bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Spending More Time Associated With Less Missed Care?
Authors: McNair Norma , Baird Jennifer , Grogan Tristan R. , Walsh Catherine M. , Liang Li-Jung , Worobel-Luk Pamela , Needleman Jack , Nuckols Teryl K. 
Published: May 2018

OBJECTIVE:
The aim of this study is to examine the relationship between nursing time use and perceptions of missed care.

BACKGROUND:
Recent literature has highlighted the problem of missed nursing care, but little is known about how nurses’ time use patterns are associated with reports of missed care.

METHODS:
In 15 nursing units at 2 hospitals, we assessed registered nurse (RN) perceptions of missed care, observed time use by RNs, and examined the relationship between time spent and degree of missed care at the nursing unit level.

RESULTS:
Patterns of time use were similar across hospitals, with 25% of time spent on documentation. For 6 different categories of nursing tasks, no association was detected between time use, including time spent on documentation, and the degree of missed care at the nursing unit level.

CONCLUSIONS:
Nursing time use cannot fully explain variation in missed care across nursing units. Further work is needed to account for patterns of missed care.
Noise Exposure on Pediatric Inpatient Units
Authors: Daraiseh Nancy M. , Hoying Cheryl L. , Vidonish William P. , Lin Li , Wagner Michael 
Published: May 2018

BACKGROUND:
Noise is a problem placing registered nurses (RNs) at risk for safety events, decreased job performance, fatigue, irritability, and hearing loss.

OBJECTIVE:
The purpose of this study is to measure noise levels and sources on pediatric inpatient units as well as to explore the health impact of noise on RNs.

METHODS:
This was a descriptive nonexperimental study with 65 pediatric RNs from 14 units. Noise (levels, source, location, and activity), heart rate (HR), and stress were measured. Correlations between sound pressure levels (SPLs), HR, and stress were examined.

RESULTS:
Mean (SD) SPLs were 75.8 (8.9) dBA and were significantly higher than SPLs for patients. Noise was significantly associated with HR but not with time in tachycardia or stress. Primary sources of noise were employee conversations in patient rooms.

CONCLUSIONS:
On all units, SPLs exceeded protection agency guidelines. Cost-prohibitive structural changes underscore the importance of using behavioral and culture modification to reduce noise.
Effects of Attentional Bias Modification on Residual Symptoms in depression. A Randomized Controlled Trial
Authors: Jonassen Rune , Harmer Catherine J. , Hilland Eva , Maglanoc Luigi A. , Kraft Brage , Browning Michael , Stiles Tore C. , Haaland Vegard Ø. , Berge Torkil , Landrø Nils Inge 
Published: May 2018

BackgroundFollowing treatment, many depressed patients have significant residual symptoms. However, large randomised controlled trials (RCT) in this population are lacking. When Attention bias modification training (ABM) leads to more positive emotional biases, associated changes in clinical symptoms have been reported. A broader and more transparent picture of the true advantage of ABM based on larger and more stringent clinical trials have been requested.AimsTo evaluate the early effect of two weeks ABM training on blinded clinician-rated and self-reported residual symptoms, and whether changes towards more positive attentional biases (AB) would be associated with symptom reduction.MethodA total of 321 patients with a history of depression were included in a preregistered randomized controlled double-blinded trial. Patients were randomised to an emotional ABM paradigm over fourteen days or a closely matched control condition. Symptoms based on the Hamilton Rating Scale for Depression (HRSD) and Beck Depression Inventory II (BDI-II) were obtained at baseline and after ABM training.ResultsABM training led to significantly greater decrease in clinician-rated symptoms of depression as compared to the control condition. No differences between ABM and placebo were found for self-reported symptoms. ABM induced a change of AB towards relatively more positive stimuli associated with greater symptom reduction.ConclusionThe current study demonstrates that ABM produces early changes in both AB and blinded clinician-rated depressive symptoms. ABM may have practical potential in the treatment of residual depression.ClinicalTrials.govID:NCT02658682
Optogenetic dissection of mitotic spindle positioning in vivo
Authors: Fielmich Lars-Eric , Schmidt Ruben , Dickinson Daniel J. , Goldstein Bob , Akhmanova Anna A. , van den Heuvel Sander J.L. 
Published: May 2018

