bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with an increased tumour mutational burden
Authors: Hallam Sally , Stockton Joanne , Bryer Claire , Whalley Celina , Pestinger Valerie , Youssef Haney , Beggs Andrew D. 
Published: November 2020

AbstractColorectal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology associated with transition from primary CRC to CPM and of patients with CPM not responding to treatment with CRS & HIPEC, to identify those suitable for treatment with CRS & HIPEC and to identify targets for existing repurposed or novel treatment strategies. A cohort of patients with CPM treated with CRS & HIPEC was recruited and divided according to prognosis. Molecular profiling of the transcriptome (n = 25), epigenome (n = 24) and genome (n = 21) of CPM and matched primary CRC was performed. CPM were characterised by frequent Wnt/ β catenin negative regulator mutations, TET2 mutations, mismatch repair mutations and high tumour mutational burden. Here we show the molecular features associated with CPM development and associated with not responding to CRS & HIPEC. Potential applications include improving patient selection for treatment with CRS & HIPEC and in future research into novel and personalised treatments targeting the molecular features identified here.
Comparison of two tDCS protocols on pain and EEG alpha-2 oscillations in women with fibromyalgia
Authors: de Melo Géssika Araújo , de Oliveira Eliane Araújo , dos Santos Andrade Suellen Mary Marinho , Fernández-Calvo Bernardino , Torro Nelson 
Published: November 2020

AbstractTranscranial Direct Current Stimulation (tDCS) has been used as an alternative treatment for pain reduction in fibromyalgia. In this study, in addition to behavioral measures, we analyzed oscillations in alpha 2 frequency band in the frontal, occipital, and parietal regions, in response to the application of two neuromodulation protocols in fibromyalgia. The study was a randomized, double-blind, placebo-controlled clinical trial with 31 women diagnosed with fibromyalgia. The participants were allocated to three groups with the anodic stimulation applied on the left motor cortex: Group 1, for five consecutive days; Group 2, for 10 consecutive days; and Group 3, sham stimulation for five consecutive days. Statistical analysis showed a reduction in pain intensity after treatment for groups in general [F (1.28) = 8.02; p = 0.008; η2 = 0.223], in addition to a reduction in alpha 2 in the frontal (p = 0.039; d = 0.384) and parietal (p = 0.021; d = 0.520) regions after the treatment on five consecutive days. We conclude that neuromodulation protocols produced similar effects on pain reduction, but differed with respect to the changes in the alpha 2 frequency band in the frontal and parietal regions.
miRNA profiles of canine cutaneous mast cell tumours with early nodal metastasis and evaluation as potential biomarkers
Authors: Zamarian Valentina , Ferrari Roberta , Stefanello Damiano , Ceciliani Fabrizio , Grieco Valeria , Minozzi Giulietta , Chiti Lavinia Elena , Arigoni Maddalena , Calogero Raffaele , Lecchi Cristina 
Published: November 2020

AbstractCutaneous mast cell tumours (MCTs) are common skin neoplasms in dogs. MicroRNAs (miRNAs) are post-transcriptional regulators involved in several cellular processes, and they can function as tumour promoters or suppressors. However, the role of miRNAs in canine MCTs has not yet been elucidated. Thus, the current study aimed to characterize miRNA profiles and to assess their value as biomarkers for MCTs. miRNA expression profiles were assessed in formalin-fixed, paraffin-embedded samples by next-generation sequencing. Ten samples were MCT tissues, and 7 were healthy adjacent tissues. Nine dysregulated miRNAs (DE-miRNAs) were then validated using RT-qPCR in a larger group of MCT samples, allowing the calculation of ROC curves and performance of multiple factor analysis (MFA). Pathway enrichment analysis was performed to investigate miRNA biological functions. The results showed that the expression of 63 miRNAs (18 up- and 45 downregulated) was significantly affected in MCTs. Five DE-miRNAs, namely, miR-21-5p, miR-92a-3p, miR-338, miR-379 and miR-885, were validated by RT-qPCR. The diagnostic accuracy of a panel of 3 DE-miRNAs—miR-21, miR-379 and miR-885—exhibited increased efficiency in discriminating animals with MCTs (AUC = 0.9854) and animals with lymph node metastasis (AUC = 0.8923). Multiple factor analysis revealed clusters based on nodal metastasis. Gene Ontology and KEGG analyses confirmed that the DE-miRNAs were involved in cell proliferation, survival and metastasis pathways. In conclusion, the present study demonstrated that the miRNA expression profile is changed in the MCT microenvironment, suggesting the involvement of the altered miRNAs in the epigenetic regulation of MCTs and identifying miR-21, miR-379 and miR-885 as promising biomarkers.
Mito Hacker: a set of tools to enable high-throughput analysis of mitochondrial network morphology
Authors: Rohani Ali , Kashatus Jennifer A. , Sessions Dane T. , Sharmin Salma , Kashatus David F. 
Published: November 2020

