bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging the gap between single-cell migration and collective dynamics
Authors: Thüroff Florian , Goychuk Andriy , Reiter Matthias , Frey Erwin 
Published: February 2019

AbstractA wealth of experimental data relating to the emergence of collective cell migration as one proceeds from the behavioral dynamics of small cohorts of cells to the coordinated migratory response of cells in extended tissues is now available. Integrating these findings into a mechanistic picture of cell migration that is applicable across such a broad range of system sizes constitutes a crucial step towards a better understanding of the basic factors that determine the emergence of collective cell motion. Here we present a cellular-automaton-based modeling framework, which focuses on the integration of high-level cell functions and their concerted effect on cellular migration patterns. In particular, we adopt a top-down approach to incorporate a coarse-grained description of cell polarity and its response to mechanical cues, and address the impact of cell adhesion on collective migration in cell groups. We demonstrate that the model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet is computationally efficient enough to allow for the simulation of (currently) up to 𝒪(104) cells. To develop a mechanistic picture that illuminates the relationship between cell functions and collective migration, we present a detailed study of small groups of cells in confined circular geometries, and discuss the emerging patterns of collective motion in terms of specific cellular properties. Finally, we apply our computational model at the level of extended tissues, and investigate stress and velocity distributions, as well as front morphologies, in expanding cellular sheets.
HEXOKINASE 1 Control of Post-Germinative Seedling Growth
Authors: Lincoln Matthew J. , Ganpudi Ashwin , Romanowski Andrés , Halliday Karen J. 
Published: February 2019

SummaryIn darkness, PHYTOCHROME INTERACTING FACTOR (PIF)-induced skotomorphogenic seedling growth, is exemplified by increased hypocotyl elongation. HEXOKINASE1 (HXK1), which is also implicated in seedling establishment, can operate as a glycolytic enzyme or as a glucose-activated sensor signalling molecule. Under light and nutrient limiting conditions, the HXK1 sensor-signalling has been shown to control hypocotyl elongation. Little is known of whether HXK1 glycolytic function, or HXK1 and PIF cross-talk, is required to control hypocotyl growth.We demonstrate HXK1 glycolytic activity is critical for cell expansion, and hypocotyl growth, post-germination. Notably, application of glucose-6-phosphate, the HXK1 enzymatic product, can restore shortgin2-1/hxk1-1mutant hypocotyls to wild-type length. Further, HXK1 sensor-signalling complex components, VHA-B1 and RPT5B, do not contribute to this response, for unlikegin2-1/hxk1-1, thevha-B1andrpt5balleles only disrupt hypocotyl growth following exogenous glucose application.mRNA-seq analysis illustrates that HXK1 and PIF signalling converge at genes with known roles in light signalling. HXK1 imposes strong regulation on chloroplast and mitochondrial encoded genes, also branched chain amino acid catabolism pathway genes, which can provide a source of respiratory substrates in starvation conditions.Our study establishes the importance of HXK1 enzymatic function in supporting cell expansion and hypocotyl growth. We demonstrate a degree of cross-talk between HXK1 and PIFs through common target gene set.
mRNA structure regulates protein expression through changes in functional half-life
Authors: Mauger David M. , Cabral B. Joseph , Presnyak Vladimir , Su Stephen V. , Reid David W. , Goodman Brooke , Link Kristian , Khatwani Nikhil , Reynders John , Moore Melissa J. , McFadyen Iain J. 
Published: February 2019

