bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of MALDI-TOF MS as a rapid test to detect carbapenem resistance in Bacteroides fragilis
Authors: Copsey-Mawer Sarah , Scotford Selina , Copsey-Mawer Bethan , Davis Carol , Perry Michael , Morris Trefor , Hughes Harriet 
Published: October 2019

Background
The frequency of resistance to carbapenems in Bacteroides fragilis isolates is rising and is conferred by a metallo-β-lactamase encoded by the cfiA gene. The utilisation of existing technologies such as MALDI-TOF MS (MTMS) may allow for the early detection of this important resistance phenotype.

Methods
168 B. fragilis isolates were tested. Meropenem MICs were performed by agar dilution and the results interpreted using EUCAST guidelines. All isolates were identified to species level by MTMS and the presence of CfiA detected using the Bruker MBT subtyping module. The presence of thecfiA gene was confirmed by PCR. Next generation sequencing (NGS) was utilised for discrepant results.

Results
108 isolates (64%) were phenotypically susceptible, with 98% of these testing negative for cfiA by both MTMS and PCR. 40 isolates (25%) were phenotypically resistant, of which 65% were positive by PCR and MTMS with 35% negative by both methods.
35% of positive isolates were found to have an IS element upstream of cfiA, and all had an MIC ≥ 64 mg/L.
Discordant results included two isolates which were susceptible, cfiApositive and IS negative, and three cfiA negative resistant isolates.

Conclusion
Overall, a good correlation was observed between methods. Discrepancies highlight an important distinction between the presence of the cfiAgene and its expression.
Although a negative MTMS result does not rule out resistance, it is a rapid and valuable tool to guide early therapeutic decisions for this important pathogen.
Authenticating Anaerobes – Use of MALDI-TOF MS to identify anaerobes in the NCTC Collection
Authors: McGregor Hannah , Pindoria Dipali , Rai Rupa , Alexander Sarah 
Published: October 2019

The National Collection of Type Cultures (NCTC) is the world’s oldest repository of medically-relevant bacteria. NCTC contains 5,500 bacterial strains, 500 of which are anaerobes, with the collection regularly receiving new Type strains and recent clinical isolates.
Fastidious anaerobes pose a unique challenge during the authentication process. NCTC must ensure that the strains are free from contamination and that the organism survives the lyophilisation process. Species-level identification of anaerobic bacterial strains is achieved using a combination of the both MALDI-TOF MS and VITEK2 instruments.
This study evaluates the use of MALDI-TOF MS (Bruker) and VITEK2 (BioMerieux) to identify the anaerobic strains in the NCTC collection. 176 NCTC strains were tested on the MALDI-TOF platform and 60 strains were identified using VITEK2.
MALDI-TOF was able to identify 79% anaerobes to genus-level and 64% to species-level. In comparison the VITEK2 identified 68% to genus and 46% to species-level. The main limiting factor for both these platforms is the database. This may be due to novel anaerobe species NCTC receives not being present on the databases. In the event of no identification, 16S ribosomal RNA sequencing is employed. Furthermore, detection of specific characteristics is carried out by specialist reference laboratories in Cardiff and Colindale, ensuring a robust collection of anaerobic bacteria for use in research and as control strains.
Hexokinase 2 is dispensable for photoreceptor development but is required for survival during aging and outer retinal stress
Authors: Weh Eric , Lutrzykowska Zuzanna , Smith Andrew , Hager Heather , Pawar Mercy , Wubben Thomas , Besirli Cagri G. 
Published: October 2019

