bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis
Authors: Zhu Youqi , Chen Jiuzhou , Sun Xueqing , Lou Yufei , Fang Miao , Zhou Fengjuan , Zhang Lei , Xin Yong
Published: May 2023

Background

There is increasing evidence that neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. However, a number of studies have come to the opposite conclusion. Therefore, our meta-analysis is to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer.

Methods

We searched Wanfang Database, China National Knowledge Network database, VIP database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library. The searched terms included’Stomach Neoplasms’, ‘Neoadjuvant Therapy’ and ‘Chemoradiotherapy’. The retrieval time was from the establishment of the corresponding database to September 2022, and our meta-analysis was performed using RevMan (version 5.3) and Stata (version 17) software.

Results

A total of 17 literatures were included, which involved 7 randomized controlled trials and 10 retrospective studies, with a total of 6831 patients. The results of meta-analysis showed that compared with NACT group, the complete response rate(RR=1.95, 95%CI 1.39-2.73, p=0.0001), the partial response rate(RR=1.44, 95%CI 1.22-1.71, p=0.0001), the objective response rate(RR=1.37, 95%CI 1.27-1.54, p=0.00001), the pathologic complete response rate(RR=3.39, 95%CI 2.17-5.30, p=0.00001), the R0 resection rate(RR=1.18, 95%CI 1.09-1.29, p=0.0001) and 3-year overall survival rate(HR=0.89, 95%CI 0.82-0.96, p=0.002) of neoadjuvant chemoradiotherapy group were significantly improved. The results of subgroup analyses of gastric cancer subgroup and gastroesophageal junction cancer subgroup were consistent with the overall results. Meanwhile, the stable disease(RR=0.59, 95%CI:0.44-0.81, P=0.0010) of neoadjuvant chemoradiotherapy group was lower than that of neoadjuvant chemotherapy group, and there were no statistical significance in the progressive disease rate(RR=0.57, 95%CI:0.31-1.03, P=0.06), five-year overall survival rate(HR=1.03, 95%CI:0.99-1.07, P=0.839), postoperative complications and adverse reactions between the neoadjuvant chemoradiotherapy group and neoadjuvant chemotherapy group.

Conclusion

Compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy might bring more survival benefits without significantly increasing adverse reactions. neoadjuvant chemoradiotherapy may be a recommended treatment for patients with locally advanced gastric cancer.

Systematic Review Registration

https://inplasy.com/inplasy-2022-12-0068/, identifier INPLASY202212068.
Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated epithelial-to-mesenchymal transition
Authors: Capobianco Enrico , McGaughey Vanessa , Seraphin Gerbenn , Heckel John , Rieger Sandra , Lisse Thomas S.
Published: May 2023

Osteosarcomas are immune-resistant and metastatic as a result of elevated nonsense-mediated RNA decay (NMD), reactive oxygen species (ROS), and epithelial-to-mesenchymal transition (EMT). Although vitamin D has anti-cancer effects, its effectiveness and mechanism of action against osteosarcomas are poorly understood. In this study, we assessed the impact of vitamin D and its receptor (VDR) on NMD-ROS-EMT signaling in in vitro and in vivo osteosarcoma animal models. Initiation of VDR signaling facilitated the enrichment of EMT pathway genes, after which 1,25(OH)2D, the active vitamin D derivative, inhibited the EMT pathway in osteosarcoma subtypes. The ligand-bound VDR directly downregulated the EMT inducer SNAI2, differentiating highly metastatic from low metastatic subtypes and 1,25(OH)2D sensitivity. Moreover, epigenome-wide motif and putative target gene analysis revealed the VDR’s integration with NMD tumorigenic and immunogenic pathways. In an autoregulatory manner, 1,25(OH)2D inhibited NMD machinery genes and upregulated NMD target genes implicated in anti-oncogenic activity, immunorecognition, and cell-to-cell adhesion. Dicer substrate siRNA knockdown of SNAI2 revealed superoxide dismutase 2 (SOD2)-mediated antioxidative responses and 1,25(OH)2D sensitization via non-canonical SOD2 nuclear-to-mitochondrial translocalization leading to overall ROS suppression. In a mouse xenograft metastasis model, the therapeutically relevant vitamin D derivative calcipotriol inhibited osteosarcoma metastasis and tumor growth shown for the first time. Our results uncover novel osteosarcoma-inhibiting mechanisms for vitamin D and calcipotriol that may be translated to human patients.
Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review
Authors: Benzazon Nathan , Colnot Julie , de Kermenguy François , Achkar Samir , de Vathaire Florent , Deutsch Eric , Robert Charlotte , Diallo Ibrahima
Published: May 2023

