bluuebunny/crossref_metadata_2025_split huggingface dataset:
20 Years of DIEAP Flap Breast Reconstruction: A Big Data Analysis
Authors: Depypere Bernard , Herregods Sofie , Denolf Jacob , Kerkhove Louis-Philippe , Mainil Laurent , Vyncke Tom , Blondeel Phillip , Depypere Herman 
Published: September 2019

AbstractWith every hospital admission, a vast amount of data is collected from every patient. Big data can help in data mining and processing of this volume of data. The goal of this study is to investigate the potential of big data analyses by analyzing clinically relevant data from the immediate postoperative phase using big data mining techniques. A second aim is to understand the importance of different postoperative parameters. We analyzed all data generated during the admission of 739 women undergoing a free DIEAP flap breast reconstruction. The patients’ complete midcare nursing report, laboratory data, operative reports and drug schedule were examined (7,405,359 data points). The duration of anesthesia does not predict the need for revision. Low Red Blood cell Counts (3.53 × 106/µL versus 3.79 × 106/µL, p < 0.001) and a low MAP (MAP = 73.37 versus 76.62; p < 0.001) postoperatively are correlated with significantly more revisions. Different drugs (asthma/COPD medication, Butyrophenones) can also play a significant role in the success of the free flap. In a world that is becoming more data driven, there is a clear need for electronic medical records which are easy to use for the practitioner, nursing staff, and the researcher. Very large datasets can be used, and big data analysis allows a relatively easy and fast interpretation all this information.
The role of NaV channels in synaptic transmission after axotomy in a microfluidic culture platform
Authors: Vysokov Nickolai , McMahon Stephen B. , Raouf Ramin 
Published: September 2019

AbstractVoltage gated sodium channels are key players in aberrant pain signaling and sensitization of nociceptors after peripheral nerve injury. The extent to which sodium channel activity after injury contributes to synaptic transmission at the first pain synapse however remains unclear. To investigate the effect of axotomy on synaptic transmission between dorsal root ganglia neurons and dorsal horn neurons, we reconstructed the first pain synapse in a novel microfluidic based compartmentalized cell culture system, which recapitulates the connectivity of peripheral pain signaling. We show that following axotomy of the distal axons, inhibition of NaV1.7 and NaV1.8 sodium channels in incoming presynaptic DRG axons is no longer sufficient to block activation of these axons and the resulting synaptic transmission to dorsal horn neurons. We found that blockade of NaV1.6 activity is highly effective in reducing activation of incoming axons contributing to synaptic transmission after axotomy of DRG neurons. The microfluidic culture system described here offers an in vitro platform to recapitulate and study the first pain synapse.
An Improved Method of Maintaining Primary Murine Cardiac Fibroblasts in Two-Dimensional Cell Culture
Authors: Landry Natalie M. , Rattan Sunil G. , Dixon Ian M. C. 
Published: September 2019

AbstractPrimary cardiac fibroblasts are notoriously difficult to maintain for extended periods of time in cell culture, due to the plasticity of their phenotype and sensitivity to mechanical input. In order to study cardiac fibroblast activation in vitro, we have developed cell culture conditions which promote the quiescent fibroblast phenotype in primary cells. Using elastic silicone substrata, both rat and mouse primary cardiac fibroblasts could be maintained in a quiescent state for more than 3 days after isolation and these cells showed low expression of myofibroblast markers, including fibronectin extracellular domain A, non-muscle myosin IIB, platelet-derived growth factor receptor-alpha and alpha-smooth muscle actin. Gene expression was also more fibroblast-like vs. that of myofibroblasts, as Tcf21 was significantly upregulated, while Fn1-EDA, Col1A1 and Col1A2 were markedly downregulated. Cell culture conditions (eg. serum, nutrient concentration) are critical for the control of temporal fibroblast proliferation. We propose that eliminating mechanical stimulus and limiting the nutrient content of cell culture media can extend the quiescent nature of primary cardiac fibroblasts for physiological analyses in vitro.
Overexpression and alternative splicing of NF-YA in breast cancer
Authors: Dolfini Diletta , Andrioletti Valentina , Mantovani Roberto 
Published: September 2019

