bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multipredictor model to predict the conversion of mild cognitive impairment to Alzheimer’s disease by using a predictive nomogram
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Huang Kexin , Lin Yanyan , Yang Lifeng , Wang Yubo , Cai Suping , Pang Liaojun , Wu Xiaoming , Huang Liyu 
Published: October 2019

Abstract
Predicting the probability of converting from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) is still a challenging task. This study aims at providing a personalized MCI-to-AD conversion estimation by using a multipredictor nomogram that integrates neuroimaging features, cerebrospinal fluid (CSF) biomarker, and clinical assessments. To do so, 290 MCI patients were collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), of whom 76 has converted to AD and 214 remained with MCI. All subjects were randomly divided into a primary and validation cohort. Radiomics signature (Rad-sig) was obtained based on 17 cerebral cortex features selected by using Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Clinical factors and amyloid-beta peptide (Aβ) concentration were selected by using Spearman correlation between the converted and not-converted patients. Then, a nomogram that combines image features, clinical factor, and Aβ concentration was constructed and validated. Furthermore, we explored the associations between various predictors from the macro- to the microperspective by assessing gene expression patterns. Our results showed that the multipredictor nomogram (C-index 0.978 and 0.956 in both cohorts, respectively) outperformed the nomogram using either Rad-sig or Aβ concentration as individual predictors. Significant associations were found between neuropsychological scores, cerebral cortex features, Aβ levels, and underlying gene pathways. Our study may have a clinical impact as a powerful predictive tool for predicting the conversion probability of MCI and providing associations between cognitive impairment, structural changes, Aβ levels, and underlying biological patterns from the macro- to the microperspective.
Visualizing locus-specific sister chromatid exchange reveals differential patterns of replication stress-induced fragile site breakage
Authors: Waisertreiger Irina , Popovich Katherine , Block Maya , Anderson Krista R. , Barlow Jacqueline H. 
Published: October 2019

AbstractChromosomal fragile sites are genomic loci sensitive to replication stress which accumulate high levels of DNA damage, and are frequently mutated in cancers. Fragile site damage is thought to arise from the aberrant repair of spontaneous replication stress, however successful fragile site repair cannot be calculated using existing techniques. Here, we report a new assay measuring recombination-mediated repair at endogenous genomic loci by combining a sister chromatid exchange (SCE) assay with fluorescent in situ hybridization (SCE-FISH). Using SCE-FISH, we find that endogenous and exogenous replication stress generated unrepaired breaks and SCEs at fragile sites. We also find that distinct sources of replication stress induce distinct patterns of breakage: ATR inhibition induces more breaks at early replicating fragile sites (ERFS), while ERFS and late-replicating common fragile sites (CFS) are equally fragile in response to aphidicolin. Furthermore, SCEs were suppressed at fragile sites near centromeres in response to replication stress, suggesting that genomic location influences DNA repair pathway choice. SCE-FISH also measured successful recombination in human primary lymphocytes, and identificed the proto-oncogeneBCL2as a replication stress-induced fragile site. These findings demonstrate that SCE-FISH frequency at fragile sites is a sensitive indicator of replication stress, and that large-scale genome organization influences DNA repair pathway choice.
GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism
Authors: Shi Qianqian , Xu Renfang , Song Guanglai , Lu Hao , Xue Dong , He Xiaozhou , Xia Ying 
Published: October 2019

AbstractTumorigenesis and metastasis depend on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. It is, however, unclear regarding the molecular mechanisms underlying the progress and metastasis of human clear-cell renal cell carcinoma in the microenvironment with fibroblasts. In this work, we investigated the effect of normal fibroblasts on the metastasis of renal cancer and the relevant signaling pathways. We isolated normal fibroblasts from normal renal tissues and used normal fibroblast-conditioned medium culture renal cancer cells. The CCK-8 and transwell assays showed that normal fibroblasts conditioned medium significantly enhanced ccRCC cell migration. IL6 mediated the cross talk between normal fibroblasts and the cancer cells, and promoted tumor cell migration through the STAT3 pathway. In contrast, GATA3 was downregulated at both mRNA and protein levels in the normal fibroblast-conditioned medium treated with renal cancer cells, but upregulated in adjacent normal tissues. GATA3 overexpression significantly reduced STAT3 phosphorylation and attenuated the migration in both renal cancer cell and IL6-stimulated renal cancer cell. Taken together, our findings suggest that the IL6/STAT3 pathway plays a crucial role in the normal fibroblast-enhanced clear-cell renal cell carcinoma metastasis, while GATA3 may mitigate this effect by inhibiting IL6/STAT3 signaling.
Molybdenum systematics of subducted crust record reactive fluid flow from underlying slab serpentine dehydration
Authors: Chen Shuo , Hin Remco C. , John Timm , Brooker Richard , Bryan Ben , Niu Yaoling , Elliott Tim 
Published: October 2019

