bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of a clinician amid the rise of mobile health technology
Authors: Yang William E , Shah Lochan M , Spaulding Erin M , Wang Jane , Xun Helen , Weng Daniel , Shan Rongzi , Wongvibulsin Shannon , Marvel Francoise A , Martin Seth S 
Published: July 2019

Abstract
Mobile health (mHealth) interventions have demonstrated promise in improving outcomes by motivating patients to adopt and maintain healthy lifestyle changes as well as improve adherence to guideline-directed medical therapy. Early results combining behavioral economic strategies with mHealth delivery have demonstrated mixed results. In reviewing these studies, we propose that the success of a mHealth intervention links more strongly with how well it connects patients back to routine clinical care, rather than its behavior modification technique in isolation. This underscores the critical role of clinician-patient partnerships in the design and delivery of such interventions, while also raising important questions regarding long-term sustainability and scalability. Further exploration of our hypothesis may increase opportunities for multidisciplinary clinical teams to connect with and engage patients using mHealth technologies in unprecedented ways.
Importance of clinical decision support system response time monitoring: a case report
Authors: Rubins David , Wright Adam , Alkasab Tarik , Ledbetter M Stephen , Miller Amy , Patel Rajesh , Wei Nancy , Zuccotti Gianna , Landman Adam 
Published: July 2019

Abstract
Clinical decision support (CDS) systems are prevalent in electronic health records and drive many safety advantages. However, CDS systems can also cause unintended consequences. Monitoring programs focused on alert firing rates are important to detect anomalies and ensure systems are working as intended. Monitoring efforts do not generally include system load and time to generate decision support, which is becoming increasingly important as more CDS systems rely on external, web-based content and algorithms. We report a case in which a web-based service caused significant increase in the time to generate decision support, in turn leading to marked delays in electronic health record system responsiveness, which could have led to patient safety events. Given this, it is critical to consider adding decision support-time generation to ongoing CDS system monitoring programs.
But-for Causation and the Implementability of Compensatory Damages Rules
Authors: Schweizer Urs 
Published: July 2019

Abstract
A damages rule is called compensatory if it requires compensation of each party who complied with the due care standard for harm caused by deficient precaution of the other party. The two main contributions of this article are as follows. First, we show that any Nash equilibrium of the game induced by a compensatory damages rule enhances welfare compared to the welfare that would have been attained if both parties had complied. This is true irrespective of whether the due care standards are set at their socially optimal level. Second, we provide a general result for evaluating the conditions under which courts have sufficient information to implement compensatory damages rules. This is the case when the available evidence allows courts to determine whether the injurer’s precaution choice was the but-for cause of any harm to the victim. The exact levels of precaution and harm need not be observable (JEL K13).
Upper limits on protolunar disc masses using ALMA observations of directly imaged exoplanets
Authors: Pérez Sebastián , Marino Sebastián , Casassus Simon , Baruteau Clément , Zurlo Alice , Flores Christian , Chauvin Gael 
Published: July 2019

ABSTRACT
The Solar system gas giants are each surrounded by many moons, with at least 50 prograde satellites thought to have formed from circumplanetary material. Just like the Sun is not the only star surrounded by planets, extrasolar gas giants are likely surrounded by satellite systems. Here, we report on Atacama Large Millimeter/Submillimeter Array (ALMA) observations of four <40 Myr old stars with directly imaged companions: PZ Tel, AB Pic, 51 Eri, and κ And. Continuum emission at 1.3 mm is undetected for any of the systems. Since these are directly imaged companions, there is knowledge of their temperatures, masses, and locations. These allow for upper limits on the amount of circumplanetary dust to be derived from detailed radiative transfer models. These protolunar disc models consider two disc sizes: 0.4 and 0.04 times the exoplanet’s Hill radius. The former is representative of hydrodynamic simulations of circumplanetary discs, while the latter a case with significant radial drift of solids. The more compact case is also motivated by the semimajor axis of Callisto, enclosing Jupiter’s Galilean satellites. All upper limits fall below the expected amount of dust required to explain regular satellite systems (∼10−4 times the mass of their central planet). Upper limits are compared with viscous evolution and debris disc models. Our analysis suggests that the non-detections can be interpreted as evidence of dust growth beyond metre sizes to form moonetesimals in time-scales ≲10 Myr. This sample increases by 50 per cent the number of ALMA non-detections of young companions available in the literature.
On the instability of Saturn’s hypothetical retrograde co-orbitals
Authors: Huang Yukun , Li Miao , Li Junfeng , Gong Shengping 
Published: July 2019

