bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells
Authors: De Kumar Bony , Parker Hugo J. , Parrish Mark E. , Lange Jeffrey J. , Slaughter Brian D. , Unruh Jay R. , Paulson Ariel , Krumlauf Robb
Published: June 2017

Homeobox a1
(
Hoxa1
) is one of the most rapidly induced genes in ES cell differentiation and it is the earliest expressed Hox gene in the mouse embryo. In this study, we used genomic approaches to identify Hoxa1-bound regions during early stages of ES cell differentiation into the neuro-ectoderm. Within 2 h of retinoic acid treatment, Hoxa1 is rapidly recruited to target sites that are associated with genes involved in regulation of pluripotency, and these genes display early changes in expression. The pattern of occupancy of Hoxa1 is dynamic and changes over time. At 12 h of differentiation, many sites bound at 2 h are lost and a new cohort of bound regions appears. At both time points the genome-wide mapping reveals that there is significant co-occupancy of Nanog (Nanog homeobox) and Hoxa1 on many common target sites, and these are linked to genes in the pluripotential regulatory network. In addition to shared target genes, Hoxa1 binds to regulatory regions of
Nanog
, and conversely Nanog binds to a 3′ enhancer of
Hoxa1
. This finding provides evidence for direct cross-regulatory feedback between
Hoxa1
and
Nanog
through a mechanism of mutual repression. Hoxa1 also binds to regulatory regions of
Sox2
(sex-determining region Y box 2),
Esrrb
(estrogen-related receptor beta), and
Myc
, which underscores its key input into core components of the pluripotential regulatory network. We propose a model whereby direct inputs of Nanog and Hoxa1 on shared targets and mutual repression between Hoxa1 and the core pluripotency network provides a molecular mechanism that modulates the fine balance between the alternate states of pluripotency and differentiation.
Logical modeling of lymphoid and myeloid cell specification and transdifferentiation
Authors: Collombet Samuel , van Oevelen Chris , Sardina Ortega Jose Luis , Abou-Jaoudé Wassim , Di Stefano Bruno , Thomas-Chollier Morgane , Graf Thomas , Thieffry Denis
Published: June 2017

Blood cells are derived from a common set of hematopoietic stem cells, which differentiate into more specific progenitors of the myeloid and lymphoid lineages, ultimately leading to differentiated cells. This developmental process is controlled by a complex regulatory network involving cytokines and their receptors, transcription factors, and chromatin remodelers. Using public data and data from our own molecular genetic experiments (quantitative PCR, Western blot, EMSA) or genome-wide assays (RNA-sequencing, ChIP-sequencing), we have assembled a comprehensive regulatory network encompassing the main transcription factors and signaling components involved in myeloid and lymphoid development. Focusing on B-cell and macrophage development, we defined a qualitative dynamical model recapitulating cytokine-induced differentiation of common progenitors, the effect of various reported gene knockdowns, and the reprogramming of pre-B cells into macrophages induced by the ectopic expression of specific transcription factors. The resulting network model can be used as a template for the integration of new hematopoietic differentiation and transdifferentiation data to foster our understanding of lymphoid/myeloid cell-fate decisions.
Stability of ferrous-iron-rich bridgmanite under reducing midmantle conditions
Authors: Shim Sang-Heon , Grocholski Brent , Ye Yu , Alp E. Ercan , Xu Shenzhen , Morgan Dane , Meng Yue , Prakapenka Vitali B.
Published: June 2017

Significance

This paper reports an unexpected change in the oxidation state of Fe in bridgmanite, the most dominant mineral in the lower mantle. The oxidation state change resolves the discrepancy between laboratory and seismic studies on the chemical composition of the lower mantle, showing that the lower mantle has major element chemistry similar to the upper mantle. The oxidation state change will also lead to a lower Fe content in bridgmanite in the midmantle, whereas the total Fe content remains the same. Such a change can lead to an increase in viscosity at 1,100- to 1,700-km depths, providing a viable mineralogical explanation on possible viscosity elevation suggested by geophysical studies at the same depth range.
An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence
Authors: Martinez Ivan , Hayes Karen E. , Barr Jamie A. , Harold Abby D. , Xie Mingyi , Bukhari Syed I. A. , Vasudevan Shobha , Steitz Joan A. , DiMaio Daniel
Published: June 2017

Significance

Quiescence is a growth-arrested cellular state; genes involved in this process are finely regulated by several factors, including miRNAs. During miRNA biogenesis, Exportin-5 transports miRNA precursors from the nucleus to the cytoplasm. In this study, we demonstrated the existence of an alternative miRNA biogenesis pathway in quiescent primary human cells. This pathway involves the repression of Exportin-5 expression by autophagy and miRNAs and the 2,2,7-trimethylguanosine-cap modification of specific primary miRNAs (pri-miRNAs), which signal their export to the cytoplasm by Exportin-1. We further showed that these pri-miRNAs are processed rapidly in the cytoplasm by a small isoform of Drosha. Collectively, these results reveal an alternative mechanism of miRNA biogenesis that will expand our understanding of miRNA regulation in normal or disease-related cells.
Characterization of the macrocyclase involved in the biosynthesis of RiPP cyclic peptides in plants
Authors: Chekan Jonathan R. , Estrada Paola , Covello Patrick S. , Nair Satish K.
Published: June 2017