AbstractFluids liberated from subducting slabs are critical in global geochemical cycles. We investigate the behaviour of Mo during slab dehydration using two suites of exhumed fragments of subducted, oceanic lithosphere. Our samples display a positive correlation of δ98/95MoNIST 3134 with Mo/Ce, from compositions close to typical mantle (−0.2‰ and 0.03, respectively) to very low values of both δ98/95MoNIST 3134 (−1‰) and Mo/Ce (0.002). Together with new, experimental data, we show that molybdenum isotopic fractionation is driven by preference of heavier Mo isotopes for a fluid phase over rutile, the dominant mineral host of Mo in eclogites. Moreover, the strongly perturbed δ98/95MoNIST 3134 and Mo/Ce of our samples requires that they experienced a large flux of oxidised fluid. This is consistent with channelised, reactive fluid flow through the subducted crust, following dehydration of the underlying, serpentinised slab mantle. The high δ98/95MoNIST 3134 of some arc lavas is the complement to this process.
The FluPRINT dataset, a multidimensional analysis of the influenza vaccine imprint on the immune system
Authors: Tomic Adriana , Tomic Ivan , Dekker Cornelia L. , Maecker Holden T. , Davis Mark M. 
Published: October 2019

AbstractMachine learning has the potential to identify novel biological factors underlying successful antibody responses to influenza vaccines. The first attempts have revealed a high level of complexity in establishing influenza immunity, and many different cellular and molecular components are involved. Of note is that the previously identified correlates of protection fail to account for the majority of individual responses across different age groups and influenza seasons. Challenges remain from the small sample sizes in most studies and from often limited data sets, such as transcriptomic data. Here we report the creation of a unified database, FluPRINT, to enable large-scale studies exploring the cellular and molecular underpinnings of successful antibody responses to influenza vaccines. Over 3,000 parameters were considered, including serological responses to influenza strains, serum cytokines, cell phenotypes, and cytokine stimulations. FluPRINT, facilitates the application of machine learning algorithms for data mining. The data are publicly available and represent a resource to uncover new markers and mechanisms that are important for influenza vaccine immunogenicity.
Radiomics Nomogram Analyses for Differentiating Pneumonia and Acute Paraquat Lung Injury
Authors: Yanling Wang , Duo Gao , Zuojun Geng , Zhongqiang Shi , Yankai Wu , Shan Lu , Hongying Cui 
Published: October 2019

AbstractParaquat poisoning has become a serious public health problem in some Asian countries because of misuse or suicide. We sought to develop and validate a radiomics nomogram incorporating radiomics signature and laboratory bio-markers, for differentiating bacterial pneumonia and acute paraquat lung injury. 180 patients with pneumonia and acute paraquat who underwent CT examinations between December 2014 and October 2017 were retrospectively evaluated for testing and validation. Clinical information including demographic data, clinical symptoms and laboratory test were also recorded. A prediction model was built by using backward logistic regression and presented on a nomogram. The radiomics-based features yielded areas under the receiver operating characteristic curve of 0.870 (95% CI 0.757–0.894), sensitivity of 0.857, specificity of 0.804, positive predictive value of 83.3%, negative predictive value of 0.818 in the primary cohort, while in the validation cohort the model showed similar results (0.865 (95% CI 0.686–0.907), 0.833, 0.792, 81.5%, respectively). The individualized nomogram included radiomics signature, body temperature, nausea and vomiting, and aspartate transaminase. We have developed a radiomics nomogram that combination of the radiomics features and clinical risk factors to differentiate paraquat lung injury and pneumonia for patients with an unclear medical history of exposure to paraquat poisoning, providing appropriate therapy decision support.
Denoising of Aligned Genomic Data
Authors: Fischer-Hwang Irena , Ochoa Idoia , Weissman Tsachy , Hernaez Mikel 
Published: October 2019

