bluuebunny/crossref_metadata_2025 huggingface dataset:
AGILE: an assembled genome mining pipeline
Authors: Hughes Graham M , Teeling Emma C
Published: September 2018

A number of limiting factors mean that traditional genome annotation tools either fail or perform sub-optimally when trying to detect coding sequences in poor quality genome assemblies/genome reports. This means that potentially useful data is accessible only to those with specific skills and expertise in assembly and annotation. We present an Assembled-Genome mIning pipeLinE (AGILE) written in Perl that combines bioinformatics tools with a number of steps to overcome the limitations imposed by such assemblies when applied to highly fragmented genomes. Our methodology uses user-specified query genes from a closely related species to mine and annotate coding sequences that would traditionally be missed by standard annotation packages. Despite a focus on mammalian genomes, the generalized implementation means that it may be applied to any genome assembly, providing a means for non-specialists to gather gene sequences for downstream analyses.

Availability and implementation

Source code and associated files are available at: https://github.com/batlabucd/GenomeMining and https://bitbucket.org/BatlabUCD/genomemining/src. Singularity and Virtual Box images available at https://figshare.com/s/a0004bf93dc43484b0c0.

Supplementary information

Supplementary data are available at Bioinformatics online.
Molecular differential diagnosis of uterine leiomyomas and leiomyosarcomas
Authors: Mas Aymara , Simón Carlos
Published: September 2018

Uterine leiomyomas (LM) and leiomyosarcomas (LMS) are considered biologically unrelated tumors due to their cytogenetic and molecular disparity. Yet, these tumors share morphological and molecular characteristics that cannot be differentiated through current clinical diagnostic tests, and thus cannot be definitively classified as benign or malignant until surgery. Newer approaches are needed for the identification of these tumors, as has been done for other tissues. The application of next generation sequencing enables the detection of new mutations that, when coupled to machine learning bioinformatic tools, advances our understanding of chromosomal instability. These approaches in the context of LM and LMS could allow the discovery of genetic variants and possible genomic markers. Additionally, the potential clinical utility of circulating cell-free tumor DNA could revolutionize the noninvasive detection and monitoring of these tumors. Here, we seek to provide a perspective on the molecular background of LM and LMS, recognizing their distinct molecular features that may lead to improved diagnosis and personalized treatments, which would have a measurable impact on women's reproductive health.
The Herschel-PACS North Ecliptic Pole Survey
Authors: Pearson Chris , Barrufet Laia , Campos Varillas Maria del Carmen , Serjeant Stephen , Clements David L , Goto Tomotsugu , Im Myungshin , Jeong Woong-Seob , Kim Seong Jin , Matsuhara Hideo , Sedgwick Chris , Valtchanov Ivan
Published: September 2018

A detailed analysis of Herschel/Photoconductor Array Camera and Spectrometer (PACS) observations at the North Ecliptic Pole is presented. High-quality maps, covering an area of 0.44 deg2, are produced and then used to derive potential candidate source lists. A rigorous quality-control pipeline has been used to create final legacy catalogues in the PACS Green 100 μm and Red 160 μm bands, containing 1384 and 630 sources respectively. These catalogues reach to more than twice the depth of the current archival Herschel/PACS Point Source Catalogue, detecting 400 and 270 more sources in the short- and long-wavelength bands, respectively. Galaxy source counts are constructed that extend down to flux densities of 6 mJy and 19 mJy (50% completeness) in the Green 100 μm and Red 160 μm bands, respectively. These source counts are consistent with previously published PACS number counts in other fields across the sky. The source counts are then compared with a galaxy evolution model which identifies a population of luminous infrared galaxies as responsible for the bulk of the galaxy evolution over the flux range (5–100 mJy) spanned by the observed counts, contributing approximate fractions of 50% and 60% to the cosmic infrared background at 100 μm and 160 μm, respectively.
Genomic, transcriptomic, and structural analysis ofPseudomonasvirus PA5oct highlights the molecular complexity among Jumbo phages
Authors: Danis-Wlodarczyk Katarzyna , Blasdel Bob G. , Jang Ho Bin , Vandenheuvel Dieter , Noben Jean-Paul , Drulis-Kawa Zuzanna , Lavigne Rob
Published: September 2018

