bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse
Authors: Brown Jessica L. , Sones Jennifer L. , Angulo Cynthia N. , Abbott Keelin , Miller Andrew D. , Boehm Ulrich , Roberson Mark S. 
Published: July 2019

AbstractExtracellular-signal-regulated kinases (ERK) 1 and 2 regulate many aspects of the hypothalamic-pituitary-gonadal axis. We sought to understand the role of ERK1/2 signaling in cells expressing a Cre allele regulated by the endogenous GnRHR promoter (GRIC-ERKdko). Adult female GRIC-ERKdko mice were hypogonadotropic and anovulatory. Gonadotropin administration and mating led to pregnancy in one-third of the ERKdko females. Litters from ERKdko females and pup weights were reduced coincident with delayed parturition and 100% neonatal mortality. Based on this, we examined Cre expression in implantation sites as a potential mechanism. GnRHR mRNA levels at e10.5 and e12.5 were comparable to pituitary levels from adult female mice at proestrus and GnRHR mRNA in decidua was enriched compared to whole implantation site. In vivo studies confirmed recombination in decidua, and GRIC-ERKdko placentas showed reduced ERK2 expression. Histopathology revealed abnormalities in placental architecture in the GRIC-ERKdko animals. Regions of apoptosis at the decidual/uterine interface at e18.5 were observed in control animals but apoptotic tone in these regions was reduced in ERKdko animals. These studies support a potential model of ERK-dependent signaling within the implantation site leading to loss of placental architecture and mis-regulation of apoptotic events at parturition occurring coincident with prolonged gestation and neonatal mortality.
Remote targeted implantation of sound-sensitive biodegradable multi-cavity microparticles with focused ultrasound
Authors: Su Xiaoqian , Thomas Reju George , Bharatula Lakshmi Deepika , Kwan James J. 
Published: July 2019

AbstractUltrasound-enhanced drug delivery has shown great promise in providing targeted burst release of drug at the site of the disease. Yet current solid ultrasound-responsive particles are non-degradable with limited potential for drug-loading. Here, we report on an ultrasound-responsive multi-cavity poly(lactic-co-glycolic acid) microparticle (mcPLGA MP) loaded with rhodamine B (RhB) with or without 4′,6-diamidino-2-phenylindole (DAPI) to represent small molecule therapeutics. After exposure to high intensity focused ultrasound (HIFU), these delivery vehicles were remotely implanted into gel and porcine tissue models, where the particles rapidly released their payload within the first day and sustained release for at least seven days. RhB-mcPLGA MPs were implanted with HIFU into and beyond the sub-endothelial space of porcine arteries without observable damage to the artery. HIFU also guided the location of implantation; RhB-mcPLGA MPs were only observed at the focus of the HIFU away from the direction of ultrasound. Once implanted, DAPI co-loaded RhB-mcPLGA MPs released DAPI into the arterial wall, staining the nucleus of the cells. Our work shows the potential for HIFU-guided implantation of drug-loaded particles as a strategy to improve the local and sustained delivery of a therapeutic for up to two weeks.
Interfacial Effect-Based Quantification of Droplet Isothermal Nucleic Acid Amplification for Bacterial Infection
Authors: Ulep Tiffany-Heather , Day Alexander S. , Sosnowski Katelyn , Shumaker Alexa , Yoon Jeong-Yeol 
Published: July 2019

AbstractBacterial infection is a widespread problem in humans that can potentially lead to hospitalization and morbidity. The largest obstacle for physicians/clinicians is the time delay in accurately identifying infectious bacteria, especially their sub-species, in order to adequately treat and diagnose such infected patients. Loop-mediated amplification (LAMP) is a nucleic acid amplification method that has been widely used in diagnostic applications due to its simplicity of constant temperature, use of up to 4 to 6 primers (rendering it highly specific), and capability of amplifying low copies of target sequences. Use of interfacial effect-based monitoring is expected to dramatically shorten the time-to-results of nucleic acid amplification techniques. In this work, we developed a LAMP-based point-of-care platform for detection of bacterial infection, utilizing smartphone measurement of contact angle from oil-immersed droplet LAMP reactions. Whole bacteria (Escherichia coli O157:H7) were assayed in buffer as well as 5% diluted human whole blood. Monitoring of droplet LAMP reactions was demonstrated in a three-compartment, isothermal proportional-integrated-derived (PID)-controlled chip. Smartphone-captured images of droplet LAMP reactions, and their contact angles, were evaluated. Contact angle decreased substantially upon target amplification in both buffer and whole blood samples. In comparison, no-target control (NTC) droplets remained stable throughout the 30 min isothermal reactions. These results were explained by the pre-adsorption of plasma proteins to an oil-water interface (lowering contact angle), followed by time-dependent amplicon formation and their preferential adsorption to the plasma protein-occupied oil-water interface. Time-to-results was as fast as 5 min, allowing physicians to quickly make their decision for infected patients. The developed assay demonstrated quantification of bacteria concentration, with a limit-of-detection at 102 CFU/μL for buffer samples, and binary target or no-target identification with a limit-of-detection at 10 CFU/μL for 5% diluted whole blood samples.
iTRAQ-based quantitative proteomic analysis of salt stress in Spica Prunellae
Authors: Liu Zixiu , Zou Lisi , Chen Cuihua , Zhao Hui , Yan Ying , Wang Chengcheng , Liu Xunhong 
Published: July 2019