ABSTRACTThe position of the mitotic spindle determines the plane of cell cleavage, and thereby the location, size, and content of daughter cells. Spindle positioning is driven by dynein-mediated pulling forces exerted on astral microtubules. This process requires an evolutionarily conserved complex of Gα-GDP, GPR-1/2Pins/LGN, and LIN-5Mud/NuMAproteins. It remains unknown whether this complex merely forms a membrane anchor for dynein, or whether the individual components have additional functions, for instance through Gα-GTP or dynein activation. To functionally dissect this system, we developed a genetic strategy for light-controlled localization of endogenous proteins inC. elegansembryos. Controlled germline expression and membrane recruitment of the Gα regulators RIC-8Ric-8Aand RGS-7Loco/RGS3, and replacement of Gα with a light-inducible membrane anchor demonstrated that Gα-GTP signaling is dispensable for pulling force generation. In the absence of Gα, cortical recruitment of GPR-1/2 or LIN-5, but not dynein itself, induced high pulling forces. Local recruitment of LIN-5 overruled normal cell-cycle and polarity regulation, and provided experimental control over the spindle and cell cleavage plane. Our results define Gα∙GDP–GPR-1/2Pins/LGNas a regulatable membrane anchor, and LIN-5Mud/NuMAas a potent activator of dynein-dependent spindle positioning forces. This study also highlights the possibilities for optogenetic control of endogenous proteins within an animal system.
Enzymatic evolution driven by entropy production
Authors: Arango-Restrepo A. , Rubi J.M. , Barragán D. 
Published: May 2018

AbstractWe show that the structural evolution of enzymes is largely influenced by the entropy produced in the enzymatic process. We have computed this quantity for the case in which the process has unstable and metastable intermediate states. By assuming that the kinetics takes place along a potential barrier, we have found that the behavior of the total entropy produced is a non-monotonic function of the intermediate state energy. By diminishing the number of metastable intermediate states, the total entropy produced decreases and consequently the enzyme kinetics and the thermodynamic efficiency are enhanced. Minimizing locally the total entropy produced for an enzymatic process with metastable intermediate states, the kinetics and the thermodynamic efficiency are raised. In contrast, in the absence of metastable intermediate states, a maximum of the entropy produced results in an improvement of the kinetic performance although the thermodynamic efficiency diminishes. Our results show that the enzymatic evolution proceeds not only to enhance the kinetics but also to optimize the total entropy produced.
Diversity of active viral infections within theSphagnummicrobiome
Authors: Stough Joshua M.A. , Kolton Max , Kostka Joel E. , Weston David J. , Pelletier Dale A. , Wilhelm Steven W. 
Published: May 2018

