bluuebunny/crossref_metadata_2025 huggingface dataset:
Repurposing Ivermectin to augment chemotherapy’s efficacy in osteosarcoma
Authors: Hu B , Tan H , Yu L , Liao Q , Guo W
Published: December 2022

Background

Osteosarcoma is the most frequent malignant bone malignancy and the current treatments are ineffective. Ivermectin, an anti-protozoal drug, has been shown to have anti-cancer activity. This work investigated the potential of repurposing ivermectin to augment chemotherapy’s efficacy in osteosarcoma.

Methods

Proliferation, migration and apoptosis assays were performed in ivermectin-treated osteosarcoma cells. Combination studies were performed. Osteosarcoma xenograft mouse model was established to investigate the in vivo efficacy of ivermectin. Intracellular reactive oxygen species (ROS) and mitochondrial superoxide, membrane potential, ATP, 8-OHdG level, protein carbonylation and lipid peroxidation were determined after ivermectin treatment.

Results

Ivermectin was effective and acted synergistically with doxorubicin in osteosarcoma cells regardless of cellular origin and genetic profiling. This was achieved through suppressing inhibiting growth and migration, and inducing caspase-dependent apoptosis. Ivermectin also significantly inhibited osteosarcoma growth in vivo and its combination with doxorubicin resulted in much greater efficacy than doxorubicin alone. Importantly, the effective dose of ivermectin was clinically feasible and did not cause significant toxicity in mice. Mechanistical analysis showed that ivermectin induced oxidative stress and damage, and mitochondrial dysfunction.

Conclusions

Our findings indicate that ivermectin has utility in treating patients with osteosarcoma, especially those resistant to chemotherapy.
Policía beyond the police
Authors: Gutiérrez Laura , Neocleous Mark
Published: December 2022

This article develops and extends the critical theory of police power by applying it to Colombia. Scholarship on police in Colombia has been undermined by a focus on the kind of creation myth that one finds in most histories of police: that policing only properly begins in a key foundational year. In Colombia, that year is 1891. This approach overlooks or downplays the importance of the concept of policía. This is the original and far more expansive police concept through which social order in Colombia was fabricated. By paying attention to the continued importance of policía, this article drastically transforms our understanding of police power and state formation in Colombia, and extends the critical theory of police power.
Case studies on aeroacoustics damping performances of Coupled Helmholtz Resonators over low frequency ranges
Authors: Zhang Zhiguo , Ji Chenzhen , Win Yin Mya
Published: December 2022

Helmholtz resonators are widely applied in industries to reduce the transmission of unwanted noise and passively attenuate tonal noise in pipes/ducts. For example, internal combustion engines take advantage of Helmholtz resonators by combining air box, subwoofers and perforated pipes/plates to reduce engine noise emission nowadays. However, the main drawback of the conventional Helmholtz resonators includes a very narrow bandwidth. To broaden the effective noise damping frequency range of Helmholtz resonators, a number of different improved designs are reported and tested recently in the literature such as applying an array of separated resonators or implementing mechanical-coupled Helmholtz resonators. In this work, we conduct a brief review on the aeroacoustics damping performance of coupled Helmholtz resonators over low frequency range. The noise damping performances could be characterized and quantified in terms of transmission loss and sound absorption coefficient. Both definitions are discussed. Comparison is then made between the separately working resonators and the mechanical-coupled ones. This is achieved by replacing the sharable flexible sidewall with a rigid sidewall. The effect of the mean grazing flow is also discussed and examined on the noise damping performances. An experimental case study of the present authors is included. Additionally, to improve the noise damping performance further, an overview of the resonators neck with different noise damping materials inserted is conducted. Finally, 3D numerical approaches in simulating the aeroacoustics damping performances of coupled Helmholtz resonators are reviewed. This case study and brief overview provides a guidance on improving the design of coupled Helmholtz resonators and an array of Helmholtz resonators.
Convenient efficiency: A media genealogy of QR codes
Authors: Nguyen Dang
Published: December 2022

This article explains the widespread adoption of Quick Response (QR) codes from a media genealogy perspective. Understanding QR codes as more than the materiality of their machinic embodiments and rather as a method of systematically and repeatedly addressing emergent problems, I argue that the operative logic of QR code is that of convenient efficiency. Convenient efficiency captures three dynamics that drive QR codes’ ubiquity: the potentiality of spontaneous system synergies (system/distributed convenience coupled with streamlined efficiency); the autonomy of the subjects involved as part of this cybernetic system (personal convenience coupled with stacked efficiency); and the relative independence of the networks/assemblages that these practices constitute (convenient efficiency). That the convergence between convenience and efficiency as driving forces in contemporary technological culture has origins in the shop floor is consequential to the way motion, time and the body become disciplined—as well as the epistemological practices that cohere around these forces.
Generalized mixed shock model for multi-component systems in the shock environment with a change point
Authors: Wang Xiaoyue , Ning Ru , Zhao Xian
Published: December 2022

