bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing crop disease resistance through genome editing: a promising approach for enhancing agricultural production
Authors: Manzoor Subaya , Nabi Sajad Un , Rather Tariq Rasool , Gani Gousia , Mir Zahoor Ahmad , Wani Ab Waheed , Ali Sajad , Tyagi Anshika , Manzar Nazia
Published: June 2024

Modern agriculture has encountered several challenges in achieving constant yield stability especially due to disease outbreaks and lack of long-term disease-resistant crop cultivars. In the past, disease outbreaks in economically important crops had a major impact on food security and the economy. On the other hand climate-driven emergence of new pathovars or changes in their host specificity further poses a serious threat to sustainable agriculture. At present, chemical-based control strategies are frequently used to control microbial pathogens and pests, but they have detrimental impact on the environment and also resulted in the development of resistant phyto-pathogens. As a replacement, cultivating engineered disease-resistant crops can help to minimize the negative impact of regular pesticides on agriculture and the environment. Although traditional breeding and genetic engineering have been instrumental in crop disease improvement but they have certain limitations such as labour intensity, time consumption, and low efficiency. In this regard, genome editing has emerged as one of the potential tools for improving disease resistance in crops by targeting multiple traits with more accuracy and efficiency. For instance, genome editing techniques, such as CRISPR/Cas9, CRISPR/Cas13, base editing, TALENs, ZFNs, and meganucleases, have proved successful in improving disease resistance in crops through targeted mutagenesis, gene knockouts, knockdowns, modifications, and activation of target genes. CRISPR/Cas9 is unique among these techniques because of its remarkable efficacy, low risk of off-target repercussions, and ease of use. Some primary targets for developing CRISPR-mediated disease-resistant crops are host-susceptibility genes (the S gene method), resistance genes (R genes) and pathogen genetic material that prevents their development, broad-spectrum disease resistance. The use of genome editing methods has the potential to notably ameliorate crop disease resistance and transform agricultural practices in the future. This review highlights the impact of phyto-pathogens on agricultural productivity. Next, we discussed the tools for improving disease resistance while focusing on genome editing. We provided an update on the accomplishments of genome editing, and its potential to improve crop disease resistance against bacterial, fungal and viral pathogens in different crop systems. Finally, we highlighted the future challenges of genome editing in different crop systems for enhancing disease resistance.
Integrated microbiome and metabolome analysis reveals that new insight into Radix pseudostellariae polysaccharide enhances PRRSV inactivated vaccine
Authors: Xu Gaolin , You Zelong , Zheng Yu , Feng Qixian , Luo Shishi , Xu Lihui , Bao Songying , Wang Quanxi
Published: June 2024

In this study, we investigated how Radix pseudostellariae polysaccharide (RPP) enhances the immune response of the inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine through interactions with the microbiome and metabolome. We pretreated sows with 10 mg/kg body weight of RPP via drinking water for 7 days prior to intramuscular injection of the PRRSV vaccine. This significantly increased the concentrations of PRRSV GP5 protein antibody, interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-γ. Oral administration of RPP also significantly improved the abundance of beneficial bacteria in the stool, such as Parabacteroides distasonis, Prevotella_copri, Eubacterium_sp., and Clostridium_sp._CAG:226, and decreased the levels of potentially pathogenic bacteria, such as Paraeggerthella and [Clostridium] innocuum, compared to the vaccine alone. These bacterial changes were confirmed using quantitative real-time polymerase chain reaction (Q-PCR). Moreover, RPP treatment significantly increased the blood concentrations of L-theanine, taurodeoxycholic acid (TDCA), and N-arachidonoyl proline, and decreased the levels of L-glutamine, oclacitinib, lipoxin C4, and leukotriene C5 in sows after immunization (p< 0.05). The concentrations of various blood metabolites were validated using sandwich enzyme-linked immunosorbent assay (ELISA), confirming the accuracy of the metabolomics data. Intriguingly, the integration of microbiome and metabolome analyses highlighted the significance of Prevotella_copri and TDCA. We consequently developed a mouse immunity model using GP5 protein and discovered that oral administration of RPP significantly enhanced the levels of GP5 protein antibodies, IL-2, IL-4, IL-10, and IFN-γ in mouse serum. It also increased the number of CD3+ and CD3+CD4+ cells in the spleen. Additionally, Prevotella_copri was administered into the large intestine via the anus for 7 days prior to the intramuscular injection of the PRRSV GP5 protein. The results demonstrated a significant increase in TDCA and GP5 antibody concentration in the mouse serum, indicating that RPP modulates Prevotella_copri to elevate its metabolite TDCA, thereby enhancing the GP5 antibody level. In conclusion, oral administration of 10 mg/kg RPP optimizes gut flora diversity and blood metabolites, particularly Prevotella_copri and TDCA, thereby improving the immune response to the inactivated PRRSV vaccine.
Non-viral-mediated gene transfer of OX40 ligand for tumor immunotherapy
Authors: Rakitina Olga A. , Kuzmich Alexey I. , Bezborodova Olga A. , Kondratieva Sofia A. , Pleshkan Victor V. , Zinovyeva Marina V. , Didych Dmitry A. , Sass Aleksandr V. , Snezhkov Eugene V. , Kostina Maria B. , Koksharov Maksim O. , Alekseenko Irina V.
Published: June 2024

Background

Immune checkpoint blockade (ICB) is rapidly becoming a standard of care in the treatment of many cancer types. However, the subset of patients who respond to this type of therapy is limited. Another way to promote antitumoral immunity is the use of immunostimulatory molecules, such as cytokines or T cell co-stimulators. The systemic administration of immunotherapeutics leads to significant immune-related adverse events (irAEs), therefore, the localized antitumoral action is needed. One way to achieve this is intratumoral non-viral gene-immune therapy, which allows for prolonged and localized gene expression, and multiple drug administration. In this study, we combined the previously described non-viral gene delivery system, PEG-PEI-TAT copolymer, PPT, with murine OX40L-encoding plasmid DNA.

