bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic muscle prefatigue weakens the functional corticomuscular coupling during isometric elbow extension contraction
Authors: Wang Lejun , Xie Zihang , Lu Aiyun , Lu Tianfeng , Zhang Shengnian , Zheng Fanhui , Niu Wenxin 
Published: December 2019

Objective
During muscle fatigue, acute changes in the interaction between the sensorimotor cortex and peripheral neurons have been widely studied. However, it is still unclear about the effect of antagonist muscle prefatigue on corticomuscular coupling and central modulation. The purpose of this study was to investigate the changes in the magnitude of electroencephalogram-electromyography (EEG-EMG) coherence and phase synchronization index (PSI) induced by antagonistic muscle prefatigue.

Methods
Twelve young male volunteers conducted a 30-s long, nonfatiguing isometric elbow extension with a target force level of 20% maximum voluntary contraction (MVC) before and after a fatiguing sustained elbow flexion contraction at 20% MVC until task failure. Coherence and PSI between the EEG recorded over the sensorimotor cortex and the surface EMG of the triceps brachii (TB) muscle were quantified for the pre- and post-fatigue elbow extension contractions.

Results
Coherence and PSI in the gamma frequency band (35–60 Hz) were found significantly decreased in the postfatigue elbow extension contraction than the prefatigue contraction. The power of the EEG in the beta and gamma band were significantly increased, while the EMG power showed no significant changes when the antagonistic muscle was prefatigued. PSI in the gamma frequency band between the EMG of the TB muscle and the EEG were found significantly decreased during postfatigue elbow extension contraction compared with prefatigue contraction.

Conclusion
Antagonistic muscle prefatigue led to significantly lower gamma band corticomuscular coherence and phase coupling during an isometric elbow extension position task. The lower corticomuscular coupling may indicate a central modulation mechanism of antagonist muscle prefatigue that related to decreased descending common drive or joint instability compensation modulation mechanism.
RASmutations drive proliferative chronic myelomonocytic leukemia via activation of a novel KMT2A-PLK1 axis
Authors: Carr Ryan M. , Vorobyev Denis , Lasho Terra , Marks David L. , Tolosa Ezequiel J. , Vedder Alexis , Almada Luciana L. , Yurchenko Andrey , Padioleau Ismael , Alver Bonnie , Coltro Giacomo , Binder Moritz , Safgren Stephanie L. , Horn Isaac , You Xiaona , Droin Nathalie , Solary Eric , Balasis Maria E. , Berger Kurt , Pin Christopher , Witzig Thomas , Buradkar Ajinkya , Graf Temeida , Valent Peter , Mangaonkar Abhishek A. , Robertson Keith D. , Howard Matthew T. , Kaufmann Scott H. , Fernandez-Zapico Martin E. , Geissler Klaus , Padron Eric , Zhang Jing , Nikolaev Sergey , Patnaik Mrinal M. 
Published: December 2019

ABSTRACTChronic myelomonocytic leukemia (CMML) is an aggressive hematological malignancy with limited treatment options. Whole exome (WES) and targeted sequencing of several independent cohorts of CMML patients, comparing dysplastic (dCMML) to proliferative (pCMML) CMML, as well as paired chronic phase disease and acute leukemic transformation (LT), associate acquisition of oncogenic RAS pathway mutations, the most common beingNRASG12D, with aggressive disease and with disease progression. Using patient derived progenitor colony assays and aNRASG12D-Vav-Cre mouse model, we further demonstrate the role of mutant RAS signaling in driving and maintaining pCMML phenotype. RNA-sequencing links RAS pathway mutations with an increased expression of genes encoding the mitotic checkpoint kinases PLK1 and WEE1. Further, we dmeoinstrated that non-mutated lysine methyltransferase KMT2A (MLL1) acts as mediator of NRAS-inducedPLK1andWEE1expression. Finally, we demonstrate the translational value of our findings by showing that pharmacological PLK1 inhibition decreases monocytosis and hepatosplenomegaly while improving hematopoiesis inRASmutant patient-derived xenografts. Hence, we define severe CMML as oncogenic RAS pathway-enriched malignancies, with a unique gene expression profile regulated byKMT2A, amenable to therapeutic intervention.
Single strain control of microbial consortia
Authors: Fedorec Alex J.H. , Karkaria Behzad D. , Sulu Michael , Barnes Chris P 
Published: December 2019

