bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles and the regulation of tumor immunity: Current progress and future directions
Authors: Wang Lingyun , Sun Zhichao , Wang Hongmei 
Published: February 2021

AbstractAs nano‐level information carriers, extracellular vesicles (EVs) contain proteins, DNA or RNA, which maintain the transmembrane transport of biomolecules and the homeostasis of normal cells. EVs can be released by most cell types and absorbed by specific recipient cells, subsequently affecting phenotypic expression. EVs are believed to play an important role in cellular communication, especially in immune cells. During tumor development, EVs of different origins have different effects on the survival and growth of tumor cells. Some tumor cell‐derived EVs can mediate tumor immunosuppressive responses by inhibiting the differentiation and maturation of dendritic cells (DCs) and by negatively regulating the expression of T cell receptors, causing tumor cells to escape immune surveillance and proliferate. EVs have therefore become a key component of tumor cell proliferation and metastasis. In contrast, EVs derived from DCs mediate antitumor immune activation by inducing the killing and inhibitory effects of the immune system. This makes it an antigen component of the antitumor response. Integrating the interaction and connection of EVs to immunosuppression and immune response is significant for the application of EVs in clinical practice. Here, we reviewed the research progress on the role of EVs in the immune regulation of tumors.
Molecular and functional profiling of apical versus basolateral small extracellular vesicles derived from primary human proximal tubular epithelial cells under inflammatory conditions
Authors: Wang Xiangju , Wilkinson Ray , Kildey Katrina , Ungerer Jacobus P. J. , Hill Michelle M. , Shah Alok K. , Mohamed Ahmed , Dutt Mriga , Molendijk Jeffrey , Healy Helen , Kassianos Andrew J. 
Published: February 2021

AbstractProximal tubular epithelial cells (PTEC) are central players in inflammatory kidney diseases. However, the complex signalling mechanism/s via which polarized PTEC mediate disease progression are poorly understood. Small extracellular vesicles (sEV), including exosomes, are recognized as fundamental components of cellular communication and signalling courtesy of their molecular cargo (lipids, microRNA, proteins). In this study, we examined the molecular content and function of sEV secreted from the apical versus basolateral surfaces of polarized human primary PTEC under inflammatory diseased conditions. PTEC were cultured under normal and inflammatory conditions on Transwell inserts to enable separate collection and isolation of apical/basolateral sEV. Significantly increased numbers of apical and basolateral sEV were secreted under inflammatory conditions compared with equivalent normal conditions. Multi‐omics analysis revealed distinct molecular profiles (lipids, microRNA, proteins) between inflammatory and normal conditions for both apical and basolateral sEV. Biological pathway analyses of significantly differentially expressed molecules associated apical inflammatory sEV with processes of cell survival and immunological disease, while basolateral inflammatory sEV were linked to pathways of immune cell trafficking and cell‐to‐cell signalling. In line with this mechanistic concept, functional assays demonstrated significantly increased production of chemokines (monocyte chemoattractant protein‐1, interleukin‐8) and immuno‐regulatory cytokine interleukin‐10 by peripheral blood mononuclear cells activated with basolateral sEV derived from inflammatory PTEC. We propose that the distinct molecular composition of sEV released from the apical versus basolateral membranes of human inflammatory PTEC may reflect specialized functional roles, with basolateral‐derived sEV pivotal in modulating tubulointerstitial inflammatory responses observed in many immune‐mediated kidney diseases. These findings provide a rationale to further evaluate these sEV‐mediated inflammatory pathways as targets for biomarker and therapeutic development.
Proteome‐minimized outer membrane vesicles from Escherichia coli as a generalized vaccine platform
Authors: Zanella Ilaria , König Enrico , Tomasi Michele , Gagliardi Assunta , Frattini Luca , Fantappiè Laura , Irene Carmela , Zerbini Francesca , Caproni Elena , Isaac Samine J. , Grigolato Martina , Corbellari Riccardo , Valensin Silvia , Ferlenghi Ilaria , Giusti Fabiola , Bini Luca , Ashhab Yaqoub , Grandi Alberto , Grandi Guido 
Published: February 2021

