bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GeometricP=WConjecture in the Painlevé Cases via Plumbing Calculus
Authors: Némethi András , Szabó Szilárd 
Published: September 2020

AbstractWe use plumbing calculus to prove the homotopy commutativity assertion of the Geometric $P=W$ conjecture in all Painlevé cases. We discuss the resulting Mixed Hodge structures on Dolbeault and Betti moduli spaces.
Mechanical stretch sustains myofibroblast phenotype and function in microtissues through latent TGF-β1 activation
Authors: Walker Matthew , Godin Michel , Pelling Andrew E 
Published: September 2020

Abstract
Developing methods to study tissue mechanics and myofibroblast activation may lead to new targets for therapeutic treatments that are urgently needed for fibrotic disease. Microtissue arrays are a promising approach to conduct relatively high-throughput research into fibrosis as they recapitulate key biomechanical aspects of the disease through a relevant 3D extracellular environment. In early work, our group developed a device called the MVAS-force to stretch microtissues while enabling simultaneous assessment of their dynamic mechanical behavior. Here, we investigated TGF-β1-induced fibroblast to myofibroblast differentiation in microtissue cultures using our MVAS-force device through assessing α-SMA expression, contractility and stiffness. In doing so, we linked cell-level phenotypic changes to functional changes that characterize the clinical manifestation of fibrotic disease. As expected, TGF-β1 treatment promoted a myofibroblastic phenotype and microtissues became stiffer and possessed increased contractility. These changes were partially reversible upon TGF-β1 withdrawal under a static condition, while, in contrast, long-term cyclic stretching maintained myofibroblast activation. This pro-fibrotic effect of mechanical stretching was absent when TGF-β1 receptors were inhibited. Furthermore, stretching promoted myofibroblast differentiation when microtissues were given latent TGF-β1. Altogether, these results suggest that external mechanical stretch may activate latent TGF-β1 and, accordingly, might be a powerful stimulus for continued myofibroblast activation to progress fibrosis. Further exploration of this pathway with our approach may yield new insights into myofibroblast activation and more effective therapeutic treatments for fibrosis.
Recommendations from Thai stakeholders about protecting HIV remission (‘cure’) trial participants: report from a participatory workshop
Authors: Peay Holly L , Ormsby Nuchanart Q , Henderson Gail E , Jupimai Thidarat , Rennie Stuart , Siripassorn Krittaecho , Kanchawee Kunakorn , Isaacson Sinéad , Cadigan R Jean , Kuczynski Kriste , Likhitwonnawut Udom 
Published: September 2020

Abstract

Background
The social/behavioral HIV Decision-Making Study (DMS) assesses informed consent and trial experiences of individuals in HIV remission trials in Thailand. We convened a 1-d multi-stakeholder participatory workshop in Bangkok. We provide a meeting summary and reactions from DMS investigators.

Methods
Workshop members viewed de-identified interview excerpts from DMS participants. They deliberated on the findings and made recommendations regarding informed choice for remission trials. Notes and recordings were used to create a summary report, which was reviewed by members and refined.

Results
Workshop members’ recommendations included HIV education and psychosocial support to establish the basis for informed choice, key trial information to be provided in everyday language, supportive decision-making processes and psychosocial care during and after the trial. Concerns included participant willingness to restart antiretrovirals after trial-mandated treatment interruption, unintended influence of the research team on decision-making and seemingly altruistic motivations for trial participation that may signal attempts to atone for stigmatized behavior.