AbstractPhotoreceptor death is the ultimate cause of vision loss in many retinal degenerative conditions. Identifying novel therapeutic avenues for prolonging photoreceptor health and function has the potential to improve vision and quality of life for patients suffering from degenerative retinal disorders. Photoreceptors are metabolically unique among other neurons in that they process the majority of their glucose via aerobic glycolysis. One of the main regulators of aerobic glycolysis is hexokinase 2 (HK2). Beyond its enzymatic function of phosphorylating glucose to glucose-6-phosphate, HK2 has additional non-enzymatic roles, including the regulation of apoptotic signaling via AKT signaling. Determining the role of HK2 in photoreceptor homeostasis may identify novel signaling pathways that can be targeted with neuroprotective agents to boost photoreceptor survival during metabolic stress. Here we show that following experimental retinal detachment, p-AKT is upregulated and HK2 translocates to mitochondria. Inhibition of AKT phosphorylation in 661W photoreceptor-like cells results in translocation of mitochondrial HK2 to the cytoplasm, increased caspase activity, and decreased cell viability. Rod-photoreceptors lacking HK2 upregulate HK1 and appear to develop normally. Interestingly, we found that HK2-deficient photoreceptors are more susceptible to acute nutrient deprivation in the experimental retinal detachment model. Additionally, HK2 appears to be important for preserving photoreceptors during aging. We show that retinal glucose metabolism is largely unchanged after HK2 deletion, suggesting that the non-enzymatic role of HK2 is important for maintaining photoreceptor health. These results suggest that HK2 expression is critical for preserving photoreceptors during acute nutrient stress and aging. More specifically, p-AKT mediated translocation of HK2 to the mitochondrial surface may be critical for protecting photoreceptors from acute and chronic stress.
The Popgen Pipeline Platform: A Software Platform for Facilitating Population Genomic Analyses
Authors: Webb Andrew , Knoblauch Jared , Sabankar Nitesh , Kallur Apeksha Sukesh , Hey Jody , Sethuraman Arun 
Published: October 2019

AbstractHere we present the Pop-Gen Pipeline Platform (PPP), a software platform with the goal of reducing the computational expertise required for conducting population genomic analyses. The PPP was designed as a collection of scripts that facilitate common population genomic workflows in a consistent and standardized Python environment. Functions were developed to encompass entire workflows, including: input preparation, file format conversion, various population genomic analyses, output generation, and visualization. By facilitating entire workflows, the PPP offers several benefits to prospective end users - it reduces the need of redundant in-house software and scripts that would require development time and may be error-prone, or incorrect. The platform has also been developed with reproducibility and extensibility of analyses in mind. The PPP is an open-source package that is available for download and use athttps://ppp.readthedocs.io/en/latest/PPP_pages/install.html
Enhancing droplet-based single-nucleus RNA-seq resolution using the semi-supervised machine learning classifier DIEM
Authors: Alvarez Marcus , Rahmani Elior , Jew Brandon , Garske Kristina M. , Miao Zong , Benhammou Jihane N. , Ye Chun Jimmie , Pisegna Joseph R. , Pietiläinen Kirsi H. , Halperin Eran , Pajukanta Päivi 
Published: October 2019

AbstractSingle-nucleus RNA sequencing (snRNA-seq) measures gene expression in individual nuclei instead of cells, allowing for unbiased cell type characterization in solid tissues. Contrary to single-cell RNA seq (scRNA-seq), we observe that snRNA-seq is commonly subject to contamination by high amounts of extranuclear background RNA, which can lead to identification of spurious cell types in downstream clustering analyses if overlooked. We present a novel approach to remove debris-contaminated droplets in snRNA-seq experiments, called Debris Identification using Expectation Maximization (DIEM). Our likelihood-based approach models the gene expression distribution of debris and cell types, which are estimated using EM. We evaluated DIEM using three snRNA-seq data sets: 1) human differentiating preadipocytes in vitro, 2) fresh mouse brain tissue, and 3) human frozen adipose tissue (AT) from six individuals. All three data sets showed various degrees of extranuclear RNA contamination. We observed that existing methods fail to account for contaminated droplets and led to spurious cell types. When compared to filtering using these state of the art methods, DIEM better removed droplets containing high levels of extranuclear RNA and led to higher quality clusters. Although DIEM was designed for snRNA-seq data, we also successfully applied DIEM to single-cell data. To conclude, our novel method DIEM removes debris-contaminated droplets from single-cell-based data fast and effectively, leading to cleaner downstream analysis. Our code is freely available for use at https://github.com/marcalva/diem.
Putting the brain in a box: a toolbox for creating Cartesian Geometric Representations with Isometric Dimensions (Cgrids)
Authors: Raemaekers Mathijs , Bruurmijn Mark , Ramsey Nick 
Published: October 2019

