bluuebunny/crossref_metadata_2025 huggingface dataset:
Stream pollution causes aggregation of wintering insectivorous birds through increased aquatic emergence
Authors: Lepori Fabio
Published: August 2022

Cross-boundary prey subsidies can propagate the effects of human impacts from streams to terrestrial ecosystems, but effects during winter are poorly known. Here I focused on this season and investigated the effects of pollution due to a sewage treatment plant (STP) on aquatic insect emergence and wintering insectivorous birds in a Swiss stream. At sites downstream of the STP, a combination of nutrient (phosphorus), organic (biochemical oxygen demand), and thermal pollution led to higher aquatic emergence compared to upstream sites (6× higher). In turn, the higher emergence led to a strong aggregational response by wintering insectivorous birds (8× higher linear densities compared to upstream sites). Polluted sites also had a different bird assemblage, which included rare wintering species that forage largely on aerial insects. A comparison between the polluted (downstream) sites and a nearby unpolluted stream produced similar differences. The magnitude and consistency of the effects illustrate how strongly stream alterations can propagate to birds through changes in aquatic emergence. Moreover, the results provide insights into the responses of linked stream-terrestrial food webs to other environmental issues that cause warming and/or pollution, including urbanization and climate change.
Transcriptomic and immunologic implications of the epithelial–mesenchymal transition model reveal a novel role of SFTA2 in prognosis of non-small-cell lung carcinoma
Authors: Li Na , Zhai Zhanqiang , Chen Yuanbiao , Li Xiaofeng
Published: August 2022

Non-small-cell lung cancer (NSCLC) is the second most common cancer worldwide, and most deaths are associated with epithelial–mesenchymal transition (EMT). Therefore, this study aimed to explore the role of EMT-related transcriptomic profiles in NSCLC and the effect of EMT-based signatures on clinical diagnosis, prognosis, and treatment responses for patients with NSCLC. After integrating the transcriptomics and clinicopathological data, we first constructed EMT clusters (C1 and C2) using machine learning algorithms, found the significant relationship between EMT clusters and survival outcomes, and then explored the impact of EMT clusters on the tumor heterogeneity, drug efficiency, and immune microenvironment of NSCLC. Prominently, differential-enriched tumor-infiltrated lymphocytes were found between EMT clusters, especially the macrophages and monocyte. Next, we identified the most significantly down-regulated gene SFTA2 in the EMT clusters C2 with poor prognosis. Using RT-qPCR and RNA-seq data from the public database, we found prominently elevated SFTA2 expression in NSCLC tissues compared with normal lung tissues, and the tumor suppressor role of SFTA2 in 82 Chinese patients with NSCLC. After Cox regression and survival analysis, we demonstrated that higher SFTA2 expression in tumor samples significantly predicts favorable prognosis of NSCLC based on multiple independent cohorts. In addition, the prognostic value of SFTA2 expression differs for patients with lung adenocarcinoma and squamous cell carcinoma. In conclusion, this study demonstrated that the EMT process is involved in the malignant progression and the constructed EMT clusters exerted significant predictive drug resistance and prognostic value for NSCLC patients. In addition, we first identified the high tumoral expression of SFTA2 correlated with better prognosis and could serve as a predictive biomarker for outcomes and treatment response of NSCLC patients.
Whole Genome Sequencing and Morphological Trait-Based Evaluation of UPOV Option 2 for DUS Testing in Rice
Authors: Liu Hong , Rao Dehua , Guo Tao , Gangurde Sunil S. , Hong Yanbin , Chen Mengqiang , Huang Zhanquan , Jiang Yuan , Xu Zhenjiang , Chen Zhiqiang
Published: August 2022

To evaluate the application potential of high-density SNPs in rice distinctness, uniformity, and stability (DUS) testing, we screened 37,929 SNP loci distributed on 12 rice chromosomes based on whole-genome resequencing of 122 rice accessions. These SNP loci were used to analyze the DUS testing of rice varieties based on the correlation between the molecular and phenotypic distances of varieties according to UPOV option 2. The results showed that statistical algorithms and the number of phenotypic traits and SNP loci all affected the correlation between the molecular and phenotypic distances of rice varieties. Relative to the other nine algorithms, the Jaccard similarity algorithm had the highest correlation of 0.6587. Both the number of SNPs and the number of phenotypes had a ceiling effect on the correlation between the molecular and phenotypic distances of varieties, and the ceiling effect of the number of SNP loci was more obvious. To overcome the correlation bottleneck, we used the genome-wide prediction method to predict 30 phenotypic traits and found that the prediction accuracy of some traits, such as the basal sheath anthocyanin color, glume length, and intensity of the green color of the leaf blade, was very low. In combination with group comparison analysis, we found that the key to overcoming the ceiling effect of correlation was to improve the resolution of traits with low predictive values. In addition, we also performed distinctness testing on rice varieties by using the molecular distance and phenotypic distance, and we found that there were large differences between the two methods, indicating that UPOV option 2 alone cannot replace the traditional phenotypic DUS testing. However, genotype and phenotype analysis together can increase the efficiency of DUS testing.
Fine-scale differences in eukaryotic communities inside and outside salmon aquaculture cages revealed by eDNA metabarcoding
Authors: Turon Marta , Nygaard Magnus , Guri Gledis , Wangensteen Owen S. , Præbel Kim
Published: August 2022