Conclusions
The workshop highlighted community perspectives and resulted in recommendations for supporting informed choice and psychosocial and physical health. These are the first such recommendations arising from a deliberative process. Although some elements are rooted in the Thai context, most are applicable across remission trials.
Predominance of CTX-M-15-producing ST131 strains among ESBL-producingEscherichia coliisolated from asylum seekers in the Netherlands
Authors: Louka Christina , Ravensbergen Sofanne J , Ott Alewijn , Zhou Xuewei , García-Cobos Silvia , Friedrich Alexander W , Pournaras Spyros , Rosema Sigrid , Rossen John W , Stienstra Ymkje , Bathoorn Erik 
Published: September 2020

AbstractObjectivesNumerous studies show increased prevalence of MDR bacteria amongst asylum seekers, but data on the molecular profiles of such strains are limited. We aimed to evaluate the molecular profiles of ESBL-producing Escherichia coli (ESBL-E. coli) strains isolated from asylum seekers and investigate their phylogenetic relatedness.MethodsWGS data of ESBL-E. coli isolates from asylum seekers, retrieved from 1 January to 31 December 2016, were analysed to assess MLST STs, fim types, phylogroups and resistance genes. Fifty-two ESBL-E. coli isolates from the Dutch–German border region were used for genome comparison purposes as a control group.ResultsAmong 112 ESBL-E. coli isolates from asylum seekers, originating mostly from Syria (n = 40) and Iraq (n = 15), the majority belonged to ST131 (21.4%) and ST10 (17.0%). The predominant gene for β-lactam resistance was blaCTX-M-15 (67.9%), followed by the often co-detected blaTEM-1B (39.3%). No mcr or carbapenemase genes were detected. The majority of the strains belonged to phylogroups B2 (38.4%) and A (32.1%), carrying fimH27 (25%) and fimH30 (19.6%). A core genome MLST minimum spanning tree did not reveal clusters containing strains from the asylum seekers and the control group. Five clusters were formed within the asylum seeker group, by strains isolated from people originating from different countries.ConclusionsThe most frequently isolated clones in this study were isolated on a regular basis within the Dutch population before the increase in the asylum seeker population. No mcr- or carbapenemase-producing clones were detected among the asylum seeker population. Minor clustering was observed amongst the asylum seeker strains.
A Comparative Study of Zhuangzi and Nietzsche’s Tragic Vision and Aestheticism
Authors: Zeng Hong , Harmon William 
Published: September 2020

Abstract
This article argues that both Zhuangzi and Nietzsche’s aestheticism is a means of overcoming their tragic vision of life. Nietzsche’s aesthetic state of Dionysian intoxication and Zhuangzi’s floating/wandering (游) involve similar, rapturous self-loss in merging with a primal unity or ground being of existence. Both seek an aestheticised, spiritual freedom that is built on an alienation from their perceived reality. Both versions of aestheticism have their price: the penalty of Zagreus in Dionysus, and the sacrifice of historical time and historical self in Zhuangzi’s thought. Beneath their aestheticised vision of primal unity, both are torn by tragic conflicts and sacrifice. Of Zhuangzi, we could say the same as Nietzsche said of the Greeks in his The Birth of Tragedy: ‘this is the real meaning of the famous Greek serenity, so often misrepresented as some kind of untroubled cheerfulness’.
Gas and star formation from HD and dust emission in a strongly lensed galaxy
Authors: Jones G C , Maiolino R , Caselli P , Carniani S 
Published: September 2020