ABSTRACT
We find an interesting fact that fictitious retrograde co-orbitals of Saturn, or small bodies inside the retrograde 1:1 resonance with Saturn, are highly unstable in our numerical simulations. It is shown that, in the presence of Jupiter, the retrograde co-orbitals will get ejected from Saturn’s co-orbital space within a time-scale of 10 Myr. This scenario reminds us of the instability of Saturn Trojans caused by both the great inequality and the secular resonances. Therefore, we carry out in-depth inspections of both mechanisms and prove that the retrograde resonance overlap, raised by great inequality, cannot serve as an explanation for the instability of the retrograde co-orbitals, due to the weakness of the retrograde 2:5 resonance with Jupiter at low eccentricity. However, we discover that both ν5 and ν6 secular resonances contribute to the slow growth of the eccentricity and are therefore possibly the primary causes of the instability inside Saturn’s retrograde co-orbital space.
Clustering and redshift-space distortions in modified gravity models with massive neutrinos
Authors: García-Farieta Jorge Enrique , Marulli Federico , Veropalumbo Alfonso , Moscardini Lauro , Casas-Miranda Rigoberto A , Giocoli Carlo , Baldi Marco 
Published: July 2019

Abstract
Modified gravity and massive neutrino cosmologies are two of the most interesting scenarios that have been recently explored to account for possible observational deviations from the concordance Λ cold dark matter (ΛCDM) model. In this context, we investigated the large-scale structure of the Universe by exploiting the dustgrain-pathfinder simulations that implement, simultaneously, the effects of f(R) gravity and massive neutrinos. To study the possibility of breaking the degeneracy between these two effects, we analysed the redshift-space distortions in the clustering of dark matter haloes at different redshifts. Specifically, we focused on the monopole and quadrupole of the two-point correlation function, both in real and redshift space. The deviations with respect to ΛCDM model have been quantified in terms of the linear growth rate parameter. We found that redshift-space distortions provide a powerful probe to discriminate between ΛCDM and modified gravity models, especially at high redshifts (z ≳ 1), even in the presence of massive neutrinos.
Single-molecule analysis of i-motif within self-assembled DNA duplexes and nanocircles
Authors: Megalathan Anoja , Cox Bobby D , Wilkerson Peter D , Kaur Anisa , Sapkota Kumar , Reiner Joseph E , Dhakal Soma 
Published: July 2019

Abstract
The cytosine (C)-rich sequences that can fold into tetraplex structures known as i-motif are prevalent in genomic DNA. Recent studies of i-motif–forming sequences have shown increasing evidence of their roles in gene regulation. However, most of these studies have been performed in short single-stranded oligonucleotides, far from the intracellular environment. In cells, i-motif–forming sequences are flanked by DNA duplexes and packed in the genome. Therefore, exploring the conformational dynamics and kinetics of i-motif under such topologically constrained environments is highly relevant in predicting their biological roles. Using single-molecule fluorescence analysis of self-assembled DNA duplexes and nanocircles, we show that the topological environments play a key role on i-motif stability and dynamics. While the human telomere sequence (C3TAA)3C3 assumes i-motif structure at pH 5.5 regardless of topological constraint, it undergoes conformational dynamics among unfolded, partially folded and fully folded states at pH 6.5. The lifetimes of i-motif and the partially folded state at pH 6.5 were determined to be 6 ± 2 and 31 ± 11 s, respectively. Consistent with the partially folded state observed in fluorescence analysis, interrogation of current versus time traces obtained from nanopore analysis at pH 6.5 shows long-lived shallow blockades with a mean lifetime of 25 ± 6 s. Such lifetimes are sufficient for the i-motif and partially folded states to interact with proteins to modulate cellular processes.
Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo
Authors: Otterstrom Jason , Castells-Garcia Alvaro , Vicario Chiara , Gomez-Garcia Pablo A , Cosma Maria Pia , Lakadamyali Melike 
Published: July 2019

