bluuebunny/crossref_metadata_2025_split huggingface dataset:
Destruction of Staphylococcus aureus biofilms by combining an antibiotic with subtilisin A or calcium gluconate
Authors: Liu JingJing , Madec Jean-Yves , Bousquet-Mélou Alain , Haenni Marisa , Ferran Aude A. 
Published: March 2021

AbstractIn S. aureus biofilms, bacteria are embedded in a matrix of extracellular polymeric substances (EPS) and are highly tolerant to antimicrobial drugs. We thus sought to identify non-antibiotic substances with broad-spectrum activity able to destroy the EPS matrix and enhance the effect of antibiotics on embedded biofilm bacteria. Among eight substances tested, subtilisin A (0.01 U/mL) and calcium gluconate (CaG, Ca2+ 1.25 mmol/L) significantly reduced the biomass of biofilms formed by at least 21/24 S. aureus isolates. Confocal laser scanning microscopy confirmed that they both eliminated nearly all the proteins and PNAG from the matrix. By contrast, antibiotics alone had nearly no effect on biofilm biomass and the selected one (oxytetracycline-OTC) could only slightly reduce biofilm bacteria. The combination of OTC with CaG or subtilisin A led to an additive reduction (average of 2 log10 CFU/mL) of embedded biofilm bacteria on the isolates susceptible to OTC (MBC < 10 μg/mL, 11/24). Moreover, these two combinations led to a reduction of the embedded biofilm bacteria higher than 3 log10 CFU/mL for 20–25% of the isolates. Further studies are now required to better understand the factors that cause the biofilm produced by specific isolates (20–25%) to be susceptible to the combinations.
Anti-mucin 1 chimeric antigen receptor T cells for adoptive T cell therapy of cholangiocarcinoma
Authors: Supimon Kamonlapat , Sangsuwannukul Thanich , Sujjitjoon Jatuporn , Phanthaphol Nattaporn , Chieochansin Thaweesak , Poungvarin Naravat , Wongkham Sopit , Junking Mutita , Yenchitsomanus Pa-thai 
Published: March 2021

AbstractCurrent treatments for cholangiocarcinoma (CCA) are largely unsuccessful due to late diagnosis at advanced stage, leading to high mortality rate. Consequently, improved therapeutic approaches are urgently needed. Chimeric antigen receptor (CAR) T cell therapy is a newly potential therapy that can recognize specific surface antigen without major histocompatibility complex (MHC) restriction. Mucin 1 (MUC1) is an attractive candidate antigen as it is highly expressed and associated with poor prognosis and survival in CCA. We, therefore, set forth to create the fourth-generation CAR (CAR4) construct containing anti-MUC1-single-chain variable fragment (scFv) and three co-stimulatory domains (CD28, CD137, and CD27) linked to CD3ζ and evaluate anti-MUC1-CAR4 T cells in CCA models. Compared to untransduced T cells, anti-MUC1-CAR4 T cells produced increased levels of TNF-α, IFN-γ and granzyme B when exposed to MUC1-expressing KKU-100 and KKU-213A CCA cells (all p < 0.05). Anti-MUC1-CAR4 T cells demonstrated specific killing activity against KKU-100 (45.88 ± 7.45%, p < 0.05) and KKU-213A cells (66.03 ± 3.14%, p < 0.001) at an effector to target ratio of 5:1, but demonstrated negligible cytolytic activity against immortal cholangiocytes. Furthermore, the anti-MUC1-CAR4 T cells could effectively disrupt KKU-213A spheroids. These activities of anti-MUC1-CAR4 T cells supports the development of this approach as an adoptive T cell therapeutic strategy for CCA.
A global association between Covid-19 cases and airborne particulate matter at regional level
Authors: Solimini Angelo , Filipponi F. , Fegatelli D. Alunni , Caputo B. , De Marco C. M. , Spagnoli A. , Vestri A. R. 
Published: March 2021