AbstractNF-Y is a CCAAT-binding trimeric transcription factor, whose regulome, interactome and oncogenic potential point to direct involvement in cellular transformation. Yet little is known about the levels of NF-Y subunits in tumors. We focused on breast carcinomas, and analyzed RNA-Seq datasets of TCGA and 54 BRCA cell lines at gene and isoforms level. We partitioned all tumors in the four major subclasses. NF-YA, but not histone-fold subunits NF-YB/NF-YC, is globally overexpressed, correlating with the proliferative Ki67 marker and a common set of 840 genes, with cell-cycle, metabolism GO terms. Their promoters are enriched in NF-Y, GC-rich and E2F sites. Surprisingly, there is an isoform switch, with the “short” isoform -NF-YAs- becoming predominant in tumors. E2F genes are also overexpressed in BRCA, but no switch in isoforms is observed. In Basal-like Claudinlow cell lines and tumors, expression of NF-YAl -long- isoform is high, together with 11 typical EMT markers and low levels of basal Keratins. Analysis of Progression-Free-Intervals indicates that tumors with unbalance of NF-YA isoforms ratios have worst clinical outcomes. The data suggest that NF-YA overexpression increases CCAAT-dependent, pro-growth genes in BRCA. NF-YAs is associated with a proliferative signature, but high levels of NF-YAl signal loss of epithelial features, EMT and acquisition of a more aggressive behavior in a subset of Claudinlow Basal-like tumors.
A high efficiency silicon nitride waveguide grating coupler with a multilayer bottom reflector
Authors: Hong Jianxun , Spring Andrew M. , Qiu Feng , Yokoyama Shiyoshi 
Published: September 2019

AbstractWe propose a high efficiency apodized grating coupler with a bottom reflector for silicon nitride photonic integrated circuits. The reflector consists of a stack of alternate silicon nitride and silicon dioxide quarter-wave films. The design, fabrication and optical characterization of the couplers has been presented. The measured fiber to detector insertion loss was −3.5 dB which corresponds to a peak coupling efficiency of −1.75 dB. A 3 dB wavelength bandwidth of 76.34 nm was demonstrated for the grating coupler with a 20-layer reflector. The fabrication process is CMOS-compatible and requires only a single etching step.
Resting-state brain functional connectivity in patients with chronic pain who responded to subanesthetic-dose ketamine
Authors: Motoyama Yasushi , Oshiro Yoshitetsu , Takao Yumiko , Sato Hitoaki , Obata Norihiko , Izuta Shinichiro , Mizobuchi Satoshi , Kan Shigeyuki 
Published: September 2019

AbstractKetamine has been used to treat chronic pain; however, it is still unknown as to what types of chronic pain is ketamine effective against. To identify the effect of administration of subanesthetic-dose ketamine in patients with chronic pain and to clarify the mechanism of the effect, we retrospectively investigated brain functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). Patients were divided into responders (Group R: ≥50% improvement on Numerical Rating Scale) and non-responders (Group NR). We compared the differences in terms of brain functional connectivity by seed-to-voxel correlation analysis. Two-sample t-test revealed significant lower connectivity between the medial prefrontal cortex (mPFC) and precuneus in Group R. We also found a significant negative correlation between the improvement rate and functional connectivity strength between the mPFC and precuneus. These findings suggest that subanesthetic-dose ketamine is effective in patients with chronic pain whose brain functional connectivity between the mPFC and precuneus is low. We believe that the current study explored for the first time the correlation between brain functional connectivity and the effect of subanesthetic-dose ketamine for chronic pain and indicated the possibility of use of the predictive marker in pharmacological treatment of chronic pain.
Metagenomic analysis using next-generation sequencing of pathogens in bronchoalveolar lavage fluid from pediatric patients with respiratory failure
Authors: Takeuchi Suguru , Kawada Jun-ichi , Horiba Kazuhiro , Okuno Yusuke , Okumura Toshihiko , Suzuki Takako , Torii Yuka , Kawabe Shinji , Wada Sho , Ikeyama Takanari , Ito Yoshinori 
Published: September 2019