AbstractThe folding of the human cortex complicates extraction of position information and recognition of patterns across the cortical surface. As straight lines correspond better to our intuitions in spatial orientation, we developed an approach for imposing Cartesian grids on portions of the cortical surface, which can then be represented in a rectangular matrix. These functions have been implemented in the Cgrid (Cartesian Geometric Representation with Isometric Dimensions) toolbox. Cgrids can be generated based on regions of interest, or combinations thereof, according to any one of the Freesurfer’s annotation schemes.The toolbox was evaluated using the surface reconstructions of T1-weighted images of 30 subjects, and 17 different Cgrids that in combination covered nearly the entire surface area of the brain. The vast majority of Cgrids (94.6%) could be generated without issues.In addition to facilitating spatial orientation and pattern recognition, the toolbox also allows detailed comparison between the left and right hemisphere, and performing surface based analysis using a volumetric data format. The output of the toolbox is fully compatible with most existing fMRI/MRI analyses packages, and is immediately suitable as input for second level analysis. The toolbox can be downloaded from:https://github.com/mathijsraemaekers/Cgrid-toolbox
Programmed deep septal pacing for the diagnosis of left bundle branch capture
Authors: Jastrzębski Marek , Moskal Paweł , Kusiak Aleksander , Bednarek Agnieszka , Sondej Tomasz , Kiełbasa Grzegorz , Bednarski Adam , Vijayaraman Pugazhendhi , Czarnecka Danuta 
Published: October 2019

AbstractBackgroundDuring permanent deep septal pacing, it is important to confirm left bundle branch (LBB) capture.ObjectiveThe effective refractory period (ERP) of the working myocardium is different than the ERP of the LBB; we hypothesized that it should be possible to differentiate LBB capture from septal myocardial capture using programmed extra-stimulus technique.MethodsIn consecutive patients undergoing pacemaker implantation who received pacing lead in a deep septal position programmed pacing was delivered from this lead. Responses to programmed pacing were categorized on the basis of QRS morphology of the extrastimuli as: myocardial (broader QRS, often slurred), selective (narrower QRS, preceded by an isoelectric interval) or non-diagnostic (unequivocal change).ResultsProgrammed deep septal pacing was performed 269 times in 143 patients; in every patient with the use of an 8-beat basic drive train of 600 ms and when possible also during supraventricular rhythm. Responses diagnostic for LBB capture were observed in 114 (79.7%) of patients. Selective LBB paced QRS was more often seen when premature beats were introduced during the intrinsic rhythm rather than after the basic drive train. The average septal-myocardial refractory period was significantly shorter than the LBB refractory period: 263.0±34.4 ms vs. 318.0±37.4 ms.ConclusionsA novel maneuver for the diagnosis of LBB capture during deep septal pacing, was formulated, assessed and found as diagnostically valuable. This method, based on the differences in refractoriness between LBB and the septal myocardium is unique in enabling the visualization of components of the usually fused, non-selective LBB paced QRS complex.Graphical abstract
Gray matter volume and estimated brain age gap are not associated with sleep-disordered breathing in subjects from the ADNI cohort
Authors: Mohajer Bahram , Abbasi Nooshin , Mohammadi Esmaeil , Khazaie Habibolah , Osorio Ricardo S. , Rosenzweig Ivana , Eickhoff Claudia R. , Zarei Mojtaba , Tahmasian Masoud , Eickhoff Simon B. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