AbstractThe scale of the biological systems we can engineer is limited by the burden that host cells can bear. Division-of-labour can spread that burden across a community of cells but competitive exclusion inevitably leads to the removal of less fit community members over time. Here, we leverage amensalism and competitive exclusion to stabilise multi-species communities by engineering a strain ofEscherichia coliwhich secretes a toxin in response to competition. We show mathematically and experimentally that such a system can produce stable populations with a composition that is tunable by easily controllable parameters. This is the first system to use competitive exclusion to create a stable two-species consortia and the first to only require the engineering of a single strain.
Cross-validation of technologies for genotypingCYP2D6andCYP2C19
Authors: Henriques Beatriz Carvalho , Buchner Amanda , Hu Xiuying , Yavorskyy Vasyl , Wang Yabing , Martens Kristina , Carr Michael , Asl Bahareh Behroozi , Hague Joshua , Maier Wolfgang , Dernovsek Mojca Z. , Henigsberg Neven , Souery Daniel , Cattaneo Annamaria , Hauser Joanna , Mors Ole , Rietschel Marcella , Pfeffer Gerald , Bousman Chad , Aitchison Katherine J. 
Published: December 2019

AbstractBackgroundCYP2D6 and CYP2C19 are cytochrome P450 enzymes involved in the metabolism of many medications from multiple therapeutic classes. Associations between patterns of variants (known as haplotypes) in the genes encoding them (CYP2D6andCYP2C19) and enzyme activities are well described. The genes in fact comprise 21% of biomarkers in drug labels. Despite this, genotyping is not common, partly attributable to its challenging nature (CYP2D6having >100 haplotypes, including those with sequence from an adjacent pseudogene, and gene duplications). We cross-validated different methodologies for identifying haplotypes in these genes against each other.MethodsNinety-two samples with a variety ofCYP2D6andCYP2C19genotypes according to prior AmpliChip CYP450 and TaqManCYP2C19*17data were selected from the Genome-based therapeutic drugs for depression (GENDEP) study. Genotyping was performed with TaqMan copy number variant (CNV) and single nucleotide variant (SNV) analysis, the next generation sequencing-based Ion S5 AmpliSeq Pharmacogenomics Panel, PharmacoScan, long-range polymerase chain reaction (L-PCR) followed by amplicon analysis, and Agena forCYP2C19. Variant pattern to haplotype translation was automated.ResultsThe inter-platform concordance forCYP2C19was high (up to 100% for available data). ForCYP2D6, the IonS5-PharmacoScan concordance was 94% for a range of variants tested apart from those with at least one extra copy of aCYP2D6gene (occurring at a frequency of 3.8%, 33/853), or those with substantial sequence derived from pseudogene, known as hybrids (3%, 26/853).ConclusionsInter-platform concordance forCYP2C19was high, and, moreover, the Ion S5 and PharmacoScan data were 100% concordant with that from a TaqManCYP2C19*2assay. We have also demonstrated feasibility of using an NGS platform for genotypingCYP2D6andCYP2C19, with automated data interpretation methodology. This points the way to a method of makingCYP2D6andCYP2C19genotyping more readily accessible.
Artiphysiology reveals visual preferences underlying V4-like blur selectivity in a deep convolutional neural network
Authors: Entezari Saba , Bair Wyeth 
Published: December 2019