AbstractNext-generation sequencing (NGS) has been applied in the field of infectious diseases. Bronchoalveolar lavage fluid (BALF) is considered a sterile type of specimen that is suitable for detecting pathogens of respiratory infections. The aim of this study was to comprehensively identify causative pathogens using NGS in BALF samples from immunocompetent pediatric patients with respiratory failure. Ten patients hospitalized with respiratory failure were included. BALF samples obtained in the acute phase were used to prepare DNA- and RNA-sequencing libraries. The libraries were sequenced on MiSeq, and the sequence data were analyzed using metagenome analysis tools. A mean of 2,041,216 total reads were sequenced for each library. Significant bacterial or viral sequencing reads were detected in eight of the 10 patients. Furthermore, candidate pathogens were detected in three patients in whom etiologic agents were not identified by conventional methods. The complete genome of enterovirus D68 was identified in two patients, and phylogenetic analysis suggested that both strains belong to subclade B3, which is an epidemic strain that has spread worldwide in recent years. Our results suggest that NGS can be applied for comprehensive molecular diagnostics as well as surveillance of pathogens in BALF from patients with respiratory infection.
αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type
Authors: Ida Koichi , Yamanoi Kazuhiro , Asaka Shiho , Takeuchi Hodaka , Miyamoto Tsutomu , Shiozawa Tanri , Nakayama Jun 
Published: September 2019

AbstractCervical adenocarcinoma, gastric type (GAS) is not associated with human papilloma virus (HPV) infection. GAS patients prognoses are significantly worse compared with cervical adenocarcinoma associated with HPV infection, as their tumors exhibit resistance to conventional chemotherapy and radiotherapy. GAS is often associated with lobular endocervical glandular hyperplasia (LEGH), which is regarded as a precursor to GAS in the latest WHO classification. Recently, we reported that a decrease in expression of terminal α1,4-linked N-acetylglucosamine (αGlcNAc) relative to that of MUC6 was already apparent in atypical LEGH in the LEGH-GAS sequence. Here, we analyzed expression of α1,4-N-acetylglucosaminyltransferase (α4GnT), the sole enzyme catalyzing αGlcNAc biosynthesis, and that of αGlcNAc and MUC6 in cases representing non-neoplastic endocervical gland (NNEG) (11 cases), LEGH (26 cases) and GAS (12 cases). α4GnT protein was detected in a “dot-like” pattern, indicating localization in the Golgi apparatus in all 26 LEGH cases and 5 of 12 GAS cases. α4GnT- and αGlcNAc-positive cells largely overlapped, suggesting that α4GnT gene expression regulates αGlcNAc biosynthesis. Interestingly, all NNEG cases were negative for α4GnT and αGlcNAc expression, but 7 of 11 NNEG and all LEGH cases were MUC6-positive. In GAS cases, patients whose tumors were α4GnT- and αGlcNAc-positive had more favorable prognosis than others. Multivariate analysis revealed that positive expressions of α4GnT and αGlcNAc were independent prognostic indicators. These results indicate that α4GnT and αGlcNAc could serve as useful markers not only to distinguish LEGH from NNEG but to evaluate prognoses of GAS patients.
Reduction of integrin alpha 4 activity through splice modulating antisense oligonucleotides
Authors: Aung-Htut May T. , Comerford Iain , Johnsen Russell , Foyle Kerrie , Fletcher Sue , Wilton Steve D. 
Published: September 2019

AbstractWith recent approvals of antisense oligonucleotides as therapeutics, there is an increasing interest in expanding the application of these compounds to many other diseases. Our laboratory focuses on developing therapeutic splice modulating antisense oligonucleotides to treat diseases potentially amendable to intervention during pre-mRNA processing, and here we report the use of oligomers to down-regulate integrin alpha 4 protein levels. Over one hundred antisense oligonucleotides were designed to induce skipping of individual exons of the ITGA4 transcript and thereby reducing protein expression. Integrin alpha 4-mediated activities were evaluated in human dermal fibroblasts and Jurkat cells, an immortalised human T lymphocyte cell line. Peptide conjugated phosphorodiamidate morpholino antisense oligomers targeting ITGA4 were also assessed for their effect in delaying disease progression in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. With the promising results in ameliorating disease progression, we are optimistic that the candidate oligomer may also be applicable to many other diseases associated with integrin alpha 4 mediated inflammation. This highly specific strategy to down-regulate protein expression through interfering with normal exon selection during pre-mRNA processing should be applicable to many other gene targets that undergo splicing during expression.
Role of mineral nutrition in alleviation of heat stress in cotton plants grown in glasshouse and field conditions
Authors: Sarwar Muhammad , Saleem Muhammad Farrukh , Ullah Najeeb , Ali Shafaqat , Rizwan Muhammad , Shahid Muhammad Rizwan , Alyemeni Mohammed Nasser , Alamri Saud A. , Ahmad Parvaiz 
Published: September 2019