Significance

The class of bioactive cyclic plant natural products called orbitides was first identified nearly half a century ago. Here we describe how a single enzyme can catalyze the cyclization of a range of ribosomally synthesized linear peptides into the corresponding cyclic products of varying ring sizes. These studies may provide a means for producing large libraries of cyclic peptides without any sequence bias.
Temperature variability is integrated by a spatially embedded decision-making center to break dormancy in
Arabidopsis
seeds
Authors: Topham Alexander T. , Taylor Rachel E. , Yan Dawei , Nambara Eiji , Johnston Iain G. , Bassel George W.
Published: June 2017

Significance

Both plants and animals make decisions in response to the environment to maximize their fitness. Plants use dormancy in seeds to move through time and space, and timing of the transition to germination is influenced by external cues, including temperature. Here, we report the presence of a decision-making center within the root tip of dormant seeds and demonstrate that it shares a similar configuration as some systems within the human brain. Unlike in humans, where this spatial structure is used to filter out noisy inputs from the environment, seeds use this arrangement to harness fluctuating temperatures and stimulate the termination of dormancy. Variable inputs therefore act as an instructive signal for seeds, enhancing the accuracy with which plants are established in ecosystems.
Dapagliflozin suppresses glucagon signaling in rodent models of diabetes
Authors: Wang May-yun , Yu Xinxin , Lee Young , McCorkle Sara Kay , Chen Shiuhwei , Li Jianping , Wang Zhao V. , Davidson Jaime A. , Scherer Philipp E. , Holland William L. , Unger Roger H. , Roth Michael G.
Published: June 2017

Significance

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose in humans with diabetes. These drugs inhibit the reabsorption of glucose in the kidney, resulting in its urine excretion. It was reported that SGLT2 inhibitors increase the secretion of glucagon and increase endogenous glucose production by the liver. These effects would elevate blood glucose, counteracting the effect of urinary glucose loss. Here we show in a rodent model of type 1 diabetes that the SGLT2 inhibitor dapagliflozin inhibited the secretion of glucagon from the pancreas. In two rodent models of severe type 2 diabetes, livers from animals treated with dapagliflozin showed decreased glucagon signaling and had reduced expression of the glucagon receptor. Our results suggest dapagliflozin lowers blood glucose concentrations in diabetic animals in part through inhibiting hepatic glucagon signaling.
When cognate status produces no benefits
Authors: Dussias Paola E. , Kroff Jorge R. Valdés , Tamargo Rosa E. Guzzardo
Published: June 2017

Experimental studies examining the production and comprehension of language switches have provided evidence for a subtle but significant “switch cost:” switched words take longer to process than non-switched words (e.g., Altarriba et al., 1996; Gollan & Ferreira, 2009; Meuter & Allport, 1999). However, bilingual speakers produce code-switches seamlessly and effortlessly (Myers-Scotton, 2002) and do not experience disruptions during the comprehension of naturally occurring code-switches (Guzzardo Tamargo, 2012). These two observations suggest that bilinguals make use of particular sources of information to seemingly alleviate the challenges associated with switching between two languages. In the work presented here, we ask whether the cognate status of switched words may be one such source of information. To examine this question, the eye movements of Spanish-English early and late bilinguals were recorded while they read sentences on a computer screen. The experimental stimuli consisted of 4 versions of the same sentence, corresponding to 4 experimental conditions. Conditions 1 and 2 were code-switched conditions with a progressive verb. In Condition 1 the switch occurred immediately before the verb (…los instructores are preparing) and in Condition 2 it occurred at the verb (…los instructores están preparing). Conditions 3 and 4 were analogous to Conditions 1 and 2 but involved a verb in the perfect form (…los instructores have prepared and los instructores han prepared). Critically, half of the verbs (48) were cognates (‘prepare’/ ‘preparar’) and half were non-cognates (‘ship’/ ‘enviar’). Bilinguals demonstrated an asymmetry in how they process code-switched sentences with the perfect structure vis-à-vis code-switched sentences with the progressive structure, and how cognate status impacted the integration of a code-switch.
Lexical retrieval difficulty in bilingual speakers with and without pathology
Authors: Goral Mira
Published: June 2017

Difficulty retrieving words that are known to the speaker is common in certain pathologies, such as aphasia and dementia, but may also occur in apathological change associated with healthy aging and with first language attrition. This chapter reviews findings from bilingual individuals who experience compromised lexical retrieval, focusing on three sub-populations. We first review lexical change in the first language of healthy bilingual adults who are immersed in their second language. Studies of bilingual speakers who acquire aphasia resulting from brain damage are then reviewed, demonstrating the complex influence of a variety of speaker- and language-related variables. Finally, data from studies with older bilinguals who experience typical and pathological aging-related language change are addressed. These three sources of evidence highlight the dynamic nature of the mental lexicon and the complex nature of lexical change in adulthood.
Achievements
Authors: Strong Samuel
Published: June 2017

