bluuebunny/crossref_metadata_2025 huggingface dataset:
Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer
Authors: Shi Ming , Liu Dan , Duan Huijun , Han Caili , Wei Bo , Qian Lu , Chen Changguo , Guo Liang , Hu Meiru , Yu Ming , Song Lun , Shen Beifen , Guo Ning
Published: December 2019

Background

Stress, anxiety and depression can cause complex physiological and neuroendocrine changes, resulting in increased level of stress related hormone catecholamine, which may constitute a primary mechanism by which physiological factors impact gene expression in tumors. In the present study, we investigated the effects of catecholamine stimulation on MMP-7 expression in gastric cancer cells and elucidated the molecular mechanisms of the up-regulation of MMP-7 level by catecholamine through an adrenergic signaling pathway.

Results

Increased MMP-7 expression was identified at both mRNA and protein levels in the gastric cancer cells in response to isoproterenol stimulation. β2-AR antigonist effectively abrogated isoproterenol-induced MMP-7 expression. The activation of STAT3 and AP-1 was prominently induced by isoproterenol stimulation and AP-1 displayed a greater efficacy than STAT3 in isoproterenol-induced MMP-7 expression. Mutagenesis of three STAT3 binding sites in MMP-7 promoter failed to repress the transactivation of MMP-7 promoter and silencing STAT3 expression was not effective in preventing isoproterenol-induced MMP-7 expression. However, isoproterenol-induced MMP-7 promoter activities were completely disappeared when the AP-1 site was mutated. STAT3 and c-Jun could physically interact and bind to the AP-1 site, implicating that the interplay of both transcriptional factors on the AP-1 site is responsible for isoproterenol-stimulated MMP-7 expression in gastric cancer cells. The expression of MMP-7 in gastric cancer tissues was found to be at the site where β2-AR was overexpressed and the levels of MMP-7 and β2-AR were the highest in the metastatic locus of gastric cancer.

Conclusions

Up-regulation of MMP-7 expression through β2-AR-mediated signaling pathway is involved in invasion and metastasis of gastric cancer.
Identification and structural analysis of C-terminally truncated collapsin response mediator protein-2 in a murine model of prion diseases
Authors: Shinkai-Ouchi Fumiko , Yamakawa Yoshio , Hara Hideyuki , Tobiume Minoru , Nishijima Masahiro , Hanada Kentaro , Hagiwara Ken'ichi
Published: December 2019

Background

Prion diseases are fatal neurodegenerative disorders that accompany an accumulation of the disease-associated form(s) of prion protein (PrPSc) in the central nervous system. The neuropathological changes in the brain begin with focal deposits of PrPSc, followed by pathomorphological abnormalities of axon terminal degeneration, synaptic loss, atrophy of dendritic trees, and eventual neuronal cell death in the lesions. However, the underlying molecular basis for these neuropathogenic abnormalities is not fully understood.

Results

In a proteomic analysis of soluble proteins in the brains of mice challenged intracerebrally with scrapie prion (Obihiro I strain), we found that the amount of the full-length form of collapsin response mediator protein-2 (CRMP-2; 61 kDa) decreased in the late stages of the disease, while the amount of its truncated form (56 kDa) increased to comparable levels observed for the full-length form. Detailed analysis by liquid chromatography-electrospray ionization-tandem mass spectrometry showed that the 56-kDa form (named CRMP-2-ΔC) lacked the sequence from serine518to the C-terminus, including the C-terminal phosphorylation sites important for the regulation of axonal growth and axon-dendrite specification in developing neurons. The invariable size of the mRNA transcript in Northern blot analysis suggested that the truncation was due to post-translational proteolysis. By overexpression of CRMP-2-ΔC in primary cultured neurons, we observed the augmentation of the development of neurite branch tips to the same levels as for CRMP-2T514A/T555A, a non-phosphorylated mimic of the full-length protein. This suggests that the increased level of CRMP-2-ΔC in the brain modulates the integrity of neurons, and may be involved in the pathogenesis of the neuronal abnormalities observed in the late stages of the disease.

Conclusions

We identified the presence of CRMP-2-ΔC in the brain of a murine model of prion disease. Of note, C-terminal truncations of CRMP-2 have been recently observed in models for neurodegenerative disorders such as ischemia, traumatic brain injury, and Wallerian degeneration. While the structural identity of CRMP-2-ΔC in those models remains unknown, the present study should provide clues to the molecular pathology of degenerating neurons in prion diseases in connection with other neurodegenerative disorders.
Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells
Authors: Levin Aviad , Hayouka Zvi , Friedler Assaf , Loyter Abraham
Published: December 2019

Background

The presence of the cellular Lens Epithelium Derived Growth Factor p75 (LEDGF/p75) protein is essential for integration of the Human immunodeficiency virus type 1 (HIV-1) cDNA and for efficient virus production. In the absence of LEDGF/p75 very little integration and virus production can be detected, as was demonstrated using LEDGF/p75-knokdown cells.