A growing body of scientific evidence indicates that exposure to low dose ionizing radiation (< 2 Gy) is associated with a higher risk of developing radio-induced cancer. Additionally, it has been shown to have significant impacts on both innate and adaptive immune responses. As a result, the evaluation of the low doses inevitably delivered outside the treatment fields (out-of-field dose) in photon radiotherapy is a topic that is regaining interest at a pivotal moment in radiotherapy. In this work, we proposed a scoping review in order to identify evidence of strengths and limitations of available analytical models for out-of-field dose calculation in external photon beam radiotherapy for the purpose of implementation in clinical routine. Papers published between 1988 and 2022 proposing a novel analytical model that estimated at least one component of the out-of-field dose for photon external radiotherapy were included. Models focusing on electrons, protons and Monte-Carlo methods were excluded. The methodological quality and potential limitations of each model were analyzed to assess their generalizability. Twenty-one published papers were selected for analysis, of which 14 proposed multi-compartment models, demonstrating that research efforts are directed towards an increasingly detailed description of the underlying physical phenomena. Our synthesis revealed great inhomogeneities in practices, in particular in the acquisition of experimental data and the standardization of measurements, in the choice of metrics used for the evaluation of model performance and even in the definition of regions considered out-of-the-field, which makes quantitative comparisons impossible. We therefore propose to clarify some key concepts. The analytical methods do not seem to be easily suitable for massive use in clinical routine, due to the inevitable cumbersome nature of their implementation. Currently, there is no consensus on a mathematical formalism that comprehensively describes the out-of-field dose in external photon radiotherapy, partly due to the complex interactions between a large number of influencing factors. Out-of-field dose calculation models based on neural networks could be promising tools to overcome these limitations and thus favor a transfer to the clinic, but the lack of sufficiently large and heterogeneous data sets is the main obstacle.
Program Evaluation: exploring health disparities that impact chronic pain referrals within a VA Health Care System
Authors: Hanson Eric R. , Quist Heidi E. , Mintert Jeffrey S. , Arshad Mahreen , Friedman Brittany L. , Pleasant Alexandra , Monico-Cristales N. Stacey , Tillman Rhonda , Mehelis Mark , Karnik Anita , Sonder Anais , Mardian Aram S.
Published: May 2023

Introduction

The present Program Evaluation study examines sociodemographic characteristics of Veterans in the Phoenix VA Health Care System who have back pain, and specifically the likelihood of those characteristics being associated with a referral to the Chronic Pain Wellness Center (CPWC) in the year 2021. We examined the following characteristics: Race/ethnicity, gender, age, mental health diagnosis, substance use disorder diagnosis, and service-connected diagnosis.

Methods

Our study used cross sectional data from the Corporate Data Warehouse for 2021. 13624 records had complete data for the variables of interest. Univariate and multivariate logistic regression was used to determine the likelihood of patients' being referred to the Chronic Pain Wellness Center.

Results

The multivariate model found under-referral to be significant for younger adults and for patients who identified as Hispanic/Latinx, Black/African American, or Native American/Alaskan. Those with depressive disorders and opioid use disorders, on the other hand, were found to be more likely to be referred to the pain clinic. Other sociodemographic characteristics were not found to be significant.

Discussion

Study limitations include the use of cross-sectional data, which cannot determine causality, and the inclusion of patients only if the ICD-10 codes of interest were recorded for an encounter in 2021 (i.e., a prior history of a particular diagnosis was not captured). In future efforts, we plan to examine, implement, and track the impact of interventions designed to mitigate these identified disparities in access to chronic pain specialty care.
Understanding pain in modern society: insights from attitudes to pain in the Medieval Period
Authors: Paley Emma G. , Johnson Mark I. , Paley Carole A.
Published: May 2023

Historical records provide knowledge about the way people lived in the past. Our perspective is that historical analyses of the Medieval Period provide insights to inform a fuller understanding of pain in the present era. In this article, we appraise critiques of the writings of people living with pain during the mid (high) to late Medieval Period (c. 1,000–1,500 AD) to gain insights into the nature, attitudes, lived experience, and sense-making of pain. In the Medieval Period, pain was understood in terms of Galen's four humours and the Church's doctrine of pain as a “divine gift”, “punishment for sin” and/or “sacrificial offering”. Many treatments for pain were precursors of those used in modern time and society considered pain to be a “shared experience”. We argue that sharing personal stories of life is a fundamental human attribute to foster social cohesion, and that nowadays sharing personal stories about pain is difficult during biomedically-focussed time-constrained clinical consultations. Exploring pain through a medieval lens demonstrates the importance of sharing stories of living with pain that are flexible in meaning, so that people can connect with a sense of self and their social world. We advocate a role for community-centred approaches to support people in the creation and sharing of their personal pain stories. Contributions from non-biomedical disciplines, such as history and the arts, can inform a fuller understanding of pain and its prevention and management.
Dietary intake assessment in children with cystic fibrosis using 3-day food diaries: a single-centre study
Authors: Gaschignard Margaux , Beaufils Fabien , Gallet Pauline , Clouzeau Haude , Menard Joris , Costanzo Aurélie , Nouard Lucie , Delhaes Laurence , Tetard Candice , Lamireau Thierry , Fayon Michael , Bui Stéphanie , Enaud Raphaël
Published: May 2023

Background

Malnutrition is both a feature and major cause of morbidity in cystic fibrosis (CF). Therefore, nutritional management is an essential element of patient care. In 2016, an international guideline for nutritional management in patients with CF was published. In light of these recommendations, the aim of this study was to investigate the dietary intake of children with CF at the University Hospital of Bordeaux.