Achievements perform an essential entertainment function in video games. They instruct and reward gamers, and they serve as status symbols or bragging rights within gaming communities. These texts can be challenging for localisers, since they have multiple functions, align with or subvert game mechanics and narrative, and can contain a range of intertextual references, understood as references to other texts, genres, or popular culture (Mangiron and O’Hagan, 2006). Their localisation, therefore, warrants special handling. In this article, I make the case for achievement texts being a unique text type based on Bernal-Merino’s (2014) classification. Further, I propose a macro-level analysis approach that enables localisers to re-render these texts’ essential component parts.
Cross-linguistic influence in scope ambiguity
Authors: Meroni Luisa , Smeets Liz , Unsworth Sharon
Published: June 2017

Cross-linguistic influence of interface-conditioned properties in bilingual language acquisition has been reported in a large number of studies and various linguistic domains. While many of these studies have found that cross-linguistic influence can occur in the form of delay, few have shown evidence for acceleration (a.o., Kupisch, 2007; Meisel, 2007; Schwartz, Nir, Leikin, Levie, & Ravid, 2014). In this paper we investigate the interpretation of indefinites in sentences containing negation by simultaneous bilingual (2L1) English-Dutch and Italian-Dutch children. Our results provide evidence for cross-linguistic influence from Italian to Dutch in the form of acceleration, only. We conclude that in cases of partial overlap between a bilingual child’s two languages, the direction of cross-linguistic influence can also depend on language-internal properties.
Subtle aspectual differences in the L2 acquisition of German
Authors: Miller David , DeLuca Vincent , Berndt Denny , Iverson Michael , Rothman Jason
Published: June 2017

We examine the acquisition of progressivity in the German simple present tense (GPT) and related constructions by English natives of L2 German, under the guise of the Feature Reassembly Hypothesis. German lacks an explicit gerundial form; the AM + infinitive (am) and BEIM + infinitive (beim) constructions express progressivity, along with the GPT. Although semantically the am and beim constructions map to the English copula + gerund, their unique syntax creates grammaticality differences. We employ three experiments testing (1) the acquisition of the aspectual properties of the GPT, and knowledge of the (2) semantic distribution of, and (3) syntax of am and beim. Data from a control group (n = 25) and adult L2s (n = 20) suggest adult L2 feature reassembly is possible, albeit complicated.
Cross-linguistic influence meets language impairment
Authors: Tsimpli Ianthi Maria , Peristeri Eleni , Andreou Maria
Published: June 2017

Our study investigates the use of articles and object clitics in the L2-Greek of child speakers of Russian with and without Specific Language Impairment. Effects of language impairment were examined in the narratives of children whose languages differ in the expression of definiteness: Russian lacks articles and allows null objects with specific reference, while Greek requires object clitics in the same context and has definite and indefinite articles. Language impairment led to more article and clitic omission in obligatory contexts, as well as more substitution errors in clitics. The bilingual children with SLI lagged behind TD bilingual Russian-Greek peers in both grammatical knowledge of functional categories related to the D system in Greek and access to discourse information influencing definiteness.
Linguistic validation of the Spanish version of the Good Death Inventory / Validación lingüística de la versión española del Good Death Inventory
Authors: Cabañero-Martínez María-José , Congost-Maestre Nereida , Fernández-de-Maya José , Jiménez-García Segundo , Richart-Martínez Miguel
Published: June 2017

This article outlines the linguistic validation of the Good Death Inventory (GDI) translation into Spanish, used to assess the quality of care at the end of a patient’s life. A standardized procedure was followed to do this that included a blind back translation process and an exploration of the conceptual adaptation of the scale into Spanish through six cognitive interviews with relatives of deceased patients. The translation of the scale (54 items) showed indicators of low difficulty. Six items required syntactic changes, 12 required semantic changes and only one item required syntactic and semantic changes. All items were considered applicable to the Spanish context. The degree of difficulty was higher for the back translation than for the translation itself. The cognitive interviews highlighted the difficulty of choosing between seven answers, especially those that were formulated as negative. Five items were difficult to understand. The Spanish version of the GDI has been adapted well to the Spanish context.
Bioenergetics Models to Estimate Numbers of Larval Lampreys Consumed by Smallmouth Bass in Elk Creek, Oregon
Authors: Schultz L. D. , Heck Michael P. , Kowalski Brandon M. , Eagles-Smith Collin A. , Coates K. , Dunham Jason B.
Published: June 2017

