bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a Pediatric Oral Health Training Curriculum for Community Health Workers
Authors: Martin Molly , Frese William , Lumsden Christie , Sandoval Anna
Published: June 2017

Objectives:

Community health workers (CHWs) are a promising approach to oral health promotion in high-risk populations. This article describes the process of creating a pediatric oral health CHW training curriculum.

Design:

Existing curricula were identified through outreach efforts to experts in the oral health and CHW fields, as well as PubMed and Google searches. After coding basic information, curricula were mapped to define oral health domains. Then group discussion was employed to determine final curriculum contents.

Setting:

United States.

Inclusion Criteria:

Curricula were included if they addressed oral health, were in English or Spanish, involved US populations, did not target dental clinicians, and whether sufficient data could be obtained.

Main Outcome Measures:

Curricula were evaluated for delivery format, number of hours, target audience, inclusion of CHWs, completeness, and oral health content.

Results:

Eighteen unique curricula were identified; 14 (78%) were CHW specific. Pathologic factors, caries formation, toothbrushing basics, flossing, nutrition, sugar-sweetened beverages, oral health recommendations, baby bottle tooth decay, fluoride treatments, and fluoride were covered to some extent in 75% of curricula. More than half did not mention types of teeth, oral health during pregnancy, antifluoride, cultural humility, and special needs populations. After comparing CHW curricula with non-CHW curricula, the original 26 oral health domains were condensed into 10 CHW training domains.

Conclusion:

Using existing evidence and expert insight, an oral health CHW training curriculum outline was created that emphasizes behaviors, social support, and navigation assistance to promote preventive oral health behaviors in families of young children. This has implications beyond oral health. CHW programs are expanding to address the social determinants of health. The process of creating this curriculum and its basic elements can be applied to other disease areas. Clearly defined trainings that are made publicly available, such as this one, support efforts to standardize the CHW field in preparation for CHW certification and reimbursement in the future.
Building Data and Information Capacity in Environmental Public Health: A Best-Worst Scaling Experiment
Authors: Wallar Lauren E. , Sargeant Jan M. , McEwen Scott A. , Mercer Nicola J. , Papadopoulos Andrew
Published: June 2017

Context:

Environmental public health practitioners rely on information technology (IT) to maintain and improve environmental health. However, current systems have limited capacity. A better understanding of the importance of IT features is needed to enhance data and information capacity.

Objective:

(1) Rank IT features according to the percentage of respondents who rated them as essential to an information management system and (2) quantify the relative importance of a subset of these features using best-worst scaling.

Design:

Information technology features were initially identified from a previously published systematic review of software evaluation criteria and a list of software options from a private corporation specializing in inspection software. Duplicates and features unrelated to environmental public health were removed. The condensed list was refined by a working group of environmental public health management to a final list of 57 IT features. The essentialness of features was electronically rated by environmental public health managers. Features where 50% to 80% of respondents rated them as essential (n = 26) were subsequently evaluated using best-worst scaling.

Setting:

Ontario, Canada.

Participants:

Environmental public health professionals in local public health.

Main Outcome Measure:

Importance scores of IT features.

Results:

The majority of IT features (47/57) were considered essential to an information management system by at least half of the respondents (n = 52). The highest-rated features were delivery to printer, software encryption capability, and software maintenance services. Of the 26 features evaluated in the best-worst scaling exercise, the most important features were orientation to all practice areas, off-line capability, and ability to view past inspection reports and results.

Conclusions:

The development of a single, unified environmental public health information management system that fulfills the reporting and functionality needs of system users is recommended. This system should be implemented by all public health units to support data and information capacity in local environmental public health. This study can be used to guide vendor evaluation, negotiation, and selection in local environmental public health, and provides an example of academia-practice partnerships and the use of best-worst scaling in public health research.
Brief Report: Appraising Viral Load Thresholds and Adherence Support Recommendations in the World Health Organization Guidelines for Detection and Management of Virologic Failure
Authors: McCluskey Suzanne M. , Boum Yap , Musinguzi Nicholas , Haberer Jessica E. , Martin Jeffrey N. , Hunt Peter W. , Marconi Vincent C. , Bangsberg David R. , Siedner Mark J.
Published: June 2017

Background:

The World Health Organization defines HIV virologic failure as 2 consecutive viral loads >1000 copies/mL, measured 3–6 months apart, with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort.

Setting:

The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation and monitored adherence with electronic pill bottles.

Methods:

We included participants on ART with a detectable HIV RNA viral load and who remained on the same regimen until the subsequent measurement. We fit logistic regression models with viral resuppression as the outcome of interest and both initial viral load level and average adherence as predictors of interest.

Results:

We analyzed 139 events. Median ART duration was 0.92 years, and 100% were on a nonnucleoside reverse-transcriptase inhibitor–based regimen. Viral resuppression occurred in 88% of those with initial HIV RNA <1000 copies/mL and 42% if HIV RNA was >1000 copies/mL (P <0.001). Adherence after detectable viremia predicted viral resuppression for those with HIV RNA <1000 copies/mL (P = 0.011) but was not associated with resuppression for those with HIV RNA >1000 copies/mL (P = 0.894; interaction term P = 0.077).