AbstractSpica Prunellae is an important Chinese herbal medicine. Because of its good curative effect on various diseases, this herb is consumed in large quantities in clinical applications. The metabolites of Spica Prunellae are known to change under salt stress; however, the difference in protein levels of Spica Prunellae between saline and normal conditions is unclear. In this study, we used proteomics techniques to identify differentially expressed proteins in Spica Prunellae under different saline conditions. (iTRAQ) MS/MS was used to detect statistically significant changes in protein between salt stress and normal conditions. Ultimately, we detected 1,937 proteins, 89 of which were detected in two different comparison. Based on GO, STRING and KEGG analyses, 35 significantly differentially expressed proteins were selected for further analysis. The results of functional and signal pathway analyses indicated that the cellular protein and carbohydrate metabolism of Spica Prunellae was weaker, calcium ion transport was higher, photosynthesis was higher, and protein production was faster under saline conditions than under normal conditions. This study provides useful information for studying the causes of differences in secondary metabolites in Spica Prunellae under salt stress and the protein mechanisms related to their quality.
Functional and metabolic impairment in cigarette smoke-exposed macrophages is tied to oxidative stress
Authors: Aridgides Daniel S. , Mellinger Diane L. , Armstrong David A. , Hazlett Haley F. , Dessaint John A. , Hampton Thomas H. , Atkins Graham T. , Carroll James L. , Ashare Alix 
Published: July 2019

AbstractCigarette smoke inhalation exposes the respiratory system to thousands of potentially toxic substances and causes chronic obstructive pulmonary disease (COPD). COPD is characterized by cycles of inflammation and infection with a dysregulated immune response contributing to disease progression. While smoking cessation can slow the damage in COPD, lung immunity remains impaired. Alveolar macrophages (AMΦ) are innate immune cells strategically poised at the interface between lungs, respiratory pathogens, and environmental toxins including cigarette smoke. We studied the effects of cigarette smoke on model THP-1 and peripheral blood monocyte derived macrophages, and discovered a marked inhibition of bacterial phagocytosis which was replicated in primary human AMΦ. Cigarette smoke decreased AMΦ cystic fibrosis transmembrane conductance regulator (CFTR) expression, previously shown to be integral to phagocytosis. In contrast to cystic fibrosis macrophages, smoke-exposed THP-1 and AMΦ failed to augment phagocytosis in the presence of CFTR modulators. Cigarette smoke also inhibited THP-1 and AMΦ mitochondrial respiration while inducing glycolysis and reactive oxygen species. These effects were mitigated by the free radical scavenger N-acetylcysteine, which also reverted phagocytosis to baseline levels. Collectively these results implicate metabolic dysfunction as a key factor in the toxicity of cigarette smoke to AMΦ, and illuminate avenues of potential intervention.
Intelligent Diagnostic Prediction and Classification System for Chronic Kidney Disease
Authors: Elhoseny Mohamed , Shankar K. , Uthayakumar J. 
Published: July 2019