Nonnative fishes have been increasingly implicated in the decline of native fishes in the Pacific Northwest. Smallmouth Bass Micropterus dolomieu were introduced into the Umpqua River in southwest Oregon in the early 1960s. The spread of Smallmouth Bass throughout the basin coincided with a decline in counts of upstream-migrating Pacific Lampreys Entosphenus tridentatus. This suggested the potential for ecological interactions between Smallmouth Bass and Pacific Lampreys, as well as freshwater-resident Western Brook Lampreys Lampetra richardsoni. To evaluate the potential effects of Smallmouth Bass on lampreys, we sampled diets of Smallmouth Bass and used bioenergetics models to estimate consumption of larval lampreys in a segment of Elk Creek, a tributary to the lower Umpqua River. We captured 303 unique Smallmouth Bass (mean: 197 mm and 136 g) via angling in July and September. We combined information on Smallmouth Bass diet and energy density with other variables (temperature, body size, growth, prey energy density) in a bioenergetics model to estimate consumption of larval lampreys. Larval lampreys were found in 6.2% of diet samples, and model estimates indicated that the Smallmouth Bass we captured consumed 925 larval lampreys in this 2-month study period. When extrapolated to a population estimate of Smallmouth Bass in this segment, we estimated 1,911 larval lampreys were consumed between July and September. Although the precision of these estimates was low, this magnitude of consumption suggests that Smallmouth Bass may negatively affect larval lamprey populations.

Received September 20, 2016; accepted March 31, 2017Published online June 6, 2017
Opioid vs Nonopioid Prescribers: Variations in Care for a Standardized Acute Back Pain Case
Authors: Hanley Kathleen , Zabar Sondra , Altshuler Lisa , Lee Hillary , Ross Jasmine , Rivera Nicomedes , Marvilli Christian , Gillespie Colleen
Published: June 2017

Background

Opioid analgesics are effective and appropriate therapy for many types of acute pain. Epidemiologic evidence supports a direct relationship between increased opioid prescribing and increases in opioid use disorders and overdoses. Objective: To tailor our residency curriculum, we designed and fielded an unannounced standardized patient (USP) case involving a patient with acute back pain who is requesting Vicodin (5/325 mg). We describe residents’ case management and examine whether their management decisions, including opioid prescribing, were related to their core clinical skills.

Methods

Results are based on 50 (USP) visits with residents in 2 urban primary care clinics. Highly trained USPs portrayed a patient with acute lower back pain who was taking leftover Vicodin with effective pain relief but was running out. We describe how residents managed this case, using both USP report and chart review data, and compare summary clinical skills scores between those who prescribed Vicodin and those who did not.

Results

Of the 50 residents, 18 prescribed Vicodin (10–60 pills). Among those who did not prescribe (32/50), most (50%) prescribed ibuprofen. Eighty-three percent of the prescribers and 72% of nonprescribers ordered physical therapy (nonsignificant). Of the 18 prescribers, 13 documented checking the prescription monitoring database. Prescribers had significantly better communication scores than nonprescribers (relationship development: 80% vs. 58% well done, P = .029; patient education: 59% vs. 31% well done, P = .018). Assessment summary scores were also higher (60% vs. 46%) but not significantly ( P = .060). Patient satisfaction and activation scores were higher in the prescribers than nonprescribers (71% vs. 39%, P = .004 and 48% vs. 26%, P = .034, respectively).

Conclusions

Most Vicodin prescribers did not follow prescribing guidelines, and they demonstrated better communication and assessment skills than the nonprescribers. Results suggest the need to guide residents in using a systematic approach to prescribing opioids safely and to develop an acceptable alternative pain management plan when they decide against prescribing.
Negotiating between individual and joint goals in ensemble musical performance
Authors: MacRitchie Jennifer , Herff Steffen A , Procopio Andrea , Keller Peter E
Published: June 2017

Successful joint action requires negotiation, especially in the event of goal incongruence. This article addresses goal incongruence in joint musical performance by manipulating the congruence of score instructions (congruent/incongruent) regarding tempo (speed) and dynamics (sound intensity) given to piano duos. The aim is to investigate how co-performers negotiate incongruent instructions for tempo and dynamics by balancing the prioritisation of individual goals versus the joint outcome and how this negotiation is modulated by musical expertise and personality (locus of control). In total, 14 pairs of pianists, who were not informed of the congruence manipulation, were placed back-to-back and were directed to achieve a successful performance over four repeated performances without verbal communication. Interpersonal coordination generally improved from the first to final performance in the congruent and incongruent conditions for both the tempo and dynamics tasks. Furthermore, in incongruent conditions, results suggest that performers prioritise the joint performance in the tempo task, but prioritise their own performance in the dynamics task. Although individual performance appears to be modulated by musical expertise, the balance of individual/joint performance across the duo is not influenced by musical part (melody vs accompaniment), expressive instruction, musical expertise or locus of control.
Commensal microbes provide first line defense against Listeria monocytogenes infection
Authors: Becattini Simone , Littmann Eric R. , Carter Rebecca A. , Kim Sohn G. , Morjaria Sejal M. , Ling Lilan , Gyaltshen Yangtsho , Fontana Emily , Taur Ying , Leiner Ingrid M. , Pamer Eric G.
Published: June 2017