Abstract
Chromatin organization is crucial for regulating gene expression. Previously, we showed that nucleosomes form groups, termed clutches. Clutch size correlated with the pluripotency grade of mouse embryonic stem cells and human induced pluripotent stem cells. Recently, it was also shown that regions of the chromatin containing activating epigenetic marks were composed of small and dispersed chromatin nanodomains with lower DNA density compared to the larger silenced domains. Overall, these results suggest that clutch size may regulate DNA packing density and gene activity. To directly test this model, we carried out 3D, two-color super-resolution microscopy of histones and DNA with and without increased histone tail acetylation. Our results showed that lower percentage of DNA was associated with nucleosome clutches in hyperacetylated cells. We further showed that the radius and compaction level of clutch-associated DNA decreased in hyperacetylated cells, especially in regions containing several neighboring clutches. Importantly, this change was independent of clutch size but dependent on the acetylation state of the clutch. Our results directly link the epigenetic state of nucleosome clutches to their DNA packing density. Our results further provide in vivo support to previous in vitro models that showed a disruption of nucleosome-DNA interactions upon hyperacetylation.
Deflating Deflationary Truthmaking
Authors: Asay Jamin , Baron Sam 
Published: July 2019

AbstractIn this paper we confront a challenge to truthmaker theory that is analogous to the objections raised by deflationists against substantive theories of truth. Several critics of truthmaker theory espouse a ‘deflationary’ attitude about truthmaking, though it has not been clearly presented as such. Our goal is to articulate and then object to the underlying rationale behind deflationary truthmaking. We begin by developing the analogy between deflationary truth and deflationary truthmaking, and then show how the latter can be found in the work of Dodd, Hornsby, Schnieder, Williamson, and others. These philosophers believe that the ambitions of truthmaker theory are easily satisfied, without recourse to ambitious ontological investigation—hence the analogy with deflationary truth. We argue that the deflationists’ agenda fails: there is no coherent deflationary theory of truthmaking. Truthmaking, once deflated, fails to address the questions at the heart of truthmaking investigation. Truthmaking cannot be had on the cheap.
Delayed sleep-onset and biological age: late sleep-onset is associated with shorter telomere length
Authors: Wynchank Dora , Bijlenga Denise , Penninx Brenda W , Lamers Femke , Beekman Aartjan T , Kooij J J Sandra , Verhoeven Josine E 
Published: July 2019

AbstractStudy ObjectivesWe evaluated the relationship between leukocyte telomere length (LTL) and sleep duration, insomnia symptoms, and circadian rhythm, to test whether sleep and chronobiological dysregulations are associated with cellular aging.MethodsData from the Netherlands Study of Depression and Anxiety (N = 2,936) were used at two waves 6 years apart, to measure LTL. Telomeres shorten during the life span and are important biomarkers for cellular aging. LTL was assessed by qualitative polymerase chain reaction and converted into base pair number. Sleep parameters were: sleep duration and insomnia symptoms from the Insomnia Rating Scale. Circadian rhythm variables were: indication of Delayed Sleep Phase Syndrome (DSPS), mid-sleep corrected for sleep debt on free days (MSFsc), sleep-onset time, and self-reported chronotype, from the Munich Chronotype Questionnaire. Generalized estimating equations analyzed the associations between LTL, sleep, and chronobiological factors, adjusted for baseline age, sex, North European ancestry, and additionally for current smoking, depression severity, obesity, and childhood trauma.ResultsIndicators of delayed circadian rhythm showed a strong and consistent effect on LTL, after adjustment for sociodemographic and health indicators. Late MSFsc (B = −49.9, p = .004), late sleep-onset time (B = −32.4, p = .001), indication of DSPS (B = −73.8, p = .036), and moderately late chronotype in adulthood (B = −71.6, p = .003) were associated with significantly shorter LTL across both waves; whereas sleep duration and insomnia symptoms were not. Extremely early chronotype showed significantly less LTL shortening than intermediate chronotype (B = 161.40, p = .037). No predictors showed accelerated LTL attrition over 6 years.ConclusionsIndividuals with delayed circadian rhythm have significantly shorter LTL, but not faster LTL attrition rates.
A CALCIUM-RICH MULTI-MINERAL INTERVENTION TO MODULATE COLONIC MICROBIAL COMMUNITIES AND METABOLOMIC PROFILES IN HUMANS: Results from a 90-day trial
Authors: Aslam Muhammad N. , Bassis Christine M. , Bergin Ingrid L. , Knuver Karsten , Zick Suzanna M. , Sen Ananda , Turgeon D. Kim , Varani James 
Published: July 2019