Results

Here we show that the failure to infect LEDGF/p75-knockdown cells has another reason aside from the lack of LEDGF/p75. It is also due to inhibition of the viral integrase (IN) enzymatic activity by an early expressed viral Rev protein. The formation of an inhibitory Rev-IN complex in virus-infected cells can be disrupted by the addition of three IN-derived, cell-permeable peptides, designated INr (IN derived-Rev interacting peptides) and INS (IN derived-integrase stimulatory peptide). The results of the present work confirm previous results showing that HIV-1 fails to infect LEDGF/p75-knockdown cells. However, in the presence of INrs and INS peptides, relatively high levels of viral cDNA integration as well as productive virus infection were obtained following infection by a wild type (WT) HIV-1 of LEDGF/p75-knockdown cells.

Conclusions

It appears that the lack of integration observed in HIV-1 infected LEDGF/p75-knockdown cells is due mainly to the inhibitory effect of Rev following the formation of a Rev-IN complex. Disruption of this inhibitory complex leads to productive infection in those cells.
Gravitation field algorithm and its application in gene cluster
Authors: Zheng Ming , Liu Gui-xia , Zhou Chun-guang , Liang Yan-chun , Wang Yan
Published: December 2019

Background

Searching optima is one of the most challenging tasks in clustering genes from available experimental data or given functions. SA, GA, PSO and other similar efficient global optimization methods are used by biotechnologists. All these algorithms are based on the imitation of natural phenomena.

Results

This paper proposes a novel searching optimization algorithm called Gravitation Field Algorithm (GFA) which is derived from the famous astronomy theory Solar Nebular Disk Model (SNDM) of planetary formation. GFA simulates the Gravitation field and outperforms GA and SA in some multimodal functions optimization problem. And GFA also can be used in the forms of unimodal functions. GFA clusters the dataset well from the Gene Expression Omnibus.

Conclusions

The mathematical proof demonstrates that GFA could be convergent in the global optimum by probability 1 in three conditions for one independent variable mass functions. In addition to these results, the fundamental optimization concept in this paper is used to analyze how SA and GA affect the global search and the inherent defects in SA and GA. Some results and source code (in Matlab) are publicly available at http://ccst.jlu.edu.cn/CSBG/GFA.
Detecting early-warning signals of type 1 diabetes and its leading biomolecular networks by dynamical network biomarkers
Authors: Liu Xiaoping , Liu Rui , Zhao Xing-Ming , Chen Luonan
Published: December 2019

Background

Type 1 diabetes (T1D) is a complex disease and harmful to human health, and most of the existing biomarkers are mainly to measure the disease phenotype after the disease onset (or drastic deterioration). Until now, there is no effective biomarker which can predict the upcoming disease (or pre-disease state) before disease onset or disease deterioration. Further, the detail molecular mechanism for such deterioration of the disease, e.g., driver genes or causal network of the disease, is still unclear.

Methods

In this study, we detected early-warning signals of T1D and its leading biomolecular networks based on serial gene expression profiles of NOD (non-obese diabetic) mice by identifying a new type of biomarker, i.e., dynamical network biomarker (DNB) which forms a specific module for marking the time period just before the drastic deterioration of T1D.

Results

Two dynamical network biomarkers were obtained to signal the emergence of two critical deteriorations for the disease, and could be used to predict the upcoming sudden changes during the disease progression. We found that the two critical transitions led to peri-insulitis and hyperglycemia in NOD mices, which are consistent with other independent experimental results from literature.

Conclusions

The identified dynamical network biomarkers can be used to detect the early-warning signals of T1D and predict upcoming disease onset before the drastic deterioration. In addition, we also demonstrated that the leading biomolecular networks are causally related to the initiation and progression of T1D, and provided the biological insight into the molecular mechanism of T1D. Experimental data from literature and functional analysis on DNBs validated the computational results.
Isolated zone I vertical fracture of first sacral vertebra: a case report
Authors: Bilgic Serkan , Kilincoglu Volkan , Yurttas Yüksel , Soylu Kenan , Sehirlioglu Ali
Published: December 2019

Isolated sacral fractures which occur by shear forces on the pelvic ring are seen less commonly and they are commonly transversely oriented. A 29-year-old Turkish female patient, who sat in front seat in the car, was unrestrained, and another car hit them from right front side of their vehicle. Physical examination revealed considerable tenderness over the right superior gluteal region and excruciating pain during sacral and iliac compression. There was no clear fracture line in her plain radiographs. CT revealed incomplete, zone I fracture located on the superior and anterior part of the first sacral vertebra. Type 1 lateral compression pelvic fractures are relatively common and they include impacted sacral and ipsilateral rami fractures. Only a few cases, related with the isolated sacral fracture, have been reported in the literature. To our knowledge, no isolated vertical zone I fracture of the first sacral vertebra which occurred with the lateral compression injury has been described previously. Fracture of the sacrum should be suspected in the presence of sacral pain and tenderness.
Voice estimation in patients after reconstructive subtotal laryngectomy
Authors: Wiskirska-Woźnica Bożena , Leszczyńska Małgorzata , Świdziński  , Czerniejewska Hanna , Jackowska Joanna , Witold Szyfter
Published: December 2019

Background

Treatment of laryngeal cancers, may include surgery, radiotherapy, chemotherapy, or a combination. Total laryngectomy (TL) has been the standard surgical treatment. Partial laryngectomy procedures were performed, their advantage over TL is preservation of laryngeal functions.