Listeria monocytogenes is a foodborne pathogen that causes septicemia, meningitis and chorioamnionitis and is associated with high mortality. Immunocompetent humans and animals, however, can tolerate high doses of L. monocytogenes without developing systemic disease. The intestinal microbiota provides colonization resistance against many orally acquired pathogens, and antibiotic-mediated depletion of the microbiota reduces host resistance to infection. Here we show that a diverse microbiota markedly reduces Listeria monocytogenes colonization of the gut lumen and prevents systemic dissemination. Antibiotic administration to mice before low dose oral inoculation increases L. monocytogenes growth in the intestine. In immunodeficient or chemotherapy-treated mice, the intestinal microbiota provides nonredundant defense against lethal, disseminated infection. We have assembled a consortium of commensal bacteria belonging to the Clostridiales order, which exerts in vitro antilisterial activity and confers in vivo resistance upon transfer into germ free mice. Thus, we demonstrate a defensive role of the gut microbiota against Listeria monocytogenes infection and identify intestinal commensal species that, by enhancing resistance against this pathogen, represent potential probiotics.
Storied Objects, Scientific Objects, and Renaissance Experiment: The Case of Malleable Glass
Authors: Keller Vera
Published: June 2017

The career of storied objects can help highlight the agency of absence and historicize the notion of scientific objects more generally. Until the sixteenth century, lost, ancient flexible glass was studied separately from malleable glass. The latter appeared as a claimed chymical product and craft recipe. The bridging of social and epistemic registers merged these accounts. Malleable glass became a prestigious scientific object. Appearing in numerous utopias, it stimulated a participatory public of scientific amateurs. Such storied objects served as vectors for spreading experimental culture, yet declined as new professions emerged. The charisma that made malleable glass a seventeenth-century scientific object led to its rejection by newly professionalized eighteenth-century chemists and its replacement by a less evocative scientific object, “malleability.”
Review of the Collected Works of John Tate
Authors: Milne J.
Published: June 2017

This is a review of Collected Works of John Tate. Parts I, II, edited by Barry Mazur and Jean-Pierre Serre. American Mathematical Society, Providence, Rhode Island, 2016.
runBNG: a software package for BioNano genomic analysis on the command line
Authors: Yuan Yuxuan , Bayer Philipp E , Lee Huey-Tyng , Edwards David
Published: June 2017

We developed runBNG, an open-source software package which wraps BioNano genomic analysis tools into a single script that can be run on the command line. runBNG can complete analyses, including quality control of single molecule maps, optical map de novo assembly, comparisons between different optical maps, super-scaffolding and structural variation detection. Compared to existing software BioNano IrysView and the KSU scripts, the major advantages of runBNG are that the whole pipeline runs on one single platform and it has a high customizability.

Availability and implementation

runBNG is written in bash, with the requirement of BioNano IrysSolve packages, GCC, Perl and Python software. It is freely available at https://github.com/appliedbioinformatics/runBNG.

Supplementary information

Supplementary data are available at Bioinformatics online.
MoDMaps3D: an interactive webtool for the quantification and 3D visualization of interrelationships in a dataset of DNA sequences
Authors: Karamichalis Rallis , Kari Lila
Published: June 2017

MoDMaps3D (Molecular Distance Maps 3D) is an alignment-free, fast, computationally lightweight webtool for computing and visualizing the interrelationships within any dataset of DNA sequences, based on pairwise comparisons between their oligomer compositions. MoDMaps3D is a general-purpose interactive webtool that is free of any requirements on sequence composition, position of the sequences in their respective genomes, presence or absence of similarity or homology, sequence length, or even sequence origin (biological or computer-generated).

Availability and implementation

MoDMaps3D is open source, cross-platform compatible, and is available under the MIT license at http://moleculardistancemaps.github.io/MoDMaps3D/. The source code is available at https://github.com/moleculardistancemaps/MoDMaps3D/.

Supplementary information

Supplementary data are available at Bioinformatics online.
DNA methylation signatures and coagulation factors in the peripheral blood leucocytes of epithelial ovarian cancer
Authors: Li Lian , Zheng Hong , Huang Yubei , Huang Caiyun , Zhang Shuang , Tian Jing , Li Pei , Sood Anil K , Zhang Wei , Chen Kexin
Published: June 2017

Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, RNA, proteins and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485 000 CpG sites in peripheral blood in 24 epithelial ovarian cancer (EOC) cases and 24 age-matched healthy controls. We selected 96 significantly differentially methylated CpG sites for validation using Illumina’s Custom VeraCode methylation assay in 206 EOC cases and 205 controls and 46 CpG sites validated in the independent replication samples. A set of 6 of these 46 CpG sites was found by the receiver operating characteristic analysis to have a prediction accuracy of 77.3% for all EOC (95% confidence interval: 72.9–81.8%). Pathway analysis of the genes associated with the 46 CpG sites revealed an enrichment of immune system process genes, including LYST (cg16962115, FDR = 1.24E−04), CADM1 (cg21933078, FDR = 1.22E−02) and NFATC1 (cg06784563, FDR = 1.46E−02). Furthermore, DNA methylation status in peripheral blood was correlated with platelet parameters/coagulation factor levels. This study discovered a panel of epigenetic liquid biopsy markers closely associated with overall immunologic conditions and platelet parameters/coagulation systems of the patients for detection of all stages and subtypes of EOC.
Full-waveform inversion of triplicated data using a normalized-correlation-coefficient-based misfit function
Authors: Tao Kai , Grand Stephen P. , Niu Fenglin
Published: June 2017

