bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Science of Motivation Applied to Clinician Burnout: Lessons for Healthcare
Authors: Norton Jameson 
Published: November 2018

SUMMARY
The science of motivation can help explain some of the root causes driving clinician burnout, a critical vulnerability in healthcare today. Research finds autonomy, mastery, and purpose to be drivers of intrinsic motivation, and healthcare leaders can use these three principles in program design and communication strategies to make progress toward rediscovering joy and passion in the life-giving work of healthcare. Leaders can achieve a competitive advantage for their organizations by applying these inherent motivators to attract, develop, and retain engaged and purposeful caregivers and by developing participative leadership to nurture a passion for caregiving.
In healthcare, we enjoy the privilege of serving with intelligent and caring people who are driven to make a difference on behalf of those they serve. But we also experience the human factors, friction, and uncertainty in a highly complex delivery and reimbursement structure. Each day in our hospitals, clinicians and staff face a marathon of adrenaline, stress, physical fatigue, mental strain, and emotional heights and depths. This reality demands grit and resilience to sustain the high standards of excellence and compassion necessary for delivering personalized care.
Before healthcare organizations launch new programs to address these challenges, however, we must align our leadership and communication approaches with the fundamental drivers of motivation that brought us to healthcare in the first place—and in a way that brings out the best in our care teams and builds their creative capacity for any future challenges.
The Impact of Hematologic Cancer and Its Treatment on Physical Activity Level and Quality of Life Among Children in Mainland China
Authors: Xia Wei , Li Ho Cheung William , Lam Ka Wai Katherine , Chung Oi Kwan Joyce , Song Peige , Chiu Sau Ying , Chan Chi-Fung Godfrey , Ho Ka Yan 
Published: November 2018

Background
The effects of hematologic cancer and its treatment on Chinese children’s physical activity level and quality of life (QoL) remain unclear despite numerous studies conducted in Western countries and Hong Kong.

Objective
The aim of this study was to examine the effects of hematologic cancer and its treatment on the physical activity level and QoL among Chinese children.

Methods
A cross-sectional study was conducted. One hundred twenty-five children who were admitted for treatment of hematologic cancer and 243 healthy counterparts of similar age participated in this study. All participants were asked to complete the Chinese University of Hong Kong: Physical Activity Rating for Children and Youth and Pediatric Quality of Life Inventory. The children with hematologic cancer also completed a therapy-related symptom checklist.

Results
There were statistically significant differences in the mean physical activity and QoL between children with hematologic cancer and their healthy counterparts. Multiple regression analyses showed that physical activity levels and the adverse effects of hematologic cancer treatment had statistically significant effects on the children’s QoL.

Conclusions
Physical activity level and QoL in children with hematologic cancer were both lower than those in their healthy counterparts.

Implications for Practice
This study provides further evidence that hematologic cancer and the adverse effects of its treatment have negative effects on Chinese children’s QoL. Although a lack of physical activity is deeply embedded in Chinese culture, nurses should take a proactive role in effecting change by educating parents about the benefits to their children’s physiologic and psychological well-being of physical activity during and after treatment.
Cortical network fingerprints predict deep brain stimulation outcome in dystonia
Authors: Gonzalez-Escamilla Gabriel , Muthuraman Muthuraman , Reich Martin M , Koirala Nabin , Riedel Christian , Glaser Martin , Lange Florian , Deuschl Günther , Volkmann Jens , Groppa Sergiu 
Published: November 2018

AbstractBackgroundDeep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigate whether patients optimally responding to DBS present distinct brain network organization and structural patterns.MethodsBased on a German multicentre cohort of eighty-two dystonia patients with segmental and generalized dystonia, who received DBS implantation in the globus pallidus internus patients were classified based on the clinical response 36 months after DBS, as superior-outcome group or moderate-outcome group, as above or below 70% motor improvement, respectively. Fifty-one patients met MRI-quality and treatment response requirements (mean age 51.3 ± 13.2 years; 25 female) and were included into further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on group network properties and individual grey matter fingerprints.ResultsThe moderate-outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. From all the structural integrity of the cortical mantle explained about 45% of the stimulation amplitude. Classification analyses achieved 88% of accuracy using individual grey matter atrophy patterns to predict DBS outcome.ConclusionsThe analysis of cortical integrity and network properties could be developed into independent predictors to identify dystonia patients who benefit from DBS.
Knowledge is power: Contingency instruction promotes threat extinction in high intolerance of uncertainty individuals
Authors: Morriss Jayne , van Reekum Carien M. 
Published: November 2018