ABSTRACTBlurry visual scenes arise from many causes and image blur is known to be important for scene interpretation, yet there have been very few studies of the visual encoding of blur in biological visual systems or in artificial visual systems trained for object recognition. Recently, a study of single neurons in the visual cortex of macaque monkeys found that a significant fraction of neurons were more responsive to blurred visual stimuli than to sharply defined stimuli. This raises two questions: (1) what types of visual features in natural scenes might underlie blur selectivity in macaque cortex, and (2) can blur selectivity be found in artificial neural networks using the simple artificial stimuli previously applied in vivo? To answer these questions, we presented simple shape stimuli to the widely studied deep convolutional neural network (CNN) known as AlexNet and used deconv-net visualization to identify features that are critical for driving blur selective units. We found that a substantial number of units in the CNN were selective for blur and that several categories of blur selectivity emerged in early-to-middle processing stages. Prominent among these is a set of units selective for spatial boundaries defined by blur contrast. These blur-contrast boundary units may serve the important task of segmentation in natural photographic images and may relate to a large body of literature on second-order boundary detection. Our results lead to the prediction that such units could exist in the visual cortex but have yet to be well characterized and localized, and they provide direction for future neurophysiological tests of blur selectivity in vivo.
Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin inStaphylococcus aureus
Authors: Friberg Cathrine , Haaber Jakob , Vestergaard Martin , Fait Anaëlle , Perrot Veronique , Levin Bruce , Ingmer Hanne 
Published: December 2019

ABSTRACTAntimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75% and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing an S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiologically relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host-specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo.
Multimodal DTI-TMS assessment of the motor system in patients with chronic ischemic stroke
Authors: Nazarova M. , Kulikova S. , Piradov M. , Limonova A. , Dobrynina L. , Konovalov R. , Novikov P. , Sehm B. , Villringer A. , Nikulin V. 
Published: December 2019

AbstractBackground and PurposeDespite the continuing efforts in multimodal assessment of the motor system after stroke, conclusive findings on the complementarity of functional and structural metrics of the corticospinal tract (CST) integrity and the role of the contralesional hemisphere are still missing. The aim of this work was to find the best combination of the motor system parameters, allowing classification of patients into three predefined groups of upper limb motor recovery.Methods35 chronic ischemic stroke patients (47 [26–66] y.o., 29 [6–58] months post-stroke) with only supratentorial lesion and unilateral upper extremity weakness were enrolled. Patients were divided into three groups depending on the upper limb motor recovery. Non-parametric statistical tests and regression analysis were used to investigate the relationships among structural and functional motor system parameters, probed by diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). In addition, stratification rules were tested, using a decision tree classifier to identify parameters explaining motor recovery.ResultsFractional anisotropy (FA) ratio in the internal capsule (IC) and absence/presence of motor evoked potentials (MEPs), were equally discriminative of the worst motor outcome group (96% accuracy). MEP presence diverged for two investigated hand muscles. Concurrently, for the three recovery groups’ classification, the best parameter combination was: IC FA ratio and Fréchet distance between the contralesional and ipsilesional CST FA profiles (91% accuracy). No other metrics had any additional value for patients’ classification.ConclusionsThis study demonstrates that IC FA ratio and MEPs absence are equally important markers for poor recovery. Importantly, we found that MEPs should be controlled in more than one hand muscle. Finally, we show that better separation between different motor recovery groups may be achieved when considering the whole CST FA profile.
VariantStore: A Large-Scale Genomic Variant Search Index
Authors: Pandey Prashant , Gao Yinjie , Kingsford Carl 
Published: December 2019

AbstractThe ability to efficiently query genomic variants from thousands of samples is critical to achieving the full potential of many medical and scientific applications such as personalized medicine. Performing variant queries based on coordinates in the reference or sample sequences is at the core of these applications. Efficiently supporting variant queries across thousands of samples is computationally challenging. Most solutions only support queries based on the reference coordinates and the ones that support queries based on coordinates across multiple samples do not scale to data containing more than a few thousand samples. We present VariantStore, a system for efficiently indexing and querying genomic variants and their sequences in either the reference or sample-specific coordinate systems. We show the scalability of VariantStore by indexing genomic variants from the TCGA-BRCA project containing 8640 samples and 5M variants in 4 Hrs and the 1000 genomes project containing 2500 samples and 924M variants in 3 Hrs. Querying for variants in a gene takes between 0.002 – 3 seconds using memory only 10% of the size of the full representation.
The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for human complex diseases
Authors: Xu Fengzhe , Fu Yuanqing , Sun Ting-yu , Jiang Zengliang , Miao Zelei , Shuai Menglei , Gou Wanglong , Ling Chu-wen , Yang Jian , Wang Jun , Chen Yu-ming , Zheng Ju-Sheng 
Published: December 2019