AbstractMitochondria are highly dynamic organelles that can exhibit a wide range of morphologies. Mitochondrial morphology can differ significantly across cell types, reflecting different physiological needs, but can also change rapidly in response to stress or the activation of signaling pathways. Understanding both the cause and consequences of these morphological changes is critical to fully understanding how mitochondrial function contributes to both normal and pathological physiology. However, while robust and quantitative analysis of mitochondrial morphology has become increasingly accessible, there is a need for new tools to generate and analyze large data sets of mitochondrial images in high throughput. The generation of such datasets is critical to fully benefit from rapidly evolving methods in data science, such as neural networks, that have shown tremendous value in extracting novel biological insights and generating new hypotheses. Here we describe a set of three computational tools,Cell Catcher,Mito CatcherandMiA, that we have developed to extract extensive mitochondrial network data on a single-cell level from multi-cell fluorescence images.Cell Catcherautomatically separates and isolates individual cells from multi-cell images;Mito Catcheruses the statistical distribution of pixel intensities across the mitochondrial network to detect and remove background noise from the cell and segment the mitochondrial network;MiAuses the binarized mitochondrial network to perform more than 100 mitochondria-level and cell-level morphometric measurements. To validate the utility of this set of tools, we generated a database of morphological features for 630 individual cells that encode 0, 1 or 2 alleles of the mitochondrial fission GTPase Drp1 and demonstrate that these mitochondrial data could be used to predict Drp1 genotype with 87% accuracy. Together, this suite of tools enables the high-throughput and automated collection of detailed and quantitative mitochondrial structural information at a single-cell level. Furthermore, the data generated with these tools, when combined with advanced data science approaches, can be used to generate novel biological insights.
Differences in serum protein electrophoretic pattern in dogs naturally infected with Babesia gibsoni and Babesia canis
Authors: Tóthová Csilla , Karasová Martina , Blaňarová Lucia , Fialkovičová Mária , Nagy Oskar 
Published: November 2020

AbstractCanine babesiosis may cause several hematological and biochemical changes, but only limited studies are available regarding the possible differences of changes in animals infected by different Babesia parasites. The study focused on the evaluation of the differences in serum protein electrophoretic pattern between dogs naturally infected with B. gibsoni (17 dogs) and B. canis (40 dogs). The mean values of total proteins, β1-, β2- and γ-globulins were in dogs infected with B. gibsoni significantly higher (P < 0.05 and P < 0.001) than in dogs infected with B. canis. The relative concentrations of albumin, α1-, α2-globulins and the A/G ratios were in the B. gibsoni infected dogs significantly lower (P < 0.001), no significant differences were found in the relative concentrations of β1- and β2-globulins. Significant differences were found in most of the evaluated parameters when comparing the results in relation to the form of B. canis infection to B. gibsoni infection. Hematological indices showed significant differences between dogs infected with B. gibsoni and the complicated form of B. canis infection. In conclusion, the obtained results suggest differences in the changes of serum protein electrophoretic pattern between dogs infected with both Babesia species and thus, in the response to the infection caused by various Babesia parasites.
Dlec1 is required for spermatogenesis and male fertility in mice
Authors: Okitsu Yu , Nagano Mamoru , Yamagata Takahiro , Ito Chizuru , Toshimori Kiyotaka , Dohra Hideo , Fujii Wataru , Yogo Keiichiro 
Published: November 2020

