bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis
Authors: Campsie Paul , Childs Peter G. , Robertson Shaun N. , Cameron Kenny , Hough James , Salmeron-Sanchez Manuel , Tsimbouri Penelope M. , Vichare Parag , Dalby Matthew J. , Reid Stuart 
Published: September 2019

AbstractIn regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of mesenchymal stem cells (MSCs) has been shown to activate mechanotransduction pathways stimulating osteogenesis in 2D and 3D culture. This has the potential to revolutionise bone graft procedures by creating cellular graft material from autologous or allogeneic sources of MSCs without using chemical induction. With the increased interest in mechanical stimulation of cells and huge potential for clinical use, it is apparent that researchers and clinicians require a scalable bioreactor system that provides consistently reproducible results with a simple turnkey approach. A novel bioreactor system is presented that consists of: a bioreactor vibration plate, calibrated and optimised for nanometre vibrations at 1 kHz, a power supply unit, which supplies a 1 kHz sine wave signal necessary to generate approximately 30 nm of vibration amplitude, and custom 6-well cultureware with toroidal shaped magnets incorporated in the base of each well for conformal attachment to the bioreactor’s magnetic vibration plate. The cultureware and vibration plate were designed using finite element analysis to determine the modal and harmonic responses, and validated by interferometric measurement. This helps ensure that the vibration plate and cultureware, and thus collagen and MSCs, all move as a rigid body, avoiding large deformations close to the resonant frequency of the vibration plate and vibration damping beyond the resonance. Assessment of osteogenic protein expression was performed to confirm differentiation of MSCs after initial biological experiments with the system, as well as atomic force microscopy of the 3D gel constructs during vibrational stimulation to verify that strain hardening of the gel did not occur. This shows that cell differentiation was the result of the nanovibrational stimulation provided by the bioreactor alone, and that other cell differentiating factors, such as stiffening of the collagen gel, did not contribute.
Galactomannan and PCR in the Central Nervous System to Detect Invasive Mold Disease - A Retrospective Analysis in Immunocompromised Children
Authors: Lehrnbecher Thomas , Rath Peter Michael , Attarbaschi Andishe , Cario Gunnar , Döring Michaela , Moser Olga , Mücke Urs , Poyer Fiona , Rieken Sarah , Temme Christian , Voigt Sebastian , Groll Andreas H. , Lauten Melchior 
Published: September 2019

AbstractInvasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, but early microbiological diagnosis is difficult. As data on the value of biomarkers in the CNS are scarce, in particular in children, we retrospectively analyzed the performance of galactomannan (GM) and PCR assays in CNS samples of 15 children with proven and probable CNS IMD and of 32 immunocompromised children without fungal infection. Galactomannan in the cerebrospinal fluid (CSF) was assessed in nine of the 15 pediatric patients and was positive in five of them. Polymerase chain reaction (PCR) was performed in eight of the 15 patients and detected nucleic acids from molds in six patients. Galactomannan and PCR in CNS samples were the only positive microbiologic parameter in the CNS in three and two patients, respectively. In four patients, PCR specified the pathogen detected in microscopy. Galactomannan and PCR results remained negative in the CSF of all immunocompromised children without evidence for CNS IMD. Our data suggest that GM and PCR in CNS specimens are valuable additional tools in diagnosing CNS IMD and should be included in the work up of all pediatric patients with suspected mold disease of the CNS.
Relative abundance of oceanic juvenile loggerhead sea turtles in relation to nest production at source rookeries: implications for recruitment dynamics
Authors: Vandeperre Frederic , Parra Hugo , Pham Christopher K. , Machete Miguel , Santos Marco , Bjorndal Karen A. , Bolten Alan B. 
Published: September 2019

