK/PGC-1α pathway
Authors: Xue Junli , Liu Yunchao , Liu Boyan , Jia Xiubin , Fang Xinsheng , Qin Shucun , Zhang Ying
Published: August 2024

Objective

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease globally, characterized by the accumulation of lipids, oxidative stress, and mitochondrial dysfunction in the liver. Celastrus orbiculatus Thunb. (COT) and its active compound celastrol (CEL) have demonstrated antioxidant and anti-inflammatory properties. Our prior research has shown the beneficial effects of COT in mitigating NAFLD induced by a high-fat diet (HFD) in guinea pigs by reducing hepatic lipid levels and inhibiting oxidative stress. This study further assessed the effects of COT on NAFLD and explored its underlying mitochondria-related mechanisms.

Methods

COT extract or CEL was administered as an intervention in C57BL/6J mice fed a HFD or in HepG2 cells treated with sodium oleate. Oral glucose tolerance test, biochemical parameters including liver enzymes, blood lipid, and pro-inflammatory factors, and steatosis were evaluated. Meanwhile, mitochondrial ultrastructure and indicators related to oxidative stress were tested. Furthermore, regulators of mitochondrial function were measured using RT-qPCR and Western blot.

Results

The findings demonstrated significant reductions in hepatic steatosis, oxidative stress, and inflammation associated with NAFLD in both experimental models following treatment with COT extract or CEL. Additionally, improvements were observed in mitochondrial structure, ATP content, and ATPase activity. This improvement can be attributed to the significant upregulation of mRNA and protein expression levels of key regulators including FGF21, AMPK, PGC-1α, PPARγ, and SIRT3.

Conclusion

These findings suggest that COT may enhance mitochondrial function by activating the FGF21/AMPK/PGC-1α signaling pathway to mitigate NAFLD, which indicated that COT has the potential to target mitochondria and serve as a novel therapeutic option for NAFLD.
Designing and implementing a resilient immutability mechanism for enhanced supply chain management in E-healthcare systems
Authors: Singla Deepak , Kumar Sanjeev , Gulzar Yonis , Mir Mohammad Shuaib , Gupta Deepali , Jaziri Wassim , Sassi Najla , Arora Shweta
Published: August 2024

Counterfeit drugs pose significant health risks due to their variable efficacy and potential harmful ingredients. To combat this issue, a reliable and secure track-and-trace system is essential for pharmaceutical supply chains. This paper proposes an Immutable and Decentralized Pharma (IDP) model, leveraging blockchain technology to ensure the safe and efficient distribution of medications. The IDP model utilizes smart contracts to record transactions between entities onto a blockchain, enabling end-to-end product tracking and provenance. Experimental results on a polygon blockchain test network demonstrate the feasibility and enhanced security of the IDP model in a collaborative environment. Our solution addresses the challenges of data privacy, openness, and authenticity inherent in centralized track-and-trace systems, providing a promising approach to eliminate counterfeits and guarantee product safety in pharmaceutical supply chains.
A float-based Ocean color vicarious calibration program
Authors: Barnard Andrew , Boss Emmanuel , Haëntjens Nils , Orrico Cristina , Chamberlain Paul , Frouin Robert , Mazloff Matthew , Tan Jing
Published: August 2024

Ocean color satellites require a procedure known as System Vicarious Calibration (SVC) after launch as the pre-launch and on-orbit calibration accuracy is insufficient. The current approach for determination of post-launch SVC uses a single fixed measurement location and may be susceptible to unexpected biases in satellite processing algorithms. Here we describe a novel SVC program which is based on a high resolution and high accuracy radiometric system integrated with an autonomous profiling float (providing a buoyancy engine, physical observations, and communication). This float + radiometer (HyperNav) system can be shipped via air, land, ocean and is deployable from small boats. This SVC program relies on multiple deployment sites with associated facilities to collect a significant amount of SVC quality data in a relatively short time. It has centralized logistics and command-and-control centers ensuring easy access to information regarding the status of each asset and to ensure floats stay within a certain ocean area. The development of the program has been associated with the launch of NASA’s PACE satellite and has been executed by academic institutions in collaboration with an industrial partner. Other approaches for a future float-based operational SVC program are discussed.
Preliminary evaluation of a novel method for computed tomography quantification of lumbosacral articular process displacement in dogs with and without degenerative lumbosacral stenosis
Authors: Carballo Oscar , Frederick Steven W. , Keys Deborah A. , Moore Sarah A. , Giles James T.
Published: August 2024

Objective

This study aimed to describe the diagnostic discrimination and reliability of a novel technique for quantifying lumbosacral articular process displacement (LSAPD) on dorsal plane computed tomography (DPCT) imaging in dogs with and without degenerative lumbosacral stenosis (DLSS).