AbstractBecause of their potent adjuvanticity, ease of manipulation and simplicity of production Gram‐negative Outer Membrane Vesicles OMVs have the potential to become a highly effective vaccine platform. However, some optimization is required, including the reduction of the number of endogenous proteins, the increase of the loading capacity with respect to heterologous antigens, the enhancement of productivity in terms of number of vesicles per culture volume. In this work we describe the use of Synthetic Biology to create Escherichia coli BL21(DE3)Δ60, a strain releasing OMVs (OMVsΔ60) deprived of 59 endogenous proteins. The strain produces large quantities of vesicles (> 40 mg/L under laboratory conditions), which can accommodate recombinant proteins to a level ranging from 5% to 30% of total OMV proteins. Moreover, also thanks to the absence of immune responses toward the inactivated endogenous proteins, OMVsΔ60 decorated with heterologous antigens/epitopes elicit elevated antigens/epitopes‐specific antibody titers and high frequencies of epitope‐specific IFN‐γ‐producing CD8+ T cells. Altogether, we believe that E. coli BL21(DE3)Δ60 have the potential to become a workhorse factory for novel OMV‐based vaccines.
Small extracellular vesicles deliver osteolytic effectors and mediate cancer‐induced osteolysis in bone metastatic niche
Authors: Ma Qinyu , Liang Mengmeng , Wu Yutong , Dou Ce , Xu Jianzhong , Dong Shiwu , Luo Fei 
Published: February 2021

AbstractExtracellular vesicles (EVs) play critical roles in regulating bone metastatic microenvironment through mediating intercellular crosstalks. However, little is known about the contribution of EVs derived from cancer cells to the vicious cycle of bone metastasis. Here, we report a direct regulatory mode between tumour cells and osteoclasts in metastatic niche of prostate cancer via vesicular miRNAs transfer. Combined analysis of miRNAs profiles both in tumour‐derived small EVs (sEVs) and osteoclasts identified miR‐152‐3p as a potential osteolytic molecule. sEVs were enriched in miR‐152‐3p, which targets osteoclastogenic regulator MAFB. Blocking miR‐152‐3p in sEVs upregulated the expression of MAFB and impaired osteoclastogenesis in vitro. In vivo experiments of xenograft mouse model found that blocking of miR‐152‐3p in sEVs significantly slowed down the loss of trabecular architecture, while systemic inhibition of miR‐152‐3p using antagomir‐152‐3p reduced the osteolytic lesions of cortical bone while preserving basic trabecular architecture. Our findings suggest that miR‐152‐3p carried by prostate cancer‐derived sEVs deliver osteolytic signals from tumour cells to osteoclasts, facilitating osteolytic progression in bone metastasis.
Low serum albumin at admission is a predictor of early colectomy in patients with moderate to severe ulcerative colitis
Authors: Tanaka Makoto , Takagi Tomohisa , Naito Yuji , Uchiyama Kazuhiko , Hotta Yuma , Toyokawa Yuki , Kashiwagi Saori , Kamada Kazuhiro , Ishikawa Takeshi , Yasuda Hiroaki , Konishi Hideyuki , Itoh Yoshito 
Published: February 2021

AbstractBackground and AimSeveral studies have identified postinduction therapy predictors of long‐term outcomes of ulcerative colitis (UC) in patients who experienced the first attack of the disease or relapsed after therapy. We aimed to identify the preinduction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC.MethodsNinety‐five patients with moderate to severe UC who underwent induction therapy at the Kyoto Prefectural University of Medicine hospital between August 2008 and March 2020 were retrospectively included and categorized into two groups: the colectomy group (n = 27) and the noncolectomy group (n = 68). The clinical parameters (age, gender, disease extent, and disease activity on admission), induction therapies administered [including 5‐aminosalicylic acid, steroids, immunomodulators, calcineurin inhibitor, and anti‐Tumor Necrosis Factor (TNF)‐α antibodies], and laboratory data (hemoglobin, albumin, C‐reactive protein, and cytomegalovirus reactivation on admission) were evaluated and compared between the two groups. Multivariate logistic regression analyses were performed to identify significant predictors of early colectomy, and P < 0.05 was considered significant.ResultsAll clinical parameters were not significant predictors of colectomy. Among laboratory parameters, the serum albumin level on admission was a significant independent predictor of colectomy (odds ratio: 6.097, 95% confidence interval: 1.8310–20.3047). Receiver operating characteristic curves were plotted for the serum albumin levels of the 95 patients at admission. The cut‐off value of serum albumin was 2.45 g/dL.ConclusionsWhen the serum albumin level of UC patients at admission is below 2.45 g/dL, we should consider presenting the option of surgical treatment to patients.
Early laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage is feasible in low‐risk patients with acute cholecystitis
Authors: Han Ji Won , Choi Young Hoon , Lee In Seok , Chun Ho Jong , Choi Ho Joong , Hong Tae Ho , You Young Kyoung 
Published: February 2021