Conclusions:

Among patients on ART with detectable HIV RNA >1000 copies/mL who remain on the same regimen, only 42% resuppressed at next measurement, and there was no association between interval adherence and viral resuppression. These data support consideration of resistance testing to help guide management of virologic failure in resource-limited settings.
Imaging in Adult Congenital Heart Disease
Authors: Gaydos Stephanie S. , Varga-Szemes Akos , Judd Rochelle N. , Suranyi Pal , Gregg David
Published: June 2017

There has been tremendous growth in the population of adults with congenital heart disease (CHD) over the last few decades because of advances in medical care. Whereas some cases are cured during childhood, most patients instead undergo palliation, which leaves them at risk for late complications. Lifelong clinical follow-up involving serial multimodality imaging is helpful to monitor and guide the treatment of late complications. Imaging of these individuals is challenging because of their unique anatomy and therefore requires careful consideration on a case-by-case basis. Knowledge of late complications associated with various diseases and surgical palliations provides a basis for selection and interpretation of an appropriate imaging study. This review highlights the most common conditions in adult CHD and the clinical questions that imaging hopes to answer, as well as the advantages and disadvantages of available imaging modalities. We illustrate clinical scenarios and the use of noninvasive imaging modalities including echocardiography, computed tomography, and magnetic resonance imaging, as well as applications in the following CHDs: tetralogy of Fallot, transposition of the great arteries, coarctation of the aorta, shunts, functional single ventricle, and coronary anomalies.
Recurrence Risk Stratification After Preoperative Chemoradiation of Esophageal Adenocarcinoma
Authors: Xi Mian , Hallemeier Christopher L. , Merrell Kenneth W. , Liao Zhongxing , Murphy Mariela A. Blum , Ho Linus , Hofstetter Wayne L. , Mehran Reza , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Maru Dipen M. , Komaki Ritsuko , Ajani Jaffer A. , Lin Steven H.
Published: June 2017

Objective:

To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT).

Background:

Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce.

Methods:

Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients.

Results:

A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort.

Conclusions:

We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.
Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity
Authors: De Silva N. Maneka G. , Sebert Sylvain , Alves Alexessander Couto , Sovio Ulla , Das Shikta , Taal Rob , Warrington Nicole M. , Lewin Alexandra M. , Kaakinen Marika , Cousminer Diana , Thiering Elisabeth , Timpson Nicholas J. , Karhunen Ville , Bond Tom , Estivill Xavier , Lindi Virpi , Bradfield Jonathan P. , Geller Frank , Coin Lachlan J.M. , Loh Marie , Barton Sheila J. , Beilin Lawrence J. , Bisgaard Hans , Bønnelykke Klaus , Alili Rohia , Hatoum Ida J. , Schramm Katharina , Cartwright Rufus , Charles Marie-Aline , Salerno Vincenzo , Clément Karine , van Duijn Cornelia M. , Moltchanova Elena , Eriksson Johan G. , Elks Cathy , Feenstra Bjarke , Flexeder Claudia , Franks Stephen , Frayling Timothy M. , Freathy Rachel M. , Elliott Paul , Widén Elisabeth , Hakonarson Hakon , Hattersley Andrew T. , Rodriguez Alina , Banterle Marco , Heinrich Joachim , Heude Barbara , Holloway John W. , Hofman Albert , Hyppönen Elina , Inskip Hazel , Kaplan Lee M. , Hedman Asa K. , Läärä Esa , Prokisch Holger , Grallert Harald , Lakka Timo A. , Lawlor Debbie A. , Melbye Mads , Ahluwalia Tarunveer S. , Marinelli Marcella , Millwood Iona Y. , Palmer Lyle J. , Pennell Craig E. , Perry John R. , Ring Susan M. , Savolainen Markku , Stefansson Kari , Thorleifsson Gudmar , Rivadeneira Fernando , Standl Marie , Sunyer Jordi , Tiesler Carla M.T. , Uitterlinden Andre G. , Prokopenko Inga , Herzig Karl-Heinz , Smith George Davey , O'Reilly Paul , Felix Janine F. , Buxton Jessica L. , Blakemore Alexandra I.F. , Ong Ken K. , Grant Struan F.A. , Jaddoe Vincent W.V. , McCarthy Mark I. , Järvelin Marjo-Riitta
Published: June 2017