Pseudomonasvirus PA5oct has a large, linear, double-stranded DNA genome (287,182 bp) and is related toEscherichiaphages 121Q/PBECO 4,Klebsiellaphage vB_KleM-RaK2,Klebsiellaphage K64-1, andCronobacterphage vB_CsaM_GAP32. A protein-sharing network analysis highlights the conserved core genes within this clade. Combining genome, RNAseq and mass spectrometry analyses of its virion proteins allowed us to accurately identify genes and elucidate regulatory elements for this phage (ncRNAs, tRNAs and promoter elements). In total PA5oct encodes 462 CDS (compared to 345in silicopredicted genes using automated annotation pipelines), of which 25.32%, have been identified as virion-associated based on ESI-MS/MS. The RNAseq-based temporal genome organization suggests a gradual take-over by viral transcripts from 21%, 69%, and 92% at 5, 15 and 25 min after infection, respectively. Like many large phages, PA5oct is not organized into contiguous regions of temporal transcription. However, although the temporal regulation of the PA5oct genome expression reveals specific genome clusters expressed in early and late infection, many genes encoding experimentally observed structural proteins surprisingly appear to remain almost untranscribed throughout the infection cycle. Within the host, operons associated with elements of a cryptic Pf1-like prophage are upregulated, as are operons responsible for Psl exopolysaccharide (pslE-J) and periplasmic nitrate reductase (napA-F) production. The characterization described here represents a crucial step towards understanding the genomic complexity as well as molecular diversity of jumbo viruses.
Microinjection into theCaenorhabditis elegansembryo using an uncoated glass needle enables cell lineage visualization and reveals cell-non-autonomous adhesion control
Authors: Kikuchi Yohei , Kimura Akatsuki
Published: September 2018

Microinjection is a useful method in cell biology, with which exogenous substances are introduced into a cell in a location- and time-specific manner. TheCaenorhabditis elegansembryo is an important model system for cell and developmental biology. Applying microinjection to theC. elegansembryo had been difficult due to the rigid eggshell surrounding the embryo. In 2013, microinjection method using a carbon-coated quartz needle for theC. elegansembryo was reported. To prepare the needle, unfortunately, special equipment is required and thus a limited number of researchers can use this method. In this study, we established a method for the microinjection of drugs, dyes, and microbeads into theC. elegansembryo using an uncoated glass needle that can be produced in a general laboratory. This method enabled us to easily detect cell lineage up to adult stages by injecting a fluorescent dye into a blastomere. We also found a cell-non-autonomous control mechanism of cell adhesion; specifically, the injection of an actin inhibitor into one cell at the 2-cell stage enhanced adhesion between daughter cells of the other cell. Our microinjection method is expected to be used for broad studies and could facilitate various discoveries usingC. elegans.
Differential requirement of MED14 and UVH6 for heterochromatin transcription upon destabilization of silencing
Authors: Bourguet Pierre , Bossoreille Stève de , López-González Leticia , Pouch-Pélissier Marie-Noëlle , Gómez-Zambrano Ángeles , Devert Anthony , Pélissier Thierry , Pogorelcnik Romain , Vaillant Isabelle , Mathieu Olivier
Published: September 2018

Constitutive heterochromatin is commonly associated with high levels of repressive epigenetic marks and is stably maintained transcriptionally silent by the concerted action of different, yet convergent, silencing pathways. Reactivation of heterochromatin transcription is generally associated with alterations in levels of these epigenetic marks. However, in mutants for particular epigenetic regulators, or upon particular environmental changes such as heat stress, heterochromatin-associated silencing is destabilized without noticeable changes in epigenetic marks. This suggests that transcription can occur in a non-permissive chromatin context, yet the factors involved remain poorly known. Here, we show that heat stress-induced transcription of heterochromatin depends on the TFIIH component UVH6 and the Mediator subunit MED14. Mutants for these two factors exhibit hypersensitivity to heat stress, and under these conditions, UVH6 and MED14 are required for transcription of a high number of loci. We further show that MED14, but not UVH6, is required for transcription when heterochromatin silencing is destabilized in the absence of stress. In this case, MED14 requires proper chromatin patterns of repressive epigenetic marks for its function. We also uncover that MED14 regulates non-CG DNA methylation at a subset of RNA-directed DNA methylation target loci. These findings provide insight into the control of heterochromatin transcription upon silencing destabilization and identify MED14 as a regulator of DNA methylation.
Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent pathway of apoptosis
Authors: Tanaka Hideaki , Okazaki Tomohiko , Yokota Mutsumi , Koike Masato , Okada Yasushi , Fujiki Yukio , Gotoh Yukiko
Published: September 2018

Summary Statements

We unveil a previously unrecognized role of peroxisomes in the regulation of mitochondrial fission-fusion dynamics, mitochondrion-dependent caspase activation, and cellular apoptosis.