AbstractExtinction-resistant threat is considered to be a central feature of pathological anxiety. Reduced threat extinction is observed in individuals with high intolerance of uncertainty (IU). Here we sought to determine whether contingency instructions could alter the course threat extinction for individuals high in IU. We tested this hypothesis in two identical experiments (Exp 1 n = 60, Exp 2 n = 82) where we recorded electrodermal activity during threat acquisition with partial reinforcement, and extinction. Participants were split into groups based on extinction instructions (instructed, uninstructed) and IU score (low, high). All groups displayed larger skin conductance responses to learned threat versus safety cues during threat acquisition, indicative of threat conditioning. In both experiments, only the uninstructed high IU groups displayed larger skin conductance responses to the learned threat versus safety cue during threat extinction. These findings suggest that uncertain threat during extinction maintains conditioned responding in individuals high in IU.
Identification of biological mechanisms underlying a multidimensional ASD phenotype using machine learning
Authors: Asif Muhammad , Martiniano Hugo F.M.C. , Marques Ana Rita , Santos João Xavier , Vilela Joana , Rasga Celia , Oliveira Guiomar , Couto Francisco M. , Vicente Astrid M. 
Published: November 2018

AbstractThe complex genetic architecture of Autism Spectrum Disorder (ASD) and its heterogeneous phenotype make molecular diagnosis and patient prognosis challenging tasks. To establish more precise genotype-phenotype correlations in ASD, we developed a novel machine learning integrative approach, which seeks to delineate associations between patients’ clinical profiles and disrupted biological processes inferred from their Copy Number Variants (CNVs) that span brain genes. Clustering analysis of relevant clinical measures from 2446 ASD cases in the Autism Genome Project identified two distinct phenotypic subgroups. Patients in these clusters differed significantly in ADOS-defined severity, adaptive behaviour profiles, intellectual ability and verbal status, the latter contributing the most for cluster stability and cohesion. Functional enrichment analysis of brain genes disrupted by CNVs in these ASD cases identified 15 statistically significant biological processes, including cell adhesion, neural development, cognition and polyubiquitination, in line with previous ASD findings. A Naive Bayes classifier, generated to predict the ASD phenotypic clusters from disrupted biological processes, achieved predictions with a high Precision (0.82) but low recall (0.39), for a subset of patients with higher biological Information Content scores. This study shows that milder and more severe clinical presentations can have distinct underlying biological mechanisms. It further highlights how machine learning approaches can reduce clinical heterogeneity using multidimensional clinical measures, and establish genotype-phenotype correlations in ASD. However, predictions are strongly dependent on patient’s information content. Findings are therefore a first step towards the translation of genetic information into clinically useful applications, but emphasize the need for larger datasets with very complete clinical and biological information.
Filamentation ofVibrio choleraeis an adaptation for surface attachment and biofilm architecture
Authors: Wucher Benjamin R. , Bartlett Thomas M. , Persat Alexandre , Nadell Carey D. 
Published: November 2018

AbstractCollective behavior in spatially structured groups, or biofilms, is the norm among microbes in their natural environments. Though microbial physiology and biofilm formation have been studied for decades, tracing the mechanistic and ecological links between individual cell properties and the emergent features of cell groups is still in its infancy. Here we use single-cell resolution confocal microscopy to explore biofilm properties of the human pathogenVibrio choleraein conditions closely mimicking its marine habitat. We find that some – but not all – pandemic isolates produce filamentous cells than can be over 50 μm long. This filamentous morphotype gains a profound competitive advantage in colonizing and spreading on particles of chitin, the material many marineVibriospecies depend on for growth outside of hosts. Furthermore, filamentous cells can produce biofilms that are independent of all currently known secreted components of theV. choleraebiofilm matrix; instead, filamentous biofilm architectural strength appears to derive from the entangled mesh of cells themselves. The advantage gained by filamentous cells in early chitin colonization and growth is counter-balanced in longer term competition experiments with matrix-secretingV. choleraevariants, whose densely packed biofilm structures displace competitors from surfaces. Overall our results reveal a novel mode of biofilm architecture that is dependent on filamentous cell morphology and advantageous in environments with rapid chitin particle turnover. This insight provides concrete links betweenV. choleraecell morphology, biofilm formation, marine ecology, and – potentially – the strain composition of cholera epidemics.
Reproductive capacity evolves in response to ecology through common developmental mechanisms in Hawai’ianDrosophila
Authors: Sarikaya Didem P. , Church Samuel H. , Lagomarsino Laura P. , Magnacca Karl N. , Montgomery Steven , Price Donald K. , Kaneshiro Kenneth Y. , Extavour Cassandra G. 
Published: November 2018

