bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later
Authors: Neuman Paul , Larsson Staffan , Lohmander L Stefan , Struglics André 
Published: October 2020

Abstract
Background. To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury.Methods. We studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples.Results. Western blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between -0.67 and -1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values. Conclusion. Higher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury.
Genome mining and UHPLC–QTOF–MS/MS to identify the potential antimicrobial compounds and determine the specificity of biosynthetic gene clusters in Bacillus subtilis NCD-2
Authors: Su Zhenhe , Chen Xiuye , Liu Xiaomeng , Guo Qinggang , Li Shezeng , Lu Xiuyun , Zhang Xiaoyun , Wang PeiPei , Dong Lihong , Zhao Weisong , Ma Ping 
Published: October 2020

Abstract
Background: Bacillus subtilis strain NCD-2 is an excellent biocontrol agent against plant soil-borne diseases and shows broad-spectrum antifungal activities. This study aimed to explore some secondary metabolite biosynthetic gene clusters and related antimicrobial compounds in strain NCD-2. An integrative approach combining genome mining and structural identification technologies using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-MS/MS), was adopted to interpret the chemical origins of metabolites with significant biological activities.Results: Genome mining revealed nine gene clusters encoding secondary metabolites with predicted functions, including fengycin, surfactin, bacillaene, subtilosin, bacillibactin, bacilysin and three unknown products. Fengycin, surfactin, bacillaene and bacillibactin were successfully detected from the fermentation broth of strain NCD-2 by UHPLC-QTOF-MS/MS. The biosynthetic gene clusters of bacillaene, subtilosin, bacillibactin, and bacilysin showed 100% amino acid sequence identities with those in B. velezensis strain FZB42, whereas the identities of the surfactin and fengycin gene clusters were only 83% and 92%, respectively. Further comparison revealed that strain NCD-2 had lost the fenC and fenD genes in the fengycin biosynthetic operon. The biosynthetic enzyme-related gene srfAB for surfactin was divided into two parts. Bioinformatics analysis suggested that FenE in strain NCD-2 had a similar function to FenE and FenC in strain FZB42, and that FenA in strain NCD-2 had a similar function to FenA and FenD in strain FZB42. Five different kinds of fengycins, with 26 homologs, and surfactin, with 4 homologs, were detected from strain NCD-2. To the best of our knowledge, this is the first report of a non-typical gene cluster related to fengycin synthesis.Conclusions: Our study revealed a number of gene clusters encoding antimicrobial compounds in the genome of strain NCD-2, including a fengycin synthetic gene cluster that might be unique by using genome mining and UHPLC–QTOF–MS/MS. The production of fengycin, surfactin, bacillaene and bacillibactin might explain the biological activities of strain NCD-2.
Exosomal miR-29b found in aqueous humour mediates calcium signaling in diabetic patients with cataract
Authors: Gao Chao , Liu Xin , Fan Fan , Yang Jianing , Zhou Xiyue , Mei Hengjun , Lin Xiaolei , Luo Yi 
Published: October 2020

Abstract
Background: Ca2+ was supposed to play an important role in the cataract formation. Exosomal miR-29b from aqueous humour may play an important role in the mechanism of diabetes and cataracts. The purpose of this study was to investigate the role of exosomal miR-29b and Ca2+ in regulating the function of human lens epithelial cells. Methods: Exosomes were isolated from human aqueous humour by ultracentrifugation, and visualized by nanoparticle tracking and transmission electron microscopy. Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs between diabetes and cataracts group (DMC) and age-related cataracts group (ARC). TargetScan was used to predict potential target of certain miRNA. The expression of CACNA1C mRNA was determined by quantitative real-time PCR and CACNA1C protein was determined by Western blotting. Concentration of Ca2+ in human aqueous humour and the culture supernatant of cells was detected by the Calcium Assay Kit. Cell Counting Kit-8 was used to determine cell viability. Results: Exosomes were isolated from human aqueous humour, which had a typical cup-shaped phenotype and a particle size distribution in accordance with micro extracellular vesicles. Exosomal miRNA sequencing revealed that miR-29b was significantly downregulated in diabetes and cataracts group (DMC) compared with age-related cataracts group (ARC). Ca2+ concentration of human aqueous humour in DMC was higher than that in ARC. The culture supernatant of cells transfected with miR-29b inhibitors had a higher concentration of Ca2+ than that transfected with miR-29b mimics. miR-29b reduced the viability of human lens epithelium cells (HLECs) by upregulating CACNA1C expression.Conclusions: Exosomes isolated from human aqueous humour contained abundant miRNAs. A significantly expressed miRNA, miR-29b, could affect the concentration of Ca2+ and regulate HLEC processes by upregulating CACNA1C.
Clinical disease progression and biomarkers in Niemann–Pick disease type C: a prospective cohort study&nbsp;
Authors: Mengel Eugen , Bembi Bruno , Toro Mireia del , Deodato Federica , Gautschi Matthias , Grunewald Stephanie , Grønborg Sabine , Héron Bénédicte , Maier Esther M , Roubertie Agathe , Santra Saikat , Tylki-Szymanska Anna , Day Simon , Symonds Tara , Hudgens Stacie , Patterson Marc C , Guldberg Christina , Ingemann Linda , Petersen Nikolaj HT , Kirkegaard Thomas , Dali Christine í 
Published: October 2020