Aquaculture impacts on marine benthic ecosystems are widely recognized and monitored. However, little is known about the community changes occurring in the water masses surrounding aquaculture sites. In the present study, we studied the eukaryotic communities inside and outside salmonid aquaculture cages through time to assess the community changes in the neighbouring waters of the farm. Water samples were taken biweekly over five months during the production phase from inside the cages and from nearby points located North and South of the salmon farm. Eukaryotic communities were analyzed by eDNA metabarcoding of the partial COI Leray-XT fragment. The results showed that eukaryotic communities inside the cages were significantly different from those in the outside environment, with communities inside the cages having higher diversity values and more indicator species associated with them. This is likely explained by the appearance of fouling species that colonize the artificial structures, but also by other species that are attracted to the cages by other means. Moreover, these effects were highly localized inside the cages, as the communities identified outside the cages, both North and South, had very similar eukaryotic composition at each point in time. Overall, the eukaryotic communities, both inside and outside the cages, showed similar temporal fluctuations through the summer months, with diversity peaks occurring at the end of July, beginning of September, and in the beginning of November, with the latter showing the highest Shannon diversity and richness values. Hence, our study suggests that seasonality, together with salmonid aquaculture, are the main drivers of eukaryotic community structure in surface waters surrounding the farm.
RUNX regulated immune-associated genes predicts prognosis in breast cancer
Authors: Fu Jingyue , Sun Handong , Xu Feng , Chen Rui , Wang Xinyang , Ding Qiang , Xia Tiansong
Published: August 2022

Background: Breast cancer is the most common malignant tumor in women. RUNX family has been involved in the regulation of different carcinogenic processes and signaling pathways with cancer, which is closely related to immunity and prognosis of various tumors, and also plays an important role in the development and prognosis of breast cancer.

Methods: We discovered the expression of RUNX family through GEPIA Dataset and then evaluated the relationship between RUNX family and immune-related genes and the prognosis of breast cancer through analyzing TCGA database. A prognostic model was established and verified via cox proportional hazards regression model using R packages. We evaluated the accuracy of the prognostic model by Kaplan-Meier curves and receiver operating characteristic (ROC) curves. Additionally, we obtained the relationship between the RUNX family and immune infiltration by TIMER database. Finally, the dual luciferase reporter assay was used to verify the regulation of RUNX3 on potential target genes ULBP2 and TRDV1, and the effects of ULBP2 and TRDV1 on the growth of breast cancer cells were explored by CCK-8, colony formation and wound healing assays.

Results: We screened out RUNX family-regulated immune-related genes associated with the prognosis of breast cancer. These predictors included PSME2, ULBP2, IL-18, TSLP, NPR3, TRDV1. Then a prognosis-related risk score model was built using the independent risk factors to provide a clinically appropriate method predicting the overall survival (OS) probability of the patients with breast cancer. In addition, a further research was made on the functions of high risk immune gene ULBP2 and low risk immune gene TRDV1 which regulated by RUNX3, the results showed that down-regulation of ULBP2 suppressed breast cancer cell proliferation and TRDV1 had the opposite functions. The prognostic model we constructed could promote the development of prognostic, and was associated with lower immune infiltration.

Conclusion: The expression of RUNX family was closely related to the prognosis of breast cancer. At the same time, RUNX family could modulate the functions of immune-related genes, and affect the development and prognosis of breast cancer. These immune-related genes regulated by RUNX family could be promising prognostic biomarkers and therapeutic targets in breast cancer.
Deciphering inhibitory mechanism of coronavirus replication through host miRNAs-RNA-dependent RNA polymerase interactome
Authors: Morenikeji Olanrewaju B. , Adegbaju Muyiwa S. , Okoh Olayinka S. , Babalola Asegunloluwa E. , Grytsay Anastasia , Braimah Olubumi A. , Akinyemi Mabel O. , Thomas Bolaji N.
Published: August 2022

Despite what we know so far, Covid-19, caused by SARS-CoV-2 virus, remains a pandemic that still require urgent healthcare intervention. The frequent mutations of the SARS-CoV-2 virus has rendered disease control with vaccines and antiviral drugs quite challenging, with newer variants surfacing constantly. There is therefore the need for newer, effective and efficacious drugs against coronaviruses. Considering the central role of RNA dependent, RNA polymerase (RdRp) as an enzyme necessary for the virus life cycle and its conservation among coronaviruses, we investigated potential host miRNAs that can be employed as broad-range antiviral drugs averse to coronaviruses, with particular emphasis on BCoV, MERS-CoV, SARS-CoV and SARS-CoV-2. miRNAs are small molecules capable of binding mRNA and regulate expression at transcriptional or translational levels. Our hypothesis is that host miRNAs have the potential of blocking coronavirus replication through miRNA-RdRp mRNA interaction. To investigate this, we retrieved the open reading frame (ORF1ab) nucleotide sequences and used them to interrogate miRNA databases for miRNAs that can bind them. We employed various bioinformatics tools to predict and identify the most effective host miRNAs. In all, we found 27 miRNAs that target RdRp mRNA sequence of multiple coronaviruses, of which three - hsa-miR-1283, hsa-miR-579-3p, and hsa-miR-664b-3p target BCoV, SARS-CoV and SARS-CoV-2. Additionally, hsa-miR-374a-5p has three bovine miRNA homologs viz bta-miR-374a, bta-miR-374b, and bta-miR-374c. Inhibiting the expression of RdRp enzyme via non-coding RNA is novel and of great therapeutic importance in the control of coronavirus replication, and could serve as a broad-spectrum antiviral, with hsa-miR-1283, hsa-miR-579-3p, and hsa-miR-664b-3p as highly promising.
Lipid nanoparticle-based mRNA vaccines in cancers: Current advances and future prospects
Authors: Huang Tao , Peng Lushan , Han Yingying , Wang Dan , He Xiaoyun , Wang Junpu , Ou Chunlin
Published: August 2022