Peroxisomes cooperate with mitochondria in the performance of cellular metabolic functions such as fatty acid oxidation and maintenance of redox homeostasis. Whether peroxisomes also regulate mitochondrial fission-fusion dynamics or mitochondrion-dependent apoptosis has remained unclear, however. We now show that genetic ablation of the peroxins Pex3 or Pex5, which are essential for peroxisome biogenesis, resulted in mitochondrial fragmentation in mouse embryonic fibroblasts (MEFs) in a manner dependent on dynamin-related protein 1 (Drp1). Conversely, treatment with 4-phenylbutyric acid, an inducer of peroxisome proliferation, resulted in mitochondrial elongation in wild-type MEFs, but not in Pex3-deficient MEFs. We further found that peroxisome deficiency increased the levels of cytosolic cytochrome c and caspase activity under basal conditions without inducing apoptosis. It also greatly enhanced etoposide-induced caspase activation and apoptosis, indicative of an enhanced cellular sensitivity to death signals. Together, our data unveil a previously unrecognized role of peroxisomes in the regulation of mitochondrial dynamics and mitochondrion-dependent apoptosis. Given that mutations of peroxin genes are responsible for lethal disorders such as Zellweger syndrome, effects of such mutations on mitochondrion-dependent apoptosis may contribute to disease pathogenesis.
Quantitative Mapping of Free-Standing Lipid Membranes on Nano-Porous Mica Substrates
Authors: Costa Luca , Carretero-Genevrier Adrian , Ferrain Etienne , Milhiet Pierre-Emmanuel , Picas Laura
Published: September 2018

The physic-chemistry of biological membranes is at the origin of fundamental cellular functions such as vesicle trafficking, cell adhesion and migration1-3. Because most of intracellular shapes and local demixing of membranes take place in the nanometer scale, AFM becomes an extremely powerful technique to assess the properties of these biological membranes. Porous substrates provide an elegant strategy to avoid the conundrum of placing soft and thin biomembranes on hard substrates for AFM studies, although the surface chemistry make the actual substrates rather challenging setups. Here, we have engineered porous systems on the most widely used substrate in AFM, mica muscovite, with tunable pore sizes from some tens to few hundreds nanometers for biological applications. We show that free-standing bilayers on nano-porous can be obtained by using well-established vesicle spreading methods and that they display equivalent nano-mechanical stability and phsyco-chemical properties to that of membranes on conventional mica supports. By reducing the pore radius < 40 nm and limiting the contribution of membrane tension to the elastic response of free-standing membranes we estimate a bending modulus of 18 kbT and 73 kbT for DOPC and DPPC bilayers, respectively. The quantitative mapping of suspended membranes shows a different mechanical response at the pore rims, which is more pronounced for DPPC and suggest a different lipid ordering. We find that the combination of membrane bending and the different lipid packing at the edges of pores shapes the curvature of free-standing membranes on pores in the range of few tens of nm.
Hygienic behaviour selection via freeze-killed honey bee brood not associated with chalkbrood resistance in eastern Australia
Authors: Gerdts Jody , Dewar R. Laurie , Simone-Finstrom Michael , Edwards Trevor , Angove Michael
Published: September 2018

Hygienic behaviour is a social immune response in honey bees shown to help provide resistance to honey bee pests and diseases. A survey of hygienic behaviour and brood diseases was conducted on 649 colonies in eastern Australia to initiate a selective breeding program targeting disease resistance and provide a level of resistance to Varroa (Varroa destructor Anderson and Trueman and V. jacobsoni Oudemans) mites should they become established in Australia. The test population showed a remarkably high baseline level of hygienic behaviour with 17% of colonies meeting or exceeding breeding selection thresholds. Colonies belonging to a breeding program were 5.8 times more likely to be highly hygienic and colonies headed by queens raised from hygienic queen mothers were 2.2 times more likely. Nectar availability (nectar yielding flowering plants within honey bee forage range) influenced hygienic behaviour expression but was not a significant predictor of level of hygienic behaviour. Surprisingly, hygienic behaviour was not a significant predictor of the presence of infection of the honey bee brood disease chalkbrood (Ascosphaera apis) and was not influential in predicting severity of chalkbrood the infection in surveyed honey bee colonies. This study, along with reports from commercial beekeepers that chalkbrood infection is on the rise, warrants a deeper exploration of the host-pathogen relationship between Apis mellifera and Ascosphaera apis in Australia.
Ancestry informative alleles captured with reduced representation library sequencing in Theobroma cacao
Authors: Osorio-Guarín Jaime A. , Quackenbush Corey R. , Cornejo Omar E.
Published: September 2018