AbstractEvidences of an association between air pollution and Covid-19 infections are mixed and inconclusive. We conducted an ecological analysis at regional scale of long-term exposure to air-borne particle matter and spread of Covid-19 cases during the first wave of epidemics. Global air pollution and climate data were calculated from satellite earth observation data assimilated into numerical models at 10 km resolution. Main outcome was defined as the cumulative number of cases of Covid-19 in the 14 days following the date when > 10 cumulative cases were reported. Negative binomial mixed effect models were applied to estimate the associations between the outcome and long-term exposure to air pollution at the regional level (PM10, PM2.5), after adjusting for relevant regional and country level covariates and spatial correlation. In total we collected 237,749 Covid-19 cases from 730 regions, 63 countries and 5 continents at May 30, 2020. A 10 μg/m3increase of pollution level was associated with 8.1% (95% CI 5.4%, 10.5%) and 11.5% (95% CI 7.8%, 14.9%) increases in the number of cases in a 14 days window, for PM2.5and PM10respectively. We found an association between Covid-19 cases and air pollution suggestive of a possible causal link among particulate matter levels and incidence of COVID-19.
Long-term treated HIV infection is associated with platelet mitochondrial dysfunction
Authors: van der Heijden Wouter A. , van de Wijer Lisa , Jaeger Martin , Grintjes Karin , Netea Mihai G. , Urbanus Rolf T. , van Crevel Reinout , van den Heuvel Lambertus P. , Brink Maaike , Rodenburg Richard J. , de Groot Philip G. , van der Ven Andre J. , de Mast Quirijn 
Published: March 2021

AbstractHIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNApl) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function. In a cohort of 208 treated PLHIV and 56 uninfected controls, mtDNApl was quantified, as well as platelet activation, platelet agonist-induced reactivity and inflammation by circulating factors and flow cytometry. In a subgroup of participants, the metabolic activity of platelets was further studied by mitochondrial function tests and the Seahorse Flux Analyzer. PLHIV had significantly lower mtDNApl compared to controls (8.5 copies/platelet (IQR: 7.0–10.7) vs. 12.2 copies/platelet (IQR: 9.5–16.6); p < 0.001), also after correction for age, sex and BMI. Prior zidovudine-use (n = 46) was associated with a trend for lower mtDNApl. PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNApl correlated positively with both platelet parameters and correlated negatively with inflammatory marker sCD163. Mitochondrial function tests in a subgroup of participants confirmed the presence of platelet mitochondrial respiration defects. Platelet mitochondrial function is disturbed in PLHIV, which may contribute to platelet dysfunction and subsequent complications. Interventions targeting the preservation of normal platelet mitochondrial function may ultimately prove beneficial for PLHIV.
Low CETP activity and unique composition of large VLDL and small HDL in women giving birth to small-for-gestational age infants
Authors: Roland Marie Cecilie Paasche , Godang Kristin , Aukrust Pål , Henriksen Tore , Lekva Tove 
Published: March 2021

AbstractCholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol (C) and HDL-C is essential for fetal development. We hypothesized that women giving birth to large-for-gestational-age (LGA) and small-for-gestational age (SGA) infants differed in longitudinal changes in lipoproteins, CETP activity and HDL-C and that placentas from women with higher or lower circulating HDL-C displayed differential expression of mRNAs involved in cholesterol/nutrient transport, insulin signaling, inflammation/ extracellular matrix (ECM) remodeling. Circulating lipids and CETP activity was measured during pregnancy, NMR lipidomics in late pregnancy, and associations with LGA and SGA infants investigated. RNA sequencing was performed in 28 placentas according to higher and lower maternal HDL-C levels. Lipidomics revealed high triglycerides in large VLDL and lipids/cholesterol/cholesteryl esters in small HDL in women giving birth to SGA infants. Placentas from women with higher HDL-C had decreased levels ofCETPexpression which was associated with mRNAs involved in cholesterol/nutrient transport, insulin signaling and inflammation/ECM remodeling. Both placental and circulating CETP levels were associated with growth of the fetus. Low circulating CETP activity at 36–38 weeks was associated with giving birth to SGA infants. Our findings suggest a link between increased maternal HDL-C levels, low CETP levels both in circulation and placenta, and SGA infants.
Influential factors and spatial–temporal distribution of tuberculosis in mainland China
Authors: Bie Siyu , Hu Xijian , Zhang Huiguo , Wang Kai , Dou Zhihui 
Published: March 2021