AbstractSphagnum-dominatedpeatlands play an important role in global carbon storage and represent significant sources of economic and ecological value. While recent efforts to describe microbial diversity and metabolic potential of theSphagnummicrobiome have demonstrated the importance of its microbial community, little is known about the viral constituents. We used metatranscriptomics to describe the diversity and activity of viruses infecting microbes within theSphagnumpeat bog. The vegetative portions of 6Sphagnumplants were obtained from a peatland in northern Minnesota and total RNA extracted and sequenced. Metatranscriptomes were assembled and contigs screened for the presence of conserved virus marker genes. Using bacteriophage capsid protein, gp23, as a marker for phage diversity, we identified 33 contigs representing undocumented phage s that were active in the community at the time of sampling. Similarly, RNA-dependent RNA polymerase and the Nucleo-Cytoplasmic Large DNA Virus (NCLDV) major capsid protein were used as markers for ssRNA viruses and NCLDV, respectively. In total 114 contigs were identified as originating from undescribed ssRNA viruses, 22 of which represent near-complete genomes. An additional 64 contigs were identified as being from NCLDVs. Finally, 7 contigs were identified as putative virophage or polinto-like viruses. We developed co-occurrence networks with these markers in relation to the expression of potential-host housekeeping generpb1to predict virus-host relationships, identifying 13 groups. Together, our approach offers new tools for the identification of virus diversity and interactions in understudied clades, and suggest viruses may play a considerable role in the ecology of theSphagnummicrobiome.SignificanceSphagnum-dominatedpeatlands play an important role in maintaining atmospheric carbon dioxide levels by modifying conditions in the surrounding soil to favor its own growth over other plant species. This slows rates of decomposition and facilitates the accumulation of fixed carbon in the form of partially decomposed biomass. The unique environment produced bySphagnumenriches for the growth of a diverse microbial consortia that benefit from and support the moss’s growth, while also maintaining the hostile soil conditions. While a growing body of research has begun to characterize the microbial groups that colonizeSphagnum, little is currently known about the ecological factors that constrain community structure and define ecosystem function. Top-down population control by viruses is almost completely undescribed. This study provides insight into the significant viral influence on theSphagnummicrobiome, and identifying new potential model systems to study virus-host interactions in the peatland ecosystem.
Monitoring changes in the Gene Ontology and their impact on genomic data analysis
Authors: Jacobson Matthew , Sedeño-Cortés Adriana Estela , Pavlidis Paul 
Published: May 2018

AbstractThe Gene Ontology (GO) is one of the most widely used resources in molecular and cellular biology, largely through the use of “enrichment analysis”. To facilitate informed use of GO, we present GOTrack (https://gotrack.msl.ubc.ca), which provides access to historical records and trends in the Gene Ontology and GO annotations (GOA). GOTrack gives users access to gene- and term-level information on annotations for nine model organisms as well as an interactive tool that measures the stability of enrichment results over time for user-provided “hit lists” of genes. To document the effects of GO evolution on enrichment, we analyzed over 2500 published hit lists of human genes (most over 9 years old). 53% of hit lists were considered to yield significantly stable enrichment results. Because stability is far from assured for any individual hit list, GOTrack can lead to more informed and cautious application of GO to genomics research.
Discovery of New CDK8 ligands with a Novel Virtual Drug Screening Tool
Authors: Chen Wei , Ren Xiaodong , Chang Chia-en A. 
Published: May 2018

AbstractSelective inhibition of CDK8 could be a promising strategy for reducing mitogenic signals in cancer cells with reduced toxic effects on normal cells. As compared with type I ligands, binding of a type II compound often achieves longer residence time. We developed a novel virtual drug screening package which takes advantage of two energy evaluation methods: Superposition and Single-Point Energy Evaluation, and VM2 free energy calculation, and applied it to the discovery of new CDK8 type II ligands. In this research we analyzed binding thermodynamics of 11 published CDK8 type II ligands, and extracted the key binding information to assist virtual drug screening for new ligands. The free energy and MD calculations on the reference CDK8-ligand complexes revealed the important factors in the binding. The urea moiety was found to be the critical structural contributor of the reference ligands. Starting with the urea moiety we implemented virtual drug screening and singled out three compounds for bio-assay testing. The ranking from the experimental result for the three compounds is completely consistent with the predicted rankings by both energy evaluation methods. A potent drug-like compound was discovered to have a Kd value of 42.5 nM with CDK8, which is comparable to the most potent reference ligands and provided a good starting point to design and synthesize a series of highly selective and potent CDK8 ligands. Therefore, our novel virtual drug screening package is accurate and efficient enough to be used in drug design projects. We believe this work has significant impact to the field of drug discovery.
Identification of regulatory elements from nascent transcription using dREG
Authors: Wang Zhong , Chu Tinyi , Choate Lauren A. , Danko Charles G. 
Published: May 2018