AbstractBackgroundLaparoscopic cholecystectomy (Lap‐C) is generally performed following percutaneous transhepatic gallbladder drainage (PTGBD) in patients with acute cholecystitis (AC). However, the timing of Lap‐C and risk factors for postoperative complications following PTGBD are still unclear.MethodsWe analyzed 331 patients with AC who underwent Lap‐C following PTGBD. Univariate and multivariate logistic regression analyses were used for identifying risk factors associated with poor surgical outcomes, including postoperative complications in the total group and the early Lap‐C subgroup (n = 152). Based on the Tokyo guideline 2013 (TG 13), all patients were divided into two groups according to the period (2009–2013, pre‐TG 13 group; 2014–2020, post‐TG 13 group), and each analysis was performed in those subgroups.ResultsWe found that early Lap‐C (≤ 42 days after PTGBD) was associated with postoperative complications (OR 2.04, P = .022). Importantly, subgroup analyses revealed that Charlson comorbidity index (CCI) (OR 6.15, P < .001) and cholecystitis severity grade (OR 2.93, P = .014) were independent risk factors of postoperative complications in the early Lap‐C group. Among the early Lap‐C group, high CCI was also an independent risk factor for surgical complications in both pre‐TG 13 (OR 14.87, P = .003) and post‐TG 13 (OR 3.23, P = .046) groups. Interestingly, we found that the incidence of postoperative complications in the low‐risk early Lap‐C group was not different from the delayed group, even in the cases of very early surgery (≤ 1 week following PTGBD).ConclusionsThese findings suggest that early Lap‐C is feasible following PTGBD, especially in low‐risk patients, although future prospective large‐scale studies are needed.
Trends and antecedents of inequalities in maternal healthcare coverage in four African countries
Authors: Asuman Derek , Fenny Ama Pokuaa , Anyamesem Odame Doreen Nyarko 
Published: February 2021

AbstractUsing data between 2003 and 2016, this paper assesses the degree and evolution of socio‐economic inequalities in maternal health outcomes in four African countries. The study measures the trends of socio‐economic inequalities in maternal healthcare and assesses the sources of socio‐economic inequalities in maternal health through a decomposition approach. We find cross‐country differences in the evolution of maternal healthcare inequalities. Rwanda and Uganda witnessed a decline in pro‐rich inequalities, whereas changes in Ethiopia and Kenya have been mixed. Further, the study finds significant contributions of personal characteristics of the woman to inequalities in maternal healthcare access.
Grading Soft Tissue Involvement in Nasopharyngeal Carcinoma Using Network and Survival Analyses: A Two‐Center Retrospective Study
Authors: Dong Annan , Huang Wenjie , Ma Huali , Cui Chunyan , Zhou Jian , Ruan Guangying , Liang Shaobo , Liu Lizhi , Li Haojiang 
Published: February 2021

AbstractBackgroundSoft tissue involvement (STI) indicates poor prognosis in nasopharyngeal carcinoma (NPC). However, only a few studies have systematically assessed this extension using network analysis.PurposeTo investigate the prognostic value of STI and to propose an improved STI grading system for NPC therapy.Study TypeRetrospective study.PopulationA total of 1225 consecutive patients with pathologically confirmed NPC treated with intensive‐modulated radiotherapy from January 2010 to March 2014 were enrolled from two centers.Field Strength/SequenceT1‐ and T2‐weighted imaging and enhanced T1‐weighted imaging with fast spin echo sequence at 1.5 or 3.0 T.AssessmentThe levator veli palatini and tensor veli palatini involvement were graded “mild,” prevertebral muscle involvement, “moderate,” medial pterygoid, lateral pterygoid, and the infratemporal fossa involvement, “severe” STI. The above STI sites were evaluated separately by three radiologists using MRI images and graded using network analysis. Overall survival (OS) and progression‐free survival (PFS) were assessed.Statistical TestsKaplan–Meier method, Cox's proportional hazards model, and concordance index (C‐index) were used.ResultsFive‐year OS and PFS rates between mild and moderate groups (90.5% vs. 81.7%, P < 0.05 and 82.9% vs. 72.5%, P < 0.05, respectively) and between moderate and severe groups (81.7% vs. 70.4%, P < 0.05 and 72.5% vs. 61.2%, P < 0.05, respectively) revealed significant differences. The C‐index of the nomogram with STI grading was higher compared with current T‐classification (OS 0.641 vs. 0.604, P < 0.05 and PFS 0.605 vs. 0.581, P < 0.05, respectively). Significant OS differences were observed between patients with severe STI who underwent induction chemotherapy (IC) and those who did not (84.5% vs. 70.7%, P < 0.05).Data ConclusionSTI grading was an independent prognostic factor for OS and PFS in NPC patients and it may be help to improve the accuracy in predicting survival outcomes. Patients with severe STI might benefit from IC to improve OS.Level of Evidence4Technical EfficacyStage 2
Magnetic Resonance Imaging‐Based Radiomics Nomogram for Prediction of the Histopathological Grade of Soft Tissue Sarcomas: A Two‐Center Study
Authors: Yan Ruixin , Hao Dapeng , Li Jie , Liu Jihua , Hou Feng , Chen Haisong , Duan Lisha , Huang Chencui , Wang Hexiang , Yu Tengbo 
Published: February 2021