As the source of chocolate, cacao has become one of the most important crops in the world. The identification of molecular markers to understand the demographic history, genetic diversity and population structure plays a pivotal role in cacao breeding programs. Here, we report the use of a modified genotyping-by-sequencing (GBS) approach for large-scale single nucleotide polymorphism (SNP) discovery and allele ancestry mapping. We identified 12,357 bi-allelic SNPs after filtering, of which, 7,009 variants were ancestry informative. The GBS approach proved to be rapid, cost-effective, and highly informative for ancestry assignment in this species.
Investigation into the binding of dyes within protein crystals
Authors: McPherson Alexander , Larson Steven B.
Published: September 2018

It was found that the crystals of at least a dozen different proteins could be thoroughly stained to an intense color with a panel of dyes. Many, if not most, of the stained protein crystals retained the dyes almost indefinitely when placed in large volumes of dye-free mother liquor. Dialysis experiments showed that most of the dyes that were retained in crystals also bound to the protein when free in solution; less frequently, some dyes bound only in the crystal. The experiments indicated a strong association of the dyes with the proteins. Four protein crystals were investigated by X-ray diffraction to ascertain the mode of binding. These were crystals of lysozyme, thaumatin, trypsin inhibited with benzamidine and satellite tobacco mosaic virus. In 30 X-ray analyses of protein crystal–dye complexes, in only three difference Fourier maps was any difference electron density present that was consistent with the binding of dye molecules, and even in these three cases (thaumatin plus thioflavin T, xylene cyanol and m-cresol purple) the amount of dye observed was inadequate to explain the intense color of the crystals. It was concluded that the dye molecules, which are clearly inside the crystals, are disordered but are paradoxically tightly bound to the protein. It is speculated that the dyes, which exhibit large hydrophobic cores and peripheral charged groups, may interact with the crystalline proteins in the manner of conventional detergents.
TssA from Aeromonas hydrophila: expression, purification and crystallographic studies
Authors: Dix Samuel R. , Sun Ruyue , Harris Matthew J. , Batters Sarah L. , Sedelnikova Svetlana E. , Baker Patrick J. , Thomas Mark S. , Rice David W.
Published: September 2018

TssA is a core subunit of the type VI secretion system, which is a major player in interspecies competition in Gram-negative bacteria. Previous studies on enteroaggregative Escherichia coli TssA suggested that it is comprised of three putative domains: a conserved N-terminal domain, a middle domain and a ring-forming C-terminal domain. X-ray studies of the latter two domains have identified their respective structures. Here, the results of the expression and purification of full-length and domain constructs of TssA from Aeromonas hydrophila are reported, resulting in diffraction-quality crystals for the middle domain (Nt2) and a construct including the middle and C-terminal domains (Nt2-CTD).
Variation of second-order piezoelectric coefficients with respect to a finite strain measure
Authors: Jurczak Grzegorz
Published: September 2018

In this article the consequence of a change of finite strain measure is theoretically considered for nonlinear piezoelectric crystals. Analytical predictions show that second-order piezoelectric coefficients are finite strain measure dependent. Therefore, the use of any finite strain measure in constitutive modelling of piezoelectric materials requires an adequate choice of higher-order piezoelectric coefficients. This allows one to avoid unwanted corrections to the elastic and electric fields in the case of nonlinear modelling of piezoelectric materials, e.g. for piezoelectric heterostructures such as quantum wells or dots. A general transformation formula for second-order piezoelectric coefficients (elastostriction) is derived. As an example, specific transformation formulae for two common crystallographic classes, namely {\bar 4}3m and 6mm, are presented. The piezoelectric coefficients for GaN and GaAs crystals, as representative cases of these crystal classes, are recalculated and their dependence on the strain measure is demonstrated. A further implication of that effect is that a complete set of second-order piezoelectric coefficients should contain additional information about the strain measure applied during calculations or measurements.
Specular reflection intensity modulated by grazing-incidence diffraction in a wide angular range
Authors: Nikolaev K. V. , Makhotkin I. A. , Yakunin S. N. , Kruijs R. W. E. van de , Chuev M. A. , Bijkerk F.
Published: September 2018