The reliability of various systems under shock models has been explored extensively in the literature, where the constant mechanism of shock impact has always been studied. Nevertheless, engineering systems operate in a more complicated shock environment due to developments, and it is worth studying the reliability of such multi-component systems in a variable shock environment. Driven by the research gaps and practical situations, this paper constructs a reliability model of multi-component systems under a generalized mixed shock model with a change point. The multi-state components operate in the shock environment I initially and it may continue to run in the shock environment II after the random change point of the environment. Two novel shock impact mechanisms of the variable environment are put forward, where a series of failure criteria based on shocks are included. Four different structures of multi-component systems are considered in this paper. It can be proved that the proposed mixed shock model is a generalization of some transformed models. A multi-stage finite Markov chain imbedding approach is established to derive the probabilistic indices of the components and entire systems. Based on the engineering applications, illustrative examples are provided to verify the effectiveness of the proposed model.
Adenine base editor–mediated correction of the common and severe IVS1-110 (G>A) β-thalassemia mutation
Authors: Hardouin Giulia , Antoniou Panagiotis , Martinucci Pierre , Felix Tristan , Manceau Sandra , Joseph Laure , Masson Cécile , Scaramuzza Samantha , Ferrari Giuliana , Cavazzana Marina , Miccio Annarita
Published: December 2022

β-Thalassemia (BT) is one of the most common genetic diseases worldwide and is caused by mutations affecting β-globin production. The only curative treatment is allogenic hematopoietic stem/progenitor cells (HSPCs) transplantation, an approach limited by compatible donor availability and immunological complications. Therefore, transplantation of autologous, genetically-modified HSPCs is an attractive therapeutic option. However, current gene therapy strategies based on the use of lentiviral vectors are not equally effective in all patients and CRISPR/Cas9 nuclease-based strategies raise safety concerns. Thus, base editing strategies aiming to correct the genetic defect in patients’ HSPCs could provide safe and effective treatment. Here, we developed a strategy to correct one of the most prevalent BT mutations (IVS1-110 [G>A]) using the SpRY-ABE8e base editor. RNA delivery of the base editing system was safe and led to ∼80% of gene correction in the HSPCs of patients with BT without causing dangerous double-strand DNA breaks. In HSPC-derived erythroid populations, this strategy was able to restore β-globin production and correct inefficient erythropoiesis typically observed in BT both in vitro and in vivo. In conclusion, this proof-of-concept study paves the way for the development of a safe and effective autologous gene therapy approach for BT.
OR2AT4 and OR1A2 counterregulate molecular pathophysiological processes of steroid-resistant inflammatory lung diseases in human alveolar macrophages
Authors: Weidinger Daniel , Jamal Jameel Kaschin , Alisch Desiree , Jacobsen Julian , Bürger Paul , Ruhe Matthias , Yusuf Faisal , Rohde Simon , Störtkuhl Klemens , Kaufmann Peter , Kronsbein Juliane , Peters Marcus , Hatt Hanns , Giannakis Nikolaos , Knobloch Jürgen
Published: December 2022

Background

Therapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are lacking. Alveolar macrophages are central in the progression of these diseases by releasing proinflammatory cytokines, making them promising targets for new therapeutic approaches. Extra nasal expressed olfactory receptors (ORs) mediate various cellular processes, but clinical data are lacking. This work investigates whether ORs in human primary alveolar macrophages could impact pathophysiological processes and could be considered as therapeutic targets.

Methods

Human primary alveolar macrophages were isolated from bronchoalveolar lavages of 50 patients with pulmonary diseases. The expression of ORs was validated using RT-PCR, immunocytochemical staining, and Western blot. Changes in intracellular calcium levels were analyzed in real-time by calcium imaging. A luminescent assay was used to measure the cAMP concentration after OR stimulation. Cytokine secretion was measured in cell supernatants 24 h after stimulation by ELISA. Phagocytic ability was measured by the uptake of fluorescent-labeled beads by flow cytometry.

Results

We demonstrated the expression of functional OR2AT4 and OR1A2 on mRNA and protein levels. Both ORs were primarily located in the plasma membrane. Stimulation with Sandalore, the ligand of OR2AT4, and Citronellal, the ligand of OR1A2, triggered a transient increase of intracellular calcium and cAMP. In the case of Sandalore, this calcium increase was based on a cAMP-dependent signaling pathway. Stimulation of alveolar macrophages with Sandalore and Citronellal reduced phagocytic capacity and release of proinflammatory cytokines.