In seismic full-waveform inversion (FWI), the choice of misfit function determines what information in data is used and ultimately affects the resolution of the inverted images of the Earth's structure. Misfit functions based on traveltime have been successfully applied in global and regional tomographic studies. However, wave propagation through the upper mantle results in multiple phases arriving at a given receiver in a narrow time interval resulting in complicated waveforms that evolve with distance. To extract waveform information as well as traveltime, we use a misfit function based on the normalized correlation coefficient (CC). This misfit function is able to capture the waveform complexities in both phase and relative amplitude within the measurement window. It is also insensitive to absolute amplitude differences between modeled and recorded data, which avoids problems due to uncertainties in source magnitude, radiation pattern, receiver site effects or even miscalibrated instruments. These features make the misfit function based on normalized CC a good candidate to achieve high-resolution images of complex geological structures when interfering phases coexist in the measurement window, such as triplication waveforms. From synthetic tests, we show the advantages of this misfit function over the cross-correlation traveltime misfit function. Preliminary inversion of data from an earthquake in Northeast China images a sharper and stronger amplitude slab stagnant in the middle of the transition zone than FWI of cross-correlation traveltime.
Automatable algorithms to identify nonmedical opioid use using electronic data: a systematic review
Authors: Canan Chelsea , Polinski Jennifer M , Alexander G Caleb , Kowal Mary K , Brennan Troyen A , Shrank William H
Published: June 2017

Objective

Improved methods to identify nonmedical opioid use can help direct health care resources to individuals who need them. Automated algorithms that use large databases of electronic health care claims or records for surveillance are a potential means to achieve this goal. In this systematic review, we reviewed the utility, attempts at validation, and application of such algorithms to detect nonmedical opioid use.

Materials and Methods

We searched PubMed and Embase for articles describing automatable algorithms that used electronic health care claims or records to identify patients or prescribers with likely nonmedical opioid use. We assessed algorithm development, validation, and performance characteristics and the settings where they were applied. Study variability precluded a meta-analysis.

Results

Of 15 included algorithms, 10 targeted patients, 2 targeted providers, 2 targeted both, and 1 identified medications with high abuse potential. Most patient-focused algorithms (67%) used prescription drug claims and/or medical claims, with diagnosis codes of substance abuse and/or dependence as the reference standard. Eleven algorithms were developed via regression modeling. Four used natural language processing, data mining, audit analysis, or factor analysis.

Discussion

Automated algorithms can facilitate population-level surveillance. However, there is no true gold standard for determining nonmedical opioid use. Users must recognize the implications of identifying false positives and, conversely, false negatives. Few algorithms have been applied in real-world settings.

Conclusion

Automated algorithms may facilitate identification of patients and/or providers most likely to need more intensive screening and/or intervention for nonmedical opioid use. Additional implementation research in real-world settings would clarify their utility.
A technology-based patient and family engagement consult service for the pediatric hospital setting
Authors: Jackson Gretchen P , Robinson Jamie R , Ingram Ebone , Masterman Mary , Ivory Catherine , Holloway Diane , Anders Shilo , Cronin Robert M
Published: June 2017

Objective

The Vanderbilt Children’s Hospital launched an innovative Technology-Based Patient and Family Engagement Consult Service in 2014. This paper describes our initial experience with this service, characterizes health-related needs of families of hospitalized children, and details the technologies recommended to promote engagement and meet needs.

Materials and Methods

We retrospectively reviewed consult service documentation for patient characteristics, health-related needs, and consultation team recommendations. Needs were categorized using a consumer health needs taxonomy. Recommendations were classified by technology type.

Results

Twenty-two consultations were conducted with families of patients ranging in age from newborn to 15 years, most with new diagnoses or chronic illnesses. The consultation team identified 99 health-related needs (4.5 per consultation) and made 166 recommendations (7.5 per consultation, 1.7 per need). Need categories included 38 informational needs, 26 medical needs, 23 logistical needs, and 12 social needs. The most common recommendations were websites (50, 30%) and mobile applications (30, 18%). The most frequent recommendations by need category were websites for informational needs (39, 50%), mobile applications for medical needs (15, 40%), patient portals for logistical needs (12, 44%), and disease-specific support groups for social needs (19, 56%).

Discussion

Families of hospitalized pediatric patients have a variety of health-related needs, many of which could be addressed by technology recommendations from an engagement consult service.

