bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution dynamic inversion imaging with motion-aberrations-free using optical flow learning networks
Authors: Li Jin , Liu Zilong 
Published: August 2019

AbstractDynamic optical imaging (e.g. time delay integration imaging) is troubled by the motion blur fundamentally arising from mismatching between photo-induced charge transfer and optical image movements. Motion aberrations from the forward dynamic imaging link impede the acquiring of high-quality images. Here, we propose a high-resolution dynamic inversion imaging method based on optical flow neural learning networks. Optical flow is reconstructed via a multilayer neural learning network. The optical flow is able to construct the motion spread function that enables computational reconstruction of captured images with a single digital filter. This works construct the complete dynamic imaging link, involving the backward and forward imaging link, and demonstrates the capability of the back-ward imaging by reducing motion aberrations.
Malaria-anemia comorbidity prevalence as a measure of malaria-related deaths in sub-Saharan Africa
Authors: Papaioannou Isidoros , Utzinger Jürg , Vounatsou Penelope 
Published: August 2019

AbstractDifferent methods and data sources have been utilized to determine the relationship between malaria and mortality in endemic countries. Most of these efforts have focused on deaths directly attributed to malaria, while they overlooked causes of mortality that might be indirectly related to the disease, for instance anemia. We estimated the association of malaria parasitaemia, anemia, and malaria-anemia comorbidity with all-cause under-five mortality and evaluated the potential of malaria-anemia comorbidity prevalence to quantify malaria-related deaths in sub-Saharan Africa. We analysed data from Demographic and Health Surveys (DHS) and employed Bayesian geostatistical models. Mortality hazard obtained from malaria-anemia comorbidity prevalence was up to 3·5 times higher compared to the hazard related to Plasmodium parasitaemia only. Malaria parasite prevalence alone could not always capture a statistically important association with under-five mortality. Geographical variation of the malaria-anemia comorbidity effect was observed in most, but not all, countries. We concluded that the malaria burden in sub-Saharan Africa is considerably underestimated when anemia in not taken into account and that the malaria-anemia comorbidity prevalence provides a useful measure of the malaria-related deaths.
The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways
Authors: Buckley Melanie L. , Williams Jessica O. , Chan Yee-Hung , Laubertová Lucia , Gallagher Hayley , Moss Joe W. E. , Ramji Dipak P. 
Published: August 2019

AbstractAtherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the inhibition of gene expression by this cytokine are poorly understood. Further studies are required given the important roles of genes whose expression is inhibited by IL-33 in key cellular processes associated with atherosclerosis such as monocyte recruitment, foam cell formation and lipoprotein metabolism. We have investigated here the roles of various known IL-33 activated signaling pathways in such inhibitory actions using RNA interference-mediated knockdown assays and monocyte chemotactic protein-1 and intercellular adhesion molecule-1 as model genes. Key roles were identified for extracellular signal-regulated kinase-1/2, p38α kinase, c-Jun N-terminal kinase-1/2, phosphoinositide 3-kinase-γ, and p50 and p65 nuclear factor-κB in such inhibitory action of IL-33. These studies provide new insights on the signaling pathways through which IL-33 inhibits the macrophage expression of key atherosclerosis-associated genes.
A simple, reproducible and cost-effective procedure to analyse gut phageome: from phage isolation to bioinformatic approach
Authors: d’Humières Camille , Touchon Marie , Dion Sara , Cury Jean , Ghozlane Amine , Garcia-Garcera Marc , Bouchier Christiane , Ma Laurence , Denamur Erick , P.C.Rocha Eduardo 
Published: August 2019