AbstractAfter hatching, juveniles of most sea turtle species undertake long migrations across ocean basins and remain in oceanic habitats for several years. Assessing population abundance and demographic parameters during this oceanic stage is challenging. Two long-recognized deficiencies in population assessment are (i) reliance on trends in numbers of nests or reproductive females at nesting beaches and (ii) ignorance of factors regulating recruitment to the early oceanic stage. To address these critical gaps, we examined 15 years of standardized loggerhead sighting data collected opportunistically by fisheries observers in the Azores archipelago. From 2001 to 2015, 429 loggerheads were sighted during 67,922 km of survey effort. We used a model-based approach to evaluate the influence of environmental factors and present the first estimates of relative abundance of oceanic-stage juvenile sea turtles. During this period, relative abundance of loggerheads in the Azores tracked annual nest abundance at source rookeries in Florida when adjusted for a 3-year lag. This concurrence of abundance patterns indicates that recruitment to the oceanic stage is more dependent on nest abundance at source rookeries than on stochastic processes derived from short term climatic variability, as previously believed.
Non-invasive Potential Circulating mRNA Markers for Colorectal Adenoma Using Targeted Sequencing
Authors: Xue Vivian W. , Cheung Moon T. , Chan Pak T. , Luk Lewis L. Y. , Lee Vivian H. , Au Thomas C. , Yu Allen C. , Cho William C. S. , Tsang Hin Fung Andy , Chan Amanda K. , Wong S. C. Cesar 
Published: September 2019

AbstractWe have developed an optimized protocol for plasma targeted mRNA sequencing in our previous study. Here, we performed plasma targeted mRNA sequencing for 40 colorectal adenoma patients and 39 colonoscopy-proven normal controls in order to find potential circulating mRNA markers for colorectal adenoma. Results showed thatGSK3AandRHOAwere differential expressed genes identified by a cut-off of fold change >2 and adjustedPvalue < 0.05. More detailed analysis showed that the expression of bothGSK3A(0.01-fold with adjustedP < 1 × 10−6) andRHOA(0.35-fold with adjustedP < 0.01) in adenoma patients was significantly lower than those in normal healthy subjects. Based on the enrichment analysis of biological process for potential markers, we found that the regulation of programmed cell death (GO: 0043067; GO: 0043069), regulation of cell death (GO: 0010941; GO: 0060548) and cell differentiation (GO: 0021861) were the main processes involved in adenoma formation. In summary, this study is a cutting-edge research on the detection of plasma mRNA in colorectal adenoma patients and normal healthy subjects.
Characterization of a novel LQT3 variant with a selective efficacy of mexiletine treatment
Authors: Kim Hyun-Ji , Kim Bok-Geon , Park Jong Eun , Ki Chang-Seok , Huh June , Youm Jae Boum , Kang Jong-Sun , Cho Hana 
Published: September 2019

AbstractPathogenic variants in the human SCN5A gene encoding the a-subunit of the principle Na+ channel (Nav1.5) are associated with long QT syndrome (LQTS) 3. LQT3 patients display variable responses to Na+ channel blockers demanding for the development of variant-specific therapeutic strategies. Here we performed a combined electrophysiological analysis with in silico simulation of variant channel to elucidate mechanisms of therapeutic responsiveness. We identified a novel SCN5A variant (A1656D) in a LQTS patient with a distinct response to mexiletine resulting in suppression of non-sustained ventricular tachycardia and manifestation of premature atrial contraction. Patch clamp analysis revealed that A1656D variant exerted gain-of-function effects including hyperpolarizing shift of the voltage-dependence of activation, depolarizing shift in the voltage-dependence of inactivation, and slowing of fast inactivation. Among ranolazine, flecainide, and mexiletine, only mexiletine restored inactivation kinetics of A1656D currents. In silico simulation to assess the effect of A1656D variant on ventricular cardiac cell excitation predicted a prolonged action potential which is consistent with the prolonged QT and non-sustained ventricular tachycardia of the patient. It also predicted that only mexiletine suppressed the prolonged action potential of human ventricular myocytes expressing A1656D. These data elucidate the underlying mechanism of the distinct response to mexiletine in this patient.
Genome wide transcriptome analysis reveals vital role of heat responsive genes in regulatory mechanisms of lentil (Lens culinaris Medikus)
Authors: Singh Dharmendra , Singh Chandan Kumar , Taunk Jyoti , Jadon Vasudha , Pal Madan , Gaikwad Kishor 
Published: September 2019