SummaryMessenger RNAs (mRNAs) encode information in both their primary sequence and their higher order structure. The independent contributions of factors like codon usage and secondary structure to regulating protein expression are difficult to establish as they are often highly correlated in endogenous sequences. Here, we used two approaches, global inclusion of modified nucleotides and rational sequence design of exogenously delivered constructs to understand the role of mRNA secondary structure independent from codon usage. Unexpectedly, highly-expressed mRNAs contained a highly-structured coding sequence (CDS). Modified nucleotides that stabilize mRNA secondary structure enabled high expression across a wide-variety of primary sequences. Using a set of eGFP mRNAs that independently altered codon usage and CDS structure, we find that the structure of the CDS regulates protein expression through changes in functional mRNA half-life (i.e. mRNA being actively translated). This work highlights an underappreciated role of mRNA secondary structure in the regulation of mRNA stability. [150 words]HighlightsProtein expression from modified mRNAs tends to follow the pattern m1 Ψ > U >mo5UProtein expression correlates with mRNA thermodynamic stability: Ψ≈ m1Ψ > U > mo5UA highly structured CDS correlates with high expressionIncreased structured mRNAs extend functional half-life
Variable Retention of Differentiation-specific DNA Replication Timing in Human Pediatric Leukemia
Authors: Rivera-Mulia Juan Carlos , Sasaki Takayo , Trevilla-Garcia Claudia , Nakamichi Naoto , Knapp David , Hammond Colin , Chang Bill , Tyner Jeffrey W. , Devidas Meenakshi , Zimmerman Jared , Klein Kyle N. , Somasundaram Vivek , Druker Brian , Gruber Tanja A. , Koren Amnon , Eaves Connie , Gilbert David M. 
Published: February 2019

ABSTRACTHuman B-lineage precursor acute lymphoid leukemias (BCP-ALLs) comprise a group of genetically and clinically distinct disease entities with features of differentiation arrest at known stages of normal B-lineage differentiation. We previously showed BCP-ALL cells display unique and clonally heritable DNA-replication timing (RT) programs; i.e., programs describing the variable order of replication of megabase-scale chromosomal units of DNA in different cell types. To determine the extent to which BCP-ALL RT programs mirror or deviate from specific stages of normal human B-cell differentiation, we transplanted immunodeficient mice with quiescent normal human CD34+ cord blood cells and obtained RT signatures of the regenerating B-lineage populations. We then compared these with RT signatures for leukemic cells from a large cohort of BCP-ALL patients. The results identify BCP-ALL subtype-specific features that resemble specific stages of B-cell differentiation and features that appear associated with relapse. These results suggest the genesis of BCP-ALL involves alterations in RT that reflect clinically relevant leukemia-specific genetic and/or epigenetic changes.SUMMARYGenome-wide DNA replication timing profiles of >100 pediatric leukemic samples and normally differentiating human B-lineage cells isolated from xenografted immunodeficient mice were generated. Comparison of these identified potentially clinically relevant features that both match and deviate from the normal profiles.
Detection of Base Analogs Incorporated During DNA Replication by Nanopore Sequencing
Authors: Georgieva Daniela , Liu Qian , Wang Kai , Egli Dieter 
Published: February 2019

ABSTRACTDNA synthesis is a fundamental requirement for cell proliferation and DNA repair, but no tools exist to identify the location, direction and speed of replication forks with base pair resolution. Mammalian cells have the ability to incorporate thymidine analogs along with the natural A, T, G and C bases during DNA synthesis, which allows for labelling of replicating or repaired DNA. Most sequencing platforms rely on base-pairing to identify the four canonical nucleotides, and are thus unable to distinguish them from these analogs. In contrast, the Oxford Nanopore Technologies (ONT) MinION infers nucleotide identity from changes in the ionic current as DNA strands are pulled through nanopores and can in principle differentiate noncanonical nucleotides from natural ones. Here, we demonstrate the use of the ONT MinION to detect 11 different thymidine analogs including CldU, BrdU, IdU, as well as, EdU alone or coupled to Biotin and other bulky adducts in synthetic DNA templates. We also show detection of IdU in the genome of mouse pluripotent stem cells. We find that different modifications generate variable shifts in ionic signals, providing a method of using analog combinations to identify the location and direction of DNA synthesis and repair at high resolution. We conclude that this novel method has the potential for single-base, genome-wide examination of DNA replication in stem cell differentiation or cell transformation.
Dynamics of living cells in a cytomorphological state space
Authors: Chang Amy Y. , Marshall Wallace F. 
Published: February 2019