Early childhood growth patterns are associated with adult metabolic health, but the underlying mechanisms are unclear. We performed genome-wide meta-analyses and follow-up in up to 22,769 European children for six early growth phenotypes derived from longitudinal data: peak height and weight velocities, age and body mass index (BMI) at adiposity peak (AP~9 months) and rebound (AR~5-6 years). We identified four associated loci (P< 5x10−8):LEPR/LEPROTwith BMI at AP,FTOandTFAP2Bwith Age at AR andGNPDA2with BMI at AR. The observed AR-associated SNPs atFTO, TFAP2BandGNPDA2represent known adult BMI-associated variants. The common BMI at AP associated variant atLEPR/LEPROTwas not associated with adult BMI but was associated withLEPROTgene expression levels, especially in subcutaneous fat (P<2x10−51). We identify strong positive genetic correlations between early growth and later adiposity traits, and analysis of the full discovery stage results for Age at AR revealed enrichment for insulin-like growth factor 1 (IGF-1) signaling and apolipoprotein pathways. This genome-wide association study suggests mechanistic links between early childhood growth and adiposity in later childhood and adulthood, highlighting these early growth phenotypes as potential targets for the prevention of obesity.
Thermodynamic Integration in 3n Dimensions without Biases or Alchemy for Protein Interactions
Authors: Chen Liao Y
Published: June 2017

Thermodynamic integration (TI), a powerful formalism for computing the Gibbs free energy, has been implemented for many biophysical processes characterized by one-dimensional order parameters with alchemical schemes that require delicate human efforts to choose/design biasing potentials for sampling the desired biophysical events and to remove their artifactitious consequences afterwards. Theoretically, an alchemical scheme is exact but practically, it causes error amplification. Small relative errors in the interaction parameters can be amplified many times in their propagation into the computed free energy [due to subtraction of similar numbers such as (105 ± 5) − (100 ± 5) = 5 ± 7], which would render the results significantly less accurate than the input interaction parameters. In this paper, we present an unsophisticated implementation of TI in 3n dimensions (3nD) (n=1,2,3…) without alchemy or biasing potentials. In TI3nD, the errors in the interaction parameters will not be amplified and human efforts are not required to design biasing potentials that generate unphysical consequences. Using TI3nD, we computed the standard free energies of three protein complexes: trometamol in Salmonella effector SpvD (n=1), biotin in avidin (n=2), and Colicin E9 endonuclease with cognate immunity protein Im9 (n=3) and the hydration energies of ten biologically relevant compounds (n=1 for water, acetamide, urea, glycerol, trometamol, ammonium and n=2 for erythritol, 1,3-propanediol, xylitol, biotin). The computed results all agree with available experimental data. Each of the 13 computations is accomplishable within two (for a hydration problem) to ten (for the protein-recognition problem) days on an inexpensive workstation (two Xeon E5-2665 2.4GHz CPUs and one nVidia P5000 GPU).
RNA-mediated Genomic Arrangements in Mammalian Cells
Authors: Gupta Sachin Kumar , Luo Liming , Yen Laising
Published: June 2017

One of the hallmarks of cancer is the formation of oncogenic fusion genes as a result of chromosomal translocations. Fusion genes are presumed to occur prior to fusion RNA expression. However, studies have reported the presence of fusion RNAs in individuals who were negative for chromosomal translocations. These observations give rise to “the cart before the horse” hypothesis, in which fusion RNA precedes the fusion gene and guides the genomic rearrangements that ultimately result in gene fusions. Yet RNA-mediated genomic rearrangement in mammalian cells has never been demonstrated. Here we provide evidence that expression of a chimeric RNA drives formation of a specified gene fusion via genomic rearrangement in mammalian cells. The process is (1) specified by the sequence of chimeric RNA involved, (2) facilitated by physiological hormone levels, (3) permissible regardless of intra-chromosomal (TMPRSS2-ERG) or inter-chromosomal (TMPRSS2-ETV1) fusion, and (4) can occur in normal cells prior to malignant transformation. We demonstrate that, contrary to “the cart before the horse” model, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion, and that this disparity can be explained by transcriptional conflict. Furthermore, we identified an endogenous RNAAZI1that acts as the ‘initiator’ RNA to induceTMPRSS2-ERGfusion. RNA-driven gene fusion demonstrated in this report provides important insight in early disease mechanism, and could have fundamental implications in the biology of mammalian genome stability, as well as gene editing technology via mechanisms native to mammalian cells.
ProbAnnoWeb and ProbAnnoPy: probabilistic annotation and gap-filling of metabolic reconstructions
Authors: King Brendan , Farrah Terry , Richards Matthew , Mundy Michael , Simeonidis Evangelos , Price Nathan D.
Published: June 2017

Gap-filling is a necessary step to produce quality genome-scale metabolic reconstructions capable of flux-balance simulation. Most available gap-filling tools use an organism-agnostic approach, where reactions are selected from a database to fill gaps without consideration of the target organism. Conversely, our likelihood based gap-filling with probabilistic annotations selects candidate reactions based on a likelihood score derived specifically from the target organism’s genome. Here, we present two new implementations of probabilistic annotation and likelihood based gap-filling: a web service called ProbAnnoWeb, and a standalone python package called ProbAnnoPy.

Availability and Implementation

Our tools are available as a web service with no installation needed (ProbAnnoWeb), available athttp://probannoweb.systemsbiology.net, and as a local python package implementation (ProbAnnoPy), available for download athttp://github.com/PriceLab/probannopy.