Methods

The resulting OX40L/PPT nanoparticles were characterized via gel mobility assay, dynamic light scattering analysis and in vitro transfection efficiency evaluation. The antitumoral efficacy of intratumorally (i.t.) administered nanoparticles was estimated using subcutaneously (s.c.) implanted CT26 (colon cancer), B16F0 (melanoma) and 4T1 (breast cancer) tumor models. The dynamics of stromal immune cell populations was analyzed using flow cytometry. Weight loss and cachexia were used as irAE indicators. The effect of combination of i.t. OX40L/PPT with intraperitoneal PD-1 ICB was estimated in s.c. CT26 tumor model.

Results

The obtained OX40L/PPT nanoparticles had properties applicable for cell transfection and provided OX40L protein expression in vitro in all three investigated cancer models. We observed that OX40L/PPT treatment successfully inhibited tumor growth in B16F0 and CT26 tumor models and showed a tendency to inhibit 4T1 tumor growth. In B16F0 tumor model, OX40L/PPT treatment led to the increase in antitumoral effector NK and T killer cells and to the decrease in pro-tumoral myeloid cells populations within tumor stroma. No irAE signs were observed in all 3 tumor models, which indicates good treatment tolerability in mice. Combining OX40L/PPT with PD-1 ICB significantly improved treatment efficacy in the CT26 subcutaneous colon cancer model, providing protective immunity against CT26 colon cancer cells.

Conclusion

Overall, the anti-tumor efficacy observed with OX40L non-viral gene therapy, whether administered alone or in combination with ICB, highlights its potential to revolutionize cancer gene therapy, thus paving the way for unprecedented advancements in the cancer therapy field.
A theoretical model and verification of soil column deformation under impact load based on the Duncan-Chang model
Authors: Jianqiu Huang , Zhuo Jin , Haiping Wang , Tao Ling , Xuejun Peng , Yu Tang , Qin Liu , Xi Li
Published: June 2024

The dynamic compaction method has been widely adopted in foundation treatment to densify the soil fillers. However, for the complexity of the impact behavior and soil mechanical properties, the theoretical research of dynamic compaction lags behind its practice for complex soil properties and stress paths. This paper presents a theoretical model applied to describe soil column plastic deformation under impact load. The relationship among stress increment, strain increment, and plastic wave velocity was derived from the aspect of propagation characteristics of stress waves in soil first. Combined with the Duncan-Chang Model, a one-dimensional theoretical model was established then. A numerical model was developed further to check the performance of the model. It showed that the deformation at the end of the soil column was mushroom-shaped. Both the axial and lateral deformation increased with the impact velocity. While some particles located at the side of the soil column end may splash under repeated impact. The theoretical deformations of the soil column were consistent with the experimental results both in the direction of axial and lateral.
Eosinophilic gastroenteritis in an elderly men associated with antibiotic use post maxillofacial space infection: a case report
Authors: Lin Ran , Ye Kangjie , Hong Min , Li Jiqiang , Zhang Zhongde , Zhang Xi
Published: June 2024

A 79-year-old man underwent operative drainage and 2-week cephalosporin treatment due to a maxillofacial space infection (bilateral submaxillaris, submentum, and left face). However, he experienced anorexia, nausea, vomiting, and emaciation in the following 2 months. It was initially considered that a malignancy might be present, thus a series of examinations were performed. Laboratory investigations showed increases in inflammatory markers and a significant eosinophilia, which seemed to be a hematological system disease. Combined with the gastrointestinal endoscopes and histology examination, the patient was diagnosed with eosinophilic gastroenteritis (EGE). After cessation of antibiotic treatment and administration of corticosteroid, our patient experienced a rapid progress in his clinical condition. Despite the low incidence, EGE should be considered in patients with unknown cause of gastrointestinal disorder, elevated eosinophilia, and so on.
Relationship between frailty and depressive symptoms in older adults: role of activities of daily living and sleep duration
Authors: Song Wei , Liu Manyu , Ye Ting , Wang Dong , Yuan Quan , Li Fen , Wang Qiushi , Ma Yana
Published: June 2024

Introduction

Previous studies have demonstrated that frailty is associated with depressive symptoms among older people and significantly increase the risk of difficulty in activities of daily living (ADL). However, uncertainties remain regarding the mechanisms behind such relationship. The aim of this study was to investigate the mediating effect of ADL in the relationship between frailty and depressive symptoms among older adults in China, and to explore to what extend sleep duration moderated the association between ADL and depressive symptoms.