Methods

The investigation was carried out on a group of 20 patients (3 female and 17 male), who underwent surgery according the techniques mentioned above. The methods of investigation were based on perceptual voice estimation (GRBAS), videolaryngostroboscopy, acoustic voice analysis, aerodynamic measure maximum phonation time, voice self-assessment (VHI).

Results and Conclusions

The perceptual voice estimation revealed a good phonation result in only 3 cases after using surgery with the Calearo method as well as the best results of MPT. The VHI reflected severe voice handicap in 2 patients (26 to 40 points). No statistically significant differences were observed between the values of the acoustic parameters in MDVP analysis after following operation -CHEP, Calearo, Sedlacek.
Reproductive phenology and pre-dispersal fruit predation in Atriplex halimus L. (Chenopodiaceae)
Authors: Romera Prado , Fernández-Illescas Francisca , Nieva F Javier J , Rodríguez-Rubio Pilar , Sánchez-Gullón Enrique , Muñoz-Rodríguez Adolfo F
Published: December 2019

Background

The flowering phenology pattern of Atriplex halimus was studied in a Mediterranean habitat in order to analyze protandry effectiveness. Fruit set evolution was recorded over two years and the impact of pre-dispersal predation by insects was also evaluated.

Results

The flowering phenology coincided in 2006 and 2007, starting in mid-July and reaching full flowering at the end of August in both years. Inflorescences are composed of glomerules with 8.78 ± 2.79 male flowers and 4.57 ± 2.58 female flowers, with no significant differences in position on the inflorescence. The peaks of male and female flower anthesis were reached in mid-August, but the male maximum occurred one week before the female. Plants at the start of flowering only bear male flowers, but female flowers soon appear. Fruit set starts at the end of August; all the flowers were transformed into fruit by mid-September and their development continued to the beginning of October, when fruit structures had matured and began to drop. Fruit predation started at the end of September and reached maximum intensity in mid-October.

Conclusions

At population level, male and female flowers seemed to open in the same weeks, but at plant and glomerule level male flowers opened one week before the females. Fruit predation levels were 62.42 and 43.14% in 2006 and 2007 respectively, with no significant differences between different parts of the inflorescence. And larvae of Coleophoridae were the most abundant predators.
Intra-abdominal pressure measurement using the FoleyManometer does not increase the risk for urinary tract infection in critically ill patients
Authors: Desie Nele , Willems Alexandra , De laet Inneke , Dits Hilde , Van Regenmortel Niels , Schoonheydt Karen , Van De Vyvere Martine , Malbrain Manu LNG
Published: December 2019

Objective

The aim of this study was to determine whether intra-abdominal pressure (IAP) monitoring using the FoleyManometer (Holtech Medical, Charlottenlund, Denmark) increases the risk of urinary tract infection (UTI).

Design

A retrospective database review was conducted.

Setting

The study was conducted in the 12-bed medical intensive care unit of ZNA Stuivenberg Hospital (Antwerp, Belgium), a tertiary hospital.

Patients

There were 5,890 patients admitted to the medical intensive care unit of which 1,097 patients underwent intrabladder pressure (IBP) monitoring as estimate for IAP.

Interventions

Crude and adjusted UTI rates were compared among patients undergoing IAP measurements with three different intrabladder methods: a modified homemade technique, a FoleyManometer with 35 ml reservoir, and a FoleyManometer low volume (FoleyManometerLV) with less than 10 ml priming volume.

Measurements and results

Four consecutive time periods of 24 months were defined and compared with regard to IAP measurement: period 1 (2000-2001), during which IAP monitoring was not used routinely (which serves as a control group), was compared with period 2 (2002-2003), using a modified homemade technique; period 3 (2004-2005), introducing the FoleyManometer; and finally period 4 (2006-2007), in which the FoleyManometerLV was introduced. The incidence of IBP measurements increased from 1.4% in period 1 to 45.4% in period 4 (p < 0.001). At the same time, the Simplified Acute Physiology Score (version 2) (SAPS-II) increased significantly from 24.4 ± 21.5 to 34.9 ± 18.7 (p < 0.001) together with the percentage of ventilated patients from 18.6% to 40.7% (p < 0.001). In total, 1,097 patients had IAP measurements via the bladder. The UTI rates were adjusted for disease severity by multiplying each crude rate with the ratio of control versus study patient SAPS-II probability of mortality. Crude and adjusted UTI rates per 1,000 catheter days (CD) were on average 16.1 and 12.8/1,000 CD, respectively, and were not significantly different between the four time periods.