AbstractTuberculosis (TB) is an infectious disease that threatens human safety. Mainland China is an area with a high incidence of tuberculosis, and the task of tuberculosis prevention and treatment is arduous. This paper aims to study the impact of seven influencing factors and spatial–temporal distribution of the relative risk (RR) of tuberculosis in mainland China using the spatial–temporal distribution model and INLA algorithm. The relative risks and confidence intervals (CI) corresponding to average relative humidity, monthly average precipitation, monthly average sunshine duration and monthly per capita GDP were 1.018 (95% CI 1.001–1.034), 1.014 (95% CI 1.006–1.023), 1.026 (95% CI 1.014–1.039) and 1.025 (95% CI 1.011–1.040). The relative risk for average temperature and pressure were 0.956 (95% CI 0.942–0.969) and 0.767 (95% CI 0.664–0.875). Spatially, the two provinces with the highest relative risks are Xinjiang and Guizhou, and the remaining provinces with higher relative risks were mostly concentrated in the Northwest and South China regions. Temporally, the relative risk decreased year by year from 2013 to 2015. It was higher from February to May each year and was most significant in March. It decreased from June to December. Average relative humidity, monthly average precipitation, monthly average sunshine duration and monthly per capita GDP had positive effects on the relative risk of tuberculosis. The average temperature and pressure had negative effects. The average wind speed had no significant effect. Mainland China should adapt measures to local conditions and develop tuberculosis prevention and control strategies based on the characteristics of different regions and time.
Metabolomics analysis reveals a modified amino acid metabolism that correlates with altered oxygen homeostasis in COVID-19 patients
Authors: Páez-Franco José C. , Torres-Ruiz Jiram , Sosa-Hernández Víctor A. , Cervantes-Díaz Rodrigo , Romero-Ramírez Sandra , Pérez-Fragoso Alfredo , Meza-Sánchez David E. , Germán-Acacio Juan Manuel , Maravillas-Montero José L. , Mejía-Domínguez Nancy R. , Ponce-de-León Alfredo , Ulloa-Aguirre Alfredo , Gómez-Martín Diana , Llorente Luis 
Published: March 2021

AbstractWe identified the main changes in serum metabolites associated with severe (n = 46) and mild (n = 19) COVID-19 patients by gas chromatography coupled to mass spectrometry. The modified metabolic profiles were associated to an altered amino acid catabolism in hypoxic conditions. Noteworthy, three α-hydroxyl acids of amino acid origin increased with disease severity and correlated with altered oxygen saturation levels and clinical markers of lung damage. We hypothesize that the enzymatic conversion of α-keto-acids to α- hydroxyl-acids helps to maintain NAD recycling in patients with altered oxygen levels, highlighting the potential relevance of amino acid supplementation during SARS-CoV-2 infection.
Simulations with Australian dragon lizards suggest movement-based signal effectiveness is dependent on display structure and environmental conditions
Authors: Bian Xue , Pinilla Angela , Chandler Tom , Peters Richard 
Published: March 2021

AbstractHabitat-specific characteristics can affect signal transmission such that different habitats dictate the optimal signal. One way to examine how the environment influences signals is by comparing changes in signal effectiveness in different habitats. Examinations of signal effectiveness between different habitats has helped to explain signal divergence/convergence between populations and species using acoustic and colour signals. Although previous research has provided evidence for local adaptations and signal divergence in many species of lizards, comparative studies in movement-based signals are rare due to technical difficulties in quantifying movements in nature and ethical restrictions in translocating animals between habitats. We demonstrate herein that these issues can be addressed using 3D animations, and compared the relative performance of the displays of four Australian lizard species in the habitats of each species under varying environmental conditions. Our simulations show that habitats differentially affect signal performance, and an interaction between display and habitat structure. Interestingly, our results are consistent with the hypothesis that the signal adapted to the noisier environment does not show an advantage in signal effectiveness, but the noisy habitat was detrimental to the performance of all displays. Our study is one of the first studies for movement-based signals that directly compares signal performance in multiple habitats, and our approach has laid the foundation for future investigations in motion ecology that have been intractable to conventional research methods.
Estimating included animal species in mixed crude drugs derived from animals using massively parallel sequencing
Authors: Nakanishi Hiroaki , Yoneyama Katsumi , Hara Masaaki , Takada Aya , Saito Kazuyuki 
Published: March 2021