ABSTRACTThe molecular gas content of high-redshift galaxies is a highly sought-after property. However, H2 is not directly observable in most environments, so its mass is probed through other emission lines (e.g. CO, [C i], [C ii]), or through a gas-to-dust ratio. Each of these methods depends on several assumptions, and are best used in parallel. In this work, we extend an additional molecular gas tracer to high-redshift studies by observing hydrogen deuteride (HD) emission in the strongly lensed z = 5.656 galaxy SPT0346−52 with ALMA. While no HD(1–0) emission is detected, we are able to place an upper limit on the gas mass of $\rm M_{H_2}\lt 6.4\times 10^{11}\, M_{\odot }$. This is used to find a limit on the $L^{\prime }_{\mathrm{ CO}}$ conversion factor of      $\rm \alpha _{CO}\lt 5.8\,M_{\odot}(K\,km\,s^{-1}\,pc^2)^{-1}$. In addition, we construct the most complete spectral energy distribution of this source to date, and fit it with a single-temperature modified blackbody using the nested sampling code multinest, yielding a best-fitting dust mass Mdust = 108.92 ± 0.02 M⊙, dust temperature 78.6 ± 0.5 K, dust emissivity spectral index β = 1.81 ± 0.03, and star formation rate SFR = 3800 ± 100 M⊙ yr−1. Using the continuum flux densities to estimate the total gas mass of the source, we find   $\rm M_{H_2}\lt 2.4\times 10^{11}\, M_{\odot }$ , assuming subsolar metallicity. This implies a CO conversion factor of αCO &lt; 2.2, which is between the standard values for MW-like galaxies and starbursts. These properties confirm that SPT0346−52 is a heavily starbursting, gas-rich galaxy.
Constraining the distance to the North Polar Spur with Gaia DR2
Authors: Das Kaustav K , Zucker Catherine , Speagle Joshua S , Goodman Alyssa , Green Gregory M , Alves João 
Published: September 2020

ABSTRACT
The North Polar Spur (NPS) is one of the largest structures observed in the Milky Way in both the radio and soft X-rays. While several predictions have been made regarding the origin of the NPS, modelling the structure is difficult without precise distance constraints. In this paper, we determine accurate distances to the southern terminus of the NPS and towards latitudes ranging up to 55°. First, we fit for the distance and extinction to stars towards the NPS using optical and near-infrared photometry and Gaia Data Release 2 astrometry. We model these per-star distance–extinction estimates as being caused by dust screens at unknown distances, which we fit for using a nested sampling algorithm. We then compare the extinction to the Spur derived from our 3D dust modelling with integrated independent measures from XMM–Newton X-ray absorption and H i column density measures. We find that we can account for nearly 100 per cent of the total column density of the NPS as lying within 140 pc for latitudes &gt;26° and within 700 pc for latitudes &lt;11°. Based on the results, we conclude that the NPS is not associated with the Galactic Centre or the Fermi bubbles. Instead, it is likely associated, especially at higher latitudes, with the Scorpius–Centaurus association.
Colocality to Cofunctionality: Eukaryotic Gene Neighborhoods as a Resource for Function Discovery
Authors: Foflonker Fatima , Blaby-Haas Crysten E 
Published: September 2020

AbstractDiverging from the classic paradigm of random gene order in eukaryotes, gene proximity can be leveraged to systematically identify functionally related gene neighborhoods in eukaryotes, utilizing techniques pioneered in bacteria. Current methods of identifying gene neighborhoods typically rely on sequence similarity to characterized gene products. However, this approach is not robust for nonmodel organisms like algae, which are evolutionarily distant from well-characterized model organisms. Here, we utilize a comparative genomic approach to identify evolutionarily conserved proximal orthologous gene pairs conserved across at least two taxonomic classes of green algae. A total of 317 gene neighborhoods were identified. In some cases, gene proximity appears to have been conserved since before the streptophyte–chlorophyte split, 1,000 Ma. Using functional inferences derived from reconstructed evolutionary relationships, we identified several novel functional clusters. A putative mycosporine-like amino acid, “sunscreen,” neighborhood contains genes similar to either vertebrate or cyanobacterial pathways, suggesting a novel mosaic biosynthetic pathway in green algae. One of two putative arsenic-detoxification neighborhoods includes an organoarsenical transporter (ArsJ), a glyceraldehyde 3-phosphate dehydrogenase-like gene, homologs of which are involved in arsenic detoxification in bacteria, and a novel algal-specific phosphoglycerate kinase-like gene. Mutants of the ArsJ-like transporter and phosphoglycerate kinase-like genes in Chlamydomonas reinhardtii were found to be sensitive to arsenate, providing experimental support for the role of these identified neighbors in resistance to arsenate. Potential evolutionary origins of neighborhoods are discussed, and updated annotations for formerly poorly annotated genes are presented, highlighting the potential of this strategy for functional annotation.
Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review
Authors: Manera Karine E , Ju Angela , Baumgart Amanda , Hannan Elyssa , Qiao Wenjing , Howell Martin , Nataatmadja Melissa , Wilkie Martin , Loud Fiona , Schwartz Daniel , Hurst Helen , Jassal Sarbjit Vanita , Figueiredo Ana , Mehrotra Rajnish , Shen Jenny , Morton Rachael L , Moraes Thyago , Walker Rachael , Cheung Catherine , Farragher Janine F , Craig Jonathan , Johnson David W , Tong Allison 
Published: September 2020

Abstract

Background
Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD.