Conclusions

Intrabladder pressure monitoring as estimate for IAP either via a closed transducer technique or the closed FoleyManometer technique seems safe and does not alter the risk of UTI in critically ill patients.
Climate change impacts on Ontario wind power resource
Authors: Yao Yao , Huang Gordon H , Lin Qianguo
Published: December 2019

Background

The availability and reliability of wind power depend largely on current and future climate conditions, which may vary in the context of climate change. A high resolution regional climate model (PRECIS) was used for dynamic downscaling of the future wind speed over Ontario. The changes of wind power density and power production were further investigated through case studies.

Results

The spatial pattern and the magnitude of wind speed from PRECIS simulation, Wind Energy Atlas and the observation indicated a successful climate simulation. Climate modelling indicated that there would be a decrease of up to 5% in wind speed over southern Ontario from present to the period of 2071–2100. It was showed in the case studies that the changes of wind power production were not in proportion to the changes of average wind speed, due to the variations of wind speed distribution.

Conclusion

The decrease of projected wind speed would be more intense in A2 than in B2 scenario, showing statistically significant differences in the grid cell mean wind speed. The changes of wind power production may not be in proportion to the changes of average wind speed. It would be reasonable to develop onshore or offshore wind energy industry around Georgian Bay and James Bay, considering the projected increasing wind speeds within these areas.
Aripiprazole as augmentation therapy in bipolar patients with current minor or subsyndromal mood symptoms
Authors: Schweitzer Isaac , Sarris Jerome , Tuckwell Virginia , Maguire Kay , Smith Deidre , Ng Chee
Published: December 2019

Background

This study aims to evaluate the effectiveness of aripiprazole augmentation of maintenance treatment for bipolar disorder in patients with minor or subsyndromal mood episodes while on a stable dose of a mood stabiliser and/or antidepressant.

Methods

All subjects had a diagnosis of bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders-4th Edition, Text Revision). Open-label aripiprazole was given over 8 weeks initially. The starting dose was 5 to 15 mg/day with a mean final dose of 11.5 mg (±4.6). Patients were assessed at weeks 0, 2, 4 and 8 with the Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Clinical Global Impression of Severity (CGI-S).

Results and discussion

Seventeen of 20 (85%) patients completed week 4, while 14 (70%) patients completed 8 weeks. For intention-to-treat data, there was a significant decrease in MADRS scores over the course of treatment, with a reduction of 6.40 points at endpoint (p < 0.0005). Improvement from baseline was significant at week 2 and remained through to week 8. Similarly, CGI-S scores significantly decreased over the course of study, but not YMRS scores. Aripiprazole was shown to be a modestly effective augmentation therapy for depressive symptoms in bipolar I and II in this small open-label study.
Re-tooling critical care to become a better intensivist: something old and something new
Authors: Marini John J
Published: December 2019

Developments in recent years have placed powerful new tools of diagnosis, therapy, and communication at the disposal of medicine in general, and of critical care in particular. The art of healing requires not only technical proficiency, but also personal connection, multidisciplinary teamwork, and commitment to the venerable traditions of our profession. The latter often seem to be under assault by today's high-pressure, high-efficiency, and increasingly business-driven hospital environments. Re-tooling critical care for the future generations of caregivers requires something old--empathetic connection--as well as the exciting newer technologies of our science and practice.
Advances in the support of respiratory failure: putting all the evidence together
Authors: Marini John J
Published: December 2019

Considerable progress has been made recently in the understanding of how best to accomplish safe and effective ventilation of patients with acute lung injury. Mechanical and nonmechanical factors contribute to causation of ventilator-associated lung injury. Intervention timing helps determine the therapeutic efficacy and outcome, and the stage and severity of the disease process may determine the patient's vulnerability as well as an intervention's value. Reducing oxygen consumption and ventilatory demands are key to a successful strategy for respiratory support of acute respiratory distress syndrome. Results from major clinical trials can be understood against the background of the complex physiology of ventilator-induced lung injury.
Winning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiology
Authors: Wischmeyer Paul E , San-Millan Inigo
Published: December 2019