AbstractWe developed a method that can detect each animal species of origin for crude drugs derived from multiple animal species based on massively parallel sequencing analysis of mitochondrial genes. The crude drugs derived from animals investigated in this study were Cervi Parvum Cornu and Trogopterorum feces, which are derived from a mix of different animal species, two chopped cicada sloughs, and two commercial Kampo drugs. The mitochondrial 12S rRNA, 16S rRNA, and cytochrome oxidase subunit I gene regions were amplified and sequenced using MiSeq. The ratios of haplotype to total number of sequences reads were calculated after sequence extraction and trimming. Haplotypes that exceeded the threshold were defined as positive haplotypes, which were compared with all available sequences using BLAST. In the Cervi Parvum Cornu and Trogopterorum feces samples, the haplotype ratios corresponded roughly to the mixture ratios, although there was a slight difference from mixture ratios depending on the gene examined. This method could also roughly estimate the compositions of chopped cicada sloughs and Kampo drugs. This analysis, whereby the sequences of several genes are elucidated, is better for identifying the included animal species. This method should be useful for quality control of crude drugs and Kampo drugs.
Impact of comorbidity burden on mortality in patients with COVID-19 using the Korean health insurance database
Authors: Cho Soo Ick , Yoon Susie , Lee Ho-Jin 
Published: March 2021

AbstractWe aimed to investigate the impact of comorbidity burden on mortality in patients with coronavirus disease (COVID-19). We analyzed the COVID-19 data from the nationwide health insurance claims of South Korea. Data on demographic characteristics, comorbidities, and mortality records of patients with COVID-19 were extracted from the database. The odds ratios of mortality according to comorbidities in these patients with and without adjustment for age and sex were calculated. The predictive value of the original Charlson comorbidity index (CCI) and the age-adjusted CCI (ACCI) for mortality in these patients were investigated using the receiver operating characteristic (ROC) curve analysis. Among 7590 patients, 227 (3.0%) had died. After age and sex adjustment, hypertension, diabetes mellitus, congestive heart failure, dementia, chronic pulmonary disease, liver disease, renal disease, and cancer were significant risk factors for mortality. The ROC curve analysis showed that an ACCI threshold > 3.5 yielded the best cut-off point for predicting mortality (area under the ROC 0.92; 95% confidence interval 0.91–0.94). Our study revealed multiple risk factors for mortality in patients with COVID-19. The high predictive power of the ACCI for mortality in our results can support the importance of old age and comorbidities in the severity of COVID-19.
Algal magnetic nickel oxide nanocatalyst in accelerated synthesis of pyridopyrimidine derivatives
Authors: Moavi Javad , Buazar Foad , Sayahi Mohammad Hosein 
Published: March 2021

AbstractThis research presents a novel biological route for the biosynthesis of nickel oxide nanoparticles (NiO NPs) using marine macroalgae extract as a reducing and coating agent under optimized synthesis conditions. XRD and TEM analyses revealed that phytosynthesized NiO NPs are crystalline in nature with a spherical shape having a mean particle size of 32.64 nm. TGA results indicated the presence of marine-derived organic constituents on the surface of NiO NPs. It is found that biogenic NiO NPs with BET surface area of 45.59 m2g−1 is a highly efficient catalyst for benign one-pot preparation of pyridopyrimidine derivatives using aqueous reaction conditions. This environmentally friendly procedure takes considerable advantages of shorter reaction times, excellent product yields (up to 96%), magnetically viable nanocatalyst (7 runs), low catalyst loadings, and free toxic chemical reagents.
Quercetin can reduce viral RNA level of O’nyong-nyong virus and resulting innate immune cytokine responses in cultured human synovial fibroblasts
Authors: Septembre-Malaterre Axelle , Bedoui Yosra , Giry Claude , Gasque Philippe , Guiraud Pascale , Sélambarom Jimmy 
Published: March 2021