AbstractCells are non-equilibrium systems that rely on a continuous exchange of matter and energy with the environment to sustain their metabolic needs. The non-equilibrium nature of this system presents considerable challenges to developing a general theory describing its behavior; however, studies have demonstrated that when studied at appropriate spatiotemporal scales, the behavior of ensembles of non-equilibrium systems can resemble that of system at equilibrium. Here we apply this principle to a population of cells within a cytomorphological state space and demonstrate that cellular transition dynamics within this space can be suitably described using equilibrium dynamics formalisms. We use this framework to map the effective energy landscape underlying the cytomorphological state space of a population of mouse embryonic fibroblasts (MEFs) and identify topographical non-uniformity in this space, indicating non-uniform occupation of cytomorphological states within an isogenic population. The introduction of exogenous apoptotic agents altered this energy landscape, inducing formation of additional energy minima that correlated directly with changes in sensitivity to apoptotic induction. The measured application of equilibrium dynamics formalism allows us to accurately capture and these findings suggest that though cells are complex non-equilibrium systems, the application of formalisms derived from equilibrium thermodynamics can provide insight into the basis of non-genetic heterogeneities as well as the relationship between morphological and functional heterogeneity.
Assessing the potential impact of Medicaid work requirements on African-Americans via a welfare reform analysis: a systematic review
Authors: Hall Garrett , Burrowes Sahai 
Published: February 2019

AbstractThe Centers for Medicare and Medicaid Services are currently approving Medicaid demonstration projects involving work and community engagement requirements. The fear among public health professionals and policymakers is that these work requirements will disproportionately limit access to health insurance for African-Americans. To investigate these new work requirements for Medicaid, we conducted a systematic review of the Temporary Assistance for Needy Families program, the last major welfare program to have such work requirements. We used the ProQuest database and selected scholarly journal studies in English and published between January 1991-August 2018. Our selection strategy yielded 14 eligible studies, eight of which focused on caseload movements and six focused on sanctions. We found that African-Americans entered TANF at a higher rate than Whites, remained on TANF longer, and were subject to sanctions more frequently and stringently than Whites were. These results suggest that African-Americans may disproportionately experience reduced access to care through sanctioning such as lockout periods. Recommended policy changes include prohibiting work activities as a condition of Medicaid coverage, strengthening Medicaid in other ways, combating discriminatory hiring practices, and easing burdensome reporting requirements.
De novo assembly and annotation of Asiatic lion (Panthera leo persica) genome
Authors: Mitra Siuli , Sreenivas Ara , Sowpati Divya Tej , Kumar Amitha Sampat , Awasthi Gowri , Kumar M. Milner , Tabusum Wajeeda , Gaur Ajay 
Published: February 2019

AbstractWe report the first draft of the whole genome assembly of a male Asiatic lion, Atul and whole transcriptomes of five Asiatic lion individuals. Evaluation of genetic diversity placed the Asiatic lion in the lowest bracket of genomic diversity index highlighting the gravity of its conservation status. Comparative analysis with other felids and mammalian genomes unraveled the evolutionary history of Asiatic lion and its position among other felids. The genome is estimated to be 2.3 Gb (Gigabase) long with 62X sequence coverage and is found to have 20,543 protein-coding genes. About 2.66% of the genome is covered by simple sequence repeats (SSRs) and 0.4% is estimated to have segmental duplications. Comparison with seven well annotated genomes indicates the presence of 6,295 single copy orthologs, 4 co-orthologs, 21 paralogs uniquely present in Asiatic lion and 8,024 other orthologs. Assessment of male and female transcriptomes gave a list of genes specifically expressed in the male.Our genomic analyses provide candidates for phenotypes characteristic to felids and lion, inviting further confirmation of their contribution through population genetic studies. An Asiatic lion-specific expansion is detected in the Cysteine Dioxygenase-I (CDO-I) family that is responsible for taurine biosynthesis in cats. Wilm’s tumor-associated protein (WT1) family, a non-Y chromosome genetic factor underlying male-sex determination and differentiation is found to have undergone expansion, interestingly like that of the human genome. Another protein family, translation machinery-associated protein 7 (TMA7) that has undergone expansion in humans, also expanded in Asiatic lion and can be further investigated as a candidate responsible for mane in lions because of its role in hair follicle morphogenesis.
Mixed-polarity random-dot stereograms alter GABA and Glx concentration in the early visual cortex
Authors: Rideaux Reuben , Goncalves Nuno , Welchman Andrew E 
Published: February 2019