Messenger RNA (mRNA) vaccines constitute an emerging therapeutic method with the advantages of high safety and efficiency as well as easy synthesis; thus, they have been widely used in various human diseases, especially in malignant cancers. However, the mRNA vaccine technology has some limitations, such as instability and low transitive efficiency in vivo, which greatly restrict its application. The development of nanotechnology in the biomedical field offers new strategies and prospects for the early diagnosis and treatment of human cancers. Recent studies have demonstrated that Lipid nanoparticle (LNP)-based mRNA vaccines can address the poor preservation and targeted inaccuracy of mRNA vaccines. As an emerging cancer therapy, mRNA vaccines potentially have broad future applications. Unlike other treatments, cancer mRNA vaccines provide specific, safe, and tolerable treatments. Preclinical studies have used personalized vaccines to demonstrate the anti-tumor effect of mRNA vaccines in the treatment of various solid tumors, including colorectal and lung cancer, using these in a new era of therapeutic cancer vaccines. In this review, we have summarized the latest applications and progress of LNP-based mRNA vaccines in cancers, and discussed the prospects and limitations of these fields, thereby providing novel strategies for the targeted therapy of cancers.
Sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma: A prospective, open-label, single-arm, phase II clinical study
Authors: Li Dailong , Xu Lu , Ji Jinxing , Bao Dan , Hu Juan , Qian Ying , Zhou Yinjie , Chen Zhuo , Li Daojun , Li Xiaopeng , Zhang Xiaoling , Wang Hao , Yi Changjun , Shi Menglu , Pang Yaqi , Liu Siqi , Xu Xinhua
Published: August 2022

Objective

To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC.

Methods

This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety.

Results

Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9–65.1%) and 91.3% (95% CI: 79.2–97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2–20.2 months). The median PFS was 9.0 months (95% CI: 7.1–10.9 months). The median DoR was 10.8 months (95% CI: 4.8–16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5–84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events.

Conclusion

Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies.

Clinical Trial Registration

https://ClinicalTrials.gov, identifier NCT04411706.
Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer
Authors: Ji Huihui , Zhang Jian-an , Liu Hejing , Li Kehan , Wang Zhi-wei , Zhu Xueqiong
Published: August 2022

Understanding the role of N6-adenosine methylation (m6A) in the tumor microenvironment (TME) is important since it can contribute to tumor development. However, the research investigating the association between m6A and TME and cervical cancer is still in its early stages. The aim of this study was to discover the possible relationship between m6A RNA methylation regulators, TME, PD-L1 expression levels, and immune infiltration in cervical cancer. We gathered RNA-seq transcriptome data and clinical information from cervical cancer patients using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. To begin, researchers assessed the differences in m6A regulatory factor expression levels between cervical cancer and normal tissues. Clustering analysis was adapted to assess PD-L1 expression, immunological score, immune cell infiltration, TME, and probable pathways in cervical cancer samples. The majority of m6A regulators were found to be considerably overexpressed in cervical cancer tissues. Using consensus clustering of 21 m6A regulators, we identified two subtypes (clusters 1/2) of cervical cancer, and we found that WHO stage and grade were associated with the subtypes. PD-L1 expression increased dramatically in cervical cancer tissues and was significantly linked to ALKBH5, FTO, METTL3, RBM15B, YTHDF1, YTHDF3, and ZC3H13 expression levels. Plasma cells and regulatory T cells (Tregs) were considerably elevated in cluster 2. Cluster 1 is involved in numerous signature pathways, including basal transcription factors, cell cycle, RNA degradation, and the spliceosome. The prognostic signature-based riskscore (METTL16, YTHDF1, and ZC3H13) was found to be an independent prognostic indicator of cervical cancer. The tumor immune microenvironment (TIME) was linked to m6A methylation regulators, and changes in their copy number will affect the quantity of tumor-infiltrating immune cells dynamically. Overall, our research discovered a powerful predictive signature based on m6A RNA methylation regulators. This signature correctly predicted the prognosis of cervical cancer patients. The m6A methylation regulator could be a critical mediator of PD-L1 expression and immune cell infiltration, and it could have a significant impact on the TIME of cervical cancer.
COVID-19 pandemic: A multidisciplinary perspective on the pathogenesis of a novel coronavirus from infection, immunity and pathological responses
Authors: Yi Jia , Miao Jiameng , Zuo Qingwei , Owusu Felix , Dong Qiutong , Lin Peizhe , Wang Qilong , Gao Rui , Kong Xianbin , Yang Long
Published: August 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), has spread to more than 200 countries and regions, having a huge impact on human health, hygiene, and economic activities. The epidemiological and clinical phenotypes of COVID-19 have increased since the onset of the epidemic era, and studies into its pathogenic mechanisms have played an essential role in clinical treatment, drug development, and prognosis prevention. This paper reviews the research progress on the pathogenesis of the novel coronavirus (SARS-CoV-2), focusing on the pathogenic characteristics, loci of action, and pathogenic mechanisms leading to immune response malfunction of SARS-CoV-2, as well as summarizing the pathological damage and pathological manifestations it causes. This will update researchers on the latest SARS-CoV-2 research and provide directions for future therapeutic drug development.
Sintilimab induced ICIAM in the treatment of advanced HCC: A case report and analysis of research progress
Authors: Ji Hongxiang , Wen Zhijian , Liu Bin , Chen Hongbiao , Lin Qian , Chen Zhan
Published: August 2022