Contact

http://Evangelos.Simeonidis@systemsbiology.org;http://Nathan.Price@systemsbiology.org
Weighted integration of short term memory and sensory signals in the oculomotor system
Authors: Deravet Nicolas , Blohm Gunnar , Orban de Xivry Jean-Jacques , Lefèvre Philippe
Published: June 2017

Oculomotor behaviors integrate sensory and prior information to overcome sensory-motor delays and noise. After much debate about this process, reliability-based integration has recently been proposed and several models of smooth pursuit now include recurrent Bayesian integration or Kalman filtering. However, there is a lack of behavioral evidence supporting these theoretical predictions.

Here, we independently manipulated the reliability of visual and prior information in a smooth pursuit task. Our results show that both smooth pursuit eye velocity and catch-up saccade amplitude were modulated by visual and prior information reliability.

We interpret these findings as the continuous reliability-based integration of a short-term memory of target motion with visual information, which support modelling work. Furthermore, we suggest that saccadic and pursuit systems share this short-term memory. We propose that this short-term memory of target motion is quickly built and continuously updated, and constitutes a general building-block present in all sensorimotor systems.
Comparative transcriptomics provides insight into the evolution of cold response in Pooideae
Authors: Grønvold Lars , Schubert Marian , Sandve Simen R. , Fjellheim Siri , Hvidsten Torgeir R.
Published: June 2017

Background

Understanding how complex traits evolve through adaptive changes in gene regulation remains a major challenge in evolutionary biology. Over the last ~50 million years, Earth has experienced climate cooling and ancestrally tropical plants have adapted to expanding temperate environments. The grass subfamily Pooideae dominates the grass flora of the temperate regions, but conserved cold-response genes that might have played a role in the cold adaptation to temperate climate remain unidentified.

Results

To establish if molecular responses to cold are conserved throughout the Pooideae phylogeny, we assembled the transcriptomes of five species spanning early to later diverging lineages, and compared short-and long-term cold response in orthologous genes based on gene expression data. We confirmed that most genes previously identified as cold responsive in barley also responded to cold in our barley experiment. Interestingly, comparing cold response across the lineages using 8633 high confidence ortholog groups revealed that nearly half of all cold responsive genes were species specific and more closely related species did not share higher numbers of cold responsive genes than more distantly related species. Also, the previously identified cold-responsive barley genes displayed low conservation of cold response across species. Nonetheless, more genes than expected by chance shared cold response, both based on previously studied genes and based on the high confidence ortholog groups. Noticeable, all five species shared short-term cold response in nine general stress genes as well as the ability to down-regulate the photosynthetic machinery during cold temperatures.

Conclusions

We observed widespread lineage specific cold response in genes with conserved sequence across the Pooideae phylogeny. This is consistent with phylogenetic dating and historic temperature data which suggest that selection pressure resulting from dramatic global cooling must have acted on already diverged lineages. To what degree lineage specific evolution acted primarily through gain or loss of cold response remains unclear, however, phylogeny-wide conservation of certain genes and processes indicated that the last common ancestor may have possessed some cold response.
Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
Authors: Mol Milsee , Kosey Dipali , Bopanna Ramanamurthy , Singh Shailza
Published: June 2017

Stochastic variations in the transcription factor target gene network influences the dynamics of protein levels. The mathematical model built, here, is useful to study the cytokine response and the resulting dynamical patterns in leishmaniasis. The fluctuations produced affect the expression rate of its target in the regulatory synthetic circuit designed by means of a negative feedback loop insertion. Thus, the faster the response time, smaller is the fluctuation of the system observed and it can be justified that the TFTG network embedded can be understood with the recurring dynamics of the designed synthetic circuit.

List of Abbreviations

TF

transcription factor

PPARα

peroxisome proliferator-activated receptor-

FAs

fatty acids

DCs

dendritic cells

TFTG network

Transcription Factor Target Gene Network

IFNg

interferon g

VL

visceral leishmaniasis

CL

cutaneous leishmaniasis

G-MCF

granulocyte macrophage colony-stimulating factor

IL

interleukin

PKC

Protein Kinase C

PBC

Periodic boundary condition

NPT

Normal Pressure temperature

NVT

Normal Volume Temperature

MD

Molecular Dynamics

RMSD

root mean square deviation

RMSF

root mean square fluctuation

LB

Luria Berttini

I

Infection

CT

Chimeric PKC

CTI

Chimeric PKC + Infection

CTM

Chimeric PKC + Miltefosine

CTIM

Chimeric PKC + Infection + Miltefosine

CC

Closeness centrality

IPTG

Isopropyl β-D-1-thiogalactopyranoside
Expanding discovery from cancer genomes by integrating protein network analyses with in vivo tumorigenesis assays
Authors: Horn Heiko , Lawrence Michael S. , Chouinard Candace R. , Shrestha Yashaswi , Hu Jessica Xin , Worstell Elizabeth , Shea Emily , Ilic Nina , Kim Eejung , Kamburov Atanas , Kashani Alireza , Hahn William C. , Campbell Joshua D. , Boehm Jesse S. , Getz Gad , Lage Kasper
Published: June 2017