AbstractLifetime reproductive capacity, or the total number of offspring that an individual can give rise to in its lifetime, is a fitness component critical to the evolutionary process. In insects, female reproductive capacity is largely determined by the number of ovarioles, the egg-producing subunits of the ovary. Recent work has provided insights into the genetic and environmental control of ovariole number inDrosophila melanogaster. However, whether regulatory mechanisms discovered under laboratory conditions also explain evolutionary variation in natural populations is an outstanding question. Here we report, for the first time, insights into the mechanisms regulating ovariole number and its evolution among Hawai’ianDrosophila, a large adaptive radiation of fruit flies in which the highest and lowest ovariole numbers of the genus have evolved within 25 million years. Using phylogenetic comparative methods, we show that ovariole number variation among Hawai’ianDrosophilais best explained by adaptation to specific oviposition substrates. Further, we show that evolution of oviposition on ephemeral egg-laying substrates is linked to changes the allometric relationship between body size and ovariole number. Finally, we provide evidence that the developmental mechanism principally responsible for controlling ovariole number inD. melanogasteralso regulates ovariole number in natural populations of Hawai’ian drosophilids. By integrating ecology, organismal growth, and cell behavior during development to understand the evolution of ovariole number, this work connects the ultimate and proximate mechanisms of evolutionary change in reproductive capacity.
Quantitative systems pharmacological analysis of drugs of abuse reveals the pleiotropy of their targets and the effector role of mTORC1
Authors: Pei Fen , Li Hongchun , Liu Bing , Bahar Ivet 
Published: November 2018

AbstractExisting treatments against drug addiction are often ineffective due to the complexity of the networks of protein-drug and protein-protein interactions (PPIs) that mediate the development of drug addiction and related neurobiological disorders. There is an urgent need for understanding the molecular mechanisms that underlie drug addiction toward designing novel preventive or therapeutic strategies. The rapidly accumulating data on addictive drugs and their targets as well as advances in machine learning methods and computing technology now present an opportunity to systematically mine existing data and draw inferences on potential new strategies. To this aim, we carried out a comprehensive analysis of cellular pathways implicated in a diverse set of 50 drugs of abuse using quantitative systems pharmacology methods. The analysis of the drug/ligand-target interactions compiled in DrugBank and STITCH databases revealed 142 known and 48 newly predicted targets, which have been further analyzed to identify the KEGG pathways enriched at different stages of drug addiction cycle, as well as those implicated in cell signaling and regulation events associated with drug abuse. Apart from synaptic neurotransmission pathways detected as a common upstream signaling module that ‘senses’ the early effects of drugs of abuse, pathways involved in neuroplasticity are distinguished as determinants of neuronal morphological changes. Notably, many signaling pathways converge on important targets such as mTORC1. The latter is proposed to act as a universal effector of the persistent restructuring of neurons in response to continued use of drugs of abuse.
Ethanol Experience Enhances Glutamatergic Ventral Hippocampal Inputs to D1 Receptor-Expressing Medium Spiny Neurons in the Nucleus Accumbens Shell
Authors: Kircher Daniel M. , Aziz Heather , Mangieri Regina A. , Morrisett Richard A. 
Published: November 2018

ABSTRACTNucleus accumbens dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) have been implicated in the formation of dependence to many drugs of abuse including alcohol. Previous studies have revealed that acute alcohol exposure suppresses glutamatergic signaling within the accumbens and repeated alcohol exposure enhances glutamatergic signaling. D1-MSNs receive glutamatergic input from several brain regions and it is not currently known how individual inputs onto D1-MSNs are altered by alcohol experience. To Address this, we used virally mediated expression of Channelrhodopsin (ChR2) in ventral hippocampal (vHipp) glutamate neurons to selectively activate vHipp to D1-MSN synapses and compared synaptic adaptations in response to low and high alcohol experiencein vitroandin vivo. Alcohol experience enhanced glutamatergic activity and abolished long-term depression (LTD) at ventral hippocampal (vHipp) to D1-MSN synapses. Following chronic alcohol experience GluA2-lacking AMPA receptors, which are Ca-permeable, were inserted into vHipp to D1-MSN synapses. These alcohol-induced adaptations of glutamatergic signaling occurred at lower levels of exposure than previously reported. The loss of LTD expression and enhancement in glutamatergic signaling from the vHipp to D1-MSNs in the nucleus accumbens may play a critical role in the formation of alcohol dependence and enhancements in ethanol consumption. Reversal of alcohol-induced insertion of Ca-permeable AMPA receptors and enhancement of glutamatergic activity at vHipp to D1-MSNs presents potential targets for intervention during early exposure to alcohol.SIGNIFICANCE STATEMENTThe work presented here is the first to elucidate how an individual glutamatergic input onto D1-MSNs of the accumbens shell (shNAc) are altered by repeated ethanol exposure. Our findings suggest that glutamatergic input from the ventral hippocampus (vHipp) onto D1-MSNs is enhanced following drinking in a two-bottle choice (2BC) paradigm and is further enhanced by chronic intermittent ethanol (CIE) vapor exposure which escalated volitional ethanol intake. A critical finding was the insertion of Ca-permeable AMPA receptors into vHipp-shNAc D1-MSN synapses following CIE exposure, and more importantly following ethanol consumption in the absence of vapor exposure. These findings suggest that enhancements of glutamatergic input from the vHipp and insertion of Ca-permeable AMPARs play a role in the formation of ethanol dependence.
Multi-scale Loading and Damage Mechanisms of Rat Tail, Plantaris, and Achilles Tendons
Authors: Lee Andrea H. , Elliott Dawn M. 
Published: November 2018