Methods

In this study, we carried out cross-sectional descriptive analysis and 1,429 participants were included in the analysis. A survey was conducted using questionnaires and instruments measuring frailty, depressive symptoms, ADL and sleep duration. Bootstrap analyses served to explore the impact of ADL in mediating frailty and depressed symptoms, as well as the effect of sleep duration in moderating ADL and depressive symptoms.

Results

Compared to the robust group, the mediating effects of ADL between frailty and depressive symptoms were significant in the prefrail group and the frail group. The interaction term between sleep duration and ADL was significantly presented in the regression on depressive symptoms. Specifically, the Johnson–Neyman technique determined a range from 8.31 to 10.19 h for sleep duration, within which the detrimental effect of frailty on depressive symptoms was offset.

Conclusion

Sleep duration moderated the indirect effect of ADL on the association between frailty and depressive symptoms. This provides support for unraveling the underlying mechanism of the association between frailty and depressive symptoms. Encouraging older adults to enhance ADL and obtain appropriate sleep duration might improve depressive symptoms for older adults with frailty and prefrailty.
Winter cover crop suppression methods influence on sunflower growth and rhizosphere communities
Authors: Morales Marianela Estefanía , Allegrini Marco , Basualdo Jessica , Iocoli Gastón Alejandro , Villamil María Bonita , Zabaloy María Celina
Published: June 2024

Sunflower (Helianthus annuus L.), a vital crop for global vegetable oil production, encounters sustainability challenges in its cultivation. This study assesses the effects of incorporating a winter cover crop (CC), Avena sativa (L.), on the subsequent growth of sunflower crops and the vitality of their rhizosphere microbial communities over a two-year period. It examines the impact of two methods for suppressing winter CC—chemical suppression using glyphosate and mechanical suppression via rolling—both with and without the addition of phosphorus (P) starter fertilizer. These approaches are evaluated in comparison to the regional best management practices for sunflower cultivation, which involve a preparatory chemical fallow period and the subsequent application of starter P fertilizer. The methodology utilized Illumina sequencing for the analysis of rhizosphere bacterial 16S rRNA genes and fungal internal transcribed spacer (ITS) amplicons. Findings indicate a significant improvement (9–37%) in sunflower growth parameters (plant height, stem diameter, head diameter, and head dry weight) when cultivated after glyphosate-suppressed winter CC compared to the chemical fallows. Conversely, rolling of winter CC generally negatively affected sunflower growth. Rhizosphere bacterial communities following chemical suppression of winter CC showed greater Pielou’s evenness, indicating a uniform distribution of species. In general, this treatment had more detrimental effects on beneficial sunflower rhizosphere bacteria such as Hymenobacter and Pseudarthrobacter than rolling of the winter CC, suggesting that the overall effect on sunflower growth may be mitigated by the redundancy within the bacterial community. As for fungal diversity, measured by the Chao-1 index, it increased in sunflowers planted after winter CC and receiving P fertilization, underscoring nutrient management’s role in microbial community structure. Significant positive correlations between fungal diversity and sunflower growth parameters at the reproductive stage were observed (r = 0.41–0.72; p < 0.05), highlighting the role of fungal communities in plant fitness. The study underscores the positive effects of winter CC inclusion and management for enhancing sunflower cultivation while promoting beneficial microbes in the crop’s rhizosphere. We advocate for strategic winter CC species selection, optimization of mechanical suppression techniques, and tailored phosphorus fertilization of sunflower to foster sustainable agriculture.
The FinO/ProQ-like protein PA2582 impacts antimicrobial resistance in Pseudomonas aeruginosa
Authors: Cianciulli Sesso Anastasia , Resch Armin , Moll Isabella , Bläsi Udo , Sonnleitner Elisabeth
Published: June 2024

Bacteria employ small regulatory RNAs (sRNA) and/or RNA binding proteins (RBPs) to respond to environmental cues. In Enterobacteriaceae, the FinO-domain containing RBP ProQ associates with numerous sRNAs and mRNAs, impacts sRNA-mediated riboregulation or mRNA stability by binding to 5′- or 3′-untranslated regions as well as to internal stem loop structures. Global RNA-protein interaction studies and sequence comparisons identified a ProQ-like homolog (PA2582/ProQPae) in Pseudomonas aeruginosa (Pae). To address the function of ProQPae, at first a comparative transcriptome analysis of the Pae strains PAO1 and PAO1ΔproQ was performed. This study revealed more than 100 differentially abundant transcripts, affecting a variety of cellular functions. Among these transcripts were pprA and pprB, encoding the PprA/PprB two component system, psrA, encoding a transcriptional activator of pprB, and oprI, encoding the outer membrane protein OprI. RNA co-purification experiments with Strep-tagged Pae ProQ protein corroborated an association of ProQPae with these transcripts. In accordance with the up-regulation of the psrA, pprA, and pprB genes in strain PAO1ΔproQ a phenotypic analysis revealed an increased susceptibility toward the aminoglycosides tobramycin and gentamicin in biofilms. Conversely, the observed down-regulation of the oprI gene in PAO1ΔproQ could be reconciled with a decreased susceptibility toward the synthetic cationic antimicrobial peptide GW-Q6. Taken together, these studies revealed that ProQPae is an RBP that impacts antimicrobial resistance in Pae.
Production of the siderophore lysochelin in rich media through maltose-promoted high-density growth of Lysobacter sp. 3655
Authors: Zhang Fang , Liu Jia , Jiang Lin , Zheng Yongbiao , Yu Lingjun , Du Liangcheng
Published: June 2024