AbstractThe present study reports the role of morphological, physiological and reproductive attributes viz. membrane stability index (MSI), osmolytes accumulations, antioxidants activities and pollen germination for heat stress tolerance in contrasting genotypes. Heat stress increased proline and glycine betaine (GPX) contents, induced superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione peroxidase (GPX) activities and resulted in higher MSI in PDL-2 (tolerant) compared to JL-3 (sensitive).In vitropollen germination of tolerant genotype was higher than sensitive one under heat stress.In vivostressed pollens of tolerant genotype germinated well on stressed stigma of sensitive genotype, while stressed pollens of sensitive genotype did not germinate on stressed stigma of tolerant genotype.De novotranscriptome analysis of both the genotypes showed that number of contigs ranged from 90,267 to 104,424 for all the samples with N50ranging from 1,755 to 1,844 bp under heat stress and control conditions. Based on assembled unigenes, 194,178 high-quality Single Nucleotide Polymorphisms (SNPs), 141,050 microsatellites and 7,388 Insertion-deletions (Indels) were detected. Expression of 10 genes was evaluated using quantitative Real Time Polymerase Chain Reaction (RT-qPCR). Comparison of differentially expressed genes (DEGs) under different combinations of heat stress has led to the identification of candidate DEGs and pathways. Changes in expression of physiological and pollen phenotyping related genes were also reaffirmed through transcriptome data. Cell wall and secondary metabolite pathways are found to be majorly affected under heat stress. The findings need further analysis to determine genetic mechanism involved in heat tolerance of lentil.
NeTFactor, a framework for identifying transcriptional regulators of gene expression-based biomarkers
Authors: Ahsen Mehmet Eren , Chun Yoojin , Grishin Alexander , Grishina Galina , Stolovitzky Gustavo , Pandey Gaurav , Bunyavanich Supinda 
Published: September 2019

AbstractBiological and regulatory mechanisms underlying many multi-gene expression-based disease biomarkers are often not readily evident. We describe an innovative framework,NeTFactor, that combines network analyses with gene expression data to identify transcription factors (TFs) that significantly and maximally regulate such a biomarker. NeTFactor uses a computationally-inferred context-specific gene regulatory network and applies topological, statistical, and optimization methods to identify regulator TFs. Application of NeTFactor to a multi-gene expression-based asthma biomarker identified ETS translocation variant 4 (ETV4) and peroxisome proliferator-activated receptor gamma (PPARG) as the biomarker’s most significant TF regulators. siRNA-based knock down of these TFs in an airway epithelial cell line model demonstrated significant reduction of cytokine expression relevant to asthma, validating NeTFactor’s top-scoring findings. While PPARG has been associated with airway inflammation, ETV4 has not yet been implicated in asthma, thus indicating the possibility of novel, disease-relevant discovery by NeTFactor. We also show that NeTFactor’s results are robust when the gene regulatory network and biomarker are derived from independent data. Additionally, our application of NeTFactor to a different disease biomarker identified TF regulators of interest. These results illustrate that the application of NeTFactor to multi-gene expression-based biomarkers could yield valuable insights into regulatory mechanisms and biological processes underlying disease.
Association between regular walking and periodontitis according to socioeconomic status: a cross-sectional study
Authors: Han Su-Jin , Bae Kwang-Hak , Lee Hyo-Jin , Kim Seon-Jip , Cho Hyun-Jae 
Published: September 2019