Study design

DPCT surveys of the lumbosacral vertebral column were performed with dogs positioned in extension and flexion. LSAPD is defined as the distance between the cranial aspects of the L7 and S1 articular processes. The LSAPD ratio is identified by dividing the LSAPD by the length of the L7 articular process. Intraclass correlation coefficients (ICCs) for intra- and inter-observer reliability were calculated, and logistic regressions were used to test for the association of LSAPD and LSAPD ratio with odds of DLSS. Significance was set at 0.05. Receiver operator characteristic (ROC) curves were calculated to determine diagnostic discrimination and optimal cutoff for LSAPD and LSAPD ratio in the diagnosis of DLSS.

Results

Intra- and inter-observer reliabilities were excellent for most measurements. In the current cohort, excluding covariates, the area under the curve (AUC) (95%CI) for LSAPD and LSAPD ratio measured in a flexed position were both 0.89 (0.82–0.96), suggesting potentially excellent discrimination for using this measurement as a marker for diagnosing DLSS, pending further studies. The cutoffs for flexed LSAPD and LSAPD ratio that maximizes Youden’s index were ≥ 1.2 mm and ≥ 9%, respectively. When age and weight were subsequently included as covariates in a multivariable analysis, a significant relationship between LSAPD or LSAPD ratio and odds of diagnosis of DLSS was not demonstrated, suggesting the need for a larger sample size.

Conclusion

The results of this study suggest that measurements of LSAPD and LSAPD ratio on DPCT are feasible and reliable, although their diagnostic discrimination in DLSS should be evaluated further in future prospective studies.
Protection efficacy and the safety of the synergy between modified Bazhen powder and PRRSV modified-live virus vaccine against HP-PRRSV in piglets
Authors: Chai Hua , Wei Yanru , Chen Wenguang , Han Guorui , Godspower Bello-Onaghise , Liu Yanyan , Dong Chunliu , Zhang Zhiyun , Li Yanhua
Published: August 2024

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.
Implications of Digitalization on the Persistence of Startups
Authors: De-Esteban-Escobar Débora , De-Pablos-Heredero Carmen , Montes-Botella José Luis , Blanco-Jiménez Francisco José
Published: August 2024

Digitalization is a transformative phenomenon catalyzing innovative paradigms and operational methodologies within the realm of business, with a pronounced impact on nascent enterprises, notably startups. The aim of this paper is to ascertain the influence of digitalization and the effects of the different sociodemographic variables, both internal and environmental, as key driving elements in the probability of a company’s success and as indicators of business persistence and growth. Taking a representative sample of entrepreneurs from the Community of Madrid, Spain, a statistical structural equation model (SEM) is built. The results show the importance that the degree of adaptation of the startup to digitization acquires in persistence, the effort to generate inter-entrepreneurship within the company, the preparation of the promoting team, their work skills, good practices, and the influence of environmental variables. This study contributes to dispelling the great uncertainty that afflicts entrepreneurs and making them understand the importance of innovation, training, and continuous updating, expansion, and renewal of knowledge and especially the value of learning about applications of new technologies, the transformation of processes within a business model, and the correct adaptation to an environment that is constantly changing.
Dispersion Analysis of Plane Wave Propagation in Lattice-Based Mechanical Metamaterial for Vibration Suppression
Authors: Tsushima Natsuki , Hayashi Yuta , Yokozeki Tomohiro
Published: August 2024

Phononic crystals based on lattice structures provide important wave dispersion characteristics as band structures, showing excellent compatibility with additive manufacturing. Although the lattice structures have shown the potential for vibration suppression, a design guideline to control the frequency range of the bandgap has not been well established. This paper studies the dispersion characteristics of plane wave propagation in lattice-based mechanical metamaterials to realize effective vibration suppression for potential aerospace applications. Triangular and hexagonal periodic lattice structures are mainly studied in this paper. The influence of different geometric parameters on the bandgap characteristics is investigated. A finite element approach with Floquet–Bloch’s principles is implemented to effectively evaluate the dispersion characteristics of waves in lattice structures, which is validated numerically and experimentally with a 3D-printed lattice plate. Based on numerical studies with the developed analysis framework, the influences of the geometric parameters of lattice plate structures on dispersion characteristics can mainly be categorized into three patterns: change in specific branches related to in-plane or out-of-plane vibrations, upward/downward shift in frequency range, and drastic change in dispersion characteristics. The results obtained from the study provide insight into the design of band structures to realize vibration suppression at specific frequencies for engineering applications.
nZVI@BC as a Soil Amendment and Its Effects on Potted Rice Growth and Soil Properties
Authors: Xiang Shuyan , Zheng Yuhong , Zhou Qingwei , Jin Meiqing , Fu Li , Wu Weihong
Published: August 2024