Conclusion

These are the first indications for utilizing olfactory receptors as therapeutic target molecules in treating steroid-resistant lung diseases with non-type 2 inflammation.
Deficiency of mindin reduces renal injury after ischemia reperfusion
Authors: Bai Tao , Wang Xiong , Qin Cong , Yang Kang , Duan Zhiguo , Cao Zhixiu , Liang Jiaqian , Wang Lei , Yuan Jingdong , Luo Pengcheng
Published: December 2022

Background

Acute renal injury (AKI) secondary to ischemia reperfusion (IR) injury continues to be a significant perioperative problem and there is no effective treatment. Mindin belongs to the mindin/F-spondin family and involves in inflammation, proliferation, and cell apoptosis. Previous studies have explored the biological functions of mindin in liver and brain ischemic injury, but its role in AKI is unknown.

Method

To investigate whether mindin has a pathogenic role, mindin knockout (KO) and wild-type (WT) mice were used to establish renal IR model. After 30 min of ischemia and 24 h of reperfusion, renal histology, serum creatinine, and inflammatory response were examined to assess kidney injury. In vitro, proinflammatory factors and inflammatory signaling pathways were measured in mindin overexpression or knockdown and vector cells after hypoxia/reoxygenation (HR).

Results

Following IR, the kidney mindin level was increased in WT mice and deletion of mindin provided significant protection for mice against IR-induced renal injury as manifested by attenuated the elevation of serum creatinine and blood urea nitrogen along with less severity for histological alterations. Mindin deficiency significantly suppressed inflammatory cell infiltration, TNF-α and MCP-1 production following renal IR injury. Mechanistic studies revealed that mindin deficiency inhibits TLR4/JNK/NF-κB signaling activation. In vitro, the expression levels of TNF-α and MCP-1 were increased in mindin overexpression cells compared with vector cells following HR. Moreover, TLR4/JNK/NF-κB signaling activation was elevated in the mindin overexpression cells in response to HR stimulation while mindin knockdown inhibited the activation of TLR4/JNK/ NF-κB signaling after HR in vitro. Further study showed that mindin protein interacted directly with TLR4 protein. And more, mindin protein was confirmed to be expressed massively in renal tubule tissues of human hydronephrosis patients.

Conclusion

These data demonstrate that mindin is a critical modulator of renal IR injury through regulating inflammatory responses. TLR4/JNK/NF-κB signaling most likely mediates the biological function of mindin in this model of renal ischemia.
Oxidized LDL promotes EMS-induced angiogenesis by increasing VEGF-A expression and secretion by endometrial cells
Authors: Ma Caiqi , Huang Wei , Wang Hui , Yao Wenxia , Liang Min , Yu Guifang , Zhou Xinke
Published: December 2022

Background

Endometriosis (EMS) is a “tumour-like” gynaecological disease with distant metastasis, and studies have shown that EMS can induce distant metastasis through vascular vessels, but the driving factors and their mechanism are not clear.

Methods

We used an EMS animal model and gene knockout technique to explore the role of EMS-induced angiogenesis in EMS metastasis in vivo and in vitro and clarify the role and molecular mechanism of oxLDL in promoting EMS-induced angiogenesis.

Results

We found that microvascular density (MVD) in metastasized ectopic endometrium and eutopic endometrial tissue was higher than that in normal endometrial tissue, and plasma oxLDL was positively correlated with the distant metastasis of EMS. Furthermore, we clarified that oxLDL enhanced the MVD of endometrial tissue by increasing VEGF-A expression and secretion in endometrial cells. Finally, we illustrated the mechanism by which oxLDL promotes VEGF-A expression through the AKT-HIF-1α signalling pathway.

Conclusion

OxLDL is a risk factor promoting distant EMS metastasis by increasing VEGF-A expression and secretion through AKT-HIF-1α signalling. This finding may provide theoretical support and therapeutic targets for the clinical prevention and treatment of EMS.
Boosting tissue-specific prediction of active cis-regulatory regions through deep learning and Bayesian optimization techniques
Authors: Cappelletti Luca , Petrini Alessandro , Gliozzo Jessica , Casiraghi Elena , Schubach Max , Kircher Martin , Valentini Giorgio
Published: December 2022

Background

Cis-regulatory regions (CRRs) are non-coding regions of the DNA that fine control the spatio-temporal pattern of transcription; they are involved in a wide range of pivotal processes such as the development of specific cell-lines/tissues and the dynamic cell response to physiological stimuli. Recent studies showed that genetic variants occurring in CRRs are strongly correlated with pathogenicity or deleteriousness. Considering the central role of CRRs in the regulation of physiological and pathological conditions, the correct identification of CRRs and of their tissue-specific activity status through Machine Learning methods plays a major role in dissecting the impact of genetic variants on human diseases. Unfortunately, the problem is still open, though some promising results have been already reported by (deep) machine-learning based methods that predict active promoters and enhancers in specific tissues or cell lines by encoding epigenetic or spectral features directly extracted from DNA sequences.