AbstractThere is increasing interest about the interplay between host genetics and gut microbiome on human complex diseases, with prior evidence mainly derived from animal models. In addition, the shared and distinct microbiome features among human complex diseases remain largely unclear. We performed a microbiome genome-wide association study to identify host genetic variants associated with gut microbiome in a Chinese population with 1475 participants. We then conducted bi-directional Mendelian randomization analyses to examine the potential causal associations between gut microbiome and human complex diseases. We found thatSaccharibacteria(also known asTM7phylum) could potentially improve renal function by affecting renal function biomarkers (i.e., creatinine and estimated glomerular filtration rate). In contrast, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by the host genetics, had potential causal effect on gut microbiome. Further disease-microbiome feature analysis suggested that gut microbiome features revealed novel relationship among human complex diseases. These results suggest that different human complex diseases share common and distinct gut microbiome features, which may help re-shape our understanding about the disease etiology in humans.
Real‐world efficacy and safety data for dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced melanoma
Authors: Takahashi Akira , Namikawa Kenjiro , Nakano Eiji , Yamazaki Naoya 
Published: December 2019

AbstractWe conducted a retrospective investigation of the efficacy and safety of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced melanoma in real‐world clinical practise. The study analyzed 50 patients who received dabrafenib and trametinib combination therapy for BRAF V600 mutation‐positive advanced melanoma in our hospital (26 men and 24 women, aged 21–86 years, inclusive; median age, 53 years). The response rate was 72.3%, with complete response (CR) achieved in eight cases (17.0%), partial response in 26 (55.3%), stable disease in nine (19.1%) and progressive disease in four (8.5%). Median progression‐free survival (PFS) was 12 months, and median overall survival (OS) was 23 months. Disease progression occurred in 29 of the 50 patients during the study period, and 25 patients died. Baseline lactate dehydrogenase and the number of organs with metastasis were important predictive factors for PFS and OS, and CR to combination therapy was a predictive factor for long‐term remission. Adverse events occurred in 88% of cases; 16% were grade 3 or worse. The adverse events observed in 50% of more of patients were rash (56%) and pyrexia (52%). The efficacy of dabrafenib and trametinib combination therapy in Japanese patients was similar to that reported in global studies, and the same adverse events were generally reported; however, rash tended to occur more frequently in the patients in our study.
Dysfunction of the endothelium and constriction of the isolated rat's middle cerebral artery in low sodium environment in the presence of vasopressin
Authors: Aleksandrowicz Marta , Klapczynska Katarzyna , Kozniewska Ewa 
Published: December 2019

AbstractHyponatraemia, a water–electrolyte disorder diagnosed in patients with subarachnoid haemorrhage (SAH), increases a risk of persistent vasospasm. In majority of cases, hyponatraemia results from inappropriate secretion of vasopressin (AVP). The effect of AVP‐associated hyponatraemia on cerebral vasculature is unknown. The present study aimed to elucidate the role of AVP in the response of the middle cerebral artery (MCA) of the rat to hyponatraemia. Isolated, cannulated, and pressurized rat MCAs were perfused/superfused with physiological (Na+ = 144 mmol/L) buffer or low‐sodium (Na+ = 121 mmol/L) buffer containing either AVP or angiotensin II (ANG II). ANG II was used to check if the effect of low plasma sodium concentration combined with AVP on the MCA tone is unique to vasopressin. At physiological Na+ concentration, vasopressin (1.4 × 10−11 mol/L) or angiotensin II (10−9 mol/L) resulted in relaxation of the MCA. Substitution of low‐sodium for the normal sodium buffer with the same concentration of AVP, resulted in the constriction of the MCA. This effect was absent after removal of the endothelium, administration of vasopressin V1 receptor antagonist or concomitant inhibition of endothelin‐1 receptors and synthesis of thromboxane A2. In contrast, no constriction of the MCA in low‐sodium buffer was observed when AVP was replaced with ANG II. Our data suggest that presence of vasopressin and low sodium ion concentration results in the change of endothelium phenotype from pro‐vasodilatory to pro‐vasoconstrictory. This phenomenon may be an overlooked factor contributing to vasospasm in SAH patients with hyponatraemia caused by inappropriate antidiuretic hormone secretion (SIADH).
Stem cell paracrine actions in tissue regeneration and potential therapeutic effect in human endometrium: a retrospective study
Authors: de Miguel‐Gómez L , Ferrero H , López‐Martínez S , Campo H , López‐Pérez N , Faus A , Hervás D , Santamaría X , Pellicer A , Cervelló I 
Published: December 2019