AbstractAt present times, healthcare systems are updated with advanced capabilities like machine learning (ML), data mining and artificial intelligence to offer human with more intelligent and expert healthcare services. This paper introduces an intelligent prediction and classification system for healthcare, namely Density based Feature Selection (DFS) with Ant Colony based Optimization (D-ACO) algorithm for chronic kidney disease (CKD). The proposed intelligent system eliminates irrelevant or redundant features by DFS in prior to the ACO based classifier construction. The proposed D-ACO framework three phases namely preprocessing, Feature Selection (FS) and classification. Furthermore, the D-ACO algorithm is tested using benchmark CKD dataset and the performance are investigated based on different evaluation factors. Comparing the D-ACO algorithm with existing methods, the presented intelligent system outperformed the other methodologies with a significant improvisation in classification accuracy using fewer features.
Xylem cavitation susceptibility and refilling mechanisms in olive trees infected by Xylella fastidiosa
Authors: Sabella Erika , Aprile Alessio , Genga Alessandra , Siciliano Tiziana , Nutricati Eliana , Nicolì Francesca , Vergine Marzia , Negro Carmine , De Bellis Luigi , Luvisi Andrea 
Published: July 2019

AbstractIn olive trees, Xylella fastidiosa colonizes xylem vessels and compromises water transport causing the olive quick decline syndrome (OQDS). The loss of hydraulic conductivity could be attributed to vessel occlusions induced both by the bacteria biofilm and by plant responses (tyloses, gums, etc.) that could trigger embolism. The ability of the infected plants to detect embolism and to respond, by activating mechanisms to restore the hydraulic conductivity, can influence the severity of the disease symptomatology. In order to investigate these mechanisms in the X. fastidiosa-resistant olive cultivar Leccino and in the susceptible Cellina di Nardò, sections of healthy olive stems were analysed by laser scanning microscope to calculate the cavitation vulnerability index. Findings indicated that the cultivar Leccino seems to be constitutively less susceptible to cavitation than the susceptible one. Among the vascular refilling mechanisms, starch hydrolysis is a well-known strategy to refill xylem vessels that suffered cavitation and it is characterized by a dense accumulation of starch grains in the xylem parenchima; SEM-EDX analysis of stem cross-sections of infected plants revealed an aggregation of starch grains in the Leccino xylem vessels. These observations could indicate that this cultivar, as well as being anatomically less susceptible to cavitation, it also could be able to activate more efficient refilling mechanisms, restoring vessel’s hydraulic conductivity. In order to verify this hypothesis, we analysed the expression levels of some genes belonging to families involved in embolism sensing and refilling mechanisms: aquaporins, sucrose transporters, carbohydrate metabolism and enzymes related to starch breakdown, alpha and beta-amylase. The obtained genes expression patterns suggested that the infected plants of the cultivar Leccino strongly modulates the genes involved in embolism sensing and refilling.
FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes
Authors: Savchenko Ekaterina , Teku Gabriel N. , Boza-Serrano Antonio , Russ Kaspar , Berns Manon , Deierborg Tomas , Lamas Nuno J. , Wichterle Hynek , Rothstein Jeffrey , Henderson Christopher E. , Vihinen Mauno , Roybon Laurent 
Published: July 2019

AbstractThe glutamate transporter 1 (GLT1) is upregulated during astrocyte development and maturation in vivo and is vital for astrocyte function. Yet it is expressed at low levels by most cultured astrocytes. We previously showed that maturation of human and mouse stem cell-derived astrocytes – including functional glutamate uptake – could be enhanced by fibroblast growth factor (FGF)1 or FGF2. Here, we examined the specificity and mechanism of action of FGF2 and other FGF family members, as well as neurotrophic and differentiation factors, on mouse embryonic stem cell-derived astrocytes. We found that some FGFs – including FGF2, strongly increased GLT1 expression and enhanced astrocyte proliferation, while others (FGF16 and FGF18) mainly affected maturation. Interestingly, BMP4 increased astrocytic GFAP expression, and BMP4-treated astrocytes failed to promote the survival of motor neurons in vitro. Whole transcriptome analysis showed that FGF2 treatment regulated multiple genes linked to cell division, and that the mRNA encoding GLT1 was one of the most strongly upregulated of all astrocyte canonical markers. Since GLT1 is expressed at reduced levels in many neurodegenerative diseases, activation of this pathway is of potential therapeutic interest. Furthermore, treatment with FGFs provides a robust means for expansion of functionally mature stem cell-derived astrocytes for preclinical investigation.
Formation of strength platform in cast Al–Si–Mg–Cu alloys
Authors: Dong Xixi , Amirkhanlou Sajjad , Ji Shouxun 
Published: July 2019