AbstractOur genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvements in accuracy, 3-4-fold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly-transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-I-hypersensitivity. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation, bound by pioneer transcription factors, or located in broad domains marked by repressive chromatin modifications. We provide a web interface to dREG that can be used by the scientific community (http://dREG.DNASequence.org).
Axon-seq decodes the motor axon transcriptome and its modulation in response to ALS
Authors: Nijssen Jik , Benitez Julio Aguila , Hoogstraaten Rein , Kee Nigel , Hedlund Eva 
Published: May 2018

SUMMARYSpinal motor axons traverse large distances to innervate target muscles, thus requiring local control of cellular events for proper functioning. To interrogate axon-specific processes we developed Axon-seq, a refined method incorporating microfluidics, RNA-seq and bioinformatic-QC. We show that the axonal transcriptome is distinct from somas and contains fewer genes. We identified 3,500-5,000 transcripts in mouse and human stem cell-derived spinal motor axons, most of which are required for oxidative energy production and ribogenesis. Axons contained transcription factor mRNAs, e.g. Ybx1, with implications for local functions. As motor axons degenerate in amyotrophic lateral sclerosis (ALS), we investigated their response to the SOD1G93A mutation, identifying 121 ALS-dysregulated transcripts. Several of these are implicated in axonal function, including Nrp1, Dbn1 and Nek1, a known ALS-causing gene. In conclusion, Axon-seq provides an improved method for RNA-seq of axons, increasing our understanding of peripheral axon biology and identifying novel therapeutic targets in motor neuron disease.
Patient-specific detection of cancer genes reveals recurrently perturbed processes in esophageal adenocarcinoma
Authors: Mourikis Thanos P. , Benedetti Lorena , Foxall Elizabeth , Temelkovski Damjan , Nulsen Joel , Perner Juliane , Cereda Matteo , Lagergren Jesper , Howell Michael , Yau Christopher , Fitzgerald Rebecca C. , Scaffidi Paola , Ciccarelli Francesca D. ,   on behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Published: May 2018

ABSTRACTThe identification of somatic alterations with a cancer promoting role is challenging in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we developed a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously (mutations, copy number alterations and structural rearrangements). Analysing 261 EACs from the OCCAMS Consortium, we discovered a large number of novel cancer genes that, together with well-known drivers, help promote cancer. Validation using 107 additional EACs confirmed the robustness of the approach. Unlike known drivers whose alterations recur across patients, the large majority of the newly discovered cancer genes are rare or patient-specific. Despite this, they converge towards perturbing cancer-related processes, including intracellular signalling, cell cycle regulation, proteasome activity and Toll-like receptor signalling. Recurrence of process perturbation, rather than individual genes, divides EACs into six clusters that differ in their molecular and clinical features and suggest patient stratifications for personalised treatments. By experimentally mimicking or reverting alterations of predicted cancer genes, we validated their contribution to cancer progression and revealed EAC acquired dependencies, thus demonstrating their potential as therapeutic targets.
Barriers and incentives for conducting research amongst the Ophthalmologists in Sub-Sahara Africa
Authors: Dhalla Kazim A , Guirguis Micheal 
Published: May 2018

AbstractBackgroundResearch is a critical component amongst the strategies to improve health outcomes of any country. The role of research assumes greater importance in Africa as it carries a larger share of global burden of diseases, blindness and low vision. “Vision 2020- the Right to Sight” is a WHO-IAPB collaborated initiative aiming to eliminate preventable blindness by the year 2020. High quality research in eye care is imperative for the initiative to succeed, however, there is a dearth of research in eye care in sub Saharan Africa in general and specifically in the Eastern, Central and Southern African (ECSA) region. Identifying the barriers that hamper research in this region is an important step towards elimination of preventable blindness.MethodsA structured questionnaire using the SurveyMonkey program was sent to ophthalmologists in the ECSA region and South Africa through their respective regional professional bodies. Data was analyzed using the SPSS program version.ResultsLack of funding, inadequate time and poor research knowledge were the main research barriers while ability to improve eye health care through research was the main incentive for conducting research.ConclusionThe barriers mainly center on financial, human and administrative infrastructure and resources. In spite of the barriers, ophthalmologists in the study region are enthusiastic in research aiming to increase evidence based knowledge to improve eye health care in line with the goals of “Vision 2020- the Right to Sight” initiative.
Replication fork collapse at a protein-DNA roadblock leads to fork reversal, promoted by the RecQ helicase
Authors: Weaver Georgia M. , Mettrick Karla A. , Corocher Tayla-Ann , Graham Adam , Grainge Ian 
Published: May 2018