AbstractNoise in genomic sequencing data is known to have effects on various stages of genomic data analysis pipelines. Variant identification is an important step of many of these pipelines, and is increasingly being used in clinical settings to aid medical practices. We propose a denoising method, dubbed SAMDUDE, which operates on aligned genomic data in order to improve variant calling performance. Denoising human data with SAMDUDE resulted in improved variant identification in both individual chromosome as well as whole genome sequencing (WGS) data sets. In the WGS data set, denoising led to identification of almost 2,000 additional true variants, and elimination of over 1,500 erroneously identified variants. In contrast, we found that denoising with other state-of-the-art denoisers significantly worsens variant calling performance. SAMDUDE is written in Python and is freely available at https://github.com/ihwang/SAMDUDE.
Zeolite RHO Synthesis Accelerated by Ultrasonic Irradiation Treatment
Authors: Ng Tiffany Yit Siew , Chew Thiam Leng , Yeong Yin Fong , Jawad Zeinab Abbas , Ho Chii-Dong 
Published: October 2019

AbstractIn recent years, there are increasing interest on applying ultrasonic irradiation for the synthesis of zeolite due to its advantages including remarkable shortened synthesis duration. In this project, the potential of ultrasonic irradiation treatment on the synthesis of zeolite RHO was investigated. Ultrasonic irradiation treatment time was varied from 30 to 120 minutes for the synthesis of zeolite RHO. The zeolite RHO solid samples were characterized with X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA) and nitrogen adsorption-desorption analysis. The application of ultrasonic irradiation treatment in this study has accelerated the synthesis of zeolite RHO where the synthesis duration has been significantly shortened to 2 days compared to 8 days required by conventional hydrothermal heating without ultrasonic irradiation treatment. Highly crystalline zeolite RHO crystals in truncated octahedron morphology were successfully formed.
The Effect of Surface Roughness on the Contact Line and Splashing Dynamics of Impacting Droplets
Authors: Quetzeri-Santiago Miguel A. , Castrejón-Pita Alfonso A. , Castrejón-Pita J. Rafael 
Published: October 2019

AbstractWhether a droplet splashes upon impact onto a solid is known to depend not only on the fluid properties and its speed, but also on the substrate characteristics. Past research has shown that splashing is heavily influenced by the substrate roughness. Indeed, in this manuscript, we demonstrate that splashing is ruled by the surface roughness, the splashing ratio, and the dynamic contact angle. Experiments consist of water and ethanol droplets impacting onto solid substrates with varying degrees of roughness. High speed imaging is used to extract the dynamic contact angle as a function of the spreading speed for these impacting droplets. During the spreading phase, the dynamic contact angle achieves an asymptotic maximum value, which depends on the substrate roughness and the liquid properties. We found that this maximum dynamic contact angle, together with the liquid properties, the ratio of the peak to peak roughness and the surface feature mean width, determines the splashing to no-splashing threshold. In addition, these parameters consistently differentiate the splashing behaviour of impacts onto smooth hydrophilic, hydrophobic and superhydrophobic surfaces.
Mitochondrial dysfunction increases pro-inflammatory cytokine production and impairs repair and corticosteroid responsiveness in lung epithelium
Authors: Hoffmann R. F. , Jonker M. R. , Brandenburg S. M. , de Bruin H. G. , ten Hacken N. H. T. , van Oosterhout A. J. M. , Heijink I. H. 
Published: October 2019