Conclusion

This service is the first of its kind, offering a potentially generalizable and scalable approach to assessing health-related needs, meeting them with technologies, and promoting patient and family engagement in the inpatient setting.
A complete logic for Database Abstract State Machines1
Authors: Ferrarotti Flavio , Schewe Klaus-Dieter , Tec Loredana , Wang Qing
Published: June 2017

In database theory, the term database transformation was used to refer to a unifying treatment for computable queries and updates. Recently, it was shown that non-deterministic database transformations can be captured exactly by a variant of ASMs, the so-called Database Abstract State Machines (DB-ASMs). In this article we present a logic for DB-ASMs, extending the logic of Nanchen and Stärk for ASMs. In particular, we develop a rigorous proof system for the logic for DB-ASMs, which is proven to be sound and complete. The most difficult challenge to be handled by the extension is a proper formalization capturing non-determinism of database transformations and all its related features such as consistency, update sets or multisets associated with DB-ASM rules. As the database part of a state of database transformations is a finite structure and DB-ASMs are restricted by allowing quantifiers only over the database part of a state, we resolve this problem by taking update sets explicitly into the logic, i.e. by using an additional modal operator $[X]$, where $X$ is interpreted as an update set $\Delta$ generated by a DB-ASM rule. The DB-ASM logic provides a powerful verification tool to study properties of database transformations.
Grazing envelope evolution towards Type IIb supernovae
Authors: Soker Noam
Published: June 2017

I propose a scenario where the majority of the progenitors of Type IIb supernovae (SNe IIb) lose most of their hydrogen-rich envelope during a grazing envelope evolution (GEE). In the GEE, the orbital radius of the binary system is about equal to the radius of the giant star, and the more compact companion accretes mass through an accretion disc. The accretion disc is assumed to launch two opposite jets that efficiently remove gas from the envelope along the orbit of the companion. The efficient envelope removal by jets prevents the binary system from entering a common envelope evolution, at least for part of the time. The GEE might be continuous or intermittent. I crudely estimate the total GEE time period to be in the range of about hundreds of years, for a continuous GEE, and up to few tens of thousands of years for intermittent GEE. The key new point is that the removal of envelope gas by jets during the GEE prevents the system from entering a common envelope evolution, and by that substantially increases the volume of the stellar binary parameter space that leads to SNe IIb, both to lower secondary masses and to closer orbital separations.
Detection of helicoidal motion in the optical jet of PKS 0521−365
Authors: Jiménez-Andrade E. F. , Chavushyan V. , León-Tavares J. , Patiño-Álvarez V. M. , Olguín-Iglesias A. , Kotilainen J. , Falomo R. , Hyvönen T.
Published: June 2017

The jet activity of active galactic nuclei (AGNs), and its interaction with the interstellar medium, may play a pivotal role in the processes that regulate the growth and star formation of its host galaxy. Observational evidence that pinpoints the conditions of such interaction is paramount to unveil the physical processes involved. We report on the discovery of extended emission-line regions exhibiting an S-shaped morphology along the optical jet of the radio-loud AGN PKS 0521−365 (z = 0.055), by using long-slit spectroscopic observations obtained with FOcal Reducer/low dispersion Spectrograph 2 on the Very Large Telescope. The velocity pattern derived from the [O ii] λ3727 Å, H β λ4861 Å and [O iii] λλ4959, 5007 Å emission lines is well fitted by a sinusoidal function of the form: v(r) = αr1/2sin(βr1/2 + γ), suggesting helicoidal motions along the jet up to distances of 20 kpc. We estimate a lower limit for the mass of the outflowing ionized gas along the jet of ∼104 M⊙. Helical magnetic fields and jet precession have been proposed to explain helicoidal paths along the jet at pc scales; nevertheless, it is not clear yet whether these hypotheses may hold at kpc scales.
Neurosurgical Patients as Human Research Subjects: Ethical Considerations in Intracranial Electrophysiology Research
Authors: Chiong Winston , Leonard Matthew K , Chang Edward F
Published: June 2017

Intracranial electrical recordings and stimulation of neurosurgical patients have been central to the advancement of human neuroscience. The use of these methods has rapidly expanded over the last decade due to theoretical and technical advances, as well as the growing number of neurosurgical patients undergoing functional procedures for indications such as epilepsy, tumor resection, and movement disorders. These methods pose the potential for ethical conflict, as they involve basic neuroscientific research utilizing invasive procedures in human patients undergoing treatment for neurological illnesses. This review addresses technical aspects, clinical contexts, and issues of ethical concern, utilizing a framework that is informed by, but also departs from, existing bioethical literature on matters in clinical research. We conclude with proposals for improving informed consent processes to address potential problems specific to intracranial electrophysiology research, a general schema for scrutinizing research-related risk associated with different methods, and a call for the development of consensus to ensure continuing scientific progress alongside crucial patient protections in this promising area of human neuroscience.
The acidic tumor microenvironment: a target for smart cancer nano-theranostics
Authors: Feng Liangzhu , Dong Ziliang , Tao Danlei , Zhang Yicheng , Liu Zhuang
Published: June 2017