Siderophores are produced by bacteria in iron-restricted conditions. However, we found maltose could induce the biosynthesis of the siderophore lysochelin in Lysobacter sp. 3655 in rich media that are not compatible with siderophore production. Maltose markedly promoted cell growth, with over 300% increase in cell density (OD600) when LB medium was added with maltose (LBM). While lysochelin was not detectable when OD600 in LBM was below 5.0, the siderophore was clearly produced when OD600 reached 7.5 and dramatically increased when OD600 was 15.0. Coincidently, the transcription of lysochelin biosynthesis genes was remarkably enhanced following the increase of OD600. Conversely, the iron concentration in the cell culture dropped to 1.2 μM when OD600 reached 15.0, which was 6-fold lower than that in the starting medium. Moreover, mutants of the maltose-utilizing genes (orf2677 and orf2678) or quorum-sensing related gene orf644 significantly lowered the lysochelin yield. Transcriptomics analysis showed that the iron-utilizing/up-taking genes were up-regulated under high cell density. Accordingly, the transcription of lysochelin biosynthetic genes and the yield of lysochelin were stimulated when the iron-utilizing/up-taking genes were deleted. Finally, lysochelin biosynthesis was positively regulated by a TetR regulator (ORF3043). The lysochelin yield in orf3043 mutant decreased to 50% of that in the wild type and then restored in the complementary strain. Together, this study revealed a previously unrecognized mechanism for lysochelin biosynthetic regulation, by which the siderophore could still be massively produced in Lysobacter even grown in a rich culture medium. This finding could find new applications in large-scale production of siderophores in bacteria.
A long journey to treat epilepsy with the gut microbiota
Authors: Li Qinrui , Gu Youyu , Liang Jingjing , Yang Zhixian , Qin Jiong
Published: June 2024

Epilepsy is a common neurological disorder that affects approximately 10.5 million children worldwide. Approximately 33% of affected patients exhibit resistance to all available antiseizure medications, but the underlying mechanisms are unknown and there is no effective treatment. Increasing evidence has shown that an abnormal gut microbiota may be associated with epilepsy. The gut microbiota can influence the function of the brain through multiple pathways, including the neuroendocrine, neuroimmune, and autonomic nervous systems. This review discusses the interactions between the central nervous system and the gastrointestinal tract (the brain–gut axis) and the role of the gut microbiota in the pathogenesis of epilepsy. However, the exact gut microbiota involved in epileptogenesis is unknown, and no consistent results have been obtained based on current research. Moreover, the target that should be further explored to identify a novel antiseizure drug is unclear. The role of the gut microbiota in epilepsy will most likely be uncovered with the development of genomics technology.
Astrocyte regulation of extracellular space parameters across the sleep-wake cycle
Authors: Sriram Sandhya , Carstens Kaira , Dewing Wayne , Fiacco Todd A.
Published: June 2024

Multiple subfields of neuroscience research are beginning to incorporate astrocytes into current frameworks of understanding overall brain physiology, neuronal circuitry, and disease etiology that underlie sleep and sleep-related disorders. Astrocytes have emerged as a dynamic regulator of neuronal activity through control of extracellular space (ECS) volume and composition, both of which can vary dramatically during different levels of sleep and arousal. Astrocytes are also an attractive target of sleep research due to their prominent role in the glymphatic system, a method by which toxic metabolites generated during wakefulness are cleared away. In this review we assess the literature surrounding glial influences on fluctuations in ECS volume and composition across the sleep-wake cycle. We also examine mechanisms of astrocyte volume regulation in glymphatic solute clearance and their role in sleep and wake states. Overall, findings highlight the importance of astrocytes in sleep and sleep research.
The association between ferritin levels and all-cause mortality in stroke patients
Authors: Xia Xuefen , Liu Jiongjiong , Fang Wenqiang , Chen Zhibo , Wang Jie , Xu Huiqin
Published: June 2024

Purpose

The purpose of study was to describe the association between ferritin and all-cause mortality of cases with stroke.

Methods

Clinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day mortality. The potential prognostic roles of Ferritin L were analyzed by Cox proportional hazard models. The independent prognostic roles of Ferritin L in the cases were analyzed by smooth curve fitting.

Results

Concerning 30-day mortality, the HR (95% CI) for a high Ferritin (≥373) was 1.925 (1.298, 2.854; p = 0.00113), compared to a low ferritin (< 373). After adjusting for multiple confounders, the HR (95% CI) for a high Ferritin (≥373) was 1.782 (1.126, 2.820; p = 0.01367), compared to a low Ferritin (< 373). A non-linear association between Ferritin and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 2,204. On the left side of the IP, there was a positive relationship between Ferritin and 30-day mortality, and the effect size, 95% CI and p value were 1.0006 (1.0004, 1.0009) p < 0.0001, respectively. On the right of the IP, the effect size, 95% CI and p value were 1.0000 (1.0000, 1.0000) and 0.3107, respectively.