Results

We present the experiments we performed to compare two Deep Neural Networks, a Feed-Forward Neural Network model working on epigenomic features, and a Convolutional Neural Network model working only on genomic sequence, targeted to the identification of enhancer- and promoter-activity in specific cell lines. While performing experiments to understand how the experimental setup influences the prediction performance of the methods, we particularly focused on (1) automatic model selection performed by Bayesian optimization and (2) exploring different data rebalancing setups for reducing negative unbalancing effects.

Conclusions

Results show that (1) automatic model selection by Bayesian optimization improves the quality of the learner; (2) data rebalancing considerably impacts the prediction performance of the models; test set rebalancing may provide over-optimistic results, and should therefore be cautiously applied; (3) despite working on sequence data, convolutional models obtain performance close to those of feed forward models working on epigenomic information, which suggests that also sequence data carries informative content for CRR-activity prediction. We therefore suggest combining both models/data types in future works.
SC3s: efficient scaling of single cell consensus clustering to millions of cells
Authors: Quah Fu Xiang , Hemberg Martin
Published: December 2022

Background

Today it is possible to profile the transcriptome of individual cells, and a key step in the analysis of these datasets is unsupervised clustering. For very large datasets, efficient algorithms are required to ensure that analyses can be conducted with reasonable time and memory requirements.

Results

Here, we present a highly efficient k-means based approach, and we demonstrate that it scales favorably with the number of cells with regards to time and memory.

Conclusions

We have demonstrated that our streaming k-means clustering algorithm gives state-of-the-art performance while resource requirements scale favorably for up to 2 million cells.
DiviK: divisive intelligent K-means for hands-free unsupervised clustering in big biological data
Authors: Mrukwa Grzegorz , Polanska Joanna
Published: December 2022

Background

Investigating molecular heterogeneity provides insights into tumour origin and metabolomics. The increasing amount of data gathered makes manual analyses infeasible—therefore, automated unsupervised learning approaches are utilised for discovering tissue heterogeneity. However, automated analyses require experience setting the algorithms’ hyperparameters and expert knowledge about the analysed biological processes. Moreover, feature engineering is needed to obtain valuable results because of the numerous features measured.

Results

We propose DiviK: a scalable stepwise algorithm with local data-driven feature space adaptation for segmenting high-dimensional datasets. The algorithm is compared to the optional solutions (regular k-means, spatial and spectral approaches) combined with different feature engineering techniques (None, PCA, EXIMS, UMAP, Neural Ions). Three quality indices: Dice Index, Rand Index and EXIMS score, focusing on the overall composition of the clustering, coverage of the tumour region and spatial cluster consistency, are used to assess the quality of unsupervised analyses. Algorithms were validated on mass spectrometry imaging (MSI) datasets—2D human cancer tissue samples and 3D mouse kidney images. DiviK algorithm performed the best among the four clustering algorithms compared (overall quality score 1.24, 0.58 and 162 ford(0, 0, 0), d(1, 1, 1) and the sum of ranks, respectively), with spectral clustering being mostly second. Feature engineering techniques impact the overall clustering results less than the algorithms themselves (partial$$\eta ^2$$η2effect size: 0.141 versus 0.345, Kendall’s concordance index: 0.424 versus 0.138 ford(0, 0, 0)).

Conclusions

DiviK could be the default choice in the exploration of MSI data. Thanks to its unique, GMM-based local optimisation of the feature space and deglomerative schema, DiviK results do not strongly depend on the feature engineering technique applied and can reveal the hidden structure in a tissue sample. Additionally, DiviK shows high scalability, and it can process at once the big omics data with more than 1.5 mln instances and a few thousand features. Finally, due to its simplicity, DiviK is easily generalisable to an even more flexible framework. Therefore, it is helpful for other -omics data (as single cell spatial transcriptomic) or tabular data in general (including medical images after appropriate embedding). A generic implementation is freely available under Apache 2.0 license athttps://github.com/gmrukwa/divik.
Regulation of feather follicle development and Msx2 gene SNP degradation in Hungarian white goose
Authors: Song Yupu , Liu Chang , Zhou Yuxuan , Lin Guangyu , Xu Chenguang , Msuthwana Petunia , Wang Sihui , Ma Jingyun , Zhuang Fangming , Fu Xianou , Wang Yudong , Liu Tuoya , Liu Qianyan , Wang Jingbo , Sui Yujian , Sun Yongfeng
Published: December 2022