AbstractOver the past several decades, it was generally believed that the strength of the industrially widely used cast Al–Si–Mg–Cu alloys enhanced monotonously with increasing Cu content. However, in this study using cast Al9Si0.5MgxCu (x = 0,0.2,0.4,0.6,0.85,1.0,1.25, in wt.%) alloys under T6 heat-treated condition, it was found that the hardness and yield strength of the heat-treated alloys showed a platform in the composition range from 0.4 wt.% to 0.85 wt.% Cu, while still increased with increasing Cu content before and after the platform. With increasing Cu content, the β-Mg2Si intermetallic phase decreased and disappeared at 0.85 wt.% Cu, while the Q–Al5Cu2Mg8Si6 and θ–Al2Cu intermetallic phases increased in the as-cast alloys. After heat treatment, the micron-scale intermetallic phases were dissolved into the Al matrix and precipitated as the nanoscale β″, Q′ and θ′ strengthening phases. With increasing Cu content, the β″ precipitate decreased and vanished at 0.85 wt.% Cu, while the Q′ and θ′ precipitates increased in the heat-treated alloys. The trade-off of the phases induces the platform in the strength of the heat-treated alloys, and further increase of the Cu content in this undetected trapped platform range is not favorited industrially as it only decreases ductility.
Down-regulated microRNA-30b-3p inhibits proliferation, invasion and migration of glioma cells via inactivation of the AKT signaling pathway by up-regulating RECK
Authors: Jian Yan , Xu Chun-Hua , Li You-Ping , Tang Bin , Xie She-Hao , Zeng Er-Ming 
Published: July 2019

Abstract
microRNAs (miRNAs) have been found to affect various cancers, and expression of numerous miRNAs is revealed in glioma. However, the role of microRNA-30b-3p (miR-30b-3p) in glioma remains elusive. Therefore, the present study aims to explore the specific mechanism by which miR-30b-3p influence the development of glioma in relation to the AKT signaling pathway. First, glioma cell lines were collected with miR-30b-3p and reversion-inducing cysteine-rich protein with kazal motifs (RECK) expression measured. The functional role of miR-30b-3p and RECK in glioma was determined via gain- and loss-of-function approaches. Subsequently, the expression of invasion- and migration-related factors (MMP-2 and MMP-9) and the AKT signaling pathway-related factors (AKT, p-AKT and PI3K-p85) was detected. Moreover, in vivo experiments were also conducted to investigate how miR-30b-3p influences in vivo tumorigenesis. The results showed that miR-30b-3p was up-regulated and RECK was down-regulated in glioma. RECK was a target gene of miR-30b-3p. Decreased miR-30b-3p and overexpressed RECK led to decreased expression of MMP-2, MMP-9 and p-AKT. Overexpressed RECK and LY294002 could decrease p-AKT and PI3K-p85 expression accompanied with unchanged expression of total protein of AKT. Additionally, proliferation, migration and invasion of glioma cells and tumor formation in nude mice were repressed owing to reduced expression of miR-30b-3p or elevated expression of RECK. In summary, miR-30b-3p inhibition suppresses metastasis of glioma cells by inactivating the AKT signaling pathway via RECK up-regulation, providing a new target for glioma treatment.
La sonde atomique tomographique
Authors: Rigutti Lorenzo , Vurpillot François , Lefebvre Williams , Vella Angela 
Published: July 2019

Au cours de la dernière décennie, la sonde atomique tomographique a élargi son domaine d’application, en partie grâce à de nouvelles approches qui l’associent à plusieurs techniques pour l’étude d’un même échantillon, permettant de lier propriétés structurales et fonctionnelles d’une variété croissante de systèmes.Mais, au-delà de ses capacités d’imagerie et d’analyse, des développements récents montrent qu’elle peut également être considérée comme un laboratoire pour l’étude du comportement de la matière sous champ intense et de l’interaction rayonnementmatière aux échelles nanométrique et atomique.
Avaliação clínica e radiológica dos pacientes submetidos a osteossíntese de rádio distal com placas bloqueadas – estudo retrospectivo
Authors: Câmara Filho Jurandyr de Abreu , Almeida Saulo Fontes 
Published: July 2019