Grazing-incidence X-ray diffraction (GID) is a well known technique for the characterization of crystal surfaces. A theoretical study has been performed of the sensitivity of GID to the structure of a crystal surface and distorted nanometre-thin surface layers. To simulate GID from crystals that have a complex subsurface structure, a matrix formalism of the dynamical diffraction theory has been applied. It has been found that the azimuthal rocking curves of a crystal that has a distorted subsurface, measured over a wide angular range, show asymmetric thickness oscillations with two distinguishable sets of frequencies: one corresponding to the diffraction in the single-crystal subsurface layer and the second corresponding to the diffraction in the single-crystal substrate. Therefore, azimuthal rocking curves allow characterization of the subsurface structure of a single crystal. Furthermore, thickness oscillations induced by evanescent diffraction modulate the specular reflection intensity, showing high-intensity modulations. This will potentially allow implementation of subsurface crystal characterization using, for instance, a laboratory-scale X-ray diffractometer.
Experimental and theoretical investigations of an X-ray LLL interferometer with a wedge-shaped mirror plate
Authors: Eyramjyan Tigran H. , Mnatsakanyan Tamara S. , Balyan Minas K.
Published: September 2018

An X-ray LLL interferometer with a wedge-shaped mirror plate is experimentally and theoretically investigated. Experimentally obtained interference patterns show that the Moiré fringes are superposed on Pendellösung fringes and the period of the Pendellösung fringes is not changed after passing the analyzer plate. An eikonal theory of interference-fringe formation in an LLL interferometer with a wedge-shaped mirror plate is developed, and provides predictions that coincide with experimentally obtained results.
Calculation of absorption and secondary scattering of X-rays by spherical amorphous materials in an asymmetric transmission geometry. Corrigendum
Authors: Bendert J. C. , Blodgett M. E. , Kelton K. F.
Published: September 2018

A revised version of Table 2 of Bendert et al. [Acta Cryst. (2013). A69, 131–139] is provided.
Structure and function ofL-threonine-3-dehydrogenase from the parasitic protozoanTrypanosoma bruceirevealed by X-ray crystallography and geometric simulations
Authors: Adjogatse Eyram , Erskine Peter , Wells Stephen A. , Kelly John M. , Wilden Jonathan D. , Chan A. W. Edith , Selwood David , Coker Alun , Wood Steve , Cooper Jonathan B.
Published: September 2018

Two of the world's most neglected tropical diseases, human African trypanosomiasis (HAT) and Chagas disease, are caused by protozoan parasites of the genusTrypanosoma. These organisms possess specialized metabolic pathways, frequently distinct from those in humans, which have potential to be exploited as novel drug targets. This study elucidates the structure and function of L-threonine-3-dehydrogenase (TDH) fromT. brucei, the causative pathogen of HAT. TDH is a key enzyme in the metabolism of L-threonine, and an inhibitor of TDH has been shown to have trypanocidal activity in the procyclic form ofT. brucei. TDH is a nonfunctional pseudogene in humans, suggesting that it may be possible to rationally design safe and specific therapies for trypanosomiasis by targeting this parasite enzyme. As an initial step, the TDH gene fromT. bruceiwas expressed and the three-dimensional structure of the enzyme was solved by X-ray crystallography. In multiple crystallographic structures,T. bruceiTDH is revealed to be a dimeric short-chain dehydrogenase that displays a considerable degree of conformational variation in its ligand-binding regions. Geometric simulations of the structure have provided insight into the dynamic behaviour of this enzyme. Furthermore, structures of TDH bound to its natural substrates and known inhibitors have been determined, giving an indication of the mechanism of catalysis of the enzyme. Collectively, these results provide vital details for future drug design to target TDH or related enzymes.
High-pressure protein crystal structure analysis of Escherichia coli dihydrofolate reductase complexed with folate and NADP+
Authors: Nagae Takayuki , Yamada Hiroyuki , Watanabe Nobuhisa
Published: September 2018