Background

Hungarian white goose has excellent down production performance and was introduced to China in 2010. The growth and development of feather follicles has an important impact on down production. Goose feather follicles can be divided into primary and secondary feather follicles, both of which originate in the embryonic stage. Msx2 (Msh Homeobox 2) plays a regulatory role in tissues and organs such as eyes, teeth, bones and skin. However, its regulatory mechanism on goose feather follicles development remains unclear.

Results

Msx2 gene first increased, then decreased and increased at the end (E13, E18, E23, E28) during embryonic feather follicle development, and the expression level was the highest at E18. The pEGFP-N1-Msx2 overexpression vector and si-Msx2 siRNA vector were constructed to transfect goose embryo dermal fibroblasts. The results showed that the cell viability of ov-Msx2 group was significantly increased, and the gene expression levels of FGF5 and TGF-β1 genes were significantly down-regulated (P < 0.05), the expressions of PCNA, Bcl2, CDK1, FOXN1 and KGF genes were significantly up-regulated (P < 0.05). After transfection of siRNA vector, the cell viability of the si-Msx2 group was significantly decreased (P < 0.01) compared with the si-NC group. TGF-β1 expression was significantly up-regulated (P < 0.05), FGF5 expression was extremely significantly up-regulated (P < 0.01), while PCNA, Bcl2, CDK1, FOXN1 and KGF gene expression was significantly down-regulated (P < 0.05). High-throughput sequencing technology was used to mine the exon SNPs of Msx2. A total of 11 SNP loci were screened, four of the SNPs located in exon 1 were missense mutations. The feather follicle diameter of the GC genotype at the G78C site is significantly larger than that of the other two genotypes.

Conclusions

Msx2 maybe inhibit the apoptosis of goose dermal fibroblasts and promotes their proliferation. G78C can be used as a potential molecular marker for downy Variety.
RpoN is required for the motility and contributes to the killing ability of Plesiomonas shigelloides
Authors: Yan Junxiang , Guo Xueqian , Li Jinghao , Li Yuehua , Sun Hongmin , Li Ang , Cao Boyang
Published: December 2022

Background

RpoN, also known as σ54, first reported inEscherichia coli, is a subunit of RNA polymerase that strictly controls the expression of different genes by identifying specific promoter elements. RpoN has an important regulatory function in carbon and nitrogen metabolism and participates in the regulation of flagellar synthesis, bacterial motility and virulence. However, little is known about the effect of RpoN inPlesiomonas shigelloides.

Results

To identify pathways controlled by RpoN, RNA sequencing (RNA-Seq) of the WT and therpoNdeletion strain was carried out for comparison. The RNA-seq results showed that RpoN regulates ~ 13.2% of theP. shigelloidestranscriptome, involves amino acid transport and metabolism, glycerophospholipid metabolism, pantothenate and CoA biosynthesis, ribosome biosynthesis, flagellar assembly and bacterial secretion system. Furthermore, we verified the results of RNA-seq using quantitative real-time reverse transcription PCR, which indicated that the absence ofrpoNcaused downregulation of more than half of the polar and lateral flagella genes inP. shigelloides, and the ΔrpoN mutant was also non-motile and lacked flagella. In the present study, the ability of the ΔrpoNmutant to kill E. coliMG1655 was reduced by 54.6% compared with that of the WT, which was consistent with results in RNA-seq, which showed that the type II secretion system (T2SS-2) genes and the type VI secretion system (T6SS) genes were repressed. By contrast, the expression of type III secretion system genes was largely unchanged in the ΔrpoNmutant transcriptome and the ability of the ΔrpoNmutant to infect Caco-2 cells was also not significantly different compared with the WT.

Conclusions

We showed that RpoN is required for the motility and contributes to the killing ability ofP. shigelloidesand positively regulates the T6SS and T2SS-2 genes.
Accumulation of DNA damage alters microRNA gene transcription in Arabidopsis thaliana
Authors: Du Juan , Liu Yang , Lu Lu , Shi Jianfei , Xu Longqian , Li Qi , Cheng Xiaofei , Chen Jinfeng , Zhang Xiaoming
Published: December 2022

Background

MicroRNAs (miRNAs) and other epigenetic modifications play fundamental roles in all eukaryotic biological processes. DNA damage repair is a key process for maintaining the genomic integrity of different organisms exposed to diverse stresses. However, the reaction of miRNAs in the DNA damage repair process is unclear.