Conclusion

Ferritin was associated with increased risk of stroke; it is important to further examine the association if the increased uric acid would increase the outcome of stroke in a longitudinal study. The non-linear relationship between Ferritin and all-cause mortality of stroke was observed. Ferritin was a risk factor for the outcome of stroke when ferritin was <2204.
Leveraging machine learning to develop a postoperative predictive model for postoperative urinary retention following lumbar spine surgery
Authors: Malnik Samuel L. , Porche Ken , Mehkri Yusuf , Yue Sijia , Maciel Carolina B. , Lucke-Wold Brandon P. , Robicsek Steven A. , Decker Matthew , Busl Katharina M.
Published: June 2024

Introduction

Postoperative urinary retention (POUR) is the inability to urinate after a surgical procedure despite having a full bladder. It is a common complication following lumbar spine surgery which has been extensively linked to increased patient morbidity and hospital costs. This study hopes to development and validate a predictive model for POUR following lumbar spine surgery using patient demographics, surgical and anesthesia variables.

Methods

This is a retrospective observational cohort study of 903 patients who underwent lumbar spine surgery over the period of June 2017 to June 2019 in a tertiary academic medical center. Four hundred and nineteen variables were collected including patient demographics, ICD-10 codes, and intraoperative factors. Least absolute shrinkage and selection operation (LASSO) regression and logistic regression models were compared. A decision tree model was fitted to the optimal model to classify each patient’s risk of developing POUR as high, intermediate, or low risk. Predictive performance of POUR was assessed by area under the receiver operating characteristic curve (AUC-ROC).

Results

903 patients were included with average age 60 ± 15 years, body mass index of 30.5 ± 6.4 kg/m2, 476 (53%) male, 785 (87%) white, 446 (49%) involving fusions, with average 2.1 ± 2.0 levels. The incidence of POUR was 235 (26%) with 63 (7%) requiring indwelling catheter placement. A decision tree was constructed with an accuracy of 87.8%.

Conclusion

We present a highly accurate and easy to implement decision tree model which predicts POUR following lumbar spine surgery using preoperative and intraoperative variables.
TractoSCR: a novel supervised contrastive regression framework for prediction of neurocognitive measures using multi-site harmonized diffusion MRI tractography
Authors: Xue Tengfei , Zhang Fan , Zekelman Leo R. , Zhang Chaoyi , Chen Yuqian , Cetin-Karayumak Suheyla , Pieper Steve , Wells William M. , Rathi Yogesh , Makris Nikos , Cai Weidong , O'Donnell Lauren J.
Published: June 2024

Neuroimaging-based prediction of neurocognitive measures is valuable for studying how the brain's structure relates to cognitive function. However, the accuracy of prediction using popular linear regression models is relatively low. We propose a novel deep regression method, namely TractoSCR, that allows full supervision for contrastive learning in regression tasks using diffusion MRI tractography. TractoSCR performs supervised contrastive learning by using the absolute difference between continuous regression labels (i.e., neurocognitive scores) to determine positive and negative pairs. We apply TractoSCR to analyze a large-scale dataset including multi-site harmonized diffusion MRI and neurocognitive data from 8,735 participants in the Adolescent Brain Cognitive Development (ABCD) Study. We extract white matter microstructural measures using a fine parcellation of white matter tractography into fiber clusters. Using these measures, we predict three scores related to domains of higher-order cognition (general cognitive ability, executive function, and learning/memory). To identify important fiber clusters for prediction of these neurocognitive scores, we propose a permutation feature importance method for high-dimensional data. We find that TractoSCR obtains significantly higher accuracy of neurocognitive score prediction compared to other state-of-the-art methods. We find that the most predictive fiber clusters are predominantly located within the superficial white matter and projection tracts, particularly the superficial frontal white matter and striato-frontal connections. Overall, our results demonstrate the utility of contrastive representation learning methods for regression, and in particular for improving neuroimaging-based prediction of higher-order cognitive abilities. Our code will be available at: https://github.com/SlicerDMRI/TractoSCR.
EEG-based driving intuition and collision anticipation using joint temporal-frequency multi-layer dynamic brain network
Authors: Liang Jialong , Wang Zhe , Han Jinghang , Zhang Lihua
Published: June 2024

Intuition plays a crucial role in human driving decision-making, and this rapid and unconscious cognitive process is essential for improving traffic safety. We used the first proposed multi-layer network analysis method, “Joint Temporal-Frequency Multi-layer Dynamic Brain Network” (JTF-MDBN), to study the EEG data from the initial and advanced phases of driving intuition training in the theta, alpha, and beta bands. Additionally, we conducted a comparative study between these two phases using multi-layer metrics as well as local and global metrics of single layers. The results show that brain region activity is more stable in the advanced phase of intuition training compared to the initial phase. Particularly in the alart state task, the JTF-MDBN demonstrated stronger connection strength. Multi-layer network analysis indicates that modularity is significantly higher for the non-alert state task than the alert state task in the alpha and beta bands. In the W4 time window (1 second before a collision), we identified significant features that can differentiate situations where a car collision is imminent from those where no collision occurs. Single-layer network analysis also revealed statistical differences in node strength and local efficiency for some EEG channels in the alpha and beta bands during the W4 and W5 time windows. Using these biomarkers to predict vehicle collision risk, the classification accuracy of a linear kernel SVM reached up to 87.5%, demonstrating the feasibility of predicting driving collisions through brain network biomarkers. These findings are important for the study of human intuition and the development of brain-computer interface-based intelligent driving hazard perception assistance systems.
Cashew nut (Anacardium occidentale L.) and cashew nut oil reduce cardiovascular risk factors in adults on weight-loss treatment: a randomized controlled three-arm trial (Brazilian Nuts Study)
Authors: Meneguelli Talitha Silva , Kravchychyn Ana Claudia Pelissari , Wendling Aline Lage , Dionísio Ana Paula , Bressan Josefina , Martino Hercia Stampini Duarte , Tako Elad , Hermsdorff Helen Hermana Miranda
Published: June 2024

Introduction

Cashew nut contains bioactive compounds that modulate satiety and food intake, but its effects on body fat during energy restriction remains unknown. This study aimed to assess the effects of cashew nut and cashew nut oil on body fat (primary outcome) as well as adiposity, cardiometabolic and liver function markers (secondary outcomes).