A high-pressure crystallographic study was conducted on Escherichia coli dihydrofolate reductase (ecDHFR) complexed with folate and NADP+ in crystal forms containing both the open and closed conformations of the M20 loop under high-pressure conditions of up to 800 MPa. At pressures between 270 and 500 MPa the crystal form containing the open conformation exhibited a phase transition from P21 to C2. Several structural changes in ecDHFR were observed at high pressure that were also accompanied by structural changes in the NADP+ cofactor and the hydration structure. In the crystal form with the closed conformation the M20 loop moved as the pressure changed, with accompanying conformational changes around the active site, including NADP+ and folate. These movements were consistent with the suggested hypothesis that movement of the M20 loop was necessary for ecDHFR to catalyze the reaction. In the crystal form with the open conformation the nicotinamide ring of the NADP+ cofactor undergoes a large flip as an intermediate step in the reaction, despite being in a crystalline state. Furthermore, observation of the water molecules between Arg57 and folate elucidated an early step in the substrate-binding pathway. These results demonstrate the possibility of using high-pressure protein crystallography as a method to capture high-energy substates or transient structures related to the protein reaction cycle.
Barriers faced by new-adopter of Last Planner System®: a case study
Authors: Perez Athena Maria , Ghosh Somik
Published: September 2018

Purpose

Documented evidence supports the improvements resulting from the use of the Last Planner System® (LPS) as a lean construction technique; however, several barriers to the implementation of the technique have been identified. The purpose of this paper is to evaluate the implementation process of LPS by a project team that is transitioning from the traditional planning and control to LPS on a typical commercial project. The paper compares the adopted implementation process with that of the recommended best practices and identifies the overlaps and variances.

Design/methodology/approach

An in-depth case study was conducted to accomplish the specific objectives: document the process of LPS implementation in detail; identify the overlaps and variance from the recommended practices; and investigate the causes for variance from the recommended practices. The authors used direct observations, document investigations and semi-structured interviews with key project participants to gather data. Constant comparison and content analysis were used as data analysis method for this study.

Findings

The paper identified critical barriers to the implementation process of LPS in the case study project, which are supported by existing literature and are considered typical of project teams that are new adopters and transitioning to the implementation of LPS.

Research limitations/implications

Based on a single case study, the outcomes may lack generalizability. However, similar findings of existing literature and evaluations by the project personnel substantiated the findings of the study.

Originality/value

The study attempted to conduct a systematic investigation on the implementation process of LPS, which is a less investigated topic. The paper draws attention to the major barriers experienced while adopting LPS in the case study project and suggested possible ways to address similar issues in the future. The barriers experienced by the case study project are typical of project teams who are new adopters and transitioning to the adoption of LPS, process and have the potential to be alleviated through the recommended practice implementation and process maintenance strategy.
Neurocognitive testing in the emergency department: A potential assessment tool for mild traumatic brain injury
Authors: Lunter Catherine M , Carroll Ellen L , Housden Charlotte , Outtrim Joanne , Forsyth Faye , Rivera Annie , Maimaris Chris , Boyle Adrian , Sahakian Barbara J , Menon David K , Newcombe Virginia FJ
Published: September 2018

Objective

Despite mild traumatic brain injury (mTBI) accounting for 80% of head injury diagnoses, recognition of individuals at risk of cognitive dysfunction remains a challenge in the acute setting. The objective of this study was to evaluate the feasibility and potential role for computerised cognitive testing as part of a complete ED head injury assessment.

Methods

mTBI patients (n = 36) who incurred a head injury within 24 h of presentation to the ED were compared to trauma controls (n = 20) and healthy controls (n = 20) on tests assessing reaction time, speed and attention, episodic memory, working memory and executive functioning. Testing occurred during their visit to the ED at a mean of 12 h post‐injury for mTBI and 9.4 h for trauma controls. These tasks were part of the Cambridge Neuropsychological Test Automated Battery iPad application. Healthy controls were tested in both a quiet environment and the ED to investigate the potential effects of noise and distraction on neurocognitive function.