Results

In this study, we found that the simultaneous mutation of zinc finger DNA 3′-phosphoesterase (ZDP) and AP endonuclease 2 (APE2), two genes that play overlapping roles in active DNA demethylation and base excision repair (BER), led to genome-wide alteration of miRNAs. The transcripts of newly transcribed miRNA-encoding genes (MIRs) decreased significantly in zdp/ape2, indicating that the mutation of ZDP and APE2 affected the accumulation of miRNAs at the transcriptional level. In addition, the introduction of base damage with the DNA-alkylating reagent methyl methanesulfonate (MMS) accelerated the reduction of miRNAs in zdp/ape2. Further mutation of FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG), a bifunctional DNA glycosylase/lyase, rescued the accumulation of miRNAs in zdp/ape2, suggesting that the accumulation of DNA damage repair intermediates induced the transcriptional repression of miRNAs.

Conclusions

Our investigation indicates that the accumulation of DNA damage repair intermediates inhibit miRNAs accumulation by inhibiting MIR transcriptions.
Effects of exogenous Strigolactone on the physiological and ecological characteristics of Pennisetum purpureum Schum. Seedlings under drought stress
Authors: Li Yan , Li Sutao , Feng Qixian , Zhang Juan , Han Xuelin , Zhang Lei , Yang Fulin , Zhou Jing
Published: December 2022

Background

Drought is one of the main environmental factors limiting plant growth and development. Pennisetum purpureum Schum. was used to explore the mitigation effects of exogenous strigolactone (SL) on drought stress during the seedling stage. The effects of different concentrations (1, 3, 5, and 7 μmol·L− 1) of SL on the photosynthesis characteristics, growth performance, and endogenous abscisic acid (ABA) of P. purpureum under drought stress were studied.

Results

Exogenous SL could effectively alleviate the inhibitory effect of drought stress on P. purpureum growth. Compared with drought stress, the net photosynthesis rate, stomatal conductance, transpiration rate, and water-use efficiency of the leaves of P. purpureum after SL treatment significantly increased, thereby exerting a significant mitigation effect on the decrease in photosystem II maximum photochemical efficiency and the performance index based on light absorption caused by drought. Moreover, the exogenous application of SL can effectively increase the fresh and dry weight of the leaves and roots and the main-root length. After applying SL for 120 h, the ABA content of P. purpureum decreased significantly. The activity of key enzymes of photosynthesis significantly increased after 48 h of external application of SL to P. purpureum.

Conclusions

SL treatment can improve the photosynthesis performance of P. purpureum leaves under drought conditions and increase the antioxidant capacity of the leaves, thereby reducing the adverse effects of drought, promoting the growth of P. purpureum, and effectively improving the drought resistance of P. purpureum.
Effects and mechanism of renal denervation on ventricular arrhythmia after acute myocardial infarction in rats
Authors: Ye Jian , Xiao Rongxue , Wang Xu , He Ruiqing , Liu Zongjun , Gao Junqing
Published: December 2022

Background

Renal denervation (RDN) can reduce ventricular arrhythmia after acute myocardial infarction (AMI), but the mechanism is not clear. The purpose of this study is to study its mechanism.

Methods

Thirty-two Sprague–Dawley rats were divided into four groups: control group, AMI group, RDN-1d + AMI group, RDN-2w + AMI group. The AMI model was established 1 day after RDN in the RDN-1d + AMI group and 2 weeks after RDN in the RDN-2w + AMI group. At the same time, 8 normal rats were subjected to AMI modelling (the AMI group). The control group consisted of 8 rats without RDN intervention or AMI modelling.

Results

The study confirmed that RDN can reduce the occurrence of ventricular tachycardia in AMI rats, reduce renal sympathetic nerve discharge, and inhibit the activity of local sympathetic nerves and cell growth factor (NGF) protein expression in the heart after AMI. In addition, RDN decreased the expression of norepinephrine (NE) and glutamate in the hypothalamus,and NE in cerebrospinal fluid, and increased the expression level of γ aminobutyric acid (GABA) in the hypothalamus after AMI.