AbstractTendinopathy, degeneration of tendon that leads to pain and dysfunction, is common in both sports and occupational settings, but multi-scale mechanisms for tendinopathy are still unknown. We recently showed that micro-scale sliding (shear) is responsible for both load transfer and damage mechanisms in rat tail tendon; however, rat tail tendon is a specialized non-load bearing tendon, and thus the load transfer and damage mechanisms are still unknown for load-bearing tendons. The objective of this study was to investigate the load transfer and damage mechanisms of load-bearing tendons using rat plantaris and Achilles tendons. We demonstrated that the micro-scale sliding is a key component for both mechanisms in plantaris tendon, similar to tail tendon. Namely, the micro-scale sliding was correlated with applied strain, demonstrating that load was transferred via micro-scale sliding in the plantaris and tail tendons. In addition, while the micro-scale strain fully recovered, the micro-scale sliding was non-recoverable and strain-dependent, and correlated with a tissue-scale mechanical parameters. When the applied strain was normalized, the % magnitudes of non-recoverable sliding was similar between the plantaris and tail tendons. Achilles tendon demonstrated some of the mechanical responses observed in plantaris and tail tendons, yet the results were inconclusive due to its complex structure. Statement of Clinical Significance: Understanding the mechanisms responsible for the pathogenesis and progression of tendinopathy can improve prevention and rehabilitation strategies and guide therapies and design of engineered constructs.
Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution
Authors: Nowotschin Sonja , Setty Manu , Kuo Ying-Yi , Lui Vincent , Garg Vidur , Sharma Roshan , Simon Claire S. , Saiz Nestor , Gardner Rui , Boutet Stéphane C. , Church Deanna M. , Hoodless Pamela A. , Hadjantonakis Anna-Katerina , Pe’er Dana 
Published: November 2018

AbstractTo comprehensively delineate the ontogeny of an organ system, we generated 112,217 singlecell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio-temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.
Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity
Authors: Jones Takako I. , Chew Guo-Liang , Barraza-Flores Pamela , Schreier Spencer , Ramirez Monique , Wuebbles Ryan D. , Burkin Dean J. , Bradley Robert K. , Jones Peter L. 
Published: November 2018

AbstractBackgroundAll types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant myogenic activation of the somatically silent DUX4 gene, which initiates a cascade of cellular events ultimately leading to FSHD pathophysiology. Therefore, FSHD is a dominant gain-of-function disease that is amenable to modeling byDUX4overexpression. However, there is large variability in the patient population. Typically, progressive skeletal muscle weakness becomes noticeable in the second or third decade of life, yet there are many genetically FSHD individuals who develop symptoms much later in life or remain relatively asymptomatic throughout their lives. Conversely, in rare cases, FSHD may present clinically prior to 5-10 yrs of age, ultimately manifesting as a very severe early onset form of the disease. Thus, there is a need to control the timing and severity of pathology in FSHD-like models.MethodsWe have recently described a line of conditionalDUX4transgenic mice,FLExDUX4, that develop a myopathy upon induction of humanDUX4-flexpression in skeletal muscle. Here, we use theFLExDUX4mouse crossed with the skeletal muscle-specific and tamoxifen inducible lineACTAl-MerCreMerto generate a highly versatile bi-transgenic mouse model with chronic, low-level DUX4-fl expression and mild pathology, that can be induced to develop more severe FSHD-like pathology in a dose-dependent response to tamoxifen. We identified conditions to reproducibly generate models exhibiting mild, moderate, or severe DUX4-dependent pathophysiology, and characterized their progression.ResultsWe assayed DUX4-fl mRNA and protein levels, fitness, strength, global gene expression, histopathology, and immune response, all of which are consistent with an FSHD-like myopathic phenotype. Importantly, we identified sex-specific and muscle-specific differences that should be considered when using these models for preclinical studies.ConclusionsTheACTA1-MCM;FLExDUX4bi-transgenic mouse model expresses a chronic low level of DUX4-fl and has mild pathology and detectable muscle weakness. The onset and progression of moderate to severe pathology can be controlled via tamoxifen injection to provide consistent and readily screenable phenotypes for assessing therapies targeting DUX4-fl mRNA and protein. Thus, these FSHD-like mouse models can be used to study a range of DUX4-fl expression and pathology dependent upon investigator need, through controlled mosaic expression ofDUX4.