Methods

We conducted a retrospective study at the Paediatric CF Centre of the University Hospital of Bordeaux. Patients aged 2–18 years with CF who completed a 3-day food diary at home between January 2015 and December 2020 were included.

Results

A total of 130 patients, with a median age of 11.8 [interquartile range (IQR): 8.3; 13.4] years, were included. The median Z-score for BMI was −0.35 (IQR: −0.9; 0.2) and 20% of the patients had a Z-score for BMI < −1. Recommended total energy intakes were achieved in 53% of the patients, particularly those with nutritional support. Recommended protein intake was met in 28% of the cases, while fat and carbohydrate intakes were met in 54%. Vitamin and micronutrient levels were normal in 80% of the patients, with the exception of vitamin K, which was within the therapeutic range in only 42% of the cases.

Conclusion

Recommended nutritional targets are difficult to achieve in patients with CF, and providing nutritional support during follow-up remains a challenge.
Biomarkers for febrile urinary tract infection in children
Authors: Shaikh Nader , Kurs-Lasky Marcia , Liu Hui , Rajakumar Vinod , Qureini Heba , Conway Isabella O. , Lee Matthew C. , Lee Sojin
Published: May 2023

Background

The current reference standard for pediatric urinary tract infection (UTI) screening, the leukocyte esterase (LE) dipstick test, has suboptimal accuracy. The objective of this study was to compare the accuracy of novel urinary biomarkers to that of the LE test.

Methods

We prospectively enrolled febrile children who were evaluated for UTI based on their presenting symptoms. We compared the accuracy of urinary biomarkers to that of the test.

Results

We included 374 children (50 with UTI, 324 without UTI, ages 1–35 months) and examined 35 urinary biomarkers. The urinary biomarkers that best discriminated between febrile children with and without UTI were urinary neutrophil gelatinase–associated lipocalin (NGAL), IL-1β, CXCL1, and IL-8. Of all examined urinary biomarkers, the urinary NGAL had the highest accuracy with a sensitivity of 90% (CI: 82–98) and a specificity of 96% (CI: 93–98).

Conclusion

Because the sensitivity of the urinary NGAL test is slightly higher than that of the LE test, it can potentially reduce missed UTI cases. Limitations of using urinary NGAL over LE include increased cost and complexity. Further investigation is warranted to determine the cost-effectiveness of urinary NGAL as a screening test for UTI.
RETRACTED: Mechanism of action of Asparagus officinalis extract against multiple myeloma using bioinformatics tools, in silico and in vitro study
Authors: Li Yanju , Yang Xu , Wang Feiqing , Zhao Jianing , Zhang Chike , Wu Dan , Yang Bo , Gao Rui , Zhao Peng , Zan Yun , Su Min , He Zhixu , Liu Yang , Wang Jishi , Tang Dongxin
Published: May 2023

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification.

Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein–protein interaction (PPI) networks and further screening of core targets.

Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that “steroid receptor activity” and the “PI3K/AKT signaling pathway” were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase.

Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.
Mechanisms of Yajieshaba in the treatment of liver fibrosis through the Keap1-Nrf2 signaling pathway
Authors: Bai Yuanmei , Wu Haimei , Zheng Lijie , Xie Yuhuan , Liu Feifan , Wan Yan , Li Qiongchao , Guo Peixin
Published: May 2023

Yajieshaba (YJSB), a traditional Dai medicine formula containing botanical drugs, is commonly employed in Yunnan due to its significant therapeutic effects on liver protection. Consequently, to determine the efficacy of YJSB and the mechanism of action of Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway against liver fibrosis. We wanted to see if YJSB could treat CCl4-induced liver fibrosis by regulating the Keap1-Nrf2 signaling pathway. YJSB significantly improved liver function biochemical indices, liver fibrosis quadruple, hydroxyproline (Hyp), and transforming growth factor-β1 (TGF-β1) levels. The staining results demonstrated that the degree of liver fibrosis was significantly reduced. YJSB reduced the content of malondialdehyde (MDA) and elevated the content of superoxide dismutase (SOD) in the liver, exhibiting antioxidant effects; meanwhile, it regulated the expression of Keap1-Nrf2 pathway protein, increased the expression of NAD(P)H: Quinone oxidoreductase (NQO1), Heme Oxygenase 1 (HO-1), Glutamate cysteine ligase modifier subunit (GCLM), and Glutamate cysteine ligase catalytic subunit (GCLC) expression in the liver decreased while Nrf2 expression increased. Fluorescence immunoassay studies demonstrated that YJSB promoted the trans-nuclearization of Nrf2. YJSB possesses anti-liver fibrosis pharmacological effects that improve liver function and effectively counteract CCl4-induced liver fibrosis damage. The mechanism of action might be related to the regulation of protein expression of the Keap1-Nrf2 pathway, increasing the ability of the body to resist oxidative stress and reduce oxidative stress injury.
Nephroprotective mechanisms of Rhizoma Chuanxiong and Radix et Rhizoma Rhei against acute renal injury and renal fibrosis based on network pharmacology and experimental validation
Authors: Li Jun , Li Tonglu , Li Zongping , Song Zhiyong , Gong Xuezhong
Published: May 2023