AbstractPhysical activity reduces the risk and mortality risk of inflammatory diseases. This study aimed to examine the relationship between regular walking and periodontitis in a Korean representative sample of adults according to socioeconomic status. Data acquired by the Sixth Korea National Health and Nutrition Examination Survey in 2014 and 2015 were used. The survey was completed by 11,921 (5,175 males; 6,746 females) participants (≥19 years). Individuals without values on periodontitis were excluded, and 9,728 participants remained. Multivariable logistic regression analysis was done using socio-demographic characteristics (age, gender, income, education), oral health-related variables (flossing, interdental brushing, community periodontal index), oral and general health status and behaviour (smoking, diabetes mellitus), and regular walking. In all models, subjects who walked regularly had significantly lower risks of periodontitis. After adjusting for age, gender, income, education, smoking, diabetes mellitus, flossing, and interdental brushing, the odds ratio for periodontitis in subjects who walked regularly was 0.793 (95% Confidence interval: 0.700–0.898). Non-regular walking groups showed similar social gradients. Risk of low socioeconomic status was not significant in the regular walking group after adjusting for age, gender, income, and education. This study found that regular walking is associated to lower prevalence of periodontitis and can attenuate the relationship between periodontitis and low socioeconomic status.
The roles of glucagon-like peptide-2 and the intestinal epithelial insulin-like growth factor-1 receptor in regulating microvillus length
Authors: Markovic Melanie A. , Brubaker Patricia L. 
Published: September 2019

AbstractMicrovilli are tiny projections on the apical end of enterocytes, aiding in the digestion and absorption of nutrients. One of their key features is uniform length, but how this is regulated is poorly understood. Glucagon-like peptide-2 (GLP-2) has been shown to increase microvillus length but, the requirement of its downstream mediator, the intestinal epithelial insulin-like growth factor-1 receptor (IE-IGF-1R), and the microvillus proteins acted upon by GLP-2, remain unknown. Using IE-IGF-1R knockout (KO) mice, treated with either long-acting human (h) (GLY2)GLP-2 or vehicle for 11d, it was found that the h(GLY2)GLP-2-induced increase in microvillus length required the IE-IGF-1R. Furthermore, IE-IGF-1R KO alone resulted in a significant decrease in microvillus length. Examination of the brush border membrane proteome as well as of whole jejunal mucosa demonstrated that villin was increased with h(GLY2)GLP-2 treatment in an IE-IGF-1R-dependent manner. Under both basal conditions and with h(GLY2)GLP-2 treatment of the IE-IGF-1R KO mice, changes in villin, IRTKS-1, harmonin, β-actin, and myosin-1a did not explain the decrease in microvillus length, in either the brush border or jejunal mucosa of KO animals. Collectively, these studies define a new role for the IE-IGF-1R within the microvillus, in both the signaling cascade induced by GLP-2, as well as endogenously.
Towards the realistic computer model of precipitation polymerization microgels
Authors: Rudyak Vladimir Yu. , Kozhunova Elena Yu. , Chertovich Alexander V. 
Published: September 2019

AbstractIn this paper we propose a new method of coarse-grained computer simulations of the microgel formation in course of free radical precipitation polymerization. For the first time, we simulate the precipitation polymerization process from a dilute solution of initial components to a final microgel particle with coarse grained molecular dynamics, and compare it to the experimental data. We expect that our simulation studies of PNIPA-like microgels will be able to elucidate the subject of nucleation and growth kinetics and to describe in detail the network topology and structure. Performed computer simulations help to determine the characteristic phases of the growth process and show the necessity of prolongated synthesis for the formation of stable microgel particles. We demonstrate the important role of dangling ends in microgels, which occupy as much as 50% of its molecular mass and have previously unattended influence on the swelling behavior. The verification of the model is made by the comparison of collapse curves and structure factors between simulated and experimental systems, and high quality matching is achieved. This work could help to open new horizons in studies that require the knowledge of detailed and realistic structures of the microgel networks.
Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Bae Jae Hyun , Park Eun-Gee , Kim Sunhee , Kim Sin Gon , Hahn Seokyung , Kim Nam Hoon 
Published: September 2019