Materials and methods

An eight-week (8-wk) randomized controlled-feeding study involved 68 adults with overweight/obesity (40 women, BMI: 33 ± 4 kg/m2). Participants were randomly assigned to one of the energy-restricted (−500 kcal/d) groups: control (CT, free-nuts), cashew nut (CN, 30 g/d), or cashew nut oil (OL, 30 mL/d). Body weight, body composition, and blood collection were assessed at the baseline and endpoint of the study.

Results

After 8-wk, all groups reduced significantly body fat (CT: −3.1 ± 2.8 kg; CN: −3.3 ± 2.7 kg; OL: −1.8 ± 2.6 kg), body weight (CT: −4.2 ± 3.8 kg; CN: −3.9 ± 3.1 kg; OL: −3.4 ± 2.4 kg), waist (CT: −5.1 ± 4.6 cm; CN: −3.9 ± 3.9 cm; OL: −3.7 ± 5.3 cm) and hip circumferences (CT: −2.9 ± 3.0 cm; CN: −2.7 ± 3.1 cm; OL: −2.9 ± 2.3 cm). CN-group reduced liver enzymes (AST: −3.1 ± 5.3 U/L; ALT: −6.0 ± 9.9 U/L), while the OL-group reduced LDL-c (−11.5 ± 21.8 mg/dL) and atherogenic index (−0.2 ± 0.5). Both intervention groups decreased neck circumference (CN: −1.0 ± 1.2 cm; OL: −0.5 ± 1.2 cm) and apo B (CN: −6.6 ± 10.7 mg/dL; OL: −7.0 ± 15.3 mg/dL).

Conclusion

After an 8-wk energy-restricted intervention, all groups reduced body fat (kg), weight, and some others adiposity indicators, with no different effect of cashew nut or cashew nut oil. However, participants in the intervention groups experienced additional reductions in atherogenic marker, liver function biomarkers, and cardiovascular risk factors (neck circumference and apo B levels), with these effects observed across the OL group, CN group, and both intervention groups, respectively.

Clinical trial registration:https://ensaiosclinicos.gov.br/rg/RBR-8xzkyp2, identifier 8xzkyp2.
Pregnant patient with Xp11.2/transcription factor E3 translocation renal cell carcinoma: a case report and literature review
Authors: Wang Yanchen , Guo Xiaoyan , Meng Zhe , Cui Yong , Sun Yaofei
Published: June 2024

MiT family translocation renal cell carcinomas (tRCCs) primarily include Xp11.2/transcription factor E3 (TFE3) gene fusion-associated renal cell carcinoma (Xp11.2 tRCC) and t(6;11)/TFEB gene fusion-associated RCC. Clinical cases of these carcinomas are rare. Fluorescence in situ hybridization can be used to identify the type, but there are no standard diagnostic and treatment methods available, and the prognosis remains controversial. Herein, we present a case of a patient with Xp11.2 tRCC at 29 weeks of gestation. The baby was successfully delivered, and radical surgery was performed for renal cancer at the same time. This is a unique and extremely rare case. We have described the case and performed a literature review to report the progress of current research on the treatment and prognosis of pregnant patients with Xp11.2/TFE3 translocation renal cell carcinoma. This study aims to contribute to improving the diagnosis and treatment of Xp11.2 tRCC in pregnant patients.
Integrating metabolic profiling of pancreatic juice with transcriptomic analysis of pancreatic cancer tissue identifies distinct clinical subgroups
Authors: Pulvirenti Alessandra , Barbagallo Marialuisa , Putignano Anna Rita , Pea Antonio , Polidori Rebecca , Upstill-Goddard Rosie , Cortese Nina , Kunderfranco Paolo , Brunelli Laura , De Simone Giulia , Pastorelli Roberta , Spaggiari Paola , Nappo Gennaro , Jamieson Nigel B. , Zerbi Alessandro , Chang David K. , Capretti Giovanni , Marchesi Federica
Published: June 2024

Introduction

Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities.

Methods

We performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides.

Results

Pancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival.

Discussion

PJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy.
Investigating the relationship between postoperative radiotherapy and intestinal flora in rectal cancer patients: a study on efficacy and radiation enteritis
Authors: Long Lin , Zhang Yexi , Zang Jianhua , Liu Peng , Liu Wei , Sun Cheng , Tian Dan , Li Ping , Tian Jin , Xiao Jun
Published: June 2024

Objective

This study aimed to investigate the impact of radiation therapy and radiation enteritis on intestinal flora, providing insights for treatment and prevention.

Methods

Fecal samples were collected from 16 patients undergoing pelvic radiotherapy at Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital). Samples were collected before and after radiotherapy (27–30Gy), and analyzed using DNA sequencing and biostatistical methods.