AbstractCoincidence of high temperature with terminal reproductive pheno-stages of cotton is chief constraint to achieve yield potential. This high temperature interfere plant defensive system, physiological process, water relations and lint yield production. In this study, we modulated the detrimental outcomes of heat stress on cotton through the foliar spray of nutrients. Cotton crop was exposed to sub-optimal and supra-optimal thermal regimes for a period of one week at squaring, flowering and boll formation stages under glass house and field conditions. Foliar spray of potassium (K-1.5%), zinc (Zn-0.2%) and boron (B-0.1%) were applied at three reproductive stages one day prior to expose high temperature regimes. High temperature increased lipid membrane damage through increased malondialdehyde (MDA) contents in cotton leaves. High temperature stress also reduced leaf chlorophyll contents, net photosynthetic rate, stomatal conductance, water potential, averaged boll weight (g) and seed cotton yield per plant. Various nutrients variably influenced growth and physiology of heat-stressed cotton plants. Zinc outclassed all other nutrients in increasing leaf SOD, CAT, POX, AsA, TPC activity, chlorophyll contents, net photosynthetic rate, stomatal conductance, water potential, boll weight and seed cotton yield per plant. For example, zinc improved seed cotton yield under supra-optimal thermal regime by 17% and under sub-optimal thermal regime by 12% of glasshouse study while 19% under high temperature sowing dates of field study than the water treated plants under the same temperatures. Conclusively, increasing intensities of temperature adversely affected the recorded responses of cotton and exogenous application of Zn efficaciously alleviated heat induced perturbations. Moreover, exogenous nutrients mediated upregulations in physiochemical attributes induced heat tolerance at morphological level.
Different role of the supplementary motor area and the insula between musicians and non-musicians in a controlled musical creativity task
Authors: de Aquino Marcella Pereira Barbosa , Verdejo-Román Juan , Pérez-García Miguel , Pérez-García Purificación 
Published: September 2019

AbstractThe ability to compose creative musical ideas depends on the cooperation of brain mechanisms involved in multiple processes, including controlled creative cognition, which is a type of creativity that has so far been poorly researched. Therefore, the objective of this study was to examine the brain evoked activations by using fMRI, in both musicians and non-musicians, during a general task of controlled musical creativity and its relationship with general creativity. Results revealed that during a rhythmic improvisation task, musicians show greater activation of the motor supplementary area, the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the insula, along with greater deactivation of the default mode network in comparison with non-musicians. For the group of musicians, we also found a positive correlation between the time improvising and the activation of the supplementary motor area, whilst in the non-musicians group improvisation time correlated with the activation of the insula. The results found for the musicians support the notion that the supplementary motor area plays a role in the representation and execution of musical behaviour, while the results in non-musicians reveal the role of the insula in the processing of novel musical information.
Transgenerational Self-Reconstruction of Disrupted Chromatin Organization After Exposure To An Environmental Stressor in Mice
Authors: Diaz-Castillo Carlos , Chamorro-Garcia Raquel , Shioda Toshi , Blumberg Bruce 
Published: September 2019

AbstractExposure to environmental stressors is known to increase disease susceptibility in unexposed descendants in the absence of detectable genetic mutations. The mechanisms mediating environmentally-induced transgenerational disease susceptibility are poorly understood. We showed that great-great-grandsons of female mice exposed to tributyltin (TBT) throughout pregnancy and lactation were predisposed to obesity due to altered chromatin organization that subsequently biased DNA methylation and gene expression. Here we analyzed DNA methylomes and transcriptomes from tissues of animals ancestrally exposed to TBT spanning generations, sexes, ontogeny, and cell differentiation state. We found that TBT elicited concerted alterations in the expression of “chromatin organization” genes and inferred that TBT-disrupted chromatin organization might be able to self-reconstruct transgenerationally. We also found that the location of “chromatin organization” and “metabolic” genes is biased similarly in mouse and human genomes, suggesting that exposure to environmental stressors in different species could elicit similar phenotypic effects via self-reconstruction of disrupted chromatin organization.
Ex situ co culturing of the sea urchin, Mespilia globulus and the coral Acropora millepora enhances early post-settlement survivorship
Authors: Craggs Jamie , Guest James , Bulling Mark , Sweet Michael 
Published: September 2019