AbstractCOPD is characterized by chronic lung inflammation and irreversible lung tissue damage. Inhaled noxious gases, including cigarette smoke, are the major risk factor for COPD. Inhaled smoke first encounters the epithelial lining of the lungs, causing oxidative stress and mitochondrial dysfunction. We investigated whether a mitochondrial defect may contribute to increased lung epithelial pro-inflammatory responses, impaired epithelial repair and reduced corticosteroid sensitivity as observed in COPD. We used wild-type alveolar epithelial cells A549 and mitochondrial DNA-depleted A549 cells (A549 Rho-0) and studied pro-inflammatory responses using (multiplex) ELISA as well as epithelial barrier function and repair (real-time impedance measurements), in the presence and absence of the inhaled corticosteroid budesonide. We observed that A549 Rho-0 cells secrete higher levels of pro-inflammatory cytokines than wild-type A549 cells and display impaired repair upon wounding. Budesonide strongly suppressed the production of neutrophil attractant CXCL8, and promoted epithelial integrity in A549 wild-type cells, while A549 Rho-0 cells displayed reduced corticosteroid sensitivity compared to wild-type cells. The reduced corticosteroid responsiveness may be mediated by glycolytic reprogramming, specifically glycolysis-associated PI3K signaling, as PI3K inhibitor LY294002 restored the sensitivity of CXCL8 secretion to corticosteroids in A549 Rho-0 cells. In conclusion, mitochondrial defects may lead to increased lung epithelial pro-inflammatory responses, reduced epithelial repair and reduced corticosteroid responsiveness in lung epithelium, thus potentially contributing to the pathogenesis of COPD.
BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases
Authors: Yin Jiawei , Xie Xiaoli , Ye Yufu , Wang Lijuan , Che Fengyuan 
Published: October 2019

AbstractTranscription factor B-cell lymphoma/leukemia 11A (BCL11A) gene encodes a zinc-finger protein that is predominantly expressed in brain and hematopoietic tissue. BCL11A functions mainly as a transcriptional repressor that is crucial in brain, hematopoietic system development, as well as fetal-to-adult hemoglobin switching. The expression of this gene is regulated by microRNAs, transcription factors and genetic variations. A number of studies have recently shown that BCL11A is involved in β-hemoglobinopathies, hematological malignancies, malignant solid tumors, 2p15-p16.1 microdeletion syndrome, and Type II diabetes. It has been suggested that BCL11A may be a potential prognostic biomarker and therapeutic target for some diseases. In this review, we summarize the current research state of BCL11A, including its biochemistry, expression, regulation, function, and its possible clinical application in human diseases.
The inhibition of tumor protein p53 by microRNA-151a-3p induced cell proliferation, migration and invasion in nasopharyngeal carcinoma
Authors: Liu Haibin , Cheng Yin , Xu Yaping , Xu He , Lin Zheng , Fan Jingping , Lang Juntian 
Published: October 2019

Abstract
A close relation between microRNA-151a-3p (miR-151a-3p) and nasopharyngeal carcinoma (NPC) has been reported, however, the molecular mechanism is still unclear. The aim of the present study was to explore the mechanism in the promotion of miR-151a-3p to NPC progression. The levels of miR-151-3p in several NPC cell lines were detected in order to screen an experimental cell line. MiR-151a-3p mimic and inhibitor were constructed and transfected into 5-8F cells and cell proliferation were detected by Cell Counting Kit-8 (CCK-8). The apoptosis rate, cell migration and invasion were determined by flow cytometry, wound healing and Transwell assays. The predicted target was further verified by luciferase reporter assay. Real-time quantification-PCR and Western blot were carried out for mRNA and protein level analysis. Tumor protein p53 was co-transfected to verify the functions of miR-151a-3p. The miR-151a-3p level in NPC tissues was much higher than that in adjacent tissues. After transfecting cells with miR-151a-3p mimic, the cell proliferation and patients’ survival rate were much increased, and this was accompanied by the increase in B-cell lymphoma 2 (Bcl-2) and decreases in Bax and cleaved caspase-3 (P&lt;0.01). Moreover, the migration rate and number of invaded cells were also remarkably increased, however, the miR-151a-3p inhibitor had opposite effects on the 5-8F cells. Noticeably, p53 was revealed as a potential target of miR-151a-3p. Co-transfection of P53 could partially reverse the promotive effects of miR-151a-3p on NPC cell progression. Our data indicated that blocking p53 expression and mediated signal pathways contribute to the positive effects of miR-151a-3p on NPC cell proliferation, migration and invasion.
Characterization of the interaction between β-catenin and sorting nexin 27: contribution of the type I PDZ-binding motif to Wnt signaling
Authors: DuChez Brian J. , Hueschen Christina L. , Zimmerman Seth P. , Baumer Yvonne , Wincovitch Stephen , Playford Martin P. 
Published: October 2019