AbstractThe microbiota of the human gut is a complex and rich community where bacteria and their viruses, the bacteriophages, are dominant. There are few studies on the phage community and no clear standard for isolating them, sequencing and analysing their genomes. Since this makes comparisons between studies difficult, we aimed at defining an easy, low-cost, and reproducible methodology. We analysed five different techniques to isolate phages from human adult faeces and developed an approach to analyse their genomes in order to quantify contamination and classify phage contigs in terms of taxonomy and lifestyle. We chose the polyethylene glycol concentration method to isolate phages because of its simplicity, low cost, reproducibility, and of the high number and diversity of phage sequences that we obtained. We also tested the reproducibility of this method with multiple displacement amplification (MDA) and showed that MDA severely decreases the phage genetic diversity of the samples and the reproducibility of the method. Lastly, we studied the influence of sequencing depth on the analysis of phage diversity and observed the beginning of a plateau for phage contigs at 20,000,000 reads. This work contributes to the development of methods for the isolation of phages in faeces and for their comparative analysis.
Integrated genomic epidemiology and phenotypic profiling of Clostridium difficile across intra-hospital and community populations in Colombia
Authors: Muñoz Marina , Restrepo-Montoya Daniel , Kumar Nitin , Iraola Gregorio , Camargo Milena , Díaz-Arévalo Diana , Roa-Molina Nelly S. , Tellez Mayra A. , Herrera Giovanny , Ríos-Chaparro Dora I. , Birchenall Claudia , Pinilla Darío , Pardo-Oviedo Juan M. , Rodríguez-Leguizamón Giovanni , Josa Diego F. , Lawley Trevor D. , Patarroyo Manuel A. , Ramírez Juan David 
Published: August 2019

AbstractClostridium difficile, the causal agent of antibiotic-associated diarrhea, has a complex epidemiology poorly studied in Latin America. We performed a robust genomic and phenotypic profiling of 53 C. difficile clinical isolates established from diarrheal samples from either intrahospital (IH) or community (CO) populations in central Colombia. In vitro tests were conducted to evaluate the cytopathic effect, the minimum inhibitory concentration of ten antimicrobial agents, the sporulation efficiency and the colony forming ability. Eleven different sequence types (STs) were found, the majority present individually in each sample, however in three samples two different STs were isolated. Interestingly, CO patients were infected with STs associated with hypervirulent strains (ST-1 in Clade-2). Three coexistence events (two STs simultaneously detected in the same sample) were observed always involving ST-8 from Clade-1. A total of 2,502 genes were present in 99% of the isolates with 95% of identity or more, it represents a core genome of 28.6% of the 8,735 total genes identified in the set of genomes. A high cytopathic effect was observed for the isolates positive for the two main toxins but negative for binary toxin (TcdA+/TcdB+/CDT− toxin production type), found only in Clade-1. Molecular markers conferring resistance to fluoroquinolones (cdeA and gyrA) and to sulfonamides (folP) were the most frequent in the analyzed genomes. In addition, 15 other markers were found mostly in Clade-2 isolates. These results highlight the regional differences that C. difficile isolates display, being in this case the CO isolates the ones having a greater number of accessory genes and virulence-associated factors.
Fluidic Self-Assembly on Electroplated Multilayer Solder Bumps with Tailored Transformation Imprinted Melting Points
Authors: Kaltwasser Mahsa , Schmidt Udo , Lösing Lars , Biswas Shantonu , Stauden Thomas , Bund Andreas , Jacobs Heiko O. 
Published: August 2019

AbstractThis communication presents fluidic self-assembly of Si-chip on a sequentially electroplated multilayer solder bump with tailored transformation imprinted melting points. The multilayer solder bump is a lead free ternary solder system, which provides a route to transform the melting point of interconnects for applications in solder directed fluidic self-assembly. The outermost metal layers form a low melting point Bi33.7In66.3 solder shell (72 °C). This solder shell enables fluidic self-assembly and self-alignment of freely in water suspended Si-dies at relatively low temperature (75 °C) leading to well-ordered chip arrays. The reduction of the free surface energy of the shell-water interface provides the driving force for the self-assembly. The lowermost metal layer is a high melting point solder and acts as a core. After the self-assembly is complete, a short reflow causes the transformation of the core and the shell yielding a stable high melting point solder with adjustable melting points. The chosen ternary solder system enables the realization of interconnects with melting points in the range of 112 °C to 206 °C.
Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment
Authors: Belligoli Anna , Compagnin Chiara , Sanna Marta , Favaretto Francesca , Fabris Roberto , Busetto Luca , Foletto Mirto , Dal Prà Chiara , Serra Roberto , Prevedello Luca , Da Re Chiara , Bardini Romeo , Mescoli Claudia , Rugge Massimo , Fioretto Paola , Conci Scilla , Bettini Silvia , Milan Gabriella , Vettor Roberto 
Published: August 2019