BackgroundPreoperative prediction of soft tissue sarcoma (STS) grade is important for treatment decisions. Therefore, formulation an STS grade model is strongly needed.PurposeTo develop and test an magnetic resonance imaging (MRI)‐based radiomics nomogram for predicting the grade of STS (low‐grade vs. high grade).Study TypeRetrospectivePopulationOne hundred and eighty patients with STS confirmed by pathologic results at two independent institutions were enrolled (training set, N = 109; external validation set, N = 71).Field Strength/SequenceUnenhanced T1‐weighted (T1WI) and fat‐suppressed T2‐weighted images (FS‐T2WI) were acquired at 1.5 T and 3.0 T.AssessmentClinical‐MRI characteristics included age, gender, tumor‐node‐metastasis (TNM) stage, American Joint Committee on Cancer (AJCC) stage, progression‐free survival (PFS), and MRI morphological features (ie, margin). Radiomics feature extraction were performed on T1WI and FS‐T2WI images by minimum redundancy maximum relevance (MRMR) method and least absolute shrinkage and selection operator (LASSO) algorithm. The selected features constructed three radiomics signatures models (RS‐T1， RS‐FST2, and RS‐Combined). Univariate and multivariate logistic regression analysis were applied for screening significant risk factors. Radiomics nomogram was constructed by incorporating the radiomics signature and risk factors.Statistical TestsClinical‐MRI characteristics were performed by a univariate analysis. Model performances (discrimination, calibration, and clinical usefulness) were validated in the external validation set. The RS‐T1 model, RS‐FST2 model, and RS‐Combined model had an area under curves (AUCs) of 0.645, 0.641, and 0.829, respectively, in the external validation set. The radiomics nomogram, incorporating significant risk factors and the RS‐Combined model had AUCs of 0.916 (95%CI, 0.866–0.966, training set) and 0.879 (95%CI, 0.791–0.967, external validation set), and demonstrated good calibration and good clinical utility.Data ConclusionThe proposed noninvasive MRI‐based radiomics models showed good performance in differentiating low‐grade from high‐grade STSs.Level of Evidence3Technical Efficacy Stage2
Stopwatch training improves cognitive functions in patients with Parkinson's disease
Authors: Honma Motoyasu , Murakami Hidetomo , Yabe Yoshiko , Kuroda Takeshi , Futamura Akinori , Sugimoto Azusa , Terao Yasuo , Masaoka Yuri , Izumizaki Masahiko , Kawamura Mitsuru , Ono Kenjiro 
Published: February 2021

AbstractParkinson's disease (PD) impairs various cognitive functions, including time perception. Dysfunctional time perception in PD is poorly understood, and no study has investigated the rehabilitation of time perception in patients with PD. We aimed to induce the recovery of time perception in PD patients and investigated the potential relationship between recovery and cognitive functions/domains other than time perception. Sixty patients with PD (27 females) and 20 healthy controls (10 females) were recruited. The participants underwent a feedback training protocol for 4 weeks to improve the accuracy of subjective spatial distance or time duration using a ruler or stopwatch, respectively. They participated in three tests at weekly intervals, each comprising 10 types of cognitive tasks and assessments. After duration feedback training for 1 month, performance on the Go/No‐go task, Stroop task, and impulsivity assessment improved in patients with PD, while no effect was observed after distance feedback training. Additionally, the effect of training on duration production correlated with extended reaction time and improved accuracy in the Go/No‐go and Stroop tasks. These findings suggest that time perception is functionally linked to inhibitory systems. If the feedback training protocol can modulate and maintain time perception, it may improve various cognitive/psychiatric functions in patients with PD. It may also be useful in the treatment of diseases other than PD that cause dysfunctions in temporal processing.
Spectroscopic and transport properties of Ba‐ and Ti‐doped BaLaInO4
Authors: Tarasova N. , Galisheva A. , Animitsa I. 
Published: February 2021