Immune checkpoint inhibitor-associated adverse reactions (irAEs) are a clinical treatment issue that requires additional attention when ICIs have significant survival benefits in patients with advanced hepatocellular carcinoma (HCC). Among them, ICIs-associated myocarditis (ICIAM) is a kind of severe irAE with a high mortality rate (17%–50%). Despite its low incidence (PD1/PD-L1 related: 0.41%–0.8%), ICIAM can significantly disturb the decision making of therapeutic schemes and even the survival outcomes of patients. ICIAM induced by sintilimab has not been reported in any complete clinical studies yet and understanding the clinical characteristics involved may inform better practices for the management. Here, we reported a 78 y/o patient with advanced HCC, who experienced ICIAM induced by sintilimab within a short course from treatment onset and found that adequate baseline examination before the implementation of the therapeutic scheme, regular monitoring of myocardial enzymonram and cardiac imaging were measures for the early detection, while glucocorticoid pulse therapy is still the best choice with timely and sufficient application. Simultaneously, the combination of other immunosuppressants may lead to better results. New-predictive markers and examination methods are still required to facilitate the early detection.
Blood pressure monitoring techniques in the natural state of multi-scenes: A review
Authors: Liu Ziyi , Zhou Congcong , Wang Hongwei , He Yong
Published: August 2022

Blood pressure is one of the basic physiological parameters of human physiology. Frequent and repeated measurement of blood pressure along with recording of environmental or other physiological parameters when measuring blood pressure may reveal important cardiovascular risk factors that can predict occurrence of cardiovascular events. Currently, wearable non-invasive blood pressure measurement technology has attracted much research attention. Several different technical routes have been proposed to solve the challenge between portability or continuity of measurement methods and medical level accuracy of measurement results. The accuracy of blood pressure measurement technology based on auscultation and oscillography has been clinically verified, while majority of other technical routes are being explored at laboratory or multi-center clinical demonstration stage. Normally, Blood pressure measurement based on oscillographic method outside the hospital can only be measured at intervals. There is a need to develop techniques for frequent and high-precision blood pressure measurement under natural conditions outside the hospital. In this paper, we discussed the current status of blood pressure measurement technology and development trends of blood pressure measurement technology in different scenarios. We focuses on the key technical challenges and the latest advances in the study of miniaturization devices based on oscillographic method at wrist and PTT related method at finger positions as well as technology processes. This study is of great significance to the application of high frequency blood pressure measurement technology.
Peripheral vitamin D levels in ankylosing spondylitis: A systematic review and meta-analysis
Authors: Diao Maohui , Peng Jun , Wang Daidong , Wang Hongbo
Published: August 2022

Objectives

Previous studies showed conflicting results regarding peripheral vitamin D levels in ankylosing spondylitis (AS). We performed this systemic review and meta-analysis to explore whether vitamin D may influence AS process.

Methods

Articles published until March 2022 were searched in databases as follows: PubMed, Web of Science, and Google Scholar. The present study included cross-sectional and case-control studies regarding vitamin D levels in patients with AS. Studies were excluded according to the following exclusion criteria: (1) we excluded studies which did not provide sufficient information regarding the comparison of vitamin D levels in AS patients and healthy controls (HC). Vitamin D levels in the two group studies should be reported or could be calculated in included studies; (2) meta-analysis, reviews and case reports. STATA 12.0 software was used to make a meta-analysis. Standard mean differences (SMDs) and 95% confidence intervals (CIs) were computed as effect size.

Results

The present meta-analysis showed no significant difference in peripheral 1,25-dihydroxyvitamin D3 (1,25OHD) levels between AS and healthy controls (HCs) in Caucasians with a random effects model [SMD: −0.68, 95% CI (−1.90, 0.54)]. Patients with AS had lower peripheral 25-hydroxyvitamin D (25OHD) levels compared with HC with a random effects model [SMD: −0.45, 95% CI: (−0.70, −0.20)]. Patients with AS had higher peripheral C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels compared with HC in Caucasian population with random effects models [CRP: SMD: 1.08, 95% CI: (0.78, 1.37); ESR: SMD: 0.86, 95% CI: (0.39, 1.34)]. However, no significant difference in alkaline phosphatase (ALP), parathyroid hormone (PTH) or calcium levels were indicated between AS and HC in Caucasian with random effects models [ALP: SMD: 0.07, 95% CI: (−0.41, 0.55); PTH: SMD: −0.15, 95% CI: (−0.56, 0.26); calcium: SMD: −0.06, 95% CI: (−0.39, 0.26)].