AbstractAlthough obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.
Optimized CRISPR/Cas9-mediated in vivo genome engineering applicable to monitoring dynamics of endogenous proteins in the mouse neural tissues
Authors: Matsuda Takahiko , Oinuma Izumi 
Published: August 2019

AbstractTo analyze the expression, localization, and functional dynamics of target proteins in situ, especially in living cells, it is important to develop a convenient, versatile, and efficient method to precisely introduce exogenous genes into the genome, which is applicable for labeling and engineering of the endogenous proteins of interest. By combining the CRISPR/Cas9 genome editing technology with an electroporation technique, we succeeded in creating knock-in alleles, from which GFP (RFP)-tagged endogenous proteins are produced, in neurons and glial cells in vivo in the developing mouse retina and brain. Correct gene targeting was confirmed by single-cell genotyping and Western blot analysis. Several gene loci were successfully targeted with high efficiency. Moreover, we succeeded in engineering the mouse genome to express foreign genes from the endogenous gene loci using a self-cleaving 2A peptide. Our method could be used to monitor the physiological changes in localization of endogenous proteins and expression levels of both mRNA and protein at a single cell resolution. This work discloses a powerful and widely applicable approach for visualization and manipulation of endogenous proteins in neural tissues.
Transcriptome profiling of microRNAs associated with latent autoimmune diabetes in adults (LADA)
Authors: Yu Ke , Huang Zhou , Zhou Jing , Lang Jianan , Wang Yan , Yin Xingqi , Zhou Yuan , Zhao Dong 
Published: August 2019

AbstractLADA (latent autoimmune diabetes in adults), a special subtype of type 1 diabetes, turns out to exhibit phenotypes mimicking the type 2 diabetes, which results in serious misdiagnosis issues. In order to better distinguish LADA from other diabetes subtypes, specific diagnostic and prognostic biomarkers of LADA are required. Circulating microRNAs (miRNAs) are recently shown to be promising biomarkers for disease diagnosis and subtyping. In this study, serum samples from LADA patients and type 2 diabetes patients were collected during the first diagnosis of diabetes and the miRNA transcriptomes of these patients and healthy individuals were profiled. Comparative analysis shows that the differentially expressed miRNAs between groups and their predicted target genes are enriched for several functions including immune regulation. Besides, a few miRNAs showing distinct expression pattern in LADA patients could discriminate LADA from type 2 diabetes, as validated by further qRT-PCR assay. In all, our study implies potential miRNA biomarkers which would be investigated in further clinical researches.
Identifying potential novel drugs against Helicobacter pylori by targeting the essential response regulator HsrA
Authors: González Andrés , Salillas Sandra , Velázquez-Campoy Adrián , Espinosa Angarica Vladimir , Fillat María F. , Sancho Javier , Lanas Ángel 
Published: August 2019