Approaches that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes, but are challenging to validate at scale and their predictive value remains unclear. We developed a robust statistic (NetSig) that integrates protein interaction networks and data from 4,742 tumor exomes and used it to accurately classify known driver genes in 60% of tested tumor types and to predict 62 new candidates. We designed a quantitative experimental framework to compare thein vivotumorigenic potential of NetSig candidates, known oncogenes and random genes in mice showing that NetSig candidates induce tumors at rates comparable to known oncogenes and 10-fold higher than random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2andTFDP2) are significantly amplified. Overall, we illustrate a scalable integrated computational and experimental workflow to expand discovery from cancer genomes.
Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates
Authors: McCall Patrick M. , Srivastava Samanvaya , Perry Sarah L. , Kovar David R. , Gardel Margaret L. , Tirrell Matthew V.
Published: June 2017

Biomolecules exist and function in cellular micro-environments that control their spatial organization, local concentration and biochemical reactivity. Due to the complexity of native cytoplasm, the development of artificial bioreactors and cellular mimics to compartmentalize, concentrate and control the local physicochemical properties is of great interest. Here, we employ self-assembling polypeptide coacervates to explore the partitioning of the ubiquitous cytoskeletal protein actin into liquid polymer-rich droplets. We find that actin spontaneously partitions into coacervate droplets and is enriched by up to ≈30-fold. Actin polymerizes into micrometer-long filaments and, in contrast to the globular protein BSA, these filaments localize predominately to the droplet periphery. We observe up to a 50-fold enhancement in the actin filament assembly rate inside coacervate droplets, consistent with the enrichment of actin within the coacervate phase. Together these results suggest that coacervates can serve as a versatile platform in which to localize and enrich biomolecules to study their reactivity in physiological environments.

SIGNIFICANCE STATEMENT

Living cells harbor many protein-rich membrane-less organelles, the biological functions of which are defined by compartment composition and properties. Significant differences between the physico-chemical properties of these crowded compartments and the dilute solutions in which biochemical reactions are traditionally studied pose a major challenge for understanding regulation of organelle composition and component activity. Here, we report the spontaneous partitioning and accelerated polymerization of the cytoskeletal protein actin inside model polypeptide coacervates as a proof-of-concept demonstration of coacervates as bioreactors for studying biomolecular reactions in cell-like environments. Our work introduces exciting avenues for the use of synthetic polymers to control the physical and biological properties of bioreactors in vitro, enabling studies of biochemical reactions in cell-like micro-environments.
A Positive Feedback Loop Ensures Propagation of ROS Production and JNK Signaling ThroughoutDrosophilaTissue Regeneration
Authors: Khan Sumbul Jawed , Nayab Fatima Abidi Syeda , Skinner Andrea , Tian Yuan , Smith-Bolton Rachel K.
Published: June 2017

Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed wholegenome mRNAseq of actively regenerating tissue from damagedDrosophilawing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescent labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the genemoladietz(mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulatesmolexpression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by wholegenome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.

Author summary

Regenerating tissue must initiate the signaling that drives regenerative growth, and then sustain that signaling long enough for regeneration to complete.Drosophilaimaginal discs, the epithelial structures in the larva that will form the adult animal during metamorphosis, have been an important model system for tissue repair and regeneration for over 60 years. Here we show that damage-induced JNK signaling leads to the upregulation of a gene calledmoladietz, which encodes a co-factor for an enzyme, NADPH dual oxidase (DUOX), that generates reactive oxygen species (ROS), a key tissue-damage signal. High expression ofmoladietzinduces continuous production of ROS in the regenerating tissue. The sustained production of ROS then continues to activate JNK signaling throughout the course of regeneration, ensuring maximal tissue regrowth.
JQ1 reduces Epstein-Barr virus-associated lymphoproliferative disease in mice without sustained oncogene repression
Authors: He Amanda , Miranda JJ L.
Published: June 2017

Small molecule inhibitors of bromodomain and extra-terminal (BET) proteins are seeing increased investigation in clinical trials for treatment of hematological malignancies. These compounds also repress oncogene expression driven by the human Epstein-Barr virus (EBV) in cell culture. We therefore tested the efficacy of the prototypical BET inhibitor JQ1 against a mouse xenograft model of post-transplantation lymphoproliferative disorder. JQ1 potently inhibits growth of lymphoblastoid cell lines (LCLs) in culture at low nM concentrations. Growth of other cell lines with similar EBV type III latency transcription programs is comparably inhibited. JQ1 also slows tumor development of an LCL xenograft in immunocompromised mice, but oncogene repression is not observed in endpoint biopsies. We find reduction of EBV-associated lymphoproliferative disease in an animal model encouraging of further studies.
Crystal structure of 4-[(3-methylbut-3-enoyl)oxy]phenyl 4-n-hexyloxybenzoate
Authors: Kuz'mina Lyudmila G. , Konstantinov Ivan I. , Churakov Andrei V. , Navasardyan Mger A.
Published: June 2017