ObjectiveDetermining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's syndrome and endometrial atrophy (AS/EA) patients after autologous CD133+ bone marrow‐derived stem cell (CD133+BMDSC) transplantation.DesignRetrospective study using human endometrial biopsies and mouse models.SettingFundación‐IVI, IIS‐La Fe, Valencia, Spain.SamplesEndometrial biopsies collected before and after CD133+BMDSC therapy, from eight women with AS/EA (NCT02144987) from the uterus of five mice with only left horns receiving CD133+BMDSC therapy.MethodsIn human samples, haematoxylin and eosin (H&E) staining, RNA arrays, PCR validation, and neutrophil elastase (NE) immunohistochemistry (IHQ). In mouse samples, PCR validation and protein immunoarrays.Main outcome measuresH&E microscopic evaluation, RNA expression levels, PCR, and growth/angiogenic factors quantification, NE IHQ signal.ResultsTreatment improved endometrial morphology and thickness for all patients. In human samples, Jun, Serpine1, and Il4 were up‐regulated whereas Ccnd1 and Cxcl8 were down‐regulated after treatment. The significant decrease of NE signal corroborated Cxcl8 expression. Animal model analysis confirmed human results and revealed a higher expression of pro‐angiogenic cytokines (IL18, HGF, MCP‐1, MIP2) in treated uterine horns.ConclusionsCD133+BMDSC seems to activate several factors through a paracrine mechanism to help tissue regeneration, modifying endometrial behaviour through an immunomodulatory milieu that precedes proliferation and angiogenic processes. Insight into these processes could bring us one step closer to a non‐invasive treatment for AS/EA patients.Tweetable abstractCD133+BMDSC therapy regenerates endometrium, modifying the immunological milieu that precedes proliferation and angiogenesis.
Evaluation of treatments for Bartholin’s cyst or abscess: a systematic review
Authors: Illingworth BJG , Stocking K , Showell M , Kirk E , Duffy JMN 
Published: December 2019

BackgroundNo consensus on the management of symptomatic cysts or abscesses of the Bartholin’s gland exists.ObjectivesTo assess the effectiveness and safety of surgical interventions for a symptomatic Bartholin’s cyst or abscess.Search StrategyWe searched bibliographical databases from inception to April 2019.Selection CriteriaRandomised trials evaluating a surgical intervention for the treatment of a symptomatic Bartholin’s cyst or abscess.Data Collection and AnalysisEight trials, reporting data from 699 women, were included. Study characteristics and methodological quality were recorded for each trial. Summary estimates were calculated using random‐effects methods.Main ResultsWhen considering the recurrence of a symptomatic Bartholin’s cyst or abscess, the evidence was consistent with notable effects in either direction (risk ratio [RR] 0.76; 95% confidence interval [CI] 0.41–1.40) when comparing marsupialisation with incision, drainage and insertion of a Word catheter. Limited inference could be made when comparing marsupialisation with incision, drainage and silver nitrate insertion (RR 1.00; 95% CI 0.57–1.75), and incision, drainage and cavity closure (RR 0.25; 95% CI 0.01–4.89). There was limited reporting of secondary outcomes, including haematoma, infectious morbidity and persistent dyspareunia.ConclusionsCurrent randomised trial evidence does not support the use of any single surgical intervention for the treatment of a symptomatic cyst or abscess of the Bartholin’s gland.Prospective RegistrationPROSPERO: International Prospective Register of Systematic Reviews; CRD42018088553.Tweetable AbstractFurther research is needed to identify an effective treatment for #Bartholin’s cyst or abscess. @jamesmnduffy