Abstract
Background: Sorting Nexin 27 (SNX27) is a 62-kDa protein localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors. In addition to a PX domain common among all of the sorting nexin family, SNX27 is the only sorting family member that contains a PDZ domain. To identify novel SNX27–PDZ binding partners, we performed a proteomic screen in mouse principal kidney cortical collecting duct cells (mpkCCD) using a GST-SNX27 fusion construct as bait. We found that the C-terminal type I PDZ binding motif (DTDL) of β-catenin, an adherens junction scaffolding protein and transcriptional co-activator, interacts directly with SNX27. Using biochemical and immunofluorescent techniques, β-catenin was identified in endosomal compartments where co-localization with SNX27 was observed. Furthermore, E-cadherin, but not Axin, GSK3 or Lef-1 was located in SNX27 protein complexes. While overexpression of wild-type β-catenin protein increased TCF-LEF dependent transcriptional activity, an enhanced transcriptional activity was not observed in cells expressing β-Catenin ΔFDTDL or diminished SNX27 expression.
These results imply importance of the C-terminal PDZ binding motif for the transcriptional activity of β-catenin and propose that SNX27 might be involved in the assembly of β-catenin complexes in the endosome.
Seltene Ursache einer gastrointestinalen Blutung
Authors: Rollandi Ludovica-Paola , Kasper Judith , Schaller Tina 
Published: October 2019

Zusammenfassung
Anamnese und klinischer Befund Wir berichten über einen 66-jährigen Patienten mit Plasmozytom, der sich mit seit 3 Tagen bestehendem Teerstuhl, Schwindel und Belastungsdyspnoe vorstellte.
Untersuchung und Diagnose Klinisch und laborchemisch wurde die Verdachtsdiagnose einer kreislaufwirksamen, aktiven gastrointestinalen Blutung gestellt. In der Gastroduodenoskopie und Sigmoidoskopie war keine aktive Blutungsquelle aufzufinden, sodass eine Computertomografie durchgeführt wurde, in der eine auffallende Ballonierung des proximalen Jejunums sowie eine abnormale, pathologische Kontrastmittelanreicherung zu sehen waren. In der anschließend zielgerichteten Jejunoskopie fiel ein aktiv blutender Tumor auf.
Therapie und Verlauf Aufgrund des bekannten Plasmozytomleidens des Patienten wurde die Verdachtsdiagnose einer aktiv blutenden extramedullären Plasmozytommetastase gestellt. Da in der Jejunoskopie nur eine temporäre Blutstillung möglich war, erfolgte eine Segmentresektion des Dünndarms. Die histologische Untersuchung bestätigte die Verdachtsdiagnose.
Folgerung Die Differenzialdiagnose der gastrointestinalen Blutung umfasst auch tumoröse Veränderungen des Dünndarms. Die CT-Diagnostik kann wichtige Hinweise auf Lokalisation und Ursache einer gastrointestinalen Blutung liefern.
Corrective Osteosynthesis in Failed Proximal Humeral Fractures
Authors: Dey Hazra Rony-Orijit , Lill Helmut , Ellwein Alexander , Warnhoff Mara , Jensen Gunnar 
Published: October 2019

AbstractDespite implant improvement and increasing standardisation of operation techniques, the rate of therapy failure of proximal humeral fracture care with primary osteosyntheses is estimated to be 10 to 20%. Most commonly failure is precipitated by: material failure, technical error, non-anatomical repositioning, avascular necrosis, lacking medial support. An additive medial stabilisation of the so-called “calcar region” can decrease failure rates significantly. An early correction osteosynthesis with the purpose of restoring the anatomy is indicated in bony, non-consolidated “fresh” fractures. Bony consolidated fractures should be classified according to Boileau and Walch. The authors of this article advice a structured and classification-adapted approach to treatment with a correction osteosynthesis. Post-traumatic deficits can be augmented utilising the following methods: correction osteosynthesis with allogeneic/autologous bone grafts, correction osteosynthesis with
hydroxyapatite grafts. For the additive stabilisation of repositioned and fixated fractures, the following are described: correction osteosynthesis with an additive ventral one-third tubular plate, correction osteosynthesis with cement-augmented screws. Based on results of endoprosthetics following fractures of the proximal humerus, the correction osteosynthesis indeed represents a real therapeutic alternative in patients that are below the age of 60, a good bone mass and with relative functional requirements.