This study investigated the effects of nano zero-valent iron-modified biochar (nZVI@BC) as a soil amendment on potted rice growth, soil properties, and heavy metal dynamics. Seven treatments with varying amounts of soil conditioner, biochar, and nZVI@BC were applied to potted rice. Results showed that nZVI@BC application significantly improved rice agronomic traits, with the 15 g·kg−1 treatment increasing the panicle formation rate by 15% and 100-grain weight by 8% compared to the control. Soil fertility was enhanced, with available phosphorus increasing from 137 to 281 mg·kg−1 in the most effective treatment. Heavy metal analysis revealed that nZVI@BC application did not increase soil heavy metal content, with Cd levels remaining below 0.3 mg·kg−1 across treatments. Notably, the 10 g·kg−1 nZVI@BC treatment showed potential for slight Cd immobilization, reducing its concentration from 0.32 to 0.26 mg·kg−1. Microbial community analysis showed that nZVI@BC altered soil microbial diversity and composition, with the 10 g·kg−1 treatment resulting in the highest fungal diversity (Chao1 index: 294.219). The relative abundance of the beneficial fungal class Agaricomycetes increased from 40% to 55% with optimal nZVI@BC application. These findings suggest that nZVI@BC has potential as an effective soil amendment for improving rice cultivation while maintaining soil health, microbial diversity, and potentially mitigating heavy metal contamination.
Morphological and Physiological Response of Maize (Zea mays L.) to Drought Stress during Reproductive Stage
Authors: Yasin Saba , Zavala-García Francisco , Niño-Medina Guillermo , Rodríguez-Salinas Pablo Alan , Gutiérrez-Diez Adriana , Sinagawa-García Sugey Ramona , Lugo-Cruz Eleazar
Published: August 2024

Maize is among the most significant crops in the world regarding production and yield, but it is highly sensitive to drought, which reduces the growth, photosynthetic efficiency, grain quality, and yield production of a plant. Quantum yield efficiency of photosystem II is a critical photosynthetic component that is susceptible to drought stress. This study intended to investigate the effects of drought stress on growth and morpho-physiological parameters using three maize hybrids (‘P-3011w’, ‘P-3092’ and ‘iku20’) with contrasting soil moisture contents (100%, 40%) at the pre-flowering stage. The stress treatment (40%) was initiated at stage V7, for a period of 15 days; the experimental units were established in a completely randomized design with split-plot arrangement along with three repetitions in 42 L pots using a substrate of peat moss, black soil and poultry manure (1:2:1). The morphological, growth-related and physiological parameters were assessed, including chlorophyll fluorescence (Fv/Fm), which was measured using a LiCor-6400-40 fluorometer. The results showed that all morphological, growth-related and physiological variables decreased under drought stress during the reproductive stage, with the exception of leaf temperature and intercellular CO2 concentration, which increased by 12% and 54%, respectively. Drought stress significantly reduced the photosynthetic chlorophyll fluorescence (43%), due to damage to photosystem II. The lowest percentage of damage to photosystem II (34%) was observed in the iku20 genotype. In contrast, P-3011w and P-3092 had the highest levels of significantly similar damage (49% and 46%, respectively). The correlation analysis showed a highly positive interaction of chlorophyll fluorescence (Fv/Fm) with net photosynthetic rate and stomatal conductance under drought conditions, and multiple regression analysis revealed that the maximum effect on net photosynthetic rate under drought was due to the damage it caused to photosystem II. Thus, iku20 might have a tendency to be able to withstand drought stress in the dry northeast region of Mexico. Overall, we concluded that the photosystem II was negatively impacted by drought stress thus causing a reduction in all physiological, morphological and growth-related variables.
A Longitudinal Tree-Based Framework for Lapse Management in Life Insurance
Authors: Valla Mathias
Published: August 2024

Developing an informed lapse management strategy (LMS) is critical for life insurers to improve profitability and gain insight into the risk of their global portfolio. Prior research in actuarial science has shown that targeting policyholders by maximising their individual customer lifetime value is more advantageous than targeting all those likely to lapse. However, most existing lapse analyses do not leverage the variability of features and targets over time. We propose a longitudinal LMS framework, utilising tree-based models for longitudinal data, such as left-truncated and right-censored (LTRC) trees and forests, as well as mixed-effect tree-based models. Our methodology provides time-informed insights, leading to increased precision in targeting. Our findings indicate that the use of longitudinally structured data significantly enhances the precision of models in predicting lapse behaviour, estimating customer lifetime value, and evaluating individual retention gains. The implementation of mixed-effect random forests enables the production of time-varying predictions that are highly relevant for decision-making. This paper contributes to the field of lapse analysis for life insurers by demonstrating the importance of exploiting the complete past trajectory of policyholders, which is often available in insurers’ information systems but has yet to be fully utilised.