Methods
We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed.

Results
Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD.

Conclusions
The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.
Three-Tesla Magnetic Resonance Imaging of Patients With Deep Brain Stimulators: Results From a Phantom Study and a Pilot Study in Patients
Authors: Davidson Benjamin , Tam Fred , Yang Benson , Meng Ying , Hamani Clement , Graham Simon J , Lipsman Nir 
Published: September 2020

Abstract

BACKGROUND
Deep brain stimulation (DBS) is a standard of care treatment for multiple neurologic disorders. Although 3-tesla (3T) magnetic resonance imaging (MRI) has become the gold-standard modality for structural and functional imaging, most centers refrain from 3T imaging in patients with DBS devices in place because of safety concerns. 3T MRI could be used not only for structural imaging, but also for functional MRI to study the effects of DBS on neurocircuitry and optimize programming.

OBJECTIVE
To use an anthropomorphic phantom design to perform temperature and voltage safety testing on an activated DBS device during 3T imaging.

METHODS
An anthropomorphic 3D-printed human phantom was constructed and used to perform temperature and voltage testing on a DBS device during 3T MRI. Based on the phantom assessment, a cohort study was conducted in which 6 human patients underwent MRI with their DBS device in an activated (ON) state.

RESULTS
During the phantom study, temperature rises were under 2°C during all sequences, with the DBS in both the deactivated and activated states. Radiofrequency pulses from the MRI appeared to modulate the electrical discharge from the DBS, resulting in slight fluctuations of voltage amplitude. Six human subjects underwent MRI with their DBS in an activated state without any serious adverse events. One patient experienced stimulation-related side effects during T1-MPRAGE scanning with the DBS in an ON state because of radiofrequency-induced modulation of voltage amplitude.

CONCLUSION
Following careful phantom-based safety testing, 3T structural and functional MRI can be safely performed in subjects with activated deep brain stimulators.
Supply Network Drivers of Risk and Performance
Authors: Bellamy Marcus A. , Osadchiy Nikolay 
Published: September 2020

Abstract
This chapter reviews historical and contemporary research in economics, operations management, and finance that adopts a network perspective for modeling interactions between agents. It argues that incorporating extended network characteristics in the analysis can yield unique insights compared to the analysis done at the level of dyads or local neighborhoods. The chapter explains how new network-based models contribute to the academic debate and advance our understanding of supply network drivers of performance and risk. This includes a discussion on the structural configuration of a firm’s interconnected portfolio of upstream supplier and downstream customer relationships and its role in influencing financial and operational performance as well as its innovation.
NR4A Transcription Factor Family: Key Regulators of Memory Formation
Authors: Matheos Dina P. , Wood Marcelo A. 
Published: September 2020

Abstract
Memory formation is one of the most important functions of the brain regarding individual identity and survival, as well as propagation of a species. Decades of research at numerous levels has begun to elucidate the complex molecular, cellular, circuit, and brain-wide mechanisms underlying learning and memory. One of the key mechanisms involves gene expression required for changes in cellular structure and function, which ultimately give rise to long-lasting changes in behavior. Here, we review a unique transcription factor family, called the nuclear orphan receptor 4a (NR4A). The Nr4a gene family is involved in the development of the dopaminergic signaling system, and dynamically regulated in the adult brain with regard to memory formation. Intriguing results from studying how epigenetic mechanisms modulate synaptic plasticity and long-term memory formation also highlight the pivotal role the Nr4a genes may have in pushing the boundaries of memory formation. We review the discovery of the Nr4a gene family, the complex nature of their activity in transcriptional regulation, and the evidence suggesting they may be one of the most important set of immediate early genes and transcription factors involved in memory, age-related memory impairments, and neurological disease related cognitive dysfunction.
Emotional Memory in the Human Brain
Authors: Faul Leonard , LaBar Kevin S. 
Published: September 2020