The molecular mechanisms of Rhizoma Chuanxiong (Chuanxiong, CX) and Rhei Radix et Rhizoma (Dahuang, DH) in treating acute kidney injury (AKI) and subsequent renal fibrosis (RF) were investigated in this study by applying network pharmacology and experimental validation. The results showed that aloe-emodin, (−)-catechin, beta-sitosterol, and folic acid were the core active ingredients, and TP53, AKT1, CSF1R, and TGFBR1 were the core target genes. Enrichment analyses showed that the key signaling pathways were the MAPK and IL-17 signaling pathways. In vivo experiments confirmed that Chuanxiong and Dahuang pretreatments significantly inhibited the levels of SCr, BUN, UNAG, and UGGT in contrast media-induced acute kidney injury (CIAKI) rats (p < 0.001). The results of Western blotting showed that compared with the control group, the protein levels of p-p38/p38 MAPK, p53, and Bax in the contrast media-induced acute kidney injury group were significantly increased, and the levels of Bcl-2 were significantly reduced (p < 0.001). Chuanxiong and Dahuang interventions significantly reversed the expression levels of these proteins (p < 0.01). The localization and quantification of p-p53 expression in immunohistochemistry technology also support the aforementioned results. In conclusion, our data also suggest that Chuanxiong and Dahuang may inhibit tubular epithelial cell apoptosis and improve acute kidney injury and renal fibrosis by inhibiting p38 MAPK/p53 signaling.
Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy
Authors: Song Shuailing , Li Xiao , Geng Chong , Guo Yaoyu , Yang Yi , Wang Chunhui
Published: May 2023

Background: Cholestasis is a common pathological process in a variety of liver diseases that may lead to liver fibrosis, cirrhosis, and even liver failure. Cholestasis relief has been regarded as a principal target in the management of multiple chronic cholestasis liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) at present. However, complicated pathogenesis and limited acknowledgments fettered therapeutic development. Therefore, this study aimed to systematically analyze miRNA-mRNA regulatory networks in cholestatic liver injury in order to provide new treatment strategies.

Methods: Gene Expression Omnibus (GEO) database (GSE159676) was used to screen differentially expressed hepatic miRNAs and mRNAs in the PSC vs. control comparison and the PBC vs. control comparison, respectively. MiRWalk 2.0 tool was used to predict miRNA-mRNA pairs. Subsequently, functional analysis and immune cell infiltration analysis were performed to explore the pivotal functions of the target genes. RT-PCR was used to verify the result.

Results: In total, a miRNA-mRNA network including 6 miRNAs (miR-122, miR-30e, let-7c, miR-107, miR-503, and miR-192) and 8 hub genes (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5) was constructed in cholestasis. Functional analysis revealed that these genes were mainly involved in the regulation of the immune system. Further analysis revealed that resting memory CD4 T cells and monocytes could potentially participate in cholestatic liver injury. The expressions of DEMis and eight hub genes were verified in ANIT-induced and BDL-induced cholestatic mouse models. Furthermore, SYK was found to have an impact on the response to UDCA, and its mechanism was possibly associated with complement activation and monocyte reduction.

Conclusion: In the present study, a miRNA-mRNA regulatory network was constructed in cholestatic liver injury, which mostly mediated immune-related pathways. Moreover, the targeted gene SYK and monocytes were found to be related to UDCA response in PBC.
Linac-integrated on-board spectral-CT/CBCT imaging using a photon-counting detector: a Monte Carlo study
Authors: Ye Fengsong , Wang Hui , Fang Jianqiang
Published: May 2023

Purpose: To investigate the feasibility of dual-modal on-board spectral-CT/CBCT imaging using a CZT photon-counting detector mounted on a Linac by Monte Carlo simulations.

Methods: In this proof-of-concept study, the Monte Carlo software platform of Geant4 Application for Tomography Emission (GATE) and a high-performance computing hardware platform were utilized to design and validate the novel on-board spectral-CT and conventional CBCT imaging system using a single CZT detector integrated into a Linac. Through the combined use of the Monte Carlo simulation and the charge transportation model based on a diffusion equation, we simulated x-ray energy spectra of the CZT detector with pixel sizes ranging of 200–1,000 μm, based on which the optimized pixel size of the detector was determined. Spatial resolution of the CBCT imaging of the system was evaluated by oversampling a tilted tungsten wire. A PMMA phantom, containing calcium and contrast elements of iodine, gadolinium, and gold, was simulated to demonstrate the spectral CT imaging capability of the system by using the K-edge spectral imaging method.

Results: Considering the trade-off between the photon-peak efficiency and spatial resolution of the detector, the pixel size of the CZT detector was determined to be 400 µm. The spatial resolution of the CBCT imaging of the system was estimated to be 19.2 lp/cm@10% modulation transfer function. The CBCT imaging of the system provided sufficient structural details of the phantom with a high image contrast. Compared to the CBCT image of the phantom, the K-edge spectral CT images differentiated the four elements contained within the phantom very well.