AbstractDeleted in lung and esophageal cancer 1 (DLEC1) is a tumour suppressor gene that is downregulated in various cancers in humans; however, the physiological and molecular functions ofDLEC1are still unclear. This study investigated the critical role ofDlec1in spermatogenesis and male fertility in mice.Dlec1was significantly expressed in testes, with dominant expression in germ cells. We disruptedDlec1in mice and analysed its function in spermatogenesis and male fertility.Dlec1deletion caused male infertility due to impaired spermatogenesis. Spermatogenesis progressed normally to step 8 spermatids inDlec1−/−mice, but in elongating spermatids, we observed head deformation, a shortened tail, and abnormal manchette organization. These phenotypes were similar to those of various intraflagellar transport (IFT)-associated gene-deficient sperm. In addition, DLEC1 interacted with tailless complex polypeptide 1 ring complex (TRiC) and Bardet–Biedl Syndrome (BBS) protein complex subunits, as well as α- and β-tubulin. DLEC1 expression also enhanced primary cilia formation and cilia length in A549 lung adenocarcinoma cells. These findings suggest that DLEC1 is a possible regulator of IFT and plays an essential role in sperm head and tail formation in mice.
Transcriptomic profiling of feline teeth highlights the role of matrix metalloproteinase 9 (MMP9) in tooth resorption
Authors: Lee S. , Bush S. J. , Thorne S. , Mawson N. , Farquharson C. , Bergkvist G. T. 
Published: November 2020

AbstractTooth resorption (TR) in domestic cats is a common and painful disease characterised by the loss of mineralised tissues from the tooth. Due to its progressive nature and unclear aetiology the only treatment currently available is to extract affected teeth. To gain insight into TR pathogenesis, we characterised the transcriptomic changes involved in feline TR by sequencing RNA extracted from 14 teeth (7 with and 7 without signs of resorption) collected from 11 cats. A paired comparison of teeth from the same cat with and without signs of resorption identified 1,732 differentially expressed genes, many of which were characteristic of osteoclast activity and differentiation, in particular matrix metalloproteinase 9 (MMP9). MMP9 expression was confirmed by qPCR and immunocytochemistry of odontoclasts located in TR lesions. A hydroxamate-based MMP9 inhibitor reduced both osteoclast formation and resorption activity while siRNA targeting MMP9 also inhibited osteoclast differentiation although had little effect on resorption activity. Overall, these results suggest that increased MMP9 expression is involved in the progress of TR pathogenesis and that MMP9 may be a potential therapeutic target in feline TR.
Overlap in processing advantages for minimal ingroups and the self
Authors: Enock Florence E. , Hewstone Miles R. C. , Lockwood Patricia L. , Sui Jie 
Published: November 2020

AbstractCognitive biases shape our perception of the world and our interactions with other people. Information related to the self and our social ingroups is prioritised for cognitive processing and can therefore form some of these key biases. However, ingroup biases may be elicited not only for established social groups, but also for minimal groups assigned by novel or random social categorisation. Moreover, whether these ‘ingroup biases’ are related to self-processing is unknown. Across three experiments, we utilised a social associative matching paradigm to examine whether the cognitive mechanisms underpinning the effects of minimal groups overlapped with those that prioritise the self, and whether minimal group allocation causes early processing advantages. We found significant advantages in response time and sensitivity (dprime) for stimuli associated with newly-assigned ingroups. Further, self-biases and ingroup-biases were positively correlated across individuals (Experiments 1 and 3). However, when the task was such that ingroup and self associations competed, only the self-advantage was detected (Experiment 2). These results demonstrate that even random group allocation quickly captures attention and enhances processing. Positive correlations between the self- and ingroup-biases suggest a common cognitive mechanism across individuals. These findings have implications for understanding how social biases filter our perception of the world.
Rampant loss of social traits during domestication of a Bacillus subtilis natural isolate
Authors: Barreto Hugo C. , Cordeiro Tiago N. , Henriques Adriano O. , Gordo Isabel 
Published: November 2020