Results

Patients with radiation enteritis showed increased α-diversity and β-diversity of intestinal flora compared to those without radiation enteritis. Differences in flora composition were observed, with higher abundance of secondary pathways such as amino acid metabolism, carbohydrate metabolism, cofactors and vitamins metabolism, and lipid metabolism.

Conclusion

The study revealed that patients developing radiation enteritis during pelvic radiation therapy had increased diversity and abundance of intestinal flora compared to those who did not develop radiation enteritis. Additionally, patients without radiation enteritis showed significantly higher diversity and abundance of intestinal flora post-radiation compared to pre-radiation.
Identification of diagnostic biomarkers and potential therapeutic targets for biliary atresia via WGCNA and machine learning methods
Authors: Xu Lei , Xiao Ting , Zou Biao , Rong Zhihui , Yao Wei
Published: June 2024

Biliary atresia (BA) is a severe and progressive biliary obstructive disease in infants that requires early diagnosis and new therapeutic targets. This study employed bioinformatics methods to identify diagnostic biomarkers and potential therapeutic targets for BA. Our analysis of mRNA expression from Gene Expression Omnibus datasets revealed 3,273 differentially expressed genes between patients with BA and those without BA (nBA). Weighted gene coexpression network analysis determined that the turquoise gene coexpression module, consisting of 298 genes, is predominantly associated with BA. The machine learning method then filtered out the top 2 important genes, CXCL8 and TMSB10, from the turquoise module. The area under receiver operating characteristic curves for TMSB10 and CXCL8 were 0.961 and 0.927 in the training group and 0.819 and 0.791 in the testing group, which indicated a high diagnostic value. Besides, combining TMSB10 and CXCL8, a nomogram with better diagnostic performance was built for clinical translation. Several studies have highlighted the potential of CXCL8 as a therapeutic target for BA, while TMSB10 has been shown to regulate cell polarity, which was related to BA progression. Our analysis with qRT PCR and immunohistochemistry also confirmed the upregulation of TMSB10 at mRNA and protein levels in BA liver samples. These findings highlight the sensitivity of CXCL8 and TMSB10 as diagnostic biomarkers and their potential as therapeutic targets for BA.
Pharmacokinetic profile of phenytoin in dried blood spot with high-performance liquid chromatography—photodiode array
Authors: Harahap Yahdiana , Ng Limeylia , Sunarsih Sunarsih
Published: June 2024

Phenytoin is a first-line antiepileptic drug with narrow therapeutic range and follows non-linear pharmacokinetics. Pharmacokinetics of phenytoin have been studied in plasma matrix before, however, there were several disadvantages. This study aimed to obtain partial validation data of the analytical method and the pharmacokinetic profile of phenytoin in Dried Blood Spot (DBS) of six healthy subjects. DBS has the advantage of only requiring small sample volumes and could be transported more efficiently. Phenytoin along with carbamazepine as the chosen internal standard was analyzed with a reversed-phase high performance-liquid chromatography system and a photodiode array detector at 205 nm. The results of partial validation, which evaluated the linearity, within-run accuracy, and precision, were within the criteria acceptance range. The pharmacokinetic profile showed that average AUC0-t was 83.81 ± 37.32 μg.h/mL and AUC0-∞ was 83.65 ± 38.89 μg.h/mL with an average ratio of 93%. Previous study quantifying phenytoin in the plasma matrix found the average AUC0-t was 39.41 ± 8.57 µg.h/mL and AUC0-∞ was 42.94 ± 9.55 µg.h/mL. Despite the difference between parameters of phenytoin analyzed in DBS and plasma matrices, the pharmacokinetic profiles obtained from both matrices were similar indicated by comparable concentration-time curves, thus, proving that DBS matrix can be used interchangeably with the plasma matrix as a more comfortable and effective alternative to phenytoin quantification in blood.
High-intensity interval training using electrical stimulation ameliorates muscle fatigue in chronic kidney disease-related cachexia by restoring mitochondrial respiratory dysfunction
Authors: Fusagawa Hiroyori , Sato Tatsuya , Yamada Takashi , Naito Azuma , Tokuda Nao , Yamauchi Nao , Ichise Nobutoshi , Ogawa Toshifumi , Karaushi Takuro , Teramoto Atsushi , Tohse Noritsugu
Published: June 2024

Background

Exercise, especially high-intensity interval training (HIIT), can increase mitochondrial respiratory capacity and enhance muscular endurance, but its systemic burden makes it difficult to safely and continuously prescribe for patients with chronic kidney disease (CKD)-related cachexia who are in poor general condition. In this study, we examined whether HIIT using electrical stimulation (ES), which does not require whole-body exercise, improves muscle endurance in the skeletal muscle of 5/6 nephrectomized rats, a widely used animal model for CKD-related cachexia.

Methods

Male Wistar rats (10 weeks old) were randomly assigned to a group of sham-operated (Sham) rats and a group of 5/6 nephrectomy (Nx) rats. HIIT was performed on plantar flexor muscles in vivo with supramaximal ES every other day for 4 weeks to assess muscle endurance, myosin heavy-chain isoforms, and mitochondrial respiratory function in Nx rats. A single session was also performed to identify upstream signaling pathways altered by HIIT using ES.