Conclusion: The simulation results demonstrated the feasibility of dual-modal on-board spectral-CT/CBCT imaging by using a single CZT photon counting detector in a Linac.
Study of data center communication network topologies using complex network propagation model
Authors: Han Xu , Huangpeng Qizi , Gao Qiannan , Fu Yude , Duan Xiaojun
Published: May 2023

Data center, as the core infrastructure of data storage and processing, calls for network security protection. Information security has been addressed in a number of specific ways. However, there are few studies that employ network topology features to prevent the transmission of viruses. When a virus spreads, different topologies display various properties. In this paper, we study three types of data center network topologies, i.e., Fat-tree, Leaf-spine, and Bcube, and quantify the propagation characteristics in every topology through the IC propagation model. The probability of the device being infected, the count of propagation sources, the access of propagation sources, and the topological parameters are all considered. Given that network security defenders can only change the topology and topological parameters, we propose a computational framework that combines factor analysis, which provides us with the selection of network topological parameters with a low virus propagation rate in the candidate parameter set. Through experiments, we find that Leaf-spine has a good inhibitory effect on viruses with high propagation probability. Meanwhile, each offers unique advantages. We hope that more data center network topologies will be studied to improve the security of all data centers using these network topologies.
Periodic and torus motions of a two-degree-of-freedom dry friction vibration system
Authors: Guo Yong
Published: May 2023

Vibration induced by dry friction is ubiquitous in various engineering fields. To explore the vibration characteristics for further studies and/or controls, it is of great theoretical and practical significances to investigate the non-linear dynamic behaviors of the friction systems. This study considers the slight vibration of a two-degree-of-freedom non-linear dry friction excitation system. The differential equations of system motion are established according to Newton’s law of motion. Moreover, the system’s non-linear dynamic is studied when the block velocity is always less than the friction surface velocity. The results indicate that the linearized matrix of the vibration system has a pair of purely imaginary eigenvalues for some critical values of the relevant parameters. The Poincaré-Birkhoff normal forms are utilized to simplify the motion equation under the non-resonant assumption to obtain a simplified equation with only the resonant terms. Furthermore, the truncated part of the simplified equation is analyzed in the case of only linear terms degeneration. Finally, numerical simulations reflect some qualitative conclusions about the system’s local dynamic properties, including equilibrium point, periodic motion, torus motion, and their stability.
Plasma-derived exosomal let-7c-5p, miR-335–3p, and miR-652–3p as potential diagnostic biomarkers for stable coronary artery disease
Authors: Han Jian , Cui Xiaogang , Yuan Tianqi , Yang Zhiming , Liu Yue , Ren Yajuan , Wu Changxin , Bian Yunfei
Published: May 2023

Objectives: Circulating exosomal microRNAs (miRNAs) have been identified as promising biomarkers for diagnosis of cardiovascular diseases. Nevertheless, the diagnostic potential of miRNAs in circulating exosomes for stable coronary artery disease (SCAD) remains unclear. We aim here to analyze the exosomal differentially expressed miRNAs (DEmiRNAs) in plasma of SCAD patients and investigate their diagnostic potential as SCAD biomarkers.

Methods: Plasma was collected from SCAD patients and healthy controls, and exosomes were isolated by ultracentrifugation. Exosomal DEmiRNAs were analyzed by small RNA sequencing and were further validated by quantitative real-time PCR (qRT-PCR) in a larger set of plasma samples. Relationships between plasma exosomal let-7c-5p, miR-335–3p, miR-652–3p, genders and Gensini Scores in patients with SCAD were analyzed using correlation analyses. Moreover, we conducted receiver operating characteristic (ROC) curves for these DEmiRNAs and analyzed their possible functions and signaling pathways.

Results: Vesicles isolated from plasma displayed all characteristics of exosomes. In the small RNA sequencing study, a total of 12 DEmiRNAs were identified, among which seven were verified to be statistically significant by qRT-PCR. The areas under the ROC curves of exosomal let-7c-5p, miR-335–3p, and miR-652–3p were 0.8472, 0.8029, and 0.8009, respectively. Exosomal miR-335–3p levels were positively correlated with Gensini scores of patients with SCAD. Bioinformatics analysis revealed that these DEmiRNAs may be involved in the pathogenesis of SCAD.

Conclusion: Our findings indicated that plasma exosomal let-7c-5p, miR-335–3p, and miR-652–3p can be used as promising biomarkers for diagnosis of SCAD. In addition, plasma exosomal miR-335–3p levels coordinated with severity of SCAD.
Correspondence between BOLD fMRI task response and cerebrovascular reactivity across the cerebral cortex
Authors: Williams Rebecca J. , Specht Jacinta L. , Mazerolle Erin L. , Lebel R. Marc , MacDonald M. Ethan , Pike G. Bruce
Published: May 2023