ABSTRACTThe offset between images projected onto the left and right retinae (binocular disparity) provides a powerful cue to the three-dimensional structure of the environment. It was previously shown that depth judgements are better when images comprise both light and dark features, rather than only dark or only light elements. Since Harris and Parker (1995) discovered the “mixed-polarity benefit”, there has been limited evidence supporting their hypothesis that the benefit is due to separate bright and dark channels. Goncalves and Welchman (2017) observed that single- and mixed-polarity stereograms evoke different levels of positive and negative activity in a deep neural network trained on natural images to make depth judgements, which also showed the mixed-polarity benefit. Motivated by this discovery, here we seek to test the potential for changes in the balance of excitation and inhibition that are produced by viewing these stimuli. In particular, we use magnetic resonance spectroscopy to measure Glx and GABA concentration in the early visual cortex of adult humans while viewing single- and mixed-polarity random-dot stereograms (RDS). We find that observers’ Glx concentration is significantly higher while GABA concentration is significantly lower when viewing mixed-polarity RDS than when viewing single-polarity RDS. These results indicate that excitation and inhibition facilitate processing of single- and mixed-polarity stereograms in the early visual cortex to different extents, consistent with recent theoretical work (Goncalves & Welchman, 2017).
FM perceptions on occupant impact and the shaping of occupant engagement practice
Authors: Valle Cristian Roberto , Verhulst Elli , Pettersen Ida Nilstad , Junghans Antje , Berker Thomas 
Published: February 2019

Purpose
This paper aims to apply frame analysis to explore the mental models by which building managers interpret the impact of building occupants on energy use and rationalize their approach to occupant engagement.

Design/methodology/approach
Findings from four energy-efficient buildings (two schools and two office buildings) in Norway are presented. The methodology includes individual semi-structured interviews with both operational and strategic facilities managers

Findings
Concepts and theoretical perspectives with the potential to shape the building managers’ perceptions include technical knowledge and expertise, management responsibilities, familiarity with occupant routines and understanding of energy-efficient technologies. No significant impact was attributed to the actions of occupants in the areas of comfort, core function and behavior. Significant impact was attributed to their movement and presence. Perceptions of impact were found to influence, yet not determine, the building managers’ choices of practice.

Practical implications
Factors with the potential to affect the adoption of occupant engagement initiatives were highlighted. This study pointed to the role that automation and centralization can play in influencing facilities managers to rescind from their management responsibilities.

Originality/value
To the knowledge of the authors, this is the first study to use framings in thoughts to investigate the process by which facilities managers rationalize occupant engagement, in relation to their perception of occupant impact on energy use.
Using informatics to improve healthcare quality
Authors: Otokiti Ahmed 
Published: February 2019

Purpose
The purpose of this paper is to provide insights into contemporary challenges associated with applying informatics and big data to healthcare quality improvement.

Design/methodology/approach
This paper is a narrative literature review.

Findings
Informatics serve as a bridge between big data and its applications, which include artificial intelligence, predictive analytics and point-of-care clinical decision making. Healthcare investment returns, measured by overall population health, healthcare operation efficiency and quality, are currently considered to be suboptimal. The challenges posed by informatics/big data span a wide spectrum from individual patients to government/regulatory agencies and healthcare providers.

Practical implications
The paper utilizes informatics and big data to improve population health and healthcare quality improvement.

Originality/value
Informatics and big data utilization have the potential to improve population health and service quality. This paper discusses the challenges posed by these methods as the author strives to achieve the aims.
Iranian hospital efficiency: a systematic review and meta-analysis
Authors: Rezaei Satar , Hajizadeh Mohammad , Nouri Bijan , Ahmadi Sina , Rezaeian Shahab , Salimi Yahya , Karyani Ali Kazemi 
Published: February 2019

Purpose
The purpose of this paper (systematic review and meta-analysis) is to synthesize and analyze studies that assessed Iranian hospital efficiency.