The structure of the title compound, C23H26O5or CH2=C(CH3)—C(O)O—C6H4—O(O)C—C6H4—OC6H13, has been determined. The molecule is non-planar and the dihedral angle between the phenyl rings is 50.72 (4)°. The crystal packing differs from those typical for mesogenic compounds. Only a weak directional interaction of the C—H...O type combines molecules in endless chains running along theaaxis.
Crystal structures of the three closely related compounds: bis[(1H-tetrazol-5-yl)methyl]nitramide, triaminoguanidinium 5-({[(1H-tetrazol-5-yl)methyl](nitro)amino}methyl)tetrazol-1-ide, and diammonium bis[(tetrazol-1-id-5-yl)methyl]nitramide monohydrate
Authors: Mitchell Lauren A. , Imler Gregory H. , Parrish Damon A. , Deschamps Jeffrey R. , Leonard Philip W. , Chavez David E.
Published: June 2017

In the molecule of neutral bis[(1H-tetrazol-5-yl)methyl]nitramide, (I), C4H6N10O2, there are two intramolecular N—H...O hydrogen bonds. In the crystal, N—H...N hydrogen bonds link molecules, forming a two-dimensional network parallel to (-201) and weak C—H...O, C—H...N hydrogen bonds, and intermolecular π–π stacking completes the three-dimensional network. The anion in the molecular salt, triaminoguanidinium 5-({[(1H-tetrazol-5-yl)methyl](nitro)amino}methyl)tetrazol-1-ide, (II), CH9N6+·C4H5N10O2−, displays intramolecular π–π stacking and in the crystal, N—H...N and N—H...O hydrogen bonds link the components of the structure, forming a three-dimensional network. In the crystal of diammonium bis[(tetrazol-1-id-5-yl)methyl]nitramide monohydrate, (III), 2NH4+·C4H4N10O22−·H2O, O—H...N, N—H...N, and N—H...O hydrogen bonds link the components of the structure into a three-dimensional network. In addition, there is intermolecular π–π stacking. In all three structures, the central N atom of the nitramide is mainlysp2-hybridized. Bond lengths indicate delocalization of charges on the tetrazole rings for all three compounds. Compound (II) was found to be a non-merohedral twin and was solved and refined in the major component.
Students’ perceived impact of learning and satisfaction with blogs
Authors: Ifinedo Princely
Published: June 2017

Purpose

Students’ use of blogging tools in learning environments is increasing across the world. The purpose of this paper is to contribute to the literature by examining the effects of relevant factors that engender satisfaction and positive impacts of the technology for learning.

Design/methodology/approach

A cross-sectional survey was used to collect data from 108 undergraduate students taking a management information systems course. The partial least squares technique of structural equation modelling was used to test the reliability and validity of the data, and the study’s hypothesised relationships or paths.

Findings

This study revealed that perceived enjoyment, compatibility, usefulness, ease of use, and confirmation have positive influence on students’ satisfaction with blog use. Perceived enjoyment had the greatest influence on students’ satisfaction with blog use for learning. Perceived impact on learning was positively influenced by perceived ease of use, enjoyment, and satisfaction.

Originality/value

A limited amount of empirical research has focussed on students’ perceptions of satisfaction and perceived impact on learning through blog use in higher educational contexts. This study adds to the growing literature in this area of study.
Interpreting variation to advance predictive restoration science
Authors: Brudvig Lars A. , Barak Rebecca S. , Bauer Jonathan T. , Caughlin T. Trevor , Laughlin Daniel C. , Larios Loralee , Matthews Jeffrey W. , Stuble Katharine L. , Turley Nash E. , Zirbel Chad R.
Published: June 2017

Ecological restoration is a global priority that holds great potential for benefiting natural ecosystems, but restoration outcomes are notoriously unpredictable. Resolving this unpredictability represents a major, but critical challenge to the science of restoration ecology.

In an effort to move restoration ecology toward a more predictive science, we consider the key issue of variability. Typically, restoration outcomes vary relative to goals (i.e. reference or desired future conditions) and with respect to the outcomes of other restoration efforts. The field of restoration ecology has largely considered only this first type of variation, often focusing on an oversimplified success vs. failure dichotomy. The causes of variation, particularly among restoration efforts, remain poorly understood for most systems.

Variation associated with restoration outcomes is a consequence of how, where and when restoration is conducted; variation is also influenced by how the outcome of restoration is measured. We propose that variation should decrease with the number of factors constraining restoration and increase with the specificity of the goal. When factors (e.g. harsh environmental conditions, limited species reintroductions) preclude most species, little variation will exist among restorations, particularly when goals are associated with metrics such as physical structure, where species may be broadly interchangeable. Conversely, when few constraints to species membership exist, substantial variation may result and this will be most pronounced when restoration is assessed by metrics such as taxonomic composition.