Conclusion

In conclusion, the study showed an inverse association between 25OHD and AS, which suggests that vitamin D may have a protective effect on AS. ESR and C-reactive protein (CRP) are important biomarkers for AS.
Ultrasound intima media thickness cut-off values for cranial and extracranial arteries in patients with suspected giant cell arteritis
Authors: López-Gloria Katerine , Castrejón Isabel , Nieto-González Juan Carlos , Rodríguez-Merlos Pablo , Serrano-Benavente Belén , González Carlos Manuel , Monteagudo Sáez Indalecio , González Teresa , Álvaro-Gracia José María , Molina-Collada Juan
Published: August 2022

Objective

To determine the optimal ultrasound (US) cut-off values for cranial and extracranial arteries intima media thickness (IMT) to discriminate between patients with and without giant cell arteritis (GCA).

Methods

Retrospective observational study including patients referred to an US fast-track clinic. All patients underwent bilateral US examination of the cranial and extracranial arteries including the IMT measurement. Clinical confirmation of GCA after 6 months was considered the gold standard for diagnosis. A receiver operating characteristic (ROC) analysis was performed to select the cut-off values on the basis of the best tradeoff values between sensitivity and specificity.

Results

A total of 157 patients were included, 47 (29.9%) with clinical confirmation of GCA after 6 months. 41 (87.2%) of patients with GCA had positive US findings (61.7% had cranial and 44.7% extracranial involvement). The best threshold IMT values were 0.44 mm for the common temporal artery; 0.34 mm for the frontal branch; 0.36 mm for the parietal branch; 1.1 mm for the carotid artery and 1 mm for the subclavian and axillary arteries. The areas under the ROC curves were greater for axillary arteries 0.996 (95% CI 0.991–1), for parietal branch 0.991 (95% CI 0.980–1), for subclavian 0.990 (95% CI 0.979–1), for frontal branch 0.989 (95% CI 0.976–1), for common temporal artery 0.984 (95% CI 0.959–1) and for common carotid arteries 0.977 (95% CI 0.961–0.993).

Conclusion

IMT cut-off values have been identified for each artery. These proposed IMT cut-off values may help to improve the diagnostic accuracy of US in clinical practice.
Treatment of Pseudomonas aeruginosa infectious biofilms: Challenges and strategies
Authors: Yin Rui , Cheng Juanli , Wang Jingyao , Li Panxin , Lin Jinshui
Published: August 2022

Pseudomonas aeruginosa, a Gram-negative bacterium, is one of the major pathogens implicated in human opportunistic infection and a common cause of clinically persistent infections such as cystic fibrosis, urinary tract infections, and burn infections. The main reason for the persistence of P. aeruginosa infections is due to the ability of P. aeruginosa to secrete extracellular polymeric substances such as exopolysaccharides, matrix proteins, and extracellular DNA during invasion. These substances adhere to and wrap around bacterial cells to form a biofilm. Biofilm formation leads to multiple antibiotic resistance in P. aeruginosa, posing a significant challenge to conventional single antibiotic therapeutic approaches. It has therefore become particularly important to develop anti-biofilm drugs. In recent years, a number of new alternative drugs have been developed to treat P. aeruginosa infectious biofilms, including antimicrobial peptides, quorum-sensing inhibitors, bacteriophage therapy, and antimicrobial photodynamic therapy. This article briefly introduces the process and regulation of P. aeruginosa biofilm formation and reviews several developed anti-biofilm treatment technologies to provide new directions for the treatment of P. aeruginosa biofilm infection.
The Maillard reaction in traditional method sparkling wine
Authors: Charnock Hannah M. , Pickering Gary J. , Kemp Belinda S.
Published: August 2022

The Maillard reaction between sugars and amino acids, peptides, or proteins generates a myriad of aroma compounds through complex and multi-step reaction pathways. While the Maillard has been primarily studied in the context of thermally processed foods, Maillard-associated products including thiazoles, furans, and pyrazines have been identified in aged sparkling wines, with associated bready, roasted, and caramel aromas. Sparkling wines produced in the bottle-fermented traditional method (Méthode Champenoise) have been the primary focus of studies related to Maillard-associated compounds in sparkling wine, and these wines undergo two sequential fermentations, with the second taking place in the final wine bottle. Due to the low temperature (15 ± 3°C) and low pH (pH 3–4) conditions during production and aging, we conclude that Maillard interactions may not proceed past intermediate stages. Physicochemical factors that affect the Maillard reaction are considered in the context of sparkling wine, particularly related to pH-dependent reaction pathways and existing literature pertaining to low temperature and/or low pH Maillard activity. A focus on the origins and composition of precursor species (amino acids and sugars) in sparkling wines is presented, as well as the potential role of metal ions in accelerating the Maillard reaction. Understanding the contributions of individual physicochemical factors to the Maillard reaction in sparkling wine enables a clearer understanding of reaction pathways and sensory outcomes. Advancements in analytical techniques for monitoring the Maillard reaction are also described, and important areas of future research on this topic are identified.
Osteoclast-like stromal giant cells in breast cancer likely belong to the spectrum of immunosuppressive tumor-associated macrophages
Authors: Sajjadi Elham , Gaudioso Gabriella , Terrasi Andrea , Boggio Francesca , Venetis Konstantinos , Ivanova Mariia , Bertolasi Letizia , Lopez Gianluca , Runza Letterio , Premoli Alice , Lorenzini Daniele , Guerini-Rocco Elena , Ferrero Stefano , Vaira Valentina , Fusco Nicola
Published: August 2022