BOLD sensitivity to baseline perfusion and blood volume is a well-acknowledged fMRI confound. Vascular correction techniques based on cerebrovascular reactivity (CVR) might reduce variance due to baseline cerebral blood volume, however this is predicated on an invariant linear relationship between CVR and BOLD signal magnitude. Cognitive paradigms have relatively low signal, high variance and involve spatially heterogenous cortical regions; it is therefore unclear whether the BOLD response magnitude to complex paradigms can be predicted by CVR. The feasibility of predicting BOLD signal magnitude from CVR was explored in the present work across two experiments using different CVR approaches. The first utilized a large database containing breath-hold BOLD responses and 3 different cognitive tasks. The second experiment, in an independent sample, calculated CVR using the delivery of a fixed concentration of carbon dioxide and a different cognitive task. An atlas-based regression approach was implemented for both experiments to evaluate the shared variance between task-invoked BOLD responses and CVR across the cerebral cortex. Both experiments found significant relationships between CVR and task-based BOLD magnitude, with activation in the right cuneus (R2 = 0.64) and paracentral gyrus (R2 = 0.71), and the left pars opercularis (R2 = 0.67), superior frontal gyrus (R2 = 0.62) and inferior parietal cortex (R2 = 0.63) strongly predicted by CVR. The parietal regions bilaterally were highly consistent, with linear regressions significant in these regions for all four tasks. Group analyses showed that CVR correction increased BOLD sensitivity. Overall, this work suggests that BOLD signal response magnitudes to cognitive tasks are predicted by CVR across different regions of the cerebral cortex, providing support for the use of correction based on baseline vascular physiology.
Test–retest reliability of kinematic and kinetic parameters during dual-task stair walking in the elderly
Authors: Li Yue , Yu Ning , Zhang Cui , Song Qipeng , Wang Jiangna , Sun Wei
Published: May 2023

Objective: This study aims to evaluate the test–retest reliability of kinematics and kinetics during single and dual-task stair walking in the elderly.

Methods: Fifteen healthy elderly adults were recruited. Kinematic and kinetic parameters were measured using an infrared motion analysis system (Vicon, Oxford Metrics Ltd., Oxford, United Kingdom) and force platforms (Switzerland, Kistler 9287BA and 9281CA). Participants were tested under single-task and dual-task (serial 3 subtractions or carrying a cup of water) conditions. Each participant completed two sessions on two separate days with a 1-week interval. Intraclass correlation coefficients (ICC), Pearson correlation coefficient (r), and Bland–Altman plot were used to assess the reliability of stair walking.

Results: When ascending stairs, the ICC of kinematics and kinetics ranged from fair to excellent (ICC = 0.500–0.979) in the single and dual tasks, except for step length (ICC = 0.394) in the single task. The r value of kinematics and kinetics ranged from 0.704 to 0.999. When descending stairs, the ICC of kinematics and kinetics ranged from good to excellent (ICC = 0.661–0.963), except for min hip moment (ICC = 0.133) and min ankle moment (ICC = 0.057) in the manual task. The r value of kinematics and kinetics ranged from 0.773 to 0.960 in the single and dual tasks. In the Bland–Altman plots, all the zero values and most of the dots fell in the 95% confidence interval, and the mean difference was found to be close to zero for all the parameters during stair walking.

Conclusion: These results obtained from this study show the good test-retest reliability of step cadence, step speed, and step width during single- and dual-task stair walking in the elderly, and the poor reliability of step length during ascending stairs. All the kinetic parameters, including min hip moment, max knee moment, and min ankle moment, had good test-retest reliability during single- and dual-task stair walking, but min hip moment and min ankle moment had poor reliability during manual-task descending stair. These results may help researchers in the assessment of biomechanics of dual-task stair walking in the elderly and to interpret the effect of interventions in this population.
Duchenne muscular dystrophy disease severity impacts skeletal muscle progenitor cells systemic delivery
Authors: Saleh Kholoud K. , Switzler Corey , Hicks Michael R. , Gane Lily , Gibbs Devin E. , Pyle April D.
Published: May 2023

Duchenne muscular dystrophy (DMD) is caused by an out-of-frame mutation in the DMD gene that results in the absence of a functional dystrophin protein, leading to a devastating progressive lethal muscle-wasting disease. Muscle stem cell-based therapy is a promising avenue for improving muscle regeneration. However, despite the efforts to deliver the optimal cell population to multiple muscles most efforts have failed. Here we describe a detailed optimized method of for the delivery of human skeletal muscle progenitor cells (SMPCs) to multiple hindlimb muscles in healthy, dystrophic and severely dystrophic mouse models. We show that systemic delivery is inefficient and is affected by the microenvironment. We found that significantly less human SMPCs were detected in healthy gastrocnemius muscle cross-sections, compared to both dystrophic and severely dystrophic gastrocnemius muscle. Human SMPCs were found to be detected inside blood vessels distinctly in healthy, dystrophic and severely dystrophic muscles, with prominent clotting identified in severely dystrophic muscles after intra arterial (IA) systemic cell delivery. We propose that muscle microenvironment and the severity of muscular dystrophy to an extent impacts the systemic delivery of SMPCs and that overall systemic stem cell delivery is not currently efficient or safe to be used in cell based therapies for DMD. This work extends our understanding of the severe nature of DMD, which should be taken into account when considering stem cell-based systemic delivery platforms.
Pinus massoniana somatic embryo maturation, mycorrhization of regenerated plantlets and its resistance to Bursaphelenchus xylophilus
Authors: Chen You-Mei , Fei Qi , Xia Xin-Rui , Ke Xin , Ye Jian-Ren , Zhu Li-Hua
Published: May 2023