Synthesis and applications. The variability we observe during restoration results from both restoration context (how, where and when restoration is conducted) and how we evaluate restoration outcomes. To advance the predictive capacity of restoration, we outline a research agenda that considers metrics of restoration outcomes, the drivers of variation among existing restoration efforts, experiments to quantify and understand variation in restoration outcomes, and the development of models to organise, interpret and forecast restoration outcomes.
Effects of uranium concentration on microbial community structure and functional potential
Authors: Sutcliffe Brodie , Chariton Anthony A. , Harford Andrew J. , Hose Grant C. , Greenfield Paul , Elbourne Liam D. H. , Oytam Yalchin , Stephenson Sarah , Midgley David J. , Paulsen Ian T.
Published: June 2017

Located in the Northern Territory of Australia, Ranger uranium mine is directly adjacent to the UNESCO World Heritage listed Kakadu National Park, with rehabilitation targets needed to ensure the site can be incorporated into the park following the mine's closure in 2026. This study aimed to understand the impact of uranium concentration on microbial communities, in order to identify and describe potential breakpoints in microbial ecosystem services. This is the first study to report in situ deployment of uranium‐spiked sediments along a concentration gradient (0–4000 mg U kg−1), with the study design maximising the advantages of both field surveys and laboratory manipulative studies. Changes to microbial communities were characterised through the use of amplicon and shotgun metagenomic next‐generation sequencing. Significant changes to taxonomic and functional community assembly occurred at a concentration of 1500 mg U kg−1 sediment and above. At uranium concentrations of ≥ 1500 mg U kg−1, genes associated with methanogenic consortia and processes increased in relative abundance, while numerous significant changes were also seen in the relative abundances of genes involved in nitrogen cycling. Such alterations in carbon and nitrogen cycling pathways suggest that taxonomic and functional changes to microbial communities may result in changes in ecosystem processes and resilience.
Partial characterisation of a bacteriocin produced by Leuconostoc mesenteroides A11 and evaluation of bacteriocin production using whey as culture medium
Authors: Okuda Nelly K , Tulini Fabricio L , Winkëlstroter Lizziane K , De Martinis Elaine Cristina P
Published: June 2017

This study aimed to partially purify and characterise the bacteriocin produced by Leuconostoc mesenteroides A11 and to evaluate the bacteriocin production in whey at different concentrations and temperatures (30 and 25 °C). The partially purified bacteriocin was obtained by chromatography and analysed by electrophoresis. Thus, the molecular weight of the bacteriocin was estimated by electrophoresis, ranging from 3.5 to 8.5 kDa. Leu conostoc mesenteroides A11 produced bacteriocins in all concentrations of whey and temperatures evaluated, indicating that it would be feasible to employ low whey concentrations and room temperature for the production of bacteriocins, thereby reducing processing costs.
Production of proteinaceous antifungal substances from Lactobacillus plantarum ALAC‐4 isolated from Inner Mongolian traditional fermented dairy food
Authors: Chen Zhongjun , Li Xiaoting , Gao Hechen
Published: June 2017

Lactic acid bacteria are of interest to the food industry due to their antimicrobial properties. In this study, five strains of Lactobacillus plantarum were isolated from traditional fermented dairy food in Inner Mongolia; the strains displayed antifungal characteristics. Lactobacillus plantarum ALAC‐4 was selected for further study due to its strong inhibitory effect on fungal development. The antifungal substances produced by L. plantarum ALAC‐4 were characterised based on treatments with heat, pH and enzymes. The antifungal metabolites were analysed using gel‐filtration chromatography and SDS‐PAGE. The results showed that the antifungal substances were heat stable and active against most of the tested fungi, and maximal activity was observed at pH values from 4.0 to 4.5. The antifungal activity was decreased by protease treatments, which indicated the proteinaceous nature of the antifungal substances. Enhanced antifungal activity occurred after 28 h of incubation in de Man, Rogosa, Sharpe (MRS) broth with a 4% inoculum level at 34 °C and initial pH of 7.0, which resulted in an increase from baseline data. The molecular mass of the antifungal substance determined by SDS‐PAGE was approximately 40.32 kDa. This study demonstrated that L. plantarum ALAC‐4 produces a peptide with a remarkable antifungal activity, which can be potentially used as a biopreservative in dairy products.
Association between inadequate antenatal care utilisation and severe perinatal and maternal morbidity: an analysis in the PreCARE cohort
Authors: Linard M , Blondel B , Estellat C , Deneux‐Tharaux C , Luton D , Oury JF , Schmitz T , Mandelbrot L , Azria E ,   the PreCARE study group
Published: June 2017

Objective

Because the effectiveness of antenatal care in reducing pregnancy complications is still discussed despite widespread recommendations of its use, we sought to assess the association between utilisation of recommended antenatal care and severe maternal (SMM) and perinatal morbidity (SPM).

Design

Prospective cohort study.

Setting

Four maternity units around Paris in 2010–2012.

Sample

9117 women with singleton pregnancies.

Methods

Logistic regression models adjusted for maternal social, demographic and medical characteristics.

Main outcome measures

Antenatal care utilisation was assessed by: (1) initiation of care after 14 weeks, (2) < 50% of recommended visits made, according to gestational age, (3) absence of the first, second or third trimester ultrasounds, (4) two modified Adequacy of Prenatal Care Utilisation indexes, combining these components. The two main outcomes were composite variables of SMM and SPM.