Background: Breast cancer with osteoclast-like stromal giant cells (OSGC) is an exceedingly rare morphological pattern of invasive breast carcinoma. The tumor immune microenvironment (TIME) of these tumors is populated by OSGC, which resemble osteoclasts and show a histiocytic-like immunophenotype. Their role in breast cancer is unknown. The osteoclast maturation in the bone is regulated by the expression of cytokines that are also present in the TIME of tumors and in breast cancer tumor-associated macrophages (TAMs). TAMs-mediated anti-tumor immune pathways are regulated by miRNAs akin to osteoclast homeostasis. Here, we sought to characterize the different cellular compartments of breast cancers with OSGC and investigate the similarities of OSGC with tumor and TIME in terms of morphology, protein, and miRNA expression, specifically emphasizing on monocytic signatures.

Methods and Results: Six breast cancers with OSGC were included. Tumor-infiltrating lymphocytes (TILs) and TAMs were separately quantified. The different cellular populations (i.e., normal epithelium, cancer cells, and OSGC) were isolated from tissue sections by laser-assisted microdissection. After RNA purification, 752 miRNAs were analyzed using a TaqMan Advanced miRNA Low-Density Array for all samples. Differentially expressed miRNAs were identified by computing the fold change (log2Ratio) using the Kolmogorov-Smirnov test and p values were corrected for multiple comparisons using the false discovery rate (FDR) approach. As a similarity analysis among samples, we used the Pearson test. The association between pairs of variables was investigated using Fisher exact test. Classical and non-classical monocyte miRNA signatures were finally applied. All OSGC displayed CD68 expression, TILs (range, 45–85%) and high TAMs (range, 35–75%). Regarding the global miRNAs profile, OSGC was more similar to cancer cells than to non-neoplastic ones. Shared deregulation of miR-143-3p, miR-195-5p, miR-181a-5p, and miR-181b-5p was observed between OSGC and cancer cells. The monocyte-associated miR-29a-3p and miR-21-3p were dysregulated in OSGCs compared with non-neoplastic or breast cancer tissues.

Conclusion: Breast cancers with OSGC have an activated TIME. Shared epigenetic events occur during the ontogenesis of breast cancer cells and OSGC but the innumophenotype and miRNA profiles of the different cellular compartmens suggest that OSGC likely belong to the spectrum of M2 TAMs.
Machine learning-based screening of an epithelial-mesenchymal transition-related long non-coding RNA signature reveals lower-grade glioma prognosis and the tumor microenvironment and predicts antitumor therapy response
Authors: Wang Nan , Gao Xin , Ji Hang , Ma Shuai , Wu Jiasheng , Dong Jiawei , Wang Fang , Zhao Hongtao , Liu Zhihui , Yan Xiuwei , Li Bo , Du Jianyang , Zhang Jiheng , Hu Shaoshan
Published: August 2022

Epithelial-mesenchymal transition (EMT) confers high invasive and migratory capacity to cancer cells, which limits the effectiveness of tumor therapy. Long non-coding RNAs (lncRNAs) can regulate the dynamic process of EMT at different levels through various complex regulatory networks. We aimed to comprehensively analyze and screen EMT-related lncRNAs to characterize lower-grade glioma (LGG) tumor biology and provide new ideas for current therapeutic approaches. We retrieved 1065 LGG samples from the Cancer Genome Atlas and Chinese Glioma Genome Atlas by machine learning algorithms, identified three hub lncRNAs including CRNDE, LINC00665, and NEAT1, and established an EMT-related lncRNA signature (EMTrLS). This novel signature had strong prognostic value and potential clinical significance. EMTrLS described LGG genomic alterations and clinical features including gene mutations, tumor mutational burden, World Health Organization (WHO) grade, IDH status, and 1p/19q status. Notably, stratified analysis revealed activation of malignancy-related and metabolic pathways in the EMTrLS-high cohort. Moreover, the population with increased EMTrLS scores had increased cells with immune killing function. However, this antitumor immune function may be suppressed by increased Tregs and macrophages. Meanwhile, the relatively high expression of immune checkpoints explained the immunosuppressive state of patients with high EMTrLS scores. Importantly, we validated this result by quantifying the course of antitumor immunity. In particular, EMTrLS stratification enabled assessment of the responsiveness of LGG to chemotherapeutic drug efficacy and PD1 blockade. In conclusion, our findings complement the foundation of molecular studies of LGG, provide valuable insight into our understanding of EMT-related lncRNAs, and offer new strategies for LGG therapy.
The mechanisms of ferroptosis and its role in alzheimer’s disease
Authors: Ma Hongyue , Dong Yan , Chu Yanhui , Guo Yanqin , Li Luxin
Published: August 2022