Pine wilt disease, caused by the pine wood nematode (PWN,Bursaphelenchus xylophilus), is a major quarantine forest disease that poses a threat to various pine species, includingPinus massoniana(masson pine), worldwide. Breeding of PWN-resistant pine trees is an important approach to prevent the disease. To expedite the production of PWN-resistantP. massonianaaccessions, we investigated the effects of maturation medium treatments on somatic embryo development, germination, survival, and rooting. Furthermore, we evaluated the mycorrhization and nematode resistance of regenerated plantlets. Abscisic acid was identified as the main factor affecting maturation, germination, and rooting of somatic embryos inP. massoniana, resulting in a maximum of 34.9 ± 9.4 somatic embryos per ml, 87.3 ± 9.1% germination rate, and 55.2 ± 29.3% rooting rate. Polyethylene glycol was identified as the main factor affecting the survival rate of somatic embryo plantlets, with a survival rate of up to 59.6 ± 6.8%, followed by abscisic acid. Ectomycorrhizal fungi inoculation withPisolithus orientalisenhanced the shoot height of plantlets regenerated from embryogenic cell line (ECL) 20-1-7. Ectomycorrhizal fungi inoculation also improved the survival rate of plantlets during the acclimatization stage, with 85% of mycorrhized plantlets surviving four months after acclimatization in the greenhouse, compared with 37% non-mycorrhized plantlets. Following PWN inoculation, the wilting rate and the number of nematodes recovered from ECL 20-1-7 were lower than those recovered from ECL 20-1-4 and 20-1-16. The wilting ratios of mycorrhizal plantlets from all cell lines were significantly lower than those of non-mycorrhizal regenerated plantlets. This plantlet regeneration system and mycorrhization method could be used in the large-scale production of nematode-resistance plantlets and to study the interaction between nematode, pines, and mycorrhizal fungi.
The role of soil temperature in mediterranean vineyards in a climate change context
Authors: Costa J. Miguel , Egipto Ricardo , Aguiar Francisca C. , Marques Paulo , Nogales Amaia , Madeira Manuel
Published: May 2023

The wine sector faces important challenges related to sustainability issues and the impact of climate change. More frequent extreme climate conditions (high temperatures coupled with severe drought periods) have become a matter of concern for the wine sector of typically dry and warm regions, such as the Mediterranean European countries. Soil is a natural resource crucial to sustaining the equilibrium of ecosystems, economic growth and people’s prosperity worldwide. In viticulture, soils have a great influence on crop performance (growth, yield and berry composition) and wine quality, as the soil is a central component of the terroir. Soil temperature (ST) affects multiple physical, chemical and biological processes occurring in the soil as well as in plants growing on it. Moreover, the impact of ST is stronger in row crops such as grapevine, since it favors soil exposition to radiation and favors evapotranspiration. The role of ST on crop performance remains poorly described, especially under more extreme climatic conditions. Therefore, a better understanding of the impact of ST in vineyards (vine plants, weeds, microbiota) can help to better manage and predict vineyards’ performance, plant-soil relations and soil microbiome under more extreme climate conditions. In addition, soil and plant thermal data can be integrated into Decision Support Systems (DSS) to support vineyard management. In this paper, the role of ST in Mediterranean vineyards is reviewed namely in terms of its effect on vines’ ecophysiological and agronomical performance and its relation with soil properties and soil management strategies. The potential use of imaging approaches, e.g. thermography, is discussed as an alternative or complementary tool to assess ST and vertical canopy temperature profiles/gradients in vineyards. Soil management strategies to mitigate the negative impact of climate change, optimize ST variation and crop thermal microclimate (leaf and berry) are proposed and discussed, with emphasis on Mediterranean systems.
Inhibition of AcrAB-TolC enhances antimicrobial activity of phytochemicals in Pectobacterium brasiliense
Authors: Pun Manoj , Khazanov Netaly , Galsurker Ortal , Kerem Zohar , Senderowitz Hanoch , Yedidia Iris
Published: May 2023

Introduction

The eons-long co-evolvement of plants and bacteria led to a plethora of interactions between the two kingdoms, in which bacterial pathogenicity is counteracted by plant-derived antimicrobial defense molecules. In return, efflux pumps (EP) form part of the resistance mechanism employed by bacteria to permit their survival in this hostile chemical environment. In this work we study the effect of combinations of efflux pump inhibitors (EPIs) and plant-derived phytochemicals on bacterial activity using Pectobacteriun brasiliense 1692 (Pb1692) as a model system.

Methods

We measured the minimal inhibitory concentration (MIC) of two phytochemicals, phloretin (Pht) and naringenin (Nar), and of one common antibiotic ciprofloxacin (Cip), either alone or in combinations with two known inhibitors of the AcrB EP of Escherichia coli, a close homolog of the AcrAB-TolC EP of Pb1692. In addition, we also measured the expression of genes encoding for the EP, under similar conditions.