Abstract
BackgroundNiemann–Pick disease type C (NPC) is a rare, progressive, neurodegenerative disease associated with neurovisceral manifestations resulting from lysosomal dysfunction and aberrant lipid accumulation. A multicentre, prospective observational study (ClinicalTrials.gov ID:NCT02435030) of individuals with genetically confirmed NPC1 or NPC2 receiving routine clinical care was conducted, to prospectively characterize and measure NPC disease progression and to investigate potential NPC-related biomarkers versus healthy individuals. Progression was measured using the abbreviated 5-domain NPC Clinical Severity Scale (NPCCSS), 17-domain NPCCSS and NPC clinical database (NPC-cdb) score. Cholesterol esterification and heat shock protein 70 (HSP70) levels were assessed from peripheral blood mononuclear cells (PBMCs), cholestane-3β,5α-,6β-triol (cholestane-triol) from serum, and unesterified cholesterol from both PBMCs and skin biopsy samples. The inter- and intra-rater reliability of the 5-domain NPCCSS was assessed by 13 expert clinicians’ rating of four participants via video recordings, repeated after ≥3 weeks. Intraclass correlation coefficients (ICCs) were calculated.ResultsOf the 36 individuals with NPC (2–18 years) enrolled, 31 (86.1%) completed the 6–14-month observation period; 30/36 (83.3%) were receiving miglustat as part of routine clinical care. A mean (±SD) increase in 5-domain NPCCSS scores of 1.4 (±2.9) was observed, corresponding to an annualized progression rate of 1.5. On the 17-domain NPCCSS, a mean (±SD) progression of 2.7 (±4.0) was reported. Compared with healthy individuals, the NPC population had significantly lower levels of cholesterol esterification (p<0.0001), HSP70 (p<0.0001) and skin unesterified cholesterol (p=0.0006). Cholestane-triol levels were significantly higher in individuals with NPC versus healthy individuals (p=0.008) and correlated with the 5-domain NPCCSS (Spearman’s correlation coefficient=0.265, p=0.0411). The 5-domain NPCCSS showed high ICC agreement in inter-rater reliability (ICC=0.995) and intra-rater reliability (ICC=0.937). ConclusionsProgression rates observed were consistent with other reports on disease progression in NPC. The 5-domain NPCCSS reliability study supports its use as an abbreviated alternative to the 17-domain NPCCSS that focuses on the most relevant domains of the disease. The data support the use of cholestane-triol as a disease monitoring biomarker and the novel methods of measuring unesterified cholesterol could be applicable to support NPC diagnosis. Levels of HSP70 in individuals with NPC were significantly decreased compared with healthy individuals.
The effect of online multimedia psychoeducational interventions on the resilience and perceived stress of hospitalized patients with COVID-19: a pilot cluster randomized parallel-controlled trial
Authors: Shaygan Maryam , Yazdani Zahra , Valibeigi Adib 
Published: October 2020