AbstractThe increasing antibiotic resistance evolved by Helicobacter pylori has alarmingly reduced the eradication rates of first-line therapies. To overcome the current circulating resistome, we selected a novel potential therapeutic target in order to identify new candidate drugs for treating H. pylori infection. We screened 1120 FDA-approved drugs for molecules that bind to the essential response regulator HsrA and potentially inhibit its biological function. Seven natural flavonoids were identified as HsrA binders. All of these compounds noticeably inhibited the in vitro DNA binding activity of HsrA, but only four of them, apigenin, chrysin, kaempferol and hesperetin, exhibited high bactericidal activities against H. pylori. Chrysin showed the most potent bactericidal activity and the most synergistic effect in combination with clarithromycin or metronidazole. Flavonoid binding to HsrA occurs preferably at its C-terminal effector domain, interacting with amino acid residues specifically involved in forming the helix-turn-helix DNA binding motif. Our results validate the use of HsrA as a novel and effective therapeutic target in H. pylori infection and provide molecular evidence of a novel antibacterial mechanism of some natural flavonoids against H. pylori. The results further support the valuable potential of natural flavonoids as candidate drugs for novel antibacterial strategies.
Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
Authors: Figueiredo Constanca , Eicke Dorothee , Yuzefovych Yuliia , Avsar Murat , Hanke Jasmin Sarah , Pflaum Michael , Schmitto Jan-Dieter , Blasczyk Rainer , Haverich Axel , Wiegmann Bettina 
Published: August 2019

AbstractLow haemocompatibility of left ventricular assist devices (LVAD) surfaces necessitates anticoagulative therapy. Endothelial cell (EC) seeding can support haemocompatibility, however, the availability of autologous ECs is limited. In contrast, allogeneic ECs are readily available in sufficient quantity, but HLA disparities induce harmful immune responses causing EC loss. In this study, we investigated the feasibility of using allogeneic low immunogenic ECs to endothelialize LVAD sintered inflow cannulas (SIC). To reduce the immunogenicity of ECs, we applied an inducible lentiviral vector to deliver short-hairpins RNA to silence HLA class I expression. HLA class I expression on ECs was conditionally silenced by up to 70%. Sufficient and comparable endothelialization rates were achieved with HLA-expressing or HLA-silenced ECs. Cell proliferation was not impaired by cell-to-Sintered Inflow Cannulas (SIC) contact or by silencing HLA expression. The levels of endothelial phenotypic and thrombogenic markers or cytokine secretion profiles remained unaffected. HLA-silenced ECs-coated SIC exhibited reduced thrombogenicity. In contrast to native ECs, HLA-silenced ECs showed lower cell lysis rates when exposed to allogeneic T cells or specific anti-HLA antibodies. Allogeneic HLA-silenced ECs could potentially become a valuable source for LVAD endothelialization to reduce immunogenicity and correspondingly the need for anticoagulative therapy which can entail severe side effects.
Structure functional insights into calcium binding during the activation of coagulation factor XIII A
Authors: Singh Sneha , Dodt Johannes , Volkers Peter , Hethershaw Emma , Philippou Helen , Ivaskevicius Vytautus , Imhof Diana , Oldenburg Johannes , Biswas Arijit 
Published: August 2019

AbstractThe dimeric FXIII-A2, a pro-transglutaminase is the catalytic part of the heterotetrameric coagulation FXIII-A2B2 complex that upon activation by calcium binding/thrombin cleavage covalently cross-links preformed fibrin clots protecting them from premature fibrinolysis. Our study characterizes the recently disclosed three calcium binding sites of FXIII-A concerning evolution, mutual crosstalk, thermodynamic activation profile, substrate binding, and interaction with other similarly charged ions. We demonstrate unique structural aspects within FXIII-A calcium binding sites that give rise to functional differences making FXIII unique from other transglutaminases. The first calcium binding site showed an antagonistic relationship towards the other two. The thermodynamic profile of calcium/thrombin-induced FXIII-A activation explains the role of bulk solvent in transitioning its zymogenic dimeric form to an activated monomeric form. We also explain the indirect effect of solvent ion concentration on FXIII-A activation. Our study suggests FXIII-A calcium binding sites could be putative pharmacologically targetable regions.
The ocular surface after successful glaucoma filtration surgery: a clinical, in vivo confocal microscopy, and immune-cytology study
Authors: Agnifili Luca , Brescia Lorenza , Oddone Francesco , Sacchi Matteo , D’Ugo Erminia , Di Marzio Guido , Perna Fabiana , Costagliola Ciro , Mastropasqua Rodolfo 
Published: August 2019