Results

Using the FICI equation, we observed synergism between the EPIs and the phytochemicals, but not between the EPIs and the antibiotic, suggesting that EP inhibition potentiated the antimicrobial activity of the plant derived compounds, but not of Cip. Docking simulations were successfully used to rationalize these experimental results.

Discussion

Our findings suggest that AcrAB-TolC plays an important role in survival and fitness of Pb1692 in the plant environment and that its inhibition is a viable strategy for controlling bacterial pathogenicity.
Molecular characterization and expression analysis of the remorin genes in tomato (Solanum lycopersicum L.)
Authors: Li Hui , Wang Xiao , Zhuo Yue , Chen Shuisen , Lin Jingwei , Ma Hui , Zhong Ming
Published: May 2023

Remorin (REMs) are plant-specific and plasma membrane-associated proteins that play an essential role in the growth and development of plants and adaptations to adverse environments. To our knowledge, a genome-scale investigation of the REM genes in tomato has never been systematically studied. In this study, a total of 17 SlREM genes were identified in the tomato genome using bioinformatics methods. Our results demonstrated that the 17 members of SlREM were classified into 6 groups based on phylogenetic analysis and unevenly distributed on the eight chromosomes of tomato. There were 15 REM homologous gene pairs between tomato and Arabidopsis. The SlREM gene structures and motif compositions were similar. Promoter sequence analysis showed that the SlREM gene promoters contained some tissue-specific, hormones and stress-related cis-regulatory elements. Expression analysis based on qRT-PCR (Real-time quantitative PCR) analysis showed that SlREM family genes were were differentially expressed in different tissues, and they responded to ABA, MeJA, SA, low-temperature, drought and NaCl treatments. These results potentially provide relevant information for further research on the biological functions of SlREM family genes.
TSPTFBS 2.0: trans-species prediction of transcription factor binding sites and identification of their core motifs in plants
Authors: Cheng Huiling , Liu Lifen , Zhou Yuying , Deng Kaixuan , Ge Yuanxin , Hu Xuehai
Published: May 2023

Introduction

An emerging approach using promoter tiling deletion via genome editing is beginning to become popular in plants. Identifying the precise positions of core motifs within plant gene promoter is of great demand but they are still largely unknown. We previously developed TSPTFBS of 265 Arabidopsis transcription factor binding sites (TFBSs) prediction models, which now cannot meet the above demand of identifying the core motif.

Methods

Here, we additionally introduced 104 maize and 20 rice TFBS datasets and utilized DenseNet for model construction on a large-scale dataset of a total of 389 plant TFs. More importantly, we combined three biological interpretability methods including DeepLIFT, in-silico tiling deletion, and in-silico mutagenesis to identify the potential core motifs of any given genomic region.

Results

For the results, DenseNet not only has achieved greater predictability than baseline methods such as LS-GKM and MEME for above 389 TFs from Arabidopsis, maize and rice, but also has greater performance on trans-species prediction of a total of 15 TFs from other six plant species. A motif analysis based on TF-MoDISco and global importance analysis (GIA) further provide the biological implication of the core motif identified by three interpretability methods. Finally, we developed a pipeline of TSPTFBS 2.0, which integrates 389 DenseNet-based models of TF binding and the above three interpretability methods.

Discussion

TSPTFBS 2.0 was implemented as a user-friendly web-server (http://www.hzau-hulab.com/TSPTFBS/), which can support important references for editing targets of any given plant promoters and it has great potentials to provide reliable editing target of genetic screen experiments in plants.
Genome-wide analysis of the MADS-box gene family involved in salt and waterlogging tolerance in barley (Hordeum vulgare L.)
Authors: Wang Feifei , Zhou Zhenxiang , Zhu Liang , Gu Yangyang , Guo Baojian , Lv Chao , Zhu Juan , Xu Rugen
Published: May 2023

MADS-box transcription factors are crucial members of regulatory networks underlying multiple developmental pathways and abiotic stress regulatory networks in plants. Studies on stress resistance-related functions of MADS-box genes are very limited in barley. To gain insight into this gene family and elucidate their roles in salt and waterlogging stress resistance, we performed genome-wide identification, characterization and expression analysis of MADS-box genes in barley. A whole-genome survey of barley revealed 83 MADS-box genes, which were categorized into type I (Mα, Mβ and Mγ) and type II (AP1, SEP1, AGL12, STK, AGL16, SVP and MIKC*) lineages based on phylogeny, protein motif structure. Twenty conserved motifs were determined and each HvMADS contained one to six motifs. We also found tandem repeat duplication was the driven force for HvMADS gene family expansion. Additionally, the co-expression regulatory network of 10 and 14 HvMADS genes was predicted in response to salt and waterlogging stress, and we proposed HvMADS11,13 and 35 as candidate genes for further exploration of the functions in abiotic stress. The extensive annotations and transcriptome profiling reported in this study ultimately provides the basis for MADS functional characterization in genetic engineering of barley and other gramineous crops.