Abstract
Background: There is evidence suggesting that quarantine might have undesirable psychological impacts on the patients. Therefore, it is important to seek for ways to increase the resilience and alleviate the psychological pressure of the patients who are quarantined due to infection with COVID-19. The present study was conducted to assess an online multimedia psychoeducational intervention regarding the feasibility, adherence, patient satisfaction and effectiveness on resilience and perceived stress of patients hospitalized with confirmed COVID-19.Method: This was a pilot cluster randomized parallel-controlled trial with hospital ward as the unit of randomization. Participants in this fully online trial were 50 consecutive patients who were hospitalized in 2 hospitals in Shiraz, after being diagnosed with COVID-19. Before the beginning of the intervention, four inpatient wards of the two hospitals were randomly assigned to either experimental or control conditions. All eligible participants in the wards allocated to the intervention condition received online multimedia psychoeducational interventions during 2 weeks, whilst the patients in the wards allocated to the control condition were offered the opportunity to receive telephone-based psychological counseling if needed. Psychoeducational interventions mainly included cognitive–behavioural techniques, stress management techniques, mindfulness-based stress reduction and positive psychotherapy. The patients were assessed regarding resilience and perceived stress at baseline and 2 weeks later. Results: Of 27 patients starting multimedia psychoeducational interventions, 26 (96.29%) completed post-assessments. A high level of adherence (80.76%) and satisfaction (Mean=29.42; SD=4.18) with the online multimedia psychoeducational interventions was found. Compared with the control group, the patients who used online multimedia psychoeducational interventions reported greater resilience (Meanintervention=81.74; Meancontrol=72.86; adjusted t (46)=2.10; p=0.04; CI: 0.39 to 17.38; dppc2=0.83) and fewer perceived stress (Meanintervention=22.15; Meancontrol=29.45; adjusted t (46)=2.66; p=0.01; CI: -12.81 to -1.78; dppc2= - 0.77) after 2 weeks. Discussion: The findings of the present study provided a successful first attempt at implementing feasible online multimedia psychoeducational interventions to promote resilience and mitigate stress among the patients who were hospitalized due to infection with COVID-19. The present results could help mental health professionals to determine which psychological techniques should be emphasized to promote patients' resilience in the context of COVID-19 disease.
Generation and molecular characteristics of a highly attenuated GPV strain through adaptation in GEF cells
Authors: Shao Hongxia , Jiang Yuchen , Yuan Huisha , Ji Lifei , Jin Wenjie , Qian Kun , Ye Jianqiang , Qin Aijian 
Published: October 2020

Abstract
Background: Goose parvoviruses (GPVs) spread globally and cause a huge economic loss to the poultry industry. Although the attenuated GPV vaccines play a key role in preventing the disease caused by GPV, the molecular basis for the attenuation of GPV is barely known. Results: A highly attenuated GPV strain, GPV-CZM-142, was generated through blindly passaging of the highly pathogenic strain, GPV-CZM, in goose embryonic fibroblasts (GEF) for 142 generations. The GEF-adapted GPV strain's virulence was 10,000 times weaker than its wild type counterpart, GPV-CZM, based on the ELD50 (50% Embryo Lethal Dose). By comparing with the wild type strain, genome sequencing analysis identified adapted mutations either in ITR or in NS and VP1 of GPV-CZM-142.Conclusions: The highly attenuated GPV strain, GPV-CZM-142, provides a GPV vaccine candidate, and the identified virulence-related mutations give a novel insight into the molecular determinants of GPV virulence.
Association Between Stroke Occurrence And Changes In Atmospheric Circulation&nbsp;
Authors: Vencloviene Jone , Radisauskas Ricardas , Kranciukaite-Butylkiniene Daina , Tamosiunas Abdonas , Vaiciulis Vidmantas , Rastenyte Daiva 
Published: October 2020

Abstract
Background: The impact of weather on morbidity from stroke was analysed in previous studies. As the risk of stroke was mostly associated with changing weather, the changes in the daily number of strokes may be associated with global changes in atmospheric circulation. The aim of our study was to detect and evaluate the association between daily numbers of ischaemic stroke (IS) and haemorrhagic stroke (HS) and the teleconnection pattern. Methods: The study was conducted in Kaunas city, Lithuania, from 2000 to 2010. The daily numbers of IS, subarachnoid haemorrhages (SAH), and intracerebral haemorrhages (ICH) were obtained from Kaunas Stroke Register. We evaluated the association between these types of stroke and the teleconnection pattern by applying Poisson regression, adjusting for the linear trend, month, and other weather variables. Results: During the study period, we analysed 4,038 cases (2,226 men and 1,812 women) of stroke. Of these, 3,245 (80.4%) cases were IS, 533 (13.2%) cases were ICH, and 260 (6.4%) cases were SAH. A change in mean daily atmospheric pressure of >3.9 hPa was associated with the risk of SAH (RR=1.49, 95% CI 1.14-1.96), and a stronger El Niño event had a protective effect against SAH (RR=0.34, 95% CI 0.16-0.69). The risk of HS was positively associated with East Atlantic/West Russia indices (RR=1.13, 95% CI 1.04-1.23). The risk of IS was negatively associated with Arctic Oscillation indices (RR=0.97, 95% CI 0.94-0.99). During November-March, a positive North Atlantic Oscillation (NAO) was associated with HS (RR=1.29, 95% CI 1.03-1.62), and a negative association between the NAO index and IS (RR=0.92, 95% CI 0.85-0.99) was found. Conclusions: The results of our study provided new evidence that the North Atlantic Oscillation, Arctic Oscillation, East Atlantic/West Russia, and El Niño-Southern Oscillation pattern may affect the risk of stroke. The impact of these teleconnection indices is not identical for different types of stroke. Emergency services should be aware of the fact that specific weather conditions are more likely to prompt calls for more severe strokes.
Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses
Authors: Álvarez-Izquierdo Maria , Pérez-Crespo Miguel , Esteban J. Guillermo , Muñoz-Antoli Carla , Toledo Rafael 
Published: October 2020