Over the last 10 years we have significantly reduced hospital mortality from sepsis and critical illness. However, the evidence reveals that over the same period we have tripled the number of patients being sent to rehabilitation settings. Further, given that as many as half of the deaths in the first year following ICU admission occur post ICU discharge, it is unclear how many of these patients ever returned home. For those who do survive, the latest data indicate that 50-70% of ICU "survivors" will suffer cognitive impairment and 60-80% of "survivors" will suffer functional impairment or ICU-acquired weakness (ICU-AW). These observations demand that we as intensive care providers ask the following questions: "Are we creating survivors ... or are we creating victims?" and "Do we accomplish 'Pyrrhic Victories' in the ICU?" Interventions to address ICU-AW must have a renewed focus on optimal nutrition, anabolic/anticatabolic strategies, and in the future employ the personalized muscle and exercise evaluation techniques utilized by elite athletes to optimize performance. Specifically, strategies must include optimal protein delivery (1.2-2.0 g/kg/day), as an athlete would routinely employ. However, as is clear in elite sports performance, optimal nutrition is fundamental but alone is often not enough. We know burn patients can remain catabolic for 2 years post burn; thus, anticatabolic agents (i.e., beta-blockers) and anabolic agents (i.e., oxandrolone) will probably also be essential. In the near future, evaluation techniques such as assessing lean body mass at the bedside using ultrasound to determine nutritional status and ultrasound-measured muscle glycogen as a marker of muscle injury and recovery could be utilized to help find the transition from the acute phase of critical illness to the recovery phase. Finally, exercise physiology testing that evaluates muscle substrate utilization during exercise can be used to diagnose muscle mitochondrial dysfunction and to guide a personalized ideal heart rate, assisting in recovery of muscle mitochondrial function and functional endurance post ICU. In the end, future ICU-AW research must focus on using a combination of modern performance-enhancing nutrition, anticatabolic/anabolic interventions, and muscle/exercise testing so we can begin to create more "survivors" and fewer victims post ICU care.
Physiology versus evidence-based guidance for critical care practice
Authors: Gattinoni Luciano , Carlesso Eleonora , Santini Alessandro
Published: December 2019

Evidence based medicine is an attempt to optimize the medical decision process through methods primarily based on evidence coming from meta-analyses, systematic reviews, and randomized controlled trials ("evidence-based medicine"), rather than on "clinical judgment" alone. The randomized trials are the cornerstones of this process. However, the randomized trials are just a method to prove or disprove a given hypothesis, which, in turn, derives from a general observation of the reality (premises or theories). In this paper we will examine some of the most recent randomized trials performed in Intensive Care, analyzing their premises, hypothesis and outcome. It is quite evident that when the premises are wrong or too vague the unavoidable consequences will be a negative outcome. We should pay when designing the trial an equal attention in defining premises and hypothesis that we pay for the trial conduction.
Effective machine-learning assembly for next-generation amplicon sequencing with very low coverage
Authors: Ranjard Louis , Wong Thomas K. F. , Rodrigo Allen G.
Published: December 2019

Background

In short-read DNA sequencing experiments, the read coverage is a key parameter to successfully assemble the reads and reconstruct the sequence of the input DNA. When coverage is very low, the original sequence reconstruction from the reads can be difficult because of the occurrence of uncovered gaps. Reference guided assembly can then improve these assemblies. However, when the available reference is phylogenetically distant from the sequencing reads, the mapping rate of the reads can be extremely low. Some recent improvements in read mapping approaches aim at modifying the reference according to the reads dynamically. Such approaches can significantly improve the alignment rate of the reads onto distant references but the processing of insertions and deletions remains challenging.

Results

Here, we introduce a new algorithm to update the reference sequence according to previously aligned reads. Substitutions, insertions and deletions are performed in the reference sequence dynamically. We evaluate this approach to assemble a western-grey kangaroo mitochondrial amplicon. Our results show that more reads can be aligned and that this method produces assemblies of length comparable to the truth while limiting error rate when classic approaches fail to recover the correct length. Finally, we discuss how the core algorithm of this method could be improved and combined with other approaches to analyse larger genomic sequences.

Conclusions

We introduced an algorithm to perform dynamic alignment of reads on a distant reference. We showed that such approach can improve the reconstruction of an amplicon compared to classically used bioinformatic pipelines. Although not portable to genomic scale in the current form, we suggested several improvements to be investigated to make this method more flexible and allow dynamic alignment to be used for large genome assemblies.
Time-resolved evaluation of compound repositioning predictions on a text-mined knowledge network
Authors: Mayers Michael , Li Tong Shu , Queralt-Rosinach Núria , Su Andrew I.
Published: December 2019

Background

Computational compound repositioning has the potential for identifying new uses for existing drugs, and new algorithms and data source aggregation strategies provide ever-improving results via in silico metrics. However, even with these advances, the number of compounds successfully repositioned via computational screening remains low. New strategies for algorithm evaluation that more accurately reflect the repositioning potential of a compound could provide a better target for future optimizations.

Results

Using a text-mined database, we applied a previously described network-based computational repositioning algorithm, yielding strong results via cross-validation, averaging 0.95 AUROC on test-set indications. However, to better approximate a real-world scenario, we built a time-resolved evaluation framework. At various time points, we built networks corresponding to prior knowledge for use as a training set, and then predicted on a test set comprised of indications that were subsequently described. This framework showed a marked reduction in performance, peaking in performance metrics with the 1985 network at an AUROC of .797. Examining performance reductions due to removal of specific types of relationships highlighted the importance of drug-drug and disease-disease similarity metrics. Using data from future timepoints, we demonstrate that further acquisition of these kinds of data may help improve computational results.