AbstractReef restoration efforts, utilising sexual coral propagation need up-scaling to have ecologically meaningful impact. Post-settlement survival bottlenecks, in part due to competitive benthic algae interactions should be addressed, to improve productivity for these initiatives. Sea urchins are keystone grazers in reef ecosystems, yet feeding behaviour of adults causes physical damage and mortality to developing coral spat. To investigate if microherbivory can be utilised for co-culture, we quantitatively assessed how varying densities of juvenile sea urchins Mespilia globulus (Linnaeus, 1758), reared alongside the coral Acropora millepora (Ehrenberg, 1834) effected survival and growth of coral recruits. Spawning of both species were induced ex situ. A comparison of A. millepora spat reared in three M. globulus densities (low 16.67 m−2, medium 37.50 m−2, high 75.00 m−2) and a non-grazed control indicated coral survival is significantly influenced by grazing activity (p < 0.001) and was highest in the highest density treatment (39.65 ± 10.88%, mean ± s.d). Urchin grazing also significantly (p < 0.001) influenced coral size (compared to non-grazing control), with colonies in the medium and high-densities growing the largest (21.13 ± 1.02 mm & 20.80 ± 0.82, mean ± s.e.m). Increased urchin density did however have a negative influence on urchin growth, a result of limited food availability.
Defining Dysbiosis for a Cluster of Chronic Diseases
Authors: Wilkins Lamont J. , Monga Manoj , Miller Aaron W. 
Published: September 2019

AbstractThe prevalence of many chronic diseases has increased over the last decades. It has been postulated that dysbiosis driven by environmental factors such as antibiotic use is shifting the microbiome in ways that increase inflammation and the onset of chronic disease. Dysbiosis can be defined through the loss or gain of bacteria that either promote health or disease, respectively. Here we use multiple independent datasets to determine the nature of dysbiosis for a cluster of chronic diseases that includes urinary stone disease (USD), obesity, diabetes, cardiovascular disease, and kidney disease, which often exist as co-morbidities. For all disease states, individuals exhibited a statistically significant association with antibiotics in the last year compared to healthy counterparts. There was also a statistically significant association between antibiotic use and gut microbiota composition. Furthermore, each disease state was associated with a loss of microbial diversity in the gut. Three genera,Bacteroides, Prevotella, andRuminococcus, were the most common dysbiotic taxa in terms of being enriched or depleted in disease populations and was driven in part by the diversity of operational taxonomic units (OTUs) within these genera. Results of the cross-sectional analysis suggest that antibiotic-driven loss of microbial diversity may increase the risk for chronic disease. However, longitudinal studies are needed to confirm the causative effect of diversity loss for chronic disease risk.
Propensity score-matching analysis comparing laparoscopic and open pancreaticoduodenectomy in elderly patients
Authors: Shin Heeji , Song Ki Byung , Kim Young Il , Lee Young-Joo , Hwang Dae Wook , Lee Jae Hoon , Shin Sang Hyun , Kwon Jaewoo , Alshammary Shadi , Park Guisuk , Park Yejong , Lee Seung Jae , Kim Song Cheol 
Published: September 2019

AbstractThere is little evidence on the safety and benefits of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients; therefore, we evaluated the feasibility and efficacy of this procedure by comparing perioperative and oncological outcomes between LPD and open pancreaticoduodenectomy (OPD) in elderly patients. We retrospectively reviewed the data of 1,693 patients who underwent PD to manage periampullary tumours at a single institution between January 2014 and June 2017. Of these patients, 326 were elderly patients aged ≥70 years, with 56 patients allocated to the LPD group and 270 to the OPD group. One-to-one propensity score matching (56:56) was used to match the baseline characteristics of patients who underwent LPD and OPD. LPD was associated with significantly fewer clinically significant postoperative pancreatic fistulas (7.1% vs. 21.4%), fewer analgesic injections (10 vs. 15.6 times; p = 0.022), and longer operative time (321.8 vs. 268.5 minutes; p = 0.001) than OPD in elderly patients. There were no significant differences in 3-year overall and disease-free survival rates between the LPD and OPD groups. LPD had acceptable perioperative and oncological outcomes compared with OPD in elderly patients. LPD is a reliable treatment option for elderly patients with periampullary tumours.