Abstract
Background: Interleukin-25 (IL-25) is recognized as the most relevant initiator of protective Th2 responses in intestinal helminth infections. It is well known that IL-25 induces resistance against several species of intestinal helminths, including the trematode Echinostoma caproni. Echinostoma caproni has been extensively used as an experimental model to study the factors determining the resistance to intestinal infections. Herein, we assessed the role of IL-25 in the generation of resistance in mice to E. caproni infections. Methods: To this purpose, we analyze the fatros that determine the production of IL-25 in mice experimentally infected with E. caproni and its consequences in the polarization of the immune response and the resistance to infection.Results: We have determined that the role of IL-25 in the polarization of the immune response differs between the primary and secondary response. IL-25 is required for the development of a Th2 phenotype in primary E. caproni infections but could also promote the differentiation to Th2 memory cell subsets that enhances type 2 responses in memory responses. However, development of Th2 responses does not induce resistance to infection. Th2 phenotype does not elicit resistance and IL-25 is responsible for the resistance regardless of the type 2 cytokine activity and STAT6 activation. Alternative activation of macrophages induced by IL-25 could be implicated in the resistance to infection. Conclusions: In contrast to primary infection, secondary infection elicits a type 2 response, even in the absence of IL-25 expression. Despite the development of a type 2 response, mice are susceptible to secondary infection in relation to the lack of IL-25. Resistance to infection is due to IL-25, which acts autonomously from Th2 response in the parasite clearance.
Seismic Hazard Microzonation of Bengkulu City, Indonesia
Authors: Mase Lindung Zalbuin , Sugianto Nanang , Refrizon Refrizon 
Published: October 2020

Abstract
It has been known that Bengkulu City (Indonesia) is vulnerable to undergo seismic damage. This study is initiated by measuring horizontal to vertical spectral ratio (H/V) to sites in Bengkulu City using microtremor. The inversion analysis is performed to generate shear wave velocity profile. Hundreds of sites are investigated in this study. The results show that observed H/V is consistent with the theoretical H/V. National Earthquake Hazard Reduction Program code is adopted to classify the site class. The results also exhibit that Bengkulu City is dominated by Site Classes C and D. In general, this study could lead local government to reconsider seismic hazard mitigation for spatial plan.
Geographically extensive larval surveys reveal an unexpected scarcity of primary vector mosquitoes in a region of persistent malaria transmission in western Zambia
Authors: Cross Dónall Eoin , Thomas Chris James , McKeown Niall , Siaziyu Vincent , Healey Amy , Willis Tom , Singini Douglas , Liywali Francis , Silumesi Andrew , Sakala Jacob , Smith Mark , Macklin Mark , Hardy Andy J , Shaw Paul W 
Published: October 2020

Abstract
BackgroundThe Barotse floodplains of the upper Zambezi River and its tributaries are a highly dynamic environment, with seasonal flooding and transhumance presenting a shifting mosaic of potential larval habitat and human and livestock bloodmeals for malaria vector mosquitoes. However, limited entomological surveillance has been undertaken to characterise the vector community in these floodplains and their environs. Such information is necessary as, despite substantial deployment of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) against Anopheles vectors, malaria transmission persists across Barotseland in Zambia’s Western Province. MethodsGeographically extensive larval surveys were undertaken in two health districts along 102 km of transects, at fine spatial resolution, during a dry season and following the peak of the successive wet season. Larvae were sampled within typical Anopheles flight range of human settlements and identified through genetic sequencing of cytochrome c oxidase I and internal transcribed spacer 2 regions of mitochondrial and nuclear DNA. This facilitated detailed comparison of taxon-specific abundance patterns between ecological zones differentiated by hydrological controls.ResultsAn unexpected paucity of primary vectors was revealed, with An. gambiae s.l. and An. funestus representing <2% of 995 sequenced anophelines. Potential secondary vectors predominated in the vector community, primarily An. coustani group species and An squamosus. Whilst the distribution of An. gambiae s.l. in the study area was highly clustered, secondary vector species were ubiquitous across the landscape in both dry and wet seasons, with some taxon-specific relationships between abundance and ecological zones by season.ConclusionsThe diversity of candidate vector species and their high relative abundance observed across diverse hydro-ecosystems indicates a highly adaptable transmission system, resilient to environmental variation and, potentially, interventions that target only part of the vector community. Larval survey results imply that residual transmission of malaria in Barotseland is being mediated predominantly by secondary vector species, whose known tendencies for crepuscular and outdoor biting renders them largely insensitive to prevalent vector control methods.