Conclusions

Evaluating a repositioning algorithm using indications unknown to input network better tunes its ability to find emerging drug indications, rather than finding those which have been randomly withheld. Focusing efforts on improving algorithmic performance in a time-resolved paradigm may further improve computational repositioning predictions.
A pan-cancer somatic mutation embedding using autoencoders
Authors: Palazzo Martin , Beauseroy Pierre , Yankilevich Patricio
Published: December 2019

Background

Next generation sequencing instruments are providing new opportunities for comprehensive analyses of cancer genomes. The increasing availability of tumor data allows to research the complexity of cancer disease with machine learning methods. The large available repositories of high dimensional tumor samples characterised with germline and somatic mutation data requires advance computational modelling for data interpretation. In this work, we propose to analyze this complex data with neural network learning, a methodology that made impressive advances in image and natural language processing.

Results

Here we present a tumor mutation profile analysis pipeline based on an autoencoder model, which is used to discover better representations of lower dimensionality from large somatic mutation data of 40 different tumor types and subtypes. Kernel learning with hierarchical cluster analysis are used to assess the quality of the learned somatic mutation embedding, on which support vector machine models are used to accurately classify tumor subtypes.

Conclusions

The learned latent space maps the original samples in a much lower dimension while keeping the biological signals from the original tumor samples. This pipeline and the resulting embedding allows an easier exploration of the heterogeneity within and across tumor types and to perform an accurate classification of tumor samples in the pan-cancer somatic mutation landscape.
BaRTv1.0: an improved barley reference transcript dataset to determine accurate changes in the barley transcriptome using RNA-seq
Authors: Rapazote-Flores Paulo , Bayer Micha , Milne Linda , Mayer Claus-Dieter , Fuller John , Guo Wenbin , Hedley Pete E. , Morris Jenny , Halpin Claire , Kam Jason , McKim Sarah M. , Zwirek Monika , Casao M. Cristina , Barakate Abdellah , Schreiber Miriam , Stephen Gordon , Zhang Runxuan , Brown John W. S. , Waugh Robbie , Simpson Craig G.
Published: December 2019

Background

The time required to analyse RNA-seq data varies considerably, due to discrete steps for computational assembly, quantification of gene expression and splicing analysis. Recent fast non-alignment tools such as Kallisto and Salmon overcome these problems, but these tools require a high quality, comprehensive reference transcripts dataset (RTD), which are rarely available in plants.

Results

A high-quality, non-redundant barley gene RTD and database (Barley Reference Transcripts – BaRTv1.0) has been generated. BaRTv1.0, was constructed from a range of tissues, cultivars and abiotic treatments and transcripts assembled and aligned to the barley cv. Morex reference genome (Mascher et al. Nature; 544: 427–433, 2017). Full-length cDNAs from the barley variety Haruna nijo (Matsumoto et al. Plant Physiol; 156: 20–28, 2011) determined transcript coverage, and high-resolution RT-PCR validated alternatively spliced (AS) transcripts of 86 genes in five different organs and tissue. These methods were used as benchmarks to select an optimal barley RTD. BaRTv1.0-Quantification of Alternatively Spliced Isoforms (QUASI) was also made to overcome inaccurate quantification due to variation in 5′ and 3′ UTR ends of transcripts. BaRTv1.0-QUASI was used for accurate transcript quantification of RNA-seq data of five barley organs/tissues. This analysis identified 20,972 significant differentially expressed genes, 2791 differentially alternatively spliced genes and 2768 transcripts with differential transcript usage.

Conclusion

A high confidence barley reference transcript dataset consisting of 60,444 genes with 177,240 transcripts has been generated. Compared to current barley transcripts, BaRTv1.0 transcripts are generally longer, have less fragmentation and improved gene models that are well supported by splice junction reads. Precise transcript quantification using BaRTv1.0 allows routine analysis of gene expression and AS.
Transcriptomic analyses reveal physiological changes in sweet orange roots affected by citrus blight
Authors: Fu Shimin , Shao Jonathan , Roy Avijit , Brlansky Ronald H. , Zhou Changyong , Hartung John S.
Published: December 2019

Background

Citrus blight is a very important progressive decline disease of commercial citrus. The etiology is unknown, although the disease can be transmitted by root grafts, suggesting a viral etiology. Diagnosis is made by demonstrating physical blockage of xylem cells that prevents the movement of water. This test was used to identify symptomatic trees from four commercial groves in Florida. Total RNA extracts of phloem-enriched scaffold root tissues were prepared from seven trees that failed to take up water and from one healthy tree. These RNA extracts were used for transcriptomic analyses using paired end RNA-Seq from an Illumina 2500 system. The expression of transcripts annotated as polyprotein of citrus endogenous pararetrovirus were estimated by both RT-qPCR and RNA-Seq.