AbstractO’nyong-nyong virus is an alphavirus closely related to chikungunya virus, causing arthralgia, rash and fever. Alphaviruses mainly target synovial fibroblasts and persists in the joints of patients, possibly leading to chronic arthritis. To date, no specific antiviral treatment is available for ONNV infection and induced-inflammation. Primary human synovial fibroblasts cells were used to assess infection by ONNV and the resulting cytokine responses. Phenolics (gallic acid, caffeic acid and chlorogenic acid, curcumin and quercetin) and a curcuminoids-rich extract from turmeric were tested for their antiviral and anti-inflammatory capacities. We showed that infection occurred in HSF cells and increased gene expression and protein secretion of two major proinflammatory CCL-2 and IL-1β markers. In ONNV-infected HSF cells (MOI 1), we found that non-cytotoxic concentrations of phenolics (10 µM) reduced the level of viral RNA (E1, E2, nsP1, nsP2) and downregulated CCL-2 and IL-1β expression and secretion. These results highlighted the high value of the flavonol quercetin to reduce viral RNA levels and inflammatory status induced by ONNV in HSF cells.
Oculomotor anticipation reveals a multitude of learning processes underlying the serial reaction time task
Authors: Tal Amir , Bloch Ayala , Cohen-Dallal Haggar , Aviv Or , Schwizer Ashkenazi Simone , Bar Moshe , Vakil Eli 
Published: March 2021

AbstractSequence learning is the cognitive faculty enabling everyday skill acquisition. In the lab, it is typically measured in speed of response to sequential stimuli, whereby faster responses are taken to indicate improved anticipation. However, response speed is an indirect measure of anticipation, that can provide only limited information on underlying processes. As a result, little is known about what is learned during sequence learning, and how that unfolds over time. In this work, eye movements that occurred before targets appeared on screen in an ocular serial reaction time (O-SRT) task provided an online indication of where participants anticipated upcoming targets. When analyzed in the context of the stimuli preceding them, oculomotor anticipations revealed several simultaneous learning processes. These processes influenced each other, as learning the task grammar facilitated acquisition of the target sequence. However, they were dissociable, as the grammar was similarly learned whether a repeating sequence inhabited the task or not. Individual differences were found in how the different learning processes progressed, allowing for similar performance to be produced for different latent reasons. This study provides new insights into the processes subserving sequence learning, and a new method for high-resolution study of it.
Prognostic impacts of glucocorticoid treatment in patients with polymyalgia rheumatica and giant cell arteritis
Authors: Emamifar Amir , Ellingsen Torkell , Hermann Anne Pernille , Hess Søren , Gerke Oke , Ahangarani Farahani Ziba , Syrak Hansen Per , Jensen Hansen Inger Marie , Thye-Rønn Peter 
Published: March 2021

AbstractIdentifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients’ outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p < 0.001), with no association with results of TAB and 18F-FDG PET/CT. Aortic PWV was significantly associated with age, male gender, left systolic and diastolic blood pressure, right diastolic blood pressure, and CRP. Total bone mineral content (BMC) was decreased in both genders (p < 0.001), while fat mass (FM) was significantly increased (p < 0.001). However, lean body mass did not significantly change during the study. Changes in FM were correlated with cumulative prednisolone dose (rho: 0.26, p = 0.031). Glucocorticoid treatment of patients with PMR/GCA had several prognostic impacts. Arterial stiffness was decreased due either to the treatment or a reduction in the inflammatory load. Additionally, treatment led to changes in body composition, including a decrease in BMC and FM excess.