AbstractIn this work, the local structure of the acceptor Ba1+хLa1–хInO4–0.5х and donor BaLaIn1–хTiхO4+0.5х doped solid solutions based on BaLaInO4 was investigated. The appearance of new types of the defects (oxygen vacancy and oxygen interstitial) in the crystal lattice was confirmed by the spectroscopic investigations. It was shown that for both solid solutions the same tendency of the increase in the symmetry of the structure and the expansion of interlayer space with increasing dopant concentration is observed. The changes in the transport properties (ionic conductivity) have the same tendency for both solid solutions. The increase in the oxygen‐ionic and protonic conductivity in the area of “low” dopant concentrations (x < 0.05) is due to the increase in the mobility of ions caused by the influence of geometric factor. The decrease in the ionic conductivity values in the area of “high” dopant concentrations (x > 0.05) is caused by the appearance of interaction between defects (concentration factor). The most conductive ionic (oxygen‐ionic and protonic) material with Ruddlesden–Popper (RP) structure based on BaLaInO4 is Ba1.1La0.9InO3.95 composition.
Novel postharvest processing strategies for value‐added applications of marine algae
Authors: Zhu Xianglu , Healy Laura , Zhang Zhihang , Maguire Julie , Sun Da‐Wen , Tiwari Brijesh K 
Published: February 2021

AbstractMarine algae are regarded as a promising nutrients resource in future as they can be sustainably cultured without land and high investment. These macroalgae are now widely processed into food and beverages, fertilizers and animal feed. Furthermore, bioactive compounds such as polysaccharides and polyphenols in seaweeds have proven to have antibacterial, antiviral and antifungal properties that can be utilized in cosmeceuticals, nutraceuticals and pharmaceuticals. As a key procedure in seaweed production, the postharvest process not only requires more laboured and energy but also affect the quality of the final product significantly. This article reviewed all current postharvest processes and technologies of seaweed and addressed potential postharvest strategies for seaweed production. © 2021 Society of Chemical Industry
Determination of principal ergot alkaloids in swine feeding
Authors: Arroyo‐Manzanares Natalia , Rodríguez‐Estévez Vicente , García‐Campaña Ana M , Castellón‐Rendón Elena , Gámiz‐Gracia Laura 
Published: February 2021

AbstractBACKGROUNDErgot alkaloids are secondary metabolites produced by fungi in the genus Claviceps. They contaminate a large variety of cereals, such as rye, triticale, wheat and barley. The ingestion of contaminated cereals might cause adverse health effects in humans and animals. In fact, pigs, cattle, sheep, and poultry are involved in sporadic outbreaks and, although there are several studies about occurrence of ergot alkaloids in grain cereals, there are scarce studies focused on compound feed.RESULTSTwelve ergot alkaloids have been quantified in 228 feed samples intended for swine. The analytes were extracted using QuEChERS with Z‐Sep+ as sorbent in the clean‐up step, which reduced the matrix effect, allowing limits of quantification between 2.1 and 21.7 μg kg–1. The analytes were subsequently quantified by ultra‐high‐performance liquid chromatography with tandem mass spectrometry (UHPLC–MS/MS). A total of 29 samples (12.7%) revealed contamination by at least one ergot alkaloid, and among contaminated samples, 65% were contaminated by more than one. Only 6 of 12 target ergot alkaloids showed concentrations above the limit of quantification. The concentrations for individual ergot alkaloids ranged between 5.9 μg kg–1 for ergosinine to 145.3 μg kg–1 for ergometrine (the predominant ergot alkaloid), while the total ergot alkaloid content ranged from 5.9 to 158.7 μg kg–1.CONCLUSIONSThe occurrence of ergot alkaloids in feed samples in Spain seems to be lower than in other regions of Europe. All the samples fulfilled current recommendations of the feed industry about practical limits for ergot alkaloids in pig feeds. This suggests that the feeds are safe for pig consumption, regarding the presence of ergot alkaloids. © 2021 Society of Chemical Industry.