Results

Transcripts from seven RNA-Seq libraries from trees affected by citrus blight were compared to a control tree. 129–148 million RNA fragments (two paired-end reads/fragment) were generated per library and were mapped to the sweet orange reference genome. In response to citrus blight stress, genes encoding aquaporins, proteins with water channel activity and several cellulose synthase genes were down-regulated, whereas genes involved in lignin and glucosinolate biosynthesis were up-regulated. Transcripts encoding proteins in pathways of carbohydrate metabolism, nucleotide synthesis, signaling, hormone metabolism, secondary metabolism, transport, and biotic stress pathways were overwhelmingly down regulated in all libraries.

Conclusion

Reduced water intake and xylem plugging were observed in the trees tested and the changes in their transcriptome were analyzed. Plants adapted to reduced water flow by regulating primary and secondary metabolism, nuclear transport and hormone associated pathways. The patterns of energy generation, transcription, translation and protein degradation were consistent with irreversible decline. The down regulation of cellulose synthase transcripts and up regulation of transcripts related to lignin production likely lead to an imbalance in the pathways leading to wood formation, and may lead to the blockage of the xylem vessels seen as the cardinal symptom of citrus blight. Transcripts of a pararetrovirus were elevated in the transcriptome of roots used in this study.
Investigations into a putative role for the novel BRASSIKIN pseudokinases in compatible pollen-stigma interactions in Arabidopsis thaliana
Authors: Doucet Jennifer , Lee Hyun Kyung , Udugama Nethangi , Xu Jianfeng , Qi Baoxiu , Goring Daphne R.
Published: December 2019

Background

In the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown.

Results

A set of stigma-expressed pseudokinase genes, termedBRASSIKINs(BKNs), were identified and found to be present in only core Brassicaceae genomes. InArabidopsis thalianaCol-0,BKN1displayed stigma-specific expression while theBKN2gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linkedBKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on thebkn1/2mutant stigmas. In further analyses, the predominant transcript for the stigma-specificBKN1was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001Arabidopsisgenomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossingArabidopsisspecies,A. lyrataandA. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes.

Conclusion

In this study, we have characterized the novel Brassicaceae-specific family ofBKNpseudokinase genes, and examined the function ofBKN1andBKN2in the context of pollen-stigma interactions inA. thalianaCol-0. Additionally, premature stop codons were identified in the predicted stigma specificBKN1gene in a number of the 1001A. thalianaecotype genomes, and this was in contrast to the out-crossingArabidopsisspecies which carried intact copies ofBKN1. Thus, understanding the function ofBKN1in other Brassicaceae species will be a key direction for future studies.
Recommendations to conduct and report systematic reviews in medical literature: a scoping review
Authors: Penedones Ana , Alves Carlos , Batel-Marques Francisco
Published: December 2019

Background

This scoping review aims to identify, review and characterize the published recommendations to conduct and/or to report a systematic review in medical interventions area.

Methods

A search was carried out in PubMed, EMBASE and Cochrane Library databases, using systematic reviews search filters. The search comprises all recommendations to conduct and/or report a systematic review. Data on methods were extracted from each recommendation. A descriptive analysis was performed.

Results

Eighty-three recommendations were identified. Approximately 60% of retrieved references were published in the last 6 years. Recommendations to both conduct and report a systematic review were issued in 47% studies. The guidance presented in each recommendation to conduct and/ or report a systematic review varied. Almost 96% of the recommendations offer guidance on systematic review methods section. The need and time for updating was only recommended in 29% of recommendations. Forty percent of recommendations endorsed their methods to any subject related to medical interventions. Half of the studies did not specify the design of studies to be included in a systematic review.

Conclusions

Several recommendations to conduct and/or report a systematic review were published and offered different guidance. Further research on the impact of such heterogeneity can improve systematic reviews quality.
Significance of serum Myostatin in hemodialysis patients
Authors: Esposito Pasquale , Battaglia Yuri , La Porta Edoardo , Grignano Maria Antonietta , Caramella Elena , Avella Alessando , Peressini Sabrina , Sessa Nicodemo , Albertini Riccardo , Di Natali Giuseppe , Lisi Claudio , Gregorini Marilena , Rampino Teresa
Published: December 2019

Background

Malnutrition and muscle wasting are common in haemodialysis (HD) patients. Their pathogenesis is complex and involves many molecules including Myostatin (Mstn), which acts as a negative regulator of skeletal muscle. The characterisation of Mstn as a biomarker of malnutrition could be useful in the prevention and management of this condition. Previous studies have reported no conclusive results on the actual relationship between serum Mstn and wasting and malnutrition. So, in this study, we evaluated Mstn profile in a cohort of regular HD patients.