AbstractAlzheimer’s disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the ApoE4 allele, from the Alzheimer’s Disease Neuroimaging Initiative. Gray-matter volume was measured using voxel-wise morphometry and differences reflecting SDB, cognitive status, and their interaction were evaluated. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants’ age from their structural scans. Cognitive decline (MCI/AD diagnosis) and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. BrainAGE was well predicted from the morphological data in HC and, as expected, elevated in MCI and particularly in AD. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status nor an SDB-by-cognitive status interaction. Also, we found neither a significant difference in BrainAGE gap (estimated - chronological age) related to SDB nor an SDB-by-cognitive status interaction. In summary, contrary to our expectations, we were not able to find a general nor a diagnostic specific effect on either gray-matter volumetric or brain aging.Statement of significanceDementia syndromes including Alzheimer’s disease (AD), are a major global concern, and unraveling modifiable predisposing risk factors is indispensable. Sleep-disordered breathing (SDB) and its most prevalent form, obstructive sleep apnea, are suggested as modifiable risk factors of AD, but their contribution to AD hallmarks, like brain atrophy and advanced brain aging, is not clear to this day. While self-reported SDB is suggested to propagate aging process and cognitive decline to AD in clinical studies, here, we demonstrated that, SDB might not necessarily associate to brain atrophy and the advanced brain aging assessed by morphological data, in AD progession. However, multimodal longitudinal studies with polysomnographic assessment of SDB are needed to confirm such fundings.
Discovery of novel Defense Regulated WD40-repeat proteins DRW1/2 and their roles in plant immunity
Authors: Miller Jimi C. , Barco Brenden , Clay Nicole K. 
Published: October 2019

ABSTRACTPlant heterotrimeric G proteins transduce extracellular signals that activate plant immunity. Plants encode canonical and non-canonical Gα and Gγ subunits, but only a single canonical Gβ subunit is known. The existence of only one Gβ subunit limits the number of heterotrimeric G protein combinations able to transduce different signals. It remains unknown whether non-canonical Gβ subunits exist. Here, we identify two WD40-repeat genes that negatively regulate plant immunity. The proteins encoded by these two genes,DEFENSE REGULATED WD40-REPEAT1 and 2 (DRW1/2), are structurally similar to AGB1. DRW2 localizes to the plasma membrane and interacts with the canonical Gα and Gγ subunits. Reduced levels ofDRWin thedrw1anddrw2single mutants resulted in greater MAPK activation in response to flagellin treatment and conferred increased resistance to the bacterial pathogenPseudomonas syringae. Furthermore, thedrw1 drw2double-mutant also displayed increased MAPK activation upon flagellin treatment and broad-spectrum resistance against bacterial and fungal pathogen infection. The function of DRW1 and DRW2 is opposite of AGB1, which promotes immune signaling, suggesting that the function of these potential non-canonical Gβ subunits are not conserved with the canonical Gβ subunit. Our study identifies additional heterotrimeric G protein components, greatly increasing the number of heterotrimeric G protein complexes that participate in signal transduction.
Allosteric regulation of Glutamate dehydrogenase deamination activity
Authors: Rashid Mubasher , Bera Soumen , Medvinsky Alexander B. , Sun Gui-Quan , Li Bai-Lian , Acquisti Claudia , Sljoka Adnan , Chakraborty Amit 
Published: October 2019

AbstractGlutamate dehydrogenase (GDH) is a key enzyme interlinking carbon and nitrogen metabolism. Recent discoveries of the GDH specific role in breast cancer, hyperinsulinism/hyperammonemia syndrome, and neurodegenerative diseases have reinvigorated interest on GDH regulation, which remains poorly understood despite extensive and long standing studies. Notwithstanding the growing evidence of the complexity of the allosteric network behind GDH regulation, a clear understanding of the enzyme dynamics involved in the process is limited to the activator Adenosine diphosphate (ADP) and the inhibitor Guanosine triphosphate (GTP). Presently, the identification of further factors involved in the allosteric network is paramount to deepen our understanding of the complex dynamics that regulate GDH enzymatic activity. Combining structural analyses of cryo-electron microscopy data with molecular dynamic simulations, here we show that the cofactor NADH is a key player in the GDH regulation process. Our structural analysis indicates that, binding to the regulatory sites in proximity of the antenna region, NADH acts as a positive allosteric modulator by enhancing both the affinity of GTP binding and inhibition of GDH catalytic activity. We further show that the binding of GTP to the NADH bound GDH produces a local conformational rearrangement that triggers an anticlockwise rotational motion of interlinked alpha-helices with specific tilted helical extension. This structural transition is a fundamental switch in the GDH enzymatic activity. It introduces a torsional stress, and the associated rotational shift in the Rossmann fold closes the catalytic cleft with consequent inhibition of the deamination process. These results shed new light on GDH regulation and may lay new foundation in the design of allosteric agents.
Formation ofS. pombeErh1 homodimer mediates gametogenic gene silencing and meiosis progression
Authors: Hazra Ditipriya , Andrić Vedrana , Palancade Benoit , Rougemaille Mathieu , Graille Marc 
Published: October 2019