AbstractThere are numerous impediments that DNA replication can encounter while copying a genome, including the many proteins that bind DNA. Collapse of the replication fork at a protein roadblock must be dealt with to enable replication to eventually restart; failure to do so efficiently leads to mutation or cell death. Several prospective models have been proposed that process a stalled or collapsed replication fork. This study shows that replication fork reversal (RFR) is the preferred pathway for dealing with a collapsed fork inEscherichia coli, along with exonuclease activity that digests the two nascent DNA strands. RFR moves the Y-shaped replication fork DNA away from the site of the blockage and generates a four-way DNA structure, the Holliday junction (HJ). Direct endo-nuclease activity at the replication fork is either slow or does not occur. The protein that had the greatest effect on HJ processing/RFR was found to be the RecQ helicase. RecG and RuvABC both played a lesser role, but did affect the HJ produced: mutations in these known HJ processing enzymes produced longer-lasting HJ intermediates, and delayed replication restart. The SOS response is not induced by the protein-DNA roadblock under these conditions and so does not affect fork processing.Author SummaryTo transfer genetic material to progeny, a cell must replicate its DNA accurately and completely. If a cell does not respond appropriately to inhibitors of the DNA replication process, genetic mutation and cell death will occur. Previous works have shown that protein-DNA complexes are the greatest source of replication fork stalling and collapse in bacteria. This work examines how the cell deals with replication fork collapse at a persistent protein blockage, at a specific locus on the chromosome ofEscherichia coli. Cells were found to process the DNA at the replication fork, moving the branch point away from the site of blockage by replication fork reversal and exonuclease activity. Our data indicate that it is the RecQ helicase that has the main controlling role in this process, and not the proteins RecG and RuvABC, as currently understood. RecQ homologs have been shown to be involved in replication fork processing in eukaryotes and their mutation predisposes humans to genome instability and cancer. Our findings suggest that RecQ proteins could play more important role in replication fork reversal than previously understood, and that this role could be conserved across domains.
Mechanosensitive clathrin platforms anchor desmin intermediate filaments in skeletal muscle
Authors: Franck Agathe , Lainé Jeanne , Moulay Gilles , Trichet Michaël , Gentil Christel , Fongy Anaïs , Bigot Anne , Benkhelifa-Ziyyat Sofia , Lacène Emmanuelle , Thao Bui Mai , Brochier Guy , Guicheney Pascale , Sacconi Sabrina , Mouly Vincent , Romero Norma , Coirault Catherine , Bitoun Marc , Vassilopoulos Stéphane 
Published: May 2018

AbstractLarge flat clathrin plaques are stable features of the plasma membrane associated with sites of strong adhesion suggesting that they could also play a role in force transduction. Here, we analyzed how clathrin plaques interact with the cytoskeleton and how they respond to mechanical cues in skeletal muscle myotubes. We show that branched actin networks surrounding clathrin plaques are directly regulated by dynamin 2, anchor intermediate filaments and sequester YAP at the plasma membrane. Dynamin 2, clathrin and desmin intermediate filaments are all required for basal YAP nucleocytoplasmic distribution and efficient nuclear translocation in response to mechanical stimuli. Dynamin 2 mutations that are responsible for centronuclear myopathy in humans disorganize the desmin network and deregulate YAP signaling both in vitro and in vivo. Thus, clathrin plaques and associated dynamin 2 are defined here as a new sensor conveying mechanical cues and integrate cell signaling with cytoskeletal regulation.