Results

Reaction time was significantly slower in the mTBI group compared to trauma patients (P = 0.015) and healthy controls (P = 0.011), and deficits were also seen in working memory compared to healthy controls (P ≤ 0.001) and in executive functioning (P = 0.021 and P < 0.001) compared to trauma and healthy controls. Performances in the control group did not differ between testing environments.

Conclusion

Computerised neurocognitive testing in the ED is feasible and can be utilised to detect deficits in cognitive performance in the mTBI population as part of a routine head injury assessment.
Yield of serious axial injury from pan scans after blunt trauma in haemodynamically stable low‐risk trauma patients
Authors: Roberts Jessica , Watts Sara , Klim Sharon , Ritchie Peter , Kelly Anne‐Maree
Published: September 2018

Objectives

Whole body computed tomography (WBCT) scanning for trauma has gained popularity but its role in low‐risk patients is controversial. We aimed to determine the rate of serious axial/truncal injury and emergency intervention in conscious, stable patients undergoing WBCT for blunt trauma in two non‐trauma centre EDs in the Victorian trauma system.

Methods

Retrospective cohort study by medical record and radiology report review. Patients were included if they were conscious, haemodynamically stable adults presenting by ambulance and having WBCT scan. Exclusion criteria were age <16 years, no history of trauma, Glasgow Coma Scale <14, systolic blood pressure <90 mmHg and intoxication with alcohol or drugs. Data collected included demographics, clinical findings, results of CT scans and emergency interventions (emergency truncal surgery, transfer to a trauma centre and/or transfusion within 24 h). The outcomes of interest were the rate of defined serious axial/truncal injury and emergency interventions.

Results

One hundred and four patients were studied. Median age was 45 years; 67% were men. Median injury severity score (ISS) was 1.5 (interquartile range 0–5); only one patient had an ISS ≥15. Ninety (87%, 78–92%) patients had no defined serious injury. Five (5%) patients had a defined emergency intervention – four trauma centre transfers and one transfusion. Two of these were not trauma‐related.

Conclusion

The rate of serious axial/truncal injury was low. The high rate of normal scans makes it likely that the risk:benefit ratio between injury identification and radiation related cancer risk is unacceptably high. This data supports a selective CT strategy in low‐risk trauma patients.
Weather risk: how does it change the yield benefits of nitrogen fertilizer and improved maize varieties in sub‐Saharan Africa?
Authors: Hurley Terrance , Koo Jawoo , Tesfaye Kindie
Published: September 2018

The purpose of this research was to explore how weather risk affects the value of nitrogen fertilizer use and improved seed variety adoption to sub‐Saharan African (SSA) maize farmers. It contributes to the literature by providing additional broad support for the hypothesis that low rates of fertilizer use and improved seed variety adoption can be attributed to the fact that the SSA landscape is heterogeneous, so fertilizer and improved seed are not always advantageous, especially when considering the potentially high cost to farmers of obtaining fertilizer and improved seed. The analysis finds a synergy between nitrogen fertilizer and improved seed varieties. While the benefits of nitrogen tend to increase overtime without improved seed varieties and the benefits of improved seed varieties tend to decrease overtime without nitrogen, combining the two provides more sustained productivity benefits. Therefore, securing both nitrogen use and improved seed variety adoption is important for promoting sustained maize productivity increases across much of SSA. The research also contributes to the literature by using a methodology for calculating willingness to pay bounds that assess the importance of farmers’ risk tolerances as a barrier to fertilizer use or improved seed variety adoption.
Development of an ‘Enteral tube feeding decision support tool’ for hip fracture patients: A modified Delphi approach
Authors: Mon Aye Su , Pulle Chrys , Bell Jack
Published: September 2018

Objectives

Malnutrition after hip fracture is recognised as the co‐morbidity most likely to impact hospital length of stay and cost. Despite this, the role of enteral tube feeding in hip fracture patients remains unclear.

Methods

A modified Delphi process was used to establish consensus for an enteral tube feeding decision support tool. Three rounds of the Delphi survey were administered to a purposeful sample of twenty multidisciplinary clinicians from the Australian and New Zealand Hip Fracture Registry.

Results

Consensus markedly improved across the three rounds (33, 44 and 87%, respectively). More than 80% of participants positively supported implementing the tool in clinical practice.