Conclusion

RDN can effectively reduce the occurrence of ventricular arrhythmia after AMI, and its main mechanism may be via the inhibition of central sympathetic nerve discharge.
FRENCH versus ESI: comparison between two nurse triage emergency scales with referent scenarios
Authors: Aubrion Antoine , Clanet Romain , Jourdan JP , Creveuil Christian , Roupie E , Macrez Richard
Published: December 2022

Objectives

Acute triage is needed to prioritize care and achieve optimal resource allocation in busy emergency departments. The main objective is to compare the FRench Emergency Nurse Classification in Hospital scale (FRENCH) to the American scale Emergency Severity Index (ESI). Secondary objectives are to compare for each scale the over and under-triage, the triage matching to the gold standard and the inter-individual sorting reproducibility between the nurses.

Methods

This is a prospective observational study conducting among the nursing staffs and nursing students, selected from Caen University College Hospital and Lisieux Hospital Center emergency departments between two months. Each group individually rank 60 referent clinical cases composed by scales designers. An assessment of scale practicality is collected after for each tool. The collected parameters are analyzed by a Cohen kappa concordance test (κ).

Results

With 8151 triage results of gold standard scenarios sorting in two scales by the same nurses, the FRENCH scale seems to give better triage results than the US ESI scale (nurse: FRENCH 60% and ESI 53%, p = 0.003 ; nursing students: FRENCH 49% and ESI 42%, p < 0.001). In the two groups ESI has also a big tendency to under-sort (p = 0.01), particularly for the most severe patients (p < 0.01). The interobserver sorting concordance for any experience gives good results for the FRENCH and the ESI without any difference (nurses : FRENCH KPQ=0.72 ESI KPQ=0.78; p = 0.32 ; students KPQ=0.44 KPQ=0.55; p = 0.22).

Conclusion

The ESI and FRENCH scales comparison on 8151 sorting results shows direct validity in favor of FRENCH one and similar interobserver agreement for both scales.
Differences in the superspreading potentials of COVID-19 across contact settings
Authors: Zhao Yanji , Zhao Shi , Guo Zihao , Yuan Ziyue , Ran Jinjun , Wu Lan , Yu Lin , Li Hujiaojiao , Shi Yu , He Daihai
Published: December 2022

Background

Superspreading events (SSEs) played a critical role in fueling the COVID-19 outbreaks. Although it is well-known that COVID-19 epidemics exhibited substantial superspreading potential, little is known about the risk of observing SSEs in different contact settings. In this study, we aimed to assess the potential of superspreading in different contact settings in Japan.

Method

Transmission cluster data from Japan was collected between January and July 2020. Infector-infectee transmission pairs were constructed based on the contact tracing history. We fitted the data to negative binomial models to estimate the effective reproduction number (R) and dispersion parameter (k). Other epidemiological issues relating to the superspreading potential were also calculated.

Results

The overall estimated R and k are 0.561 (95% CrI: 0.496, 0.640) and 0.221 (95% CrI: 0.186, 0.262), respectively. The transmission in community, healthcare facilities and school manifest relatively higher superspreading potentials, compared to other contact settings. We inferred that 13.14% (95% CrI: 11.55%, 14.87%) of the most infectious cases generated 80% of the total transmission events. The probabilities of observing superspreading events for entire population and community, household, health care facilities, school, workplace contact settings are 1.75% (95% CrI: 1.57%, 1.99%), 0.49% (95% CrI: 0.22%, 1.18%), 0.07% (95% CrI: 0.06%, 0.08%), 0.67% (95% CrI: 0.31%, 1.21%), 0.33% (95% CrI: 0.13%, 0.94%), 0.32% (95% CrI: 0.21%, 0.60%), respectively.

Conclusion

The different potentials of superspreading in contact settings highlighted the need to continuously monitoring the transmissibility accompanied with the dispersion parameter, to timely identify high risk settings favoring the occurrence of SSEs.
The multitarget fecal immunochemical test versus the fecal immunochemical test for programmatic colorectal cancer screening: a cross-sectional intervention study with paired design
Authors: Wisse P. H. A. , de Klaver W. , van Wifferen F. , Meiqari L. , Bierkens M. , Greuter M. J. E. , Carvalho B. , van Leerdam M. E. , Spaander M. C. W. , Dekker E. , Coupé V. M. H. , de Wit M. , Meijer G. A.
Published: December 2022

Background

Many screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program.

Method

The mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants.

Discussion

The outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening.

Trial registration

Clinicaltrials.gov; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist=.
Comparative proteomic analysis of children FSGS FFPE tissues
Authors: Ni Jiajia , Tian Sha , Bai Lin , Lv Qianying , Liu Jialu , Liu Jiaojiao , Fang Ye , Zhai Yihui , Shen Qian , Rao Jia , Ding Chen , Xu Hong
Published: December 2022

Background

In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephrotic syndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS).