Methods

We performed a cross-sectional study, enrolling 37 patients undergoing bicarbonate-HD (BHD) or haemodiafiltration (HDF) at least for six months. 20 sex-matched healthy subjects comprised the control group. Mstn serum levels were evaluated by ELISA before and after HD. We collected clinical and biochemical data, evaluated insulin resistance, body composition, malnutrition [by Malnutrition Inflammation Score (MIS)] and tested muscle function (by hand-grip strength, six-minute walking test and a questionnaire on fatigue).

Results

Mstn levels were not significantly different between HD patients and controls (4.7 ± 2.8 vs 4.5 ± 1.3 ng/ml). In addition, while a decrease in Mstn was observed after HD treatment, there were no differences between BHD and HDF. In whole group of HD patients Mstn was positively correlated with muscle mass (r = 0.82, p < 0.001) and inversely correlated with age (r = − 0.63, p < 0.01) and MIS (r = − 0.39, p = 0.01). No correlations were found between Mstn and insulin resistance, such as between Mstn levels and parameters of muscle strength and fatigue. In multivariate analysis, Mstn resulted inversely correlated with fat body content (β = − 1.055, p = 0.002).

Conclusions

Circulating Mstn is related to muscle mass and nutritional status in HD patients, suggesting that it may have a role in the regulation of skeletal muscle and metabolic processes. However, also considering the lack of difference of serum Mstn between healthy controls and HD patients and the absence of correlations with muscle function tests, our findings do not support the use of circulating Mstn as a biomarker of muscle wasting and malnutrition in HD.
Propeller perforator flaps from the dorsal digital artery perforator chain for repairing soft tissue defects of the finger
Authors: Hu Haoliang , Chen Hong , Hong Jinjiong , Mao Weisheng , Tian Mintao , Wang Liping , Dong Jianghui , Li Xueyuan
Published: December 2019

Background

When restoring the appearance and function of the fingers, hand surgeons face a challenge in choosing a suitable surgical method to repair finger skin defects.

Methods

In this study, we designed a long elliptical flap based on a propeller perforator flap and located slightly toward the dorsal lateral aspect of the finger. The flap with a pedicle consisting of the dorsal perforator of the distal digital artery and dorsal digital artery perforator chain is rotated to cover a large wound on the distal end. From December 2014 to December 2017, 10 patients with finger soft tissue defects were treated with the propeller perforator flap described in this study.

Results

All flaps survived after surgery, and 2 had a transient venous congestion. After a follow-up period of 3 to 12 months, the static two-point discrimination of the flap was 8.06 ± 1.75 mm, and the range of motion was 149.4 ± 12.9°. This designed flap can span several angiosomes supplied by the perforators. Due to the inclusion of a vessel chain between the dorsal digital artery perforators, the length-to-width ratio of the flap can be up to 3:1.

Conclusions

This technique increases the size of flap that can be harvested safely while retaining a reliable blood supply. The present study describes a new method for repairing soft tissue defects of the finger by using the technique of propeller perforator flaps based on dorsal digital artery perforator chains.

Trial registration

The registration number of this study is ChiCTR1800014588; it has been retrospectively registered with Chinese Clinical Trial Registry (chictr.org.cn), 18/11/2019.
In vitro anti-allergic activity of Moringa oleifera Lam. extracts and their isolated compounds
Authors: Abd Rani Nur Zahirah , Kumolosasi Endang , Jasamai Malina , Jamal Jamia Azdina , Lam Kok Wai , Husain Khairana
Published: December 2019

Background

Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols. The plant also has been traditionally used for alleviating allergic conditions. This study was aimed to examine the anti-allergic activity of M. oleifera extracts and its isolated compounds.

Method

M. oleifera leaves, seeds and pods were extracted with 80% of ethanol. Individual compounds were isolated using a column chromatographic technique and elucidated based on the nuclear magnetic resonance (NMR) and electrospray ionisation mass spectrometry (ESIMS) spectral data. The anti-allergic activity of the extracts, isolated compounds and ketotifen fumarate as a positive control was evaluated using rat basophilic leukaemia (RBL-2H3) cells for early and late phases of allergic reactions. The early phase was determined based on the inhibition of beta-hexosaminidase and histamine release; while the late phase was based on the inhibition of interleukin (IL-4) and tumour necrosis factor (TNF-α) release.

Results

Two new compounds; ethyl-(E)–undec-6-enoate (1) and 3,5,6-trihydroxy-2-(2,3,4,5,6-pentahydroxyphenyl)-4H-chromen-4-one (2) together with six known compounds; quercetin (3), kaempferol (4), β-sitosterol-3-O-glucoside (5), oleic acid (6), glucomoringin (7), 2,3,4-trihydroxybenzaldehyde (8) and stigmasterol (9) were isolated from M. oleifera extracts. All extracts and the isolated compounds inhibited mast cell degranulation by inhibiting beta-hexosaminidase and histamine release, as well as the release of IL-4 and TNF-α at varying levels compared with ketotifen fumarate.

Conclusion

The study suggested that M. oleifera and its isolated compounds potentially have an anti-allergic activity by inhibiting both early and late phases of allergic reactions.