ABSTRACTAquamin, a calcium-, magnesium-, and multiple trace element-rich natural product has polyp prevention efficacy based on preclinical studies. The overall goal of this study was to determine the safety and tolerability of Aquamin when used as a dietary chemopreventative in humans. Additionally, we determined the effects of Aquamin on the colonic microbial community and attendant metabolomic profile. Thirty healthy male and female human participants were enrolled in a 90-day trial in which the effects of Aquamin (delivering 800 mg of calcium per day) were compared to those of calcium alone or placebo. Before and after the interventional period, colonic biopsies and stool specimens were obtained. All 30 participants completed the study without serious adverse events. There were no changes in liver function markers. Compared to pretreatment values, intervention with Aquamin led to a reduction in total bacterial DNA and a shift in the microbial community. Treatment with calcium alone also produced a decline in total bacteria, but smaller than seen with Aquamin, while no reduction was observed with placebo. In parallel with microbial changes, a reduction in bile acid levels and a slight increase in the level of the short chain fatty acid (SCFA) acetate in stool specimens from Aquamin-treated participants was noted. No change in bile acids or SCFAs was observed with calcium alone or placebo. We conclude from these studies that Aquamin is safe and tolerable in healthy human participants and may produce beneficial alterations in the colonic microbial community and the attendant metabolomic profile.
Short term supplementation of celecoxib shifted butyrate production on a simulated model of the gut microbial ecosystem and amelioratedin vitroinflammation
Authors: Hernandez-Sanabria Emma , Heiremans Evelien , Arroyo Marta Calatayud , Props Ruben , Leclercq Laurent , Snoeys Jan , Van de Wiele Tom 
Published: July 2019

ABSTRACTCelecoxib has been demonstrated effective in the prevention and treatment of chronic inflammatory disorders through inhibition of altered cyclooxygenase-2 (COX-2) pathways. Despite the benefits for preventing colorectal cancer (CRC), continuous administration may increase risk of cardiovascular events. Understanding microbiome-drug-host interactions is fundamental for improving drug disposition and safety responses of colon-targeted formulations, but little information is available on the bidirectional interaction between individual microbiomes and celecoxib. Here we conductedin vitrobatch incubations of faecal microbiota to evaluate the short-term impact of celecoxib on activity and composition of colon bacterial communities. Celecoxib-exposed microbiota shifted metabolic activity and community composition, whereas total transcriptionally active bacterial population was not significantly changed. Butyrate production decreased by 50% in a donor-dependent manner, suggesting that celecoxib impactsin vitrofermentation. Microbiota-derived acetate has been associated with inhibition of cancer markers and our results suggest uptake of acetate for bacterial functions when celecoxib was supplied, which potentially favoured bacterial competition for acetyl-CoA. We further assessed whether colon microbiota modulates anti-inflammatory efficacy of celecoxib using both a simplified inflammation model, and a novelin vitrosimulation of the enterohepatic metabolism. Celecoxib was responsible for only 5% of the variance in bacterial community composition but celecoxib-exposed microbiota preserved barrier function and decreased concentrations of IL-8 and CXCL16 in a donor-dependent manner in our two cell models simulating inflammatory milieu in the gut. Our results suggest that celecoxib-microbiome-host interactions may not only elicit adaptations in community composition but also in microbiota functionality and may need to be considered for guaranteeing efficient COX-2 inhibition.IMPORTANCEAs inter-individual changes in the microbiome composition and functionality may be a confounder on pharmacotherapy, we obtained mechanistic understanding on how short-term celecoxib exposure impacts the functional activities of colon communities. Celecoxib-exposed microbiota shifted metabolic activity without impacting numbers of total active bacteria, but only community composition. Thus, increased relative abundance of particular genera during celecoxib supplementation may just indicate changes in maintenance energy. Focus on the influence of acetyl-CoA on cancer cells and verifying whether changes in acetate:propionate:butyrate ratios rather than in taxonomic diversity can be used as markers of decreased inflammation may be the next frontiers for predicting successful NSAID therapy, and ultimately for developing microbiome-based therapies.
Natural versus Random Proteins: Nouvel Neural Network Approach Based on Time Series Analysis
Authors: Tsygvintsev Alexei 
Published: July 2019