AbstractThis study was conducted to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual renal outcomes in patients with type 2 diabetes. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2017 to identify randomized controlled trials comparing SGLT2 inhibitors with placebo or antidiabetic drugs and reporting any renal outcomes in patients with type 2 diabetes. Additionally, we identified 4 articles which were published after the predefined period to include relevant data. A meta-analysis was performed to calculate weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) for each renal outcome. We included 48 studies involving 58,165 patients in the analysis. SGLT2 inhibitors significantly lowered urine albumin-to-creatinine ratio (UACR) (WMD, −14.64 mg/g; 95% CI, −25.15 to −4.12;P = 0.006) compared with controls. The UACR-lowering effects of SGLT2 inhibitors were greater with a higher baseline UACR. Overall changes in estimated glomerular filtration rate (eGFR) were comparable between two groups (WMD, 0.19 mL/min/1.73 m2; 95% CI, −0.44 to 0.82;P = 0.552). However, SGLT2 inhibitors significantly slowed eGFR decline in patients with a higher baseline eGFR and a longer duration of treatment. Compared with controls, SGLT2 inhibitors significantly reduced the risk of microalbuminuria (RR, 0.69; 95% CI, 0.49 to 0.97;P = 0.032), macroalbuminuria (RR, 0.49; 95% CI, 0.33 to 0.73;P < 0.001), and worsening nephropathy (RR, 0.73; 95% CI, 0.58 to 0.93;P = 0.012). In addition, the risk of end-stage renal disease was significantly lower in SGLT2 inhibitors than in controls (RR, 0.70; 95% CI, 0.57 to 0.87;P = 0.001). In conclusion, SGLT2 inhibitors had beneficial renal effects by lowering the risk of albuminuria development or progression and reducing the risk of end-stage renal disease compared with placebo or other antidiabetic drugs.
Luciferase gene of a Caribbean fireworm (Syllidae) from Puerto Rico
Authors: Mitani Yasuo , Yasuno Rie , Futahashi Ryo , Oakley Todd H. , Ohmiya Yoshihiro 
Published: September 2019

AbstractThe fireworms Odontosyllis spp. are globally distributed and well-known for their characteristic and fascinating mating behavior, with secreted mucus emitting bluish-green light. However, knowledge about the molecules involved in the light emission are still scarce. The fireworms are believed to emit light with a luciferin-luciferase reaction, but biochemical evidence of the luciferase is established for only one species living in Japan and no information is available for its luciferin structure. In this study, we identified a luciferase gene from a related Puerto Rican fireworm. We identified eight luciferase-like genes in this Puerto Rican fireworm, finding amino acid identities between Japanese and Puerto Rican luciferase-like genes to be less than 60%. We confirmed cross reactivity of extracts of the Japanese fireworm luciferin with a recombinant Puerto Rican luciferase (PR1). The emission spectrum of recombinant PR1 was similar to the crude extract of the native luciferase, suggesting that PR1 is a functional luciferase of this Puerto Rican fireworm. Our results indicate that the molecular mechanism of luminescence is widely conserved among fireworms.
Low on-treatment diastolic blood pressure and cardiovascular outcome: A post-hoc analysis using NHLBI SPRINT Research Materials
Authors: Sobieraj Piotr , Lewandowski Jacek , Siński Maciej , Gaciong Zbigniew 
Published: September 2019

AbstractRecent studies including the SPRINT trial have shown beneficial effects of intensive systolic blood pressure reduction over the standard approach. The awareness of the J-curve for diastolic blood pressure (DBP) causes some uncertainty regarding the net clinical effects of blood pressure reduction. The current analysis was performed to investigate effects of low on-treatment DBP on cardiovascular risk in the SPRINT population. The primary composite outcome was the occurrence of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure or death from cardiovascular causes. The prevalence of primary outcomes was significantly higher in subjects within low DBP in both standard (44–67 mmHg [10.8%] vs 67–73 mmHg [6.7%] vs 73–78 mmHg [5.1%] vs 78–83 mmHg [4.4%] vs 83–113 mmHg [4.3%], p < 0.001) and intensive treatment (38–61 mmHg [6.7%] vs 61–66 mmHg [4.1%] vs 66–70 mmHg [4.5%] vs 70–74 mmHg [2.7%] vs 74–113 mmHg [3.4%], p < 0.001) arms. After adjusting for covariates, low DBP showed no significant effects on cardiovascular risk. Therefore, while reaching blood pressure targets, low DBP should not be a matter of concern.