AbstractWe investigated the ocular surface (OS) system modifications after completely successful glaucoma surgery in thirty-eight patients undergoing trabeculectomy (surgical group), using laser scanning confocal microscopy (LSCM) and impression cytology (IC). Twenty-six medically controlled glaucomatous patients served as controls (medical group). LSCM, IC, and the ocular surface disease index (OSDI) and National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) questionnaires, were performed at baseline and after six months. The main outcomes were: goblet cell density (GCD), limbal dendritic cell density (LDCD), subbasal corneal nerve inhomogeneity (SCNI), Meibomian gland density and inhomogeneity (MGD, MGI), and HLA-DR positivity. There were no significant baseline differences between groups. At the sixth month, the surgical group showed a GCD increase (p < 0.001), and a LDCD, SCNI, MGI, HLA-DR (p < 0.001), OSDI and NEI VFQ-25 scores decrease (p < 0.05). The medical group did not show significant OS modifications, showing LSCM and IC parameters significantly worse compared to the surgical group (p < 0.001). The OSDI score correlated with GCD, MGI, SCNI, LDCD, and HLA-DR (p < 0.001; p < 0.05; p < 0.01). The present study found that the whole OS system objectively improved after completely successful glaucoma filtration surgery. These changes positively affected the OSDI score, but not the NEI VFQ-25 score.
Solvent demulsification-dispersive liquid-liquid microextraction based on solidification of floating organic drop coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 13 organophosphate esters in aqueous samples
Authors: Luo Qing , Wang Shiyu , Adeel Muhammad , Shan Yue , Wang Hui , Sun Li-na 
Published: August 2019

AbstractThis study developed a novel method for the determination of 13 organophosphate esters (OPEs) in aqueous samples through the optimization of solvent demulsification-dispersive liquid-liquid microextraction based on solidification of floating organic drop procedure coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry. The proposed method was rapid and accurate and could be used in field applications. Under the most suitable conditions, the limit of detection and limit of quantification ranged from 0.16 ng/L to 20.0 ng/L and from 0.55 ng/L to 66.7 ng/L, respectively. The enrichment factors (EFs) ranged from 30 to 46. The relative standard deviations were less than 15%. The spiked recoveries ranged between 68.2% and 97.7% in the analysis of actual aqueous samples. The proposed method was convenient, environment friendly, and time and solvent saving and could be used in field applications compared with other methods. Various concentrations and types of OPEs were detected in tap water, river water, and effluent of sewage treatment plant. Effluent samples had the highest detected levels and types of OPEs.
Iron accumulation in tumor-associated macrophages marks an improved overall survival in patients with lung adenocarcinoma
Authors: Thielmann Carl Maximilian , Costa da Silva Milene , Muley Thomas , Meister Michael , Herpel Esther , Muckenthaler Martina U. 
Published: August 2019

AbstractIron-loaded tumor-associated macrophages (iTAMs) show a pro-inflammatory phenotype, hallmarked by anti-tumorigenic activity and an ability to attenuate tumor growth. Here we explored the relevance of these findings in lung cancer patients by investigating the impact of the iTAM content in the tumor microenvironment (TME) on patient survival. We analyzed 102 human non-small cell lung cancer (NSCLC) paraffin-embedded archival tissue samples for iron levels and macrophage numbers. Interestingly, patients with lung adenocarcinoma accumulating iron in the TME show higher numbers of M1-like pro-inflammatory TAMs and a survival advantage compared to iron-negative patients. By contrast, in patients with lung squamous cell carcinoma iron in the TME does not affect survival, suggesting a unique influence of iron on different histological subtypes of non-small cell lung cancer (NSCLC). We conclude that in lung adenocarcinoma iron may serve as a prognostic marker for patient survival and as a potential therapeutic target for anti-cancer therapy.