AbstractWe study the set of about 35000 primary structures of natural proteins of length more than 360 residues and the same size set generated via partial or total randomization. Associated to every sequence composed of 20 amino acids, a time series is formed from hydropathy values of the first 360 residues. To measure the absolute deviations of hydropathy index on different time scales, the 24-dimensional vector of total log-amplitudes is introduced. We describe then a configuration of the 1-hidden layer neural network which is trained to solve the binary classification problem of natural and random sequences. A satisfactory distinguishing accuracy random/natural of 88% is obtained.
A temporal record of the past with a spectrum of time constants in the monkey entorhinal cortex
Authors: Bright Ian M. , Meister Miriam L.R. , Cruzado Nathanael A. , Tiganj Zoran , Buffalo Elizabeth A. , Howard Marc W. 
Published: July 2019

AbstractEpisodic memory is believed to be intimately related to our experience of the passage of time. Indeed, neurons in the hippocampus and other brain regions critical to episodic memory code for the passage of time at a range of time scales. The origin of this temporal signal, however, remains unclear. Here, we examined temporal responses in the entorhinal cortex of macaque monkeys as they viewed complex images. Many neurons in the entorhinal cortex were responsive to image onset, showing large deviations from baseline firing shortly after image onset but relaxing back to baseline at different rates. This range of relaxation rates allowed for the time since image onset to be decoded on the scale of seconds. Further, these neurons carried information about image content, suggesting that neurons in the entorhinal cortex carry information not only about when an event took place but also the identity of that event. Taken together, these findings suggest that the primate entorhinal cortex uses a spectrum of time constants to construct a temporal record of the past in support of episodic memory.
The Bric-à-Brac transcription factors are necessary for formation of functional germline stem cell niches through control ofdppexpression in theDrosophila melanogasterovary
Authors: Miscopein Saler Laurine , Bartoletti Mathieu , Hauser Virginie , Pret Anne-Marie , Theodore Laurent , Chalvet Fabienne , Netter Sophie 
Published: July 2019

AbstractMany studies have focused on the mechanisms of stem cell maintenanceviatheir interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. AdultDrosophila melanogasterovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack called a Terminal Filament (TF) and underlying Cap Cells (CCs) and Escort Cells (ECs), which are in direct contact with GSCs. In the adult, the Engrailed (En) transcription factor is specifically expressed in niche cells where it directly controls expression of thedecapentaplegicgene (dpp) encoding a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules, which are key factors for GSC maintenance. In late third instar larval ovaries, in response to BMP signaling from newly-formed niches, adjacent primordial germ cells become GSCs. Thebric-à-bracparalogs (bab1andbab2) encode BTB/POZ-domain containing transcription factors, that are also expressed in developing GSCs niches where they are required for TF formation. Here, we demonstrate that Bab1 and Bab2 display redundant cell autonomous function for TF morphogenesis and we identify a new function for these genes in GSC establishment. Moreover, we show that Bab proteins controldppexpression in otherwise correctly specified CCs, independently of En and its paralog Invected (Inv). In fact, our results also indicate thaten/invfunction in larval stages are neither essential for TF formation, nor GSC establishment. Finally, whenbab2was overexpressed in ovarian somatic cells outside of the niche, whereen/invwere not expressed, ectopic BMP signaling activation was induced in adjacent germ cells of adult ovaries, which formed GSC-like tumors. Together, these results indicate that Bab transcription factors are positive regulators of BMP signaling for acquisition of GSC status.