Resumo
Objetivo O objetivo do presente trabalho foi realizar um estudo retrospectivo, com base no arquivo médico dos prontuários e das radiografias dos pacientes, avaliando seus dados socioeconômicos, assim como clinicamente e radiograficamente, os pacientes submetidos a osteossíntese de rádio distal com placas bloqueadas.
Métodos Avaliou-se clinicamente e radiologicamente o pós-operatório, no Serviço da clínica de Ortopedia e Traumatologia do nosso hospital, entre os anos de 2016 e 2017.
Resultados Na avaliação radiográfica, foram encontrados 22 (75,86%) resultados excelentes, 6 (20,69%) bons e 1 (3,45%) regular. Na avaliação clínica, o desvio ulnar obteve média de 28,40, desvio padrão (DP) de 3,0 e coeficiente de variação de 10,56%. O desvio radial obteve média de 22,93, DP de 2,2 e coeficiente de variação de 9,59%. A amplitude de movimento em flexão obteve média de 59,43, DP de 9,86 e coeficiente de variação de 16,59%. Já a extensão obteve média de 53,83, DP de 5,09 e coeficiente de variação de 9,46%.
Conclusão Concluímos que há correlação estatística entre os dados clínicos e radiográficos, e que a placa bloqueada é um método de tratamento com alto índice de sucesso no procedimento cirúrgico das fraturas de rádio distal.
Femoral Component Malrotation Produces Quadriceps Weakness and Impaired Ambulatory Function following Total Knee Arthroplasty: Results of a Forward-Dynamic Computer Model
Authors: Nettrour John F. , Razu Swithin S. , Keeney James A. , Guess Trent M. 
Published: July 2019

AbstractProper placement of the prosthetic components is believed to be an important factor in successful total knee arthroplasty (TKA). Implant positioning errors have been associated with postoperative pain, suboptimal function, and inferior patient-reported outcome measures. The purpose of this study was to investigate the biomechanical effects of femoral component malrotation on quadriceps function and normal ambulation. For the investigation, publicly available data were used to create a validated forward-dynamic, patient-specific computer model. The incorporated data included medical imaging, gait laboratory measurements, knee loading information, electromyographic data, strength testing, and information from the surgical procedure. The ideal femoral component rotation was set to the surgical transepicondylar axis and walking simulations were subsequently performed with increasing degrees of internal and external rotation of the femoral component. The muscle force outputs were then recorded for the quadriceps musculature as a whole, as well as for the individual constituent muscles. The quadriceps work requirements during walking were then calculated for the different rotational simulations. The highest forces generated by the quadriceps were seen during single-limb stance phase as increasing degrees of femoral internal rotation produced proportional increases in quadriceps force requirements. The individual muscles of the quadriceps displayed different sensitivities to the rotational variations introduced into the simulations with the vastus lateralis showing the greatest changes with rotational positioning. Increasing degrees of internal rotation of femoral component were also seen to demand increasing quadriceps work to support normal ambulation. In conclusion, internal malrotation of the femoral component during TKA produces a mechanically disadvantaged state which is characterized by greater required quadriceps forces (especially the vastus lateralis) and greater quadriceps work to support normal ambulation.
Planning on CT-Based 3D Virtual Models Can Accurately Predict the Component Size for Total Knee Arthroplasty
Authors: León-Muñoz Vicente J. , Lisón-Almagro Alonso J. , López-López Mirian 
Published: July 2019

AbstractThe ability to predict accurate sizing of the implant components for total knee arthroplasty surgery can have several benefits in the operating room, in terms of simplifying the workflow and reducing the number of required instrument trays. Planning on a three-dimensional (3D) virtual model can be used to predict size. The aim of this study was to quantify the accuracy of the surgeon-validated plan prediction on a computed tomography (CT)-based system. The clinical records of 336 cases (267 patients), operated using a CT-based patient-specific instrumentation, have been reviewed for the size of implanted components. Preoperative default planning (according to the preferences of the surgeon) and approved planning have been compared with the size of implanted components for both the femur and tibia. The prosthesis size, preplanned by the manufacturers, was modified by the surgeon during the validation process in 0.9% of cases for the femoral component and in 2.7% of cases for the tibial component. The prosthesis size, preplanned by the surgeon after the validation process, was used in 95.8% for the femur and 92.6% for the tibia. Concordance on the size of the surgeon-validated plan and the finally implanted size was perfect for both, the femoral (κ  =  0.951; 95% confidence interval [CI]: 0.92–0.98) and the tibial component (κ  =  0.902; 95% CI: 0.86–0.94). The most frequent change of size (51%) was an increase by one size of the planned tibial component. Planning of knee arthroplasty surgery on a 3D virtual, CT-based model is useful to surgeons to help predict the size of the implants to be used in surgery. The system we have used can accurately predict the component size for both the femur and tibia. This study reflects a study of level III evidence.