Abstract
Across a lifetime, people tend to remember some experiences better than others, and often these biases in memory are fueled by the emotions felt when initially encoding an event. The neuroscientific study of emotional memory has advanced considerably since researchers first detailed a critical role for the amygdala in enhancing memory consolidation for arousing experiences. It is now known that the influence of emotion on memory is both a more selective and multifaceted process than initially thought. Consequently, the neural mechanisms that govern emotional memory involve an expansive set of distributed connections between the amygdala and other medial temporal lobe structures, along with prefrontal and sensory regions, that interact with noradrenergic, dopaminergic, and glucocorticoid neuromodulatory systems to both enhance and impair items in memory. Recent neurocognitive models have detailed specific mechanisms to explain how and why the influence of emotion on memory is so varied, including arousal-based accounts for the selective consolidation of information based on stimulus priority, as well as top-down cognitive factors that moderate these effects. Still other lines of research consider the time-dependent influence of stress on memory, valence-based differences in neural recapitulation at retrieval, and the mechanisms of emotional memory modification over time. While appreciating these many known ways in which emotions influence different stages of memory processing, here we also identify gaps in the literature and present future directions to improve a neurobiological understanding of emotional memory processes.
Insights into Cognitive Disorders in Aging and Mental Illness: Molecular Influences on Circuits of the Prefrontal Cortex
Authors: Arnsten Amy 
Published: September 2020

Abstract
The newly evolved prefrontal cortex underlies our highest order cognitivewe functions yet is remarkably vulnerable to dysfunction in most mental disorders. The prefrontal cortex subserves working memory and top-down control, operations that are weakened in both cognitive and affective disorders. Prefrontal microcircuits contain extensive recurrent excitatory connections that allow representation of information in the absence of sensory stimulation, the foundation of abstract thought and goal-directed behavior. Basic research has discovered that the strength of these prefrontal cortical synaptic connections is governed by unique molecular mechanisms, where both neurotransmission and neuromodulation differ from those in classical circuits. These include exceptionally powerful regulation by the arousal systems, which magnify calcium-cAMP signaling to open or close ion channels near the synapse to rapidly alter synaptic strength, a process called Dynamic Network Connectivity. The magnification of intracellular calcium actions renders these synapses particularly vulnerable to degeneration in schizophrenia, aging, and Alzheimer’s disease.
Regulating Medicines in the European Union
Authors: Mahalatchimy Aurélie 
Published: September 2020

Abstract
This chapter describes the framework for regulation of medicines in the European Union. The overall goal of this framework is to ensure that medicines are of good quality, safe, and effective with a positive benefit-risk ratio before accessing the European market to guarantee a high level of public health protection and European competitiveness. EU law regulates medicines all along the therapeutic chain with emphasis on bringing medicines to market and managing risks. The EU framework is complicated by the fact that both EU-level and Member State-level authorities have responsibility for regulation of medicines. Overall, EU law is dominant from clinical research to marketing authorization while national law is dominant for healthcare services and reimbursement issues. Each Member State has its own medicines regulatory authority, known as a “national competent authority.” As the chapter illustrates, responsibility for some aspects of the broader medicines regulatory framework falls to these national authorities. After defining medicines under EU law, this chapter presents the relevant legal frames and discussed the challenges raised regarding the regulatory pathways to bring medicines to market, their risk management along the medicines life cycle, the innovation and competition policies and rules that support the development of medicines, and the specific framework that exists for Advanced Therapy Medicinal Products.