Results

In the non-trained plantar flexor muscles from Nx rats, the muscle endurance was significantly lower than that in plantar flexor muscles from Sham rats. The proportion of myosin heavy chain IIa/x, mitochondrial content, mitochondrial respiratory capacity, and formation of mitochondrial respiratory supercomplexes in the plantaris muscle were also significantly decreased in the non-trained plantar flexor muscles from Nx rats than compared to those in plantar flexor muscles from Sham rats. Treatment with HIIT using ES for Nx rats significantly improved these molecular and functional changes to the same degrees as those in Sham rats. Furthermore, a single session of HIIT with ES significantly increased the phosphorylation levels of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), pathways that are essential for mitochondrial activation signaling by exercise, in the plantar muscles of both Nx and Sham rats.

Conclusion

The findings suggest that HIIT using ES ameliorates muscle fatigue in Nx rats via restoration of mitochondrial respiratory dysfunction with activation of AMPK and p38 MAPK signaling. Our ES-based HIIT protocol can be performed without placing a burden on the whole body and be a promising intervention that is implemented even in conditions of reduced general performance status such as CKD-related cachexia.
Determination of genomic regions associated with early storage root formation and bulking in cassava
Authors: Abah Simon Peter , Mbe Joseph Okpani , Dzidzienyo Daniel Kwadjo , Njoku Damian , Onyeka Joseph , Danquah Eric Yirenkyi , Offei Samuel Kwane , Kulakow Peter , Egesi Chiedozie Ngozi
Published: June 2024

Early cassava storage root formation and bulking is a medium of escape that farmers and processors tend to adopt in cases of abiotic and biotic stresses like drought, flood, and destruction by domestic animals. In this study, 220 cassava genotypes from the International Institute of Tropical Agriculture (IITA), National Root Crops Research Institute (NRCRI), International Center for Tropical Agriculture (CIAT), local farmers (from farmer’s field), and NextGen project were evaluated in three locations (Umudike, Benue, and Ikenne). The trials were laid out using a split plot in a randomized incomplete block design (alpha lattice) with two replications in 2 years. The storage roots for each plant genotype were sampled or harvested at 3, 6, 9, and 12 month after planting (MAP). All data collected were analyzed using the R-statistical package. The result showed moderate to high heritability among the traits, and there were significant differences (p< 0.05) among the performances of the genotypes. The genome-wide association mapping using the BLINK model detected 45 single-nucleotide polymorphism (SNP) markers significantly associated with the four early storage root bulking and formation traits on Chromosomes 1, 2, 3, 4, 5, 6, 8, 9, 10, 13, 14, 17, and 18. A total of 199 putative candidate genes were found to be directly linked to early storage root bulking and formation. The functions of these candidate genes were further characterized to regulate i) phytohormone biosynthesis, ii) cellular growth and development, and iii) biosynthesis of secondary metabolites for accumulation of starch and defense. Genome-wide association study (GWAS) also revealed the presence of four pleiotropic SNPs, which control starch content, dry matter content, dry yield, and bulking and formation index. The information on the GWAS could be used to develop improved cassava cultivars by breeders. Five genotypes (W940006, NR090146, TMS982123, TMS13F1060P0014, and NR010161) were selected as the best early storage root bulking and formation genotypes across the plant age. These selected cultivars should be used as sources of early storage root bulking and formation in future breeding programs.
Mental health index of the elderly population in Medellín (Colombia)−2021: a factorial analysis
Authors: Ochoa-Nieto Sandra Patricia , Benjumea-Gómez Luisa María , Cardona-Arango Doris , Segura-Cardona Ángela , Segura-Cardona Alejandra , Robledo-Marín Carlos
Published: June 2024

Introduction

There are several risk factors associated with developing mental disorders among people over 60 years of age. Mental health encompasses multiple domains or capacities, which can comprise the psychological wellbeing of older people. Therefore, resilient coping, self-compassion, self-esteem, hopelessness, quality of life, and depression are considered the characteristics and adaptive mechanisms that bring together the main risk and protective factors for imbalance in mental wellbeing.

Objective

This study aimed to establish the demographic, social, and family factors, as well as the clinical characteristics and lifestyle habits that influence the mental health of the elderly people in the city of Medellín, in the year 2021, to build a mental health index.

Methodology

This study adopts a quantitative approach, employs retrospective temporality, and utilizes secondary sources. A cross-sectional survey was carried out with the SABAM Project (health and mental wellbeing of older adults from five cities in Colombia in 2021 by its Spanish acronym) database (secondary source), which is part of the research group “Public Health Observatory” of CES University (Medellín, Colombia). The database comprised 500 records of people aged over 60 years from the city of Medellín in 2021. While constructing the index, a principal component analysis was used, along with the Varimax method for factor analysis rotation.

Results

The median age of the general population was 67 years (IQR 63–72); for men, the median age was 66 years (IQR 63–71) and for women, the median age was 67 years (IQR 63–72). An association was found between low socioeconomic levels, alcohol consumption, and the level of higher education (university—postgraduate) with low levels of the Mental Health Index in people over 60 years of age in Medellín during the year 2021.

Conclusion

A quantitative model was developed to predict either a positive or negative prognosis in the mental wellbeing of the population over 60 years of age in the city of Medellín. The model was also used for the development of a sociodemographic profile highlighting the impact on mental health among people over 60 years of age with limited economic resources.