AbstractTimely and accurate expression of the genetic information relies on the integration of environmental cues and the activation of regulatory networks involving transcriptional and post-transcriptional mechanisms. In fission yeast, meiosis-specific transcripts are selectively targeted for degradation during mitosis by the EMC complex, composed of Erh1, the ortholog of human ERH, and the YTH family RNA-binding protein Mmi1. Here, we present the crystal structure of Erh1 and show that it assembles as a homodimer. Mutations of amino acid residues to disrupt Erh1 homodimer formation result in loss-of-function phenotypes, similar toerh1∆cells: expression of meiotic genes is derepressed in mitotic cells and meiosis progression is severely compromised. Interestingly, formation of Erh1 homodimer is dispensable for interaction with Mmi1, suggesting that only fully assembled EMC complexes consisting of two Mmi1 molecules bridged by an Erh1 dimer are functionally competent. We also show that Erh1 does not contribute to Mmi1-dependent down-regulation of the meiosis regulator Mei2, supporting the notion that Mmi1 performs additional functions beyond EMC. Overall, our results provide a structural basis for the assembly of the EMC complex and highlight its biological relevance in gametogenic gene silencing and meiosis progression.
Reinforcement learning for human-robot shared control
Authors: Li Yanan , Tee Keng Peng , Yan Rui , Ge Shuzhi Sam 
Published: October 2019

Purpose
This paper aims to propose a general framework of shared control for human–robot interaction.

Design/methodology/approach
Human dynamics are considered in analysis of the coupled human–robot system. Motion intentions of both human and robot are taken into account in the control objective of the robot. Reinforcement learning is developed to achieve the control objective subject to unknown dynamics of human and robot. The closed-loop system performance is discussed through a rigorous proof.

Findings
Simulations are conducted to demonstrate the learning capability of the proposed method and its feasibility in handling various situations.

Originality/value
Compared to existing works, the proposed framework combines motion intentions of both human and robot in a human–robot shared control system, without the requirement of the knowledge of human’s and robot’s dynamics.
Development of a knowledge management system for the NOMAD instrument onboard the ExoMars TGO spacecraft
Authors: Hetey Laszlo , Neefs Eddy , Thomas Ian , Zender Joe , Vandaele Ann-Carine , Berkenbosch Sophie , Ristic Bojan , Bonnewijn Sabrina , Delanoye Sofie , Leese Mark , Mason Jon , Patel Manish 
Published: October 2019

Purpose
This paper aims to describe the development of a knowledge management system (KMS) for the Nadir and Occultation for Mars Discovery (NOMAD) instrument on board the ESA/Roscosmos 2016 ExoMars Trace Gas Orbiter (TGO) spacecraft. The KMS collects knowledge acquired during the engineering process that involved over 30 project partners. In addition to the documentation and technical data (explicit knowledge), a dedicated effort was made to collect the gained experience (tacit knowledge) that is crucial for the operational phase of the TGO mission and also for future projects. The system is now in service and provides valuable information for the scientists and engineers working with NOMAD.

Design/methodology/approach
The NOMAD KMS was built around six areas: official documentation, technical specifications and test results, lessons learned, management data (proposals, deliverables, progress reports and minutes of meetings), picture files and movie files. Today, the KMS contains 110 GB of data spread over 11,000 documents and more than 13,000 media files. A computer-aided design (CAD) library contains a model of the full instrument as well as exported sub-parts in different formats. A context search engine for both documents and media files was implemented.

Findings
The conceived KMS design is basic, flexible and very robust. It can be adapted to future projects of a similar size.

Practical implications
The paper provides practical guidelines on how to retain the knowledge from a larger aerospace project. The KMS tool presented here works offline, requires no maintenance and conforms to data protection standards.

Originality/value
This paper shows how knowledge management requirements for space missions can be fulfilled. The paper demonstrates how to transform the large collection of project data into a useful tool and how to address usability aspects.