Alzheimer’s disease (AD) accounts for two-thirds of all dementia cases, affecting 50 million people worldwide. Only four of the more than 100 AD drugs developed thus far have successfully improved AD symptoms. Furthermore, these improvements are only temporary, as no treatment can stop or reverse AD progression. A growing number of recent studies have demonstrated that iron-dependent programmed cell death, known as ferroptosis, contributes to AD-mediated nerve cell death. The ferroptosis pathways within nerve cells include iron homeostasis regulation, cystine/glutamate (Glu) reverse transporter (system xc−), glutathione (GSH)/glutathione peroxidase 4 (GPX4), and lipid peroxidation. In the regulation pathway of AD iron homeostasis, abnormal iron uptake, excretion and storage in nerve cells lead to increased intracellular free iron and Fenton reactions. Furthermore, decreased Glu transporter expression leads to Glu accumulation outside nerve cells, resulting in the inhibition of the system xc− pathway. GSH depletion causes abnormalities in GPX4, leading to excessive accumulation of lipid peroxides. Alterations in these specific pathways and amino acid metabolism eventually lead to ferroptosis. This review explores the connection between AD and the ferroptosis signaling pathways and amino acid metabolism, potentially informing future AD diagnosis and treatment methodologies.
Standard operating procedures for biobank in oncology
Authors: Bonizzi Giuseppina , Zattoni Lorenzo , Capra Maria , Cassi Cristina , Taliento Giulio , Ivanova Mariia , Guerini-Rocco Elena , Fumagalli Marzia , Monturano Massimo , Albini Adriana , Viale Giuseppe , Orecchia Roberto , Fusco Nicola
Published: August 2022

Biobanks are biorepositories that collect, process, store, catalog, and distribute human biological samples, and record the associated data. The role and action field of these strategic infrastructures for implementing precision medicine in translational research is continuously evolving. To ensure the optimal quality at all stages of biobanking, specific protocols are required and should be elaborated according to updated guidelines, recommendations, laws, and rules. This article illustrates the standard operating procedures, including protocols, troubleshooting, and quality controls, of a fully certified biobank in a referral Cancer Center. This model involves all clinical departments and research groups to support the dual mission of academic cancer centers, i.e. to provide high-quality care and high-quality research. All biobanking activities based on the type of biological specimens are detailed and the most tricky methodological aspects are discussed, from patients’ informed consent to specimen management.
Multi-predictor modeling for predicting early Parkinson’s disease and non-motor symptoms progression
Authors: Dou Kaixin , Ma Jiangnan , Zhang Xue , Shi Wanda , Tao Mingzhu , Xie Anmu
Published: August 2022

Background

Identifying individuals with high-risk Parkinson’s disease (PD) at earlier stages is an urgent priority to delay disease onset and progression. In the present study, we aimed to develop and validate clinical risk models using non-motor predictors to distinguish between early PD and healthy individuals. In addition, we constructed prognostic models for predicting the progression of non-motor symptoms [cognitive impairment, Rapid-eye-movement sleep Behavior Disorder (RBD), and depression] in de novo PD patients at 5 years of follow-up.

Methods

We retrieved the data from the Parkinson’s Progression Markers Initiative (PPMI) database. After a backward variable selection approach to identify predictors, logistic regression analyses were applied for diagnosis model construction, and cox proportional-hazards models were used to predict non-motor symptom progression. The predictive models were internally validated by correcting measures of predictive performance for “optimism” or overfitting with the bootstrap resampling approach.

Results

For constructing diagnostic models, the final model reached a high accuracy with an area under the curve (AUC) of 0.93 (95% CI: 0.91–0.96), which included eight variables (age, gender, family history, University of Pennsylvania Smell Inventory Test score, Montreal Cognitive Assessment score, RBD Screening Questionnaire score, levels of cerebrospinal fluid α-synuclein, and SNCA rs356181 polymorphism). For the construction of prognostic models, our results showed that the AUC of the three prognostic models improved slightly with increasing follow-up time. The overall AUCs fluctuated around 0.70. The model validation established good discrimination and calibration for predicting PD onset and progression of non-motor symptoms.

Conclusion

The findings of our study facilitate predicting the individual risk at an early stage based on the predictors derived from these models. These predictive models provide relatively reliable information to prevent PD onset and progression. However, future validation analysis is still needed to clarify these findings and provide more insight into the predictive models over more extended periods of disease progression in more diverse samples.
12012 fundamental mechanisms behind nanotechnology applications in oil and gas: Emerging nano-EOR processes
Authors: Wang Ningyu , Zhao Yuzhou , Prodanović Maša , Balhoff Matthew T. , Huh Chun
Published: August 2022