The acidic tumor microenvironment (TME), which mainly results from the high glycolytic rate of tumor cells, has been characterized as a hallmark of solid tumors and found to be a pivotal factor participating in tumor progression. Recently, due to the increasing understanding of the acidic TME, it has been shown that the acidic TME could be utilized as a multifaceted target during the design of various pH-responsive nanoscale theranostic platforms for the precise diagnosis and effective treatment of cancers. In this article, we will give a focused overview on the latest progress in utilizing this characteristic acidic TME as the target of nano-theranostics to enable cancer-specific imaging and therapy. The future perspectives in the development of acidic TME-targeting nanomedicine strategies will be discussed afterwards.
Addiction Research Training Programs: Four Case Studies and Recommendations for Evaluation
Authors: Campbell Aimee N.C. , Back Sudie E. , Ostroff Jamie S. , Hien Denise A. , Gourevitch Marc N. , Sheffer Christine E. , Brady Kathleen T. , Hanley Kathleen , Bereket Sewit , Book Sarah
Published: June 2017

The presence of structured addiction research training programs helps to ensure that the scientific workforce includes well-trained, diverse scientists necessary to reduce the negative impact of alcohol, drug, and tobacco use disorders. Although the field has made significant progress in the development of standards for clinical training in addiction medicine, there remains significant room for improvement in the training of addiction researchers, and also opportunities to synergize across addiction research training programs. The purpose of this commentary is to describe 4 National Institutes of Health (NIH)-sponsored addiction research training programs, highlight critical components, and provide recommendations for more comprehensive and effective program evaluation. Moving forward, evaluation of addiction research training programs would be enhanced by the use of conceptual models to inform process and outcome evaluations, the application of innovative methods to ensure long-term data collection, the improvement of mentorship evaluation measures, and the integration of training methods from other fields of study. We encourage NIH and others in the field to be proactive in establishing core metrics for evaluation across programs. Furthermore, centralized tracking of NIH-funded addiction research trainees, analysis of aggregate data across programs, and innovative methods to effectively disseminate program materials and processes are recommended.
Investigating the Fear Avoidance Model in People With Whiplash
Authors: Pedler Ashley , Kamper Steven J. , Maujean Annick , Sterling Michele
Published: June 2017

Objectives:

The aims of this study were to examine the relationship between fear of movement and activity levels in people with whiplash-associated disorders (WAD) over the first 3 months postinjury, to determine the mediating effect of: fear of movement on the relationship between catastrophizing and activity levels, and activity levels on the relationship between fear of movement and disability in patients with WAD.

Materials and Methods:

Ambulatory monitoring of physical activity was conducted for a minimum of 8 waking hours on 2 consecutive days within 4 weeks postinjury and at 12 weeks postinjury for 103 (74 female) people with WAD. Time spent in upright postures (uptime) and time in motion (TIM) were collected along with measures of pain, disability, pain catastrophizing, and fear of movement. The association of self-report outcome measures with uptime and TIM were examined. Mediation analyses were performed to determine the mediating effect of: fear of movement on the relationship between catastrophizing and activity, and activity levels on the relationship between fear of movement and disability.

Results:

Fear of movement was significantly related to uptime but not TIM. Mediation analyses showed that the relationship between fear of movement and disability was not mediated by activity levels, and that the relationship between catastrophizing and activity levels was not mediated by fear of movement.

Discussion:

Our data suggests measures of Fear Avoidance Model are not related to general physical activity in people with WAD. Investigation of movements specific to the cervical spine and alternative explanatory models may be required.
Pain-related Activity Management Patterns and Function in Patients With Fibromyalgia Syndrome
Authors: Racine Mélanie , Galán Santiago , de la Vega Rocío , Tomé Pires Catarina , Solé Ester , Nielson Warren R. , Miró Jordi , Moulin Dwight E. , Jensen Mark P.
Published: June 2017

Objectives:

To clarify the importance of avoidance, pacing, and overdoing pain-related activity management patterns as predictors of adjustment in patients with fibromyalgia syndrome.

Methods:

A total of 119 tertiary care patients with fibromyalgia syndrome who agreed to be part of an activity management pain program completed a survey, which requested information about demographics, pain intensity and pain interference, psychological and physical function, and pain-related activity management patterns. Hierarchical regression analyses were used to identify the unique contributions of the 3 different pain-related activity management patterns (avoidance, pacing, and overdoing) to the prediction of pain interference, psychological function, and physical function.

Results:

The avoidance pattern was a significant and unique predictor of worse psychological and physical function as well as greater pain interference. Pacing was significantly associated with less pain interference and better psychological function, whereas overdoing was not found to predict patient functioning.

Discussion:

The findings confirm the importance of pain-related activity management patterns as predictors of patient function, and support the necessity of addressing these factors in chronic pain treatment. In addition, the results suggest that targeting increases in activity pacing and decreases in pain avoidance, specifically, might yield the best patient outcomes. However, further research to evaluate this possibility is necessary.