Methods

Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models.

Results

In total, we quantified more than 4000 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥2, P<0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells.

Conclusions

In this study, the potential mechanism and candidates related to steroid resistance in children FSGS patients were identified. It could be helpful in identifying potential therapeutic targets and predicting outcomes with these proteomic changes for children FSGS patients.
Prevalence of dental caries in children with congenital heart disease
Authors: Koerdt Steffen , Hartz Julia , Hollatz Stefan , Heiland Max , Neckel Norbert , Ewert Peter , Oberhoffer Renate , Deppe Herbert
Published: December 2022

Background

Congenital heart defects (CHD) affect about 8 out of 1000 births worldwide. Most of the patients reach adulthood and are exposed to an increased risk of endocarditis. Since bacteria already enter the bloodstream during everyday activities, oral hygiene is given special importance in the prevention of endocarditis.

Methods

In this study 81 boys (55.1%) and 66 (44.9%) girls with CHD received a dental exam and additionally an assessment using the DIAGNOdent® pen. This study group consisting of patients with CHD was matched with a healthy epidemiological control group in Germany.

Results

Eighty-one boys (55.1%) and 66 (44.9%) girls were examined. The mean age was 11 ± 4 years.

38.8% showed at least one untreated carious lesions. 37.4% had a dmft/DMFT ≥2 and thus represented a group with an increased caries risk.

The dmft value was 2.12 ± 1.25 in the age group 3-6 year olds. In the group of the 7-12 year old patients the DMFT/dmft was 2.06 ± 2.27, whereas DMFT in 13-17 year olds was at 2.12 ± 1.58. However, children and adolescents with CHD had a higher DMF index than healthy children in the same age group.

Conclusions

The present study reveals that more than one third of those examined have a dental condition in need of rehabilitation. In future, close interdisciplinary cooperation between pediatric cardiologists and dentists should ensure regular dental check-ups.
Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT
Authors: Ayoub Zeina , Khader Jamal , Bulbul Muhammad , Khauli Raja B. , Andraos Therese Y. , Shamseddine Ali , Mukherji Deborah , Geara Fady B.
Published: December 2022

Background

A nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA.

Methods

Between 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan–Meier methods and predictors of outcomes using multi-variable cox regression model.

Results

In the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972–9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference.

Conclusion

In HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.
Effectiveness of an integrated model of oral health-promoting schools in improving children's knowledge and the KAP of their parents, Iran
Authors: Tahani Bahareh , Asgari Imaneh , Golkar Shayan , Ghorani Amir , Hasan Zadeh Tehrani Nooshin , Arezoo Moghadam Fatemeh
Published: December 2022

Introduction

The aim of our study was to investigate the effect of an Oral Health Promoting School (OHPS) model on children's oral health in Iran.

Methods

This interventional quasi-experimental study was conducted in the academic year 2019–20 among 354 primary school students and their parents. A questionnaire including 17 questions was distributed among children before and 5 months after the program (The ranges of possible scores = 0–17). Training workshops for the parents based on the theoretical domains framework were designed. Using educational sessions, pamphlets, tooth brushing dairies, assignments to do at home, educational videos and messages as reminders in social networks, parents were educated about dental caries, its risk factors and prevention principles. Best recommended oral health behaviors including tooth brushing and the use of fluoridated tooth paste were also educated. A questionnaire consisting of 18 knowledge (The ranges of possible scores = 0–18), 13 attitude and 10 practice questions were distributed among parents before and after the workshops. The data were fed into SPSS and analyzed by descriptive and analytic statistics such as T-test, ANOVA and Correlation Coefficients (α = 0.05).

Results

The mean pre-test knowledge (7.8 ± 1.7) was increased significantly in three schools after program,p < 0.001. In the post-test, girls gained significantly higher scores (9.61 ± 1.98 vs. 9.06 ± 1.4,p = 0.025). Among 147 parents, the mean knowledge was raised from 12.3 ± 3.1 (5–18) to 15 ± 3.03 (6–18),p < 0.001. Knowledge score of the parents attending both sessions was higher. Practice of the parents regarding the use of fluoridated tooth-paste was significantly improved (p < 0.001). Also, their attitude toward the ability of children to take care of their teeth was improved (p = 0.029). Based on the self-report of parents, 71.4% (n = 47) of mothers and 45.6% (n = 67) of their children used to brush once or two times daily and there was a correlation between their behaviors (p < 0.001, Spearman Correlation Coefficient = 0.4).

Conclusion

It seems that the education provided in OHPS had positive effects on increasing students' awareness and to some extent, the knowledge, attitude and practice of the parents.