Design/methodology/approach
A systematic literature search was conducted using both international (the Institute for Scientific Information, Scopus and PubMed) and Iranian scientific (Magiran, IranMedex and Scientific Information Database) databases. The review included original studies that used the Pabon Lasso Model to examine Iranian hospital performance, published in Persian or English. A self-administered checklist was used to collect data. In total, 12 questions were used for quality assessment.

Findings
In total, 34 studies met our inclusion criteria. The fixed-effects meta-analysis indicated that 19.2 percent (95% confidence interval (CI): 15.6–23.2 percent) of hospitals were in Zone 1 (poor performance: low bed turnover rate (BTR) and bed occupancy rate (BOR) and high average hospital stay (ALoS)), 23.7 percent (95% CI: 20.1–27.8 percent) were in Zone 2, 31.7 percent (95% CI: 27.7–36 percent) in Zone 3 (good performance: high BTR and BOR and low ALoS) and 25.4 percent (95% CI: 21.7–29.5 percent) in Zone 4.

Practical implications
Results help Iranian health policymakers to understand hospital performance, which, in turn, may lead to promoting greater awareness and policy attention to improve Iranian hospital efficiency.

Originality/value
This study indicated that most Iranian hospitals had sub-optimal performance. Further studies are required to understand factors that explain the country’s hospital inefficiency.
Verifying alternative measures of healthcare service quality
Authors: Shafei Ingy , Walburg Jan , Taher Ahmed 
Published: February 2019

Purpose
The purpose of this paper is to determine the best measure among several alternatives (SERVQUAL, weighted SERVQUAL, SERVPERF, weighted SERVPERF) and develop a scale which healthcare providers can use for measurement of healthcare service quality.

Design/methodology/approach
The study involved two phases. The first phase was through a series of in-depth interviews with experts and patients followed by a pilot study. Subsequently, the second phase involved a quantitative phase through surveys with 384 patients. Alternative measures were analyzed using coefficient (Cronbach) α, composite reliability, factor analysis and logistic regression analysis.

Findings
Findings confirmed “Weighted SERVPERF” using an interactive methodology as the most appropriate for measurement of healthcare service quality.

Originality/value
Using the model and scale developed, healthcare providers will be able to measure healthcare service quality and identify areas of shortfall and act accordingly to improve delivery through allocating resources in service areas that would generate the greatest returns in customer satisfaction. Enhancing satisfaction will ultimately generate patient loyalty and positive recommendation behavior.
TORS for OSA: a practice, pitfalls and literature review
Authors: Hassaan Amro , Trinidade Aaron , Kotecha Bhik , Tolley Neil 
Published: February 2019

Purpose
Trans-oral robotic surgery (TORS) is increasingly employed in obstructive sleep apnoea (OSA) management. Objective outcomes are generally assessed through polysomnography. Pre-operative magnetic resonance imaging (MRI) can be a useful adjunct in objective upper airway assessment, in particular the tongue base, providing useful information for surgical planning and outcome assessment, though care must be taken in patient positioning during surgery. The purpose of this paper is to identify pitfalls in this process and suggest a protocol for pre-operative MRI scanning in OSA.

Design/methodology/approach
This study is a four-patient prospective case-series and literature review. Outcome measures include pre- and post-operative volumetric changes in the pharynx as measured on MRI and apnoea–hypopnea indices (AHI), with cure being OSA resolution or a 50 per cent reduction in AHI.

Findings
All patients achieved AHI reduction and/or OSA cure following TORS, despite a decrease in pharyngeal volume measurements at the tongue base level. This study and others lacked standardisation in the MRI scanning protocol, which resulted in an inability to effectively compare pre- and post-operative scans. Pitfalls were related to variation in head/tongue position, soft-tissue marker usage and assessed area boundary limits.

Practical implications
TORS appears to be effective in OSA management. A new protocol for patient positioning and anatomical landmarks is suggested.

Originality/value
The findings could provide directly comparable data between scans and may allow correlation between tongue base volumetric changes and AHI through subsequent and historical study meta-analysis.