AbstractMost model bacteria have been domesticated in laboratory conditions. Yet, the tempo with which a natural isolate diverges from its ancestral phenotype under domestication to a novel laboratory environment is poorly understood. Such knowledge, however is essential to understanding the rate of evolution, the time scale over which a natural isolate can be propagated without loss of its natural adaptive traits, and the reliability of experimental results across labs. Using experimental evolution, phenotypic assays, and whole-genome sequencing, we show that within a week of propagation in a common laboratory environment, a natural isolate of Bacillus subtilis acquires mutations that cause changes in a multitude of traits. A single adaptive mutational step in the gene coding for the transcriptional regulator DegU impairs a DegU-dependent positive autoregulatory loop and leads to loss of robust biofilm architecture, impaired swarming motility, reduced secretion of exoproteases, and to changes in the dynamics of sporulation across environments. Importantly, domestication also resulted in improved survival when the bacteria face pressure from cells of the innate immune system. These results show that degU is a target for mutations during domestication and underscores the importance of performing careful and extremely short-term propagations of natural isolates to conserve the traits encoded in their original genomes.
Bioinspired material architectures from bighorn sheep horncore velar bone for impact loading applications
Authors: Aguirre Trevor G. , Fuller Luca , Ingrole Aniket , Seek Tim W. , Wheatley Benjamin B. , Steineman Brett D. , Donahue Tammy L. Haut , Donahue Seth W. 
Published: November 2020

AbstractRocky Mountain bighorn sheep rams (Ovis canadensis canadensis) routinely conduct intraspecific combat where high energy cranial impacts are experienced. Previous studies have estimated cranial impact forces to be up to 3400 N during ramming, and prior finite element modeling studies showed the bony horncore stores 3 × more strain energy than the horn during impact. In the current study, the architecture of the porous bone within the horncore was quantified, mimicked, analyzed by finite element modeling, fabricated via additive manufacturing, and mechanically tested to determine the suitability of the novel bioinspired material architecture for use in running shoe midsoles. The iterative biomimicking design approach was able to tailor the mechanical behavior of the porous bone mimics. The approach produced 3D printed mimics that performed similarly to ethylene–vinyl acetate shoe materials in quasi-static loading. Furthermore, a quadratic relationship was discovered between impact force and stiffness in the porous bone mimics, which indicates a range of stiffness values that prevents impact force from becoming excessively high. These findings have implications for the design of novel bioinspired material architectures for minimizing impact force.
Prediction of survival and recurrence in patients with pancreatic cancer by integrating multi-omics data
Authors: Baek Bin , Lee Hyunju 
Published: November 2020

AbstractPredicting the prognosis of pancreatic cancer is important because of the very low survival rates of patients with this particular cancer. Although several studies have used microRNA and gene expression profiles and clinical data, as well as images of tissues and cells, to predict cancer survival and recurrence, the accuracies of these approaches in the prediction of high-risk pancreatic adenocarcinoma (PAAD) still need to be improved. Accordingly, in this study, we proposed two biological features based on multi-omics datasets to predict survival and recurrence among patients with PAAD. First, the clonal expansion of cancer cells with somatic mutations was used to predict prognosis. Using whole-exome sequencing data from 134 patients with PAAD from The Cancer Genome Atlas (TCGA), we found five candidate genes that were mutated in the early stages of tumorigenesis with high cellular prevalence (CP). CDKN2A, TP53, TTN, KCNJ18, and KRAS had the highest CP values among the patients with PAAD, and survival and recurrence rates were significantly different between the patients harboring mutations in these candidate genes and those harboring mutations in other genes (p = 2.39E−03, p = 8.47E−04, respectively). Second, we generated an autoencoder to integrate the RNA sequencing, microRNA sequencing, and DNA methylation data from 134 patients with PAAD from TCGA. The autoencoder robustly reduced the dimensions of these multi-omics data, and the K-means clustering method was then used to cluster the patients into two subgroups. The subgroups of patients had significant differences in survival and recurrence (p = 1.41E−03, p = 4.43E−04, respectively). Finally, we developed a prediction model for prognosis using these two biological features and clinical data. When support vector machines, random forest, logistic regression, and L2 regularized logistic regression were used as prediction models, logistic regression analysis generally revealed the best performance for both disease-free survival (DFS) and overall survival (OS) (accuracy [ACC] = 0.762 and area under the curve [AUC] = 0.795 for DFS; ACC = 0.776 and AUC = 0.769 for OS). Thus, we could classify patients with a high probability of recurrence and at a high risk of poor outcomes. Our study provides insights into new personalized therapies on the basis of mutation status and multi-omics data.
Concomitant genetic ablation of L-type Cav1.3 (α1D) and T-type Cav3.1 (α1G) Ca2+ channels disrupts heart automaticity
Authors: Baudot Matthias , Torre Eleonora , Bidaud Isabelle , Louradour Julien , Torrente Angelo G. , Fossier Lucile , Talssi Leïla , Nargeot Joël , Barrère-Lemaire Stéphanie , Mesirca Pietro , Mangoni Matteo E. 
Published: November 2020