As the important role of enhanced oil recovery (EOR) in meeting the world’s energy requirement is growing, use of nanoparticles in lieu of, or in combination with, the existing EOR agents to expand EOR’s applicable range is receiving significant attention. Two of the most actively investigated applications are: 1) wettability alteration by addition of nanoparticles into the waterflood injection water, and 2) use of nanoparticle-stabilized Pickering foams and emulsions mainly for EOR process mobility control. As comprehensive reviews are recently available on these topics, two other emerging nanoparticle applications are critically reviewed here: 1) nanoparticle addition for enhanced polymer flooding, and 2) use of magnetic nanoparticles for oil displacement control. Three and five proposed mechanisms of these two applications are critically reviewed, respectively. The most recent progresses are covered, and the challenges and possible future works are discussed.
Association between sleep quality, migraine and migraine burden
Authors: Duan Shaojie , Ren Zhiying , Xia Hui , Wang Ziyao , Zheng Tao , Liu Zunjing
Published: August 2022

Background

The relationship between sleep and migraine is well known to be bidirectional. However, few studies have systematically assessed the association between sleep quality and the risk of developing migraine, and its gender and age differences are unclear. And there is currently limited evidence on the associations between sleep quality and migraine-related burdens.

Objective

The objectives of this study were to: (1) explore the association between sleep quality and the risk of developing migraine, and its gender and age differences; (2) investigate the associations between sleep quality and the total pain burden, severity, disability, headache impact, quality of life, anxiety, and depression of migraine patients.

Methods

This study consecutively enrolled 134 migraine patients and 70 sex- and age-matched healthy control subjects. Sleep quality was assessed through the Pittsburgh Sleep Quality Index (PSQI). Logistic regression and linear regression analyses were used to explore the associations between sleep quality with the risk of developing migraine and the migraine-related burdens.

Results

The prevalence of poor sleep quality in migraine patients was significantly higher than that in subjects without migraine (P < 0.001). After adjusting for various confounding factors, the risk of migraine with poor sleep quality remained 3.981 times that of those with good sleep quality. The subgroup analysis showed that there were significant additive interactions between poor sleep quality and the risk of migraine in gender, age, and education level (P for interaction < 0.05), and the stronger correlations were found in females, populations with ages more than 35 years old, and with lower education levels. In addition, multivariate linear regression analysis showed that poor sleep quality was significantly and independently associated with the total pain burden, severity, headache impact, quality of life, anxiety, and depression in migraine patients (P trend < 0.05).

Conclusion

Poor sleep quality was significantly independently associated with an increased risk of developing migraine and the migraine-related burdens. Strengthening PSQI assessment is valuable for the early prevention and treatment of migraine patients.
The role of cross-sectional imaging of the extracranial and intracranial vasculature in embolic stroke of undetermined source
Authors: Baradaran Hediyeh , Kamel Hooman , Gupta Ajay
Published: August 2022

Despite an extensive workup, nearly one third of ischemic strokes are defined as Embolic Stroke of Undetermined Source (ESUS), indicating that no clear etiologic cause has been identified. Since large vessel atherosclerotic disease is a major cause of ischemic stroke, we focus on imaging of large vessel atherosclerosis to identify further sources of potential emboli which may be contributing to ESUS. For a stroke to be considered ESUS, both the extracranial and intracranial vessels must have <50% stenosis. Given the recent paradigm shift in our understanding of the role of plaque vulnerability in ischemic stroke risk, we evaluate the role of imaging specific high-risk extracranial plaque features in non-stenosing plaque and their potential contributions to ESUS. Further, intracranial vessel-wall MR is another potential tool to identify non-stenosing atherosclerotic plaques which may also contribute to ESUS. In this review, we discuss the role of cross-sectional imaging of the extracranial and intracranial arteries and how imaging may potentially uncover high risk plaque features which may be contributing to ischemic strokes.
A comparative study of amplitude of low-frequence fluctuation of resting-state fMRI between the younger and older treatment-resistant depression in adults
Authors: Sun Jifei , Guo Chunlei , Ma Yue , Du Zhongming , Wang Zhi , Luo Yi , Chen Limei , Gao Deqiang , Li Xiaojiao , Xu Ke , Hong Yang , Yu Xue , Xiao Xue , Fang Jiliang , Liu Yong
Published: August 2022

Background

Treatment-resistant depression (TRD) may have different physiopathological neuromechanism in different age groups. This study used the amplitude of low frequency fluctuations (ALFF) to initially compare abnormalities in local functional brain activity in younger and older patients with TRD.

Materials and methods

A total of 21 older TRD patients, 19 younger TRD, 19 older healthy controls (HCs), and 19 younger HCs underwent resting-state functional MRI scans, and the images were analyzed using the ALFF and further analyzed for correlation between abnormal brain regions and clinical symptoms in TRD patients of different age groups.

Results

Compared with the older TRD, the younger TRD group had increased ALFF in the left middle frontal gyrus and decreased ALFF in the left caudate nucleus. Compared with the matched HC group, ALFF was increased in the right middle temporal gyrus and left pallidum in the older TRD group, whereas no significant differences were found in the younger TRD group. In addition, ALFF values in the left middle frontal gyrus in the younger TRD group and in the right middle temporal gyrus in the older TRD were both positively correlated with the 17-item Hamilton Rating Scale for Depression score.

Conclusion

Different neuropathological mechanisms may exist in TRD patients of different ages, especially in the left middle frontal gyrus and left caudate nucleus. This study is beneficial in providing potential key targets for the clinical management of TRD patients of different ages.