Results

According to the modified Adequacy of Prenatal Care Utilisation index, 34.6% of women had inadequate antenatal care utilisation; the incidence of severe maternal morbidity (SMM) was 2.9% and severe perinatal morbidity (SPM) 5.5%. A percentage of recommended visits below 50% (2.6% of women) was associated with SMM [adjusted odds ratio (OR) 2.40 (1.38–4.17)] and SPM [aOR 2.27 (1.43–3.59)]. Late initiation of care (17.0% of women) was not associated with SMM or SPM. Failure to undergo the recommended ultrasounds (16, 17 and 22% of women) was associated with SPM. Inadequate antenatal care utilisation according to the index was associated with SPM [aOR 1.37 (1.05–1.80)].

Conclusion

Inadequate antenatal care utilisation is associated with SMM and SPM, to degrees that vary with the component of care and the outcome considered.

Tweetable abstract

Inadequate antenatal care utilisation is associated with severe maternal and perinatal morbidity.
Uptake in sympathetic ganglia on 68Ga‐PSMA‐HBED PET/CT: A potential pitfall in scan interpretation
Authors: Kanthan Gowri L , Hsiao Edward , Vu Dzung , Schembri Geoffrey Paul
Published: June 2017

Introduction

The aim of this study was to assess the frequency of PSMA‐HBED uptake in coeliac and stellate ganglia in patients presenting for PSMA‐HBED PET/CT scan.

Methods

Prostate‐specific membrane antigen‐HBED PET/CT scans of 100 consecutive patients were analysed. Coeliac and stellate ganglia were identified by their anatomical location. PSMA‐HBED uptake in these ganglia was recorded as either present or absent. If present, the SUVmax value for each ganglion was measured and compared to SUVmax of mediastinal blood pool.

Results

Of the 100 patients, 45 had PSMA‐HBED uptake in the right coeliac ganglion and 81 had PSMA‐HBED uptake in the left coeliac ganglion. The mean SUVmax for the right coeliac ganglion was 2.6 (range 1.2–4.0) and for the left, 2.7 (range 1.2–6.5). An SUVmax 1.5 times greater than that of mediastinal blood pool activity was found in 25 of right and 47 of left coeliac ganglia. Stellate ganglion uptake of PSMA‐HBED was identified in 54 of right and 74 of left stellate ganglia. The mean SUVmax for the right and left stellate ganglia were 2.2 (range 1.6–3.6) and 2.4 (range 1.4–4.2) respectively. An SUVmax 1.5 times greater than that of mediastinal blood pool activity was found in 12 of right and 32 of left coeliac ganglia.

Conclusion

Uptake in coeliac and stellate ganglia is a frequent finding on PSMA‐HBED PET/CT imaging. Often this uptake can be sufficiently high to cause potential diagnostic confusion. It is important to be aware of this physiologic uptake to avoid incorrect diagnosis of metastatic prostate carcinoma.
Very brief physician advice and supplemental proactive telephone calls to promote smoking reduction and cessation in Chinese male smokers with no intention to quit: a randomized trial
Authors: Wu Lei , He Yao , Jiang Bin , Zhang Di , Tian Hui , Zuo Fang , Lam Tai Hing
Published: June 2017

Background and aims

There is inconsistent evidence that behavioural support to promote smoking reduction is effective at increasing smoking cessation. We examined the effectiveness of brief physician advice together with four very brief telephone calls in promoting smoking cessation among Chinese men via reduction compared with equivalent advice on diet and exercise.

Design

A two‐group pragmatic randomized controlled trial.

Participants and Setting

Male patients attending the Endocrinology and Acupuncture out‐patient clinics of a general hospital in Beijing, China.

Intervention and comparators

Physicians advised participants allocated to the smoking‐reduction intervention (SRI, n = 181) group to reduce smoking to at least half of their current consumption within 1 month at baseline. At follow‐up, a telephone counsellor repeated this advice if the participant had not reduced their cigarette consumption. Participants who had reduced consumption were encouraged to quit smoking. Physicians gave participants in the exercise and diet advice (EDA, n = 188) control group brief advice about physical activity and healthy diet at baseline, and a telephone counsellor reinforced this at each follow‐up interview. Both groups had one face‐to‐face interview at baseline plus five telephone interviews and interventions (approximately 1 minute each) at 1 week and 1‐, 3‐, 6‐ and 12‐month follow‐up.

Measurements

The primary outcome was self‐reported 6‐month prolonged abstinence rate at 12‐month follow‐up interview.

Findings

By intention‐to‐treat, the self‐reported 6‐month prolonged abstinence rate at 12‐month follow‐up in the SRI groups (19 quitters, 15.7%) was higher, but not significantly, than the EDA control group (10 quitters, 7.8%), and the adjusted odds ratio (OR) and 95% confidence interval (CI) was 2.26 (0.97–5.26), P = 0.062. The self‐reported 7‐day point prevalence quit rate (secondary outcome) in the SRI group was significantly higher than the control group at each follow‐up interview (at 12‐month follow‐up: 13.3 versus 6.9%, OR (95% CI) = 2.09 (1.01, 4.34), P = 0.049).

Conclusions

A very brief, proactive and low‐cost smoking‐reduction intervention without medications for Chinese male smokers with no intention to quit appears to increase smoking abstinence.