AbstractCardiac automaticity is set by pacemaker activity of the sinus node (SAN). In addition to the ubiquitously expressed cardiac voltage-gated L-type Cav1.2 Ca2+ channel isoform, pacemaker cells within the SAN and the atrioventricular node co-express voltage-gated L-type Cav1.3 and T-type Cav3.1 Ca2+ channels (SAN-VGCCs). The role of SAN-VGCCs in automaticity is incompletely understood. We used knockout mice carrying individual genetic ablation of Cav1.3 (Cav1.3−/−) or Cav3.1 (Cav3.1−/−) channels and double mutant Cav1.3−/−/Cav3.1−/− mice expressing only Cav1.2 channels. We show that concomitant loss of SAN-VGCCs prevents physiological SAN automaticity, blocks impulse conduction and compromises ventricular rhythmicity. Coexpression of SAN-VGCCs is necessary for impulse formation in the central SAN. In mice lacking SAN-VGCCs, residual pacemaker activity is predominantly generated in peripheral nodal and extranodal sites by f-channels and TTX-sensitive Na+ channels. In beating SAN cells, ablation of SAN-VGCCs disrupted late diastolic local intracellular Ca2+ release, which demonstrates an important role for these channels in supporting the sarcoplasmic reticulum based “Ca2+clock” mechanism during normal pacemaking. These data implicate an underappreciated role for co-expression of SAN-VGCCs in heart automaticity and define an integral role for these channels in mechanisms that control the heartbeat.
Phenotype prediction and characterization of 25 pharmacogenes in Thais from whole genome sequencing for clinical implementation
Authors: Mauleekoonphairoj John , Chamnanphon Monpat , Khongphatthanayothin Apichai , Sutjaporn Boosamas , Wandee Pharawee , Poovorawan Yong , Nademanee Koonlawee , Pongpanich Monnat , Chariyavilaskul Pajaree 
Published: November 2020

AbstractPublicly available pharmacogenomics (PGx) databases enable translation of genotype data into clinically actionable information. As variation within pharmacogenes is population-specific, this study investigated the spectrum of 25 clinically relevant pharmacogenes in the Thai population (n = 291) from whole genome sequencing. The bioinformatics tool Stargazer was used for phenotype prediction, through assignment of alleles and detection of structural variation. Known and unreported potentially deleterious PGx variants were identified. Over 25% of Thais carried a high-risk diplotype in CYP3A5, CYP2C19, CYP2D6, NAT2, SLCO1B1, and UGT1A1. CYP2D6 structural variants accounted for 83.8% of all high-risk diplotypes. Of 39 known PGx variants identified, six variants associated with adverse drug reactions were common. Allele frequencies of CYP3A5*3 (rs776746), CYP2B6*6 (rs2279343), and NAT2 (rs1041983) were significantly higher in Thais than East-Asian and global populations. 121 unreported variants had potential to exert clinical impact, majority were rare and population-specific, with 60.3% of variants absent from gnomAD database. This study demonstrates the population-specific variation in clinically relevant pharmacogenes, the importance of CYP2D6 structural variation detection in the Thai population, and potential of unreported variants in explaining drug response. These findings are essential in development of dosing guidelines, PGx testing, clinical trials, and drugs.