Conclusions

This study describes experienced, multidisciplinary clinician consensus and support for an ‘Enteral tube feeding decision support tool’ to be applied in acute hip fracture settings. Further studies are being undertaken to identify the impact of the checklist tool on informed consent decision processes in this population.
Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4
Authors: Heim Kathleen R. , Mulla Melissa J. , Potter Julie A. , Han Christina S. , Guller Seth , Abrahams Vikki M.
Published: September 2018

Problem

Hyperglycemia increases the risk of preeclampsia. Hyperglycemia induces a placental trophoblast inflammatory (IL‐1β, IL‐6, IL‐8), antiangiogenic (sFlt‐1, sEndoglin), and anti‐migratory profile. The IL‐1β response is mediated via inflammasome activation by the damage‐associated molecular pattern (DAMP), uric acid. The objective of this study was to determine the role of high‐mobility group box‐1 (HMGB1), a DAMP that activates Toll‐like receptor 4 (TLR4), in human first trimester trophoblast responses to hyperglycemia. The trophoblast response to excess glucose under different oxygen tensions was also investigated.

Method of study

The human first trimester trophoblast cell line (Sw.71) was exposed to glucose mimicking normoglycemia (5 mmol/L) and hyperglycemia (10 mmol/L), either alone or with the TLR4 antagonist, LPS‐RS; or the HMGB1 inhibitor, glycyrrhizin. Cells were also treated with glucose under hyperoxic (21% O2), normoxic (8% O2), and hypoxic (2% O2) conditions. Cell‐free supernatants were assayed by ELISA and bioassays for inflammatory: IL‐1β, IL‐6, and IL‐8; inflammasome‐associated: uric acid and caspase‐1; angiogenic: sEndoglin, sFlt‐1, and PlGF; and the DAMP, HMGB1. Cell migration was measured using a two‐chamber colormetric assay.

Results

Excess glucose triggered a trophoblast sterile inflammatory IL‐8 and antimigratory response through HMGB1 activation of TLR4. The IL‐1β and sFlt‐1/PlGF response was TLR4‐mediated, but HMGB1‐independent, suggesting another DAMP may be involved. Hyperoxia rather than normoxia or hypoxia was a major driver of trophoblast dysfunction in response to excess glucose.

Conclusion

The findings from this study indicate a novel mechanism by which hyperglycemia may impact trophoblast function, early placentation, and ultimately, pregnancy outcome.
Use of fetal fibronectin testing in women transferred for threatened preterm labour in remote far north Queensland
Authors: Downing Sandra G. , Wright Rebecca , Marquardt Tonia , Callander Emily
Published: September 2018

Background

Threatened preterm labour is a common reason for medical transfer from remote communities; however, many transferred women do not deliver preterm. A tool for prediction of preterm birth such as fetal fibronectin may reduce transfers and related social and economic costs.

Aim

To review the use of fetal fibronectin testing in women transferred for threatened preterm labour from Cape York to Cairns Hospital between 2011 and 2015 and determine the role testing could play in reducing transfers and associated costs.

Materials/methods

Records from the Royal Flying Doctor Service and Cairns Hospital were accessed. Women transferred solely for threatened preterm labour were included in the study. Fetal fibronectin testing, hospital admission, outpatient stays and birth outcome data were collated and analysed. Costs were assigned using the National Hospital Cost Data Collection, round 19.

Results

Forty‐seven women were included in the study; however, only 20 underwent fetal fibronectin testing. Transfer of 30 women who had either a negative test or were not tested but delivered at term resulted in 41 inpatient nights and 443 excess outpatient nights, costing an estimated AU$57 408. Aeromedical transfers were estimated to cost a further $151 500.

Conclusion

Adherence to clinical guidelines and greater availability and use of fetal fibronectin testing in Cape York have the potential to reduce aeromedical transfers for threatened preterm labour. Substantial inpatient and excess outpatient stays could be avoided with associated reduction in health system and social costs. Strategies to improve adherence to guidelines and increase access to testing are required.
Effects of different cryopreservation methods on DNA integrity and sperm chromatin quality in men
Authors: Lusignan M. F. , Li X. , Herrero B. , Delbes G. , Chan P. T. K.
Published: September 2018

Background

Cryopreserved human sperm are used in assisted reproductive technology. However, the effect of cryopreservation on spermDNAintegrity is unclear.

Objectives

The objectives of this study were to: (i) determine the impact of semen cryopreservation on human spermDNAintegrity and chromatin structure; (ii) test if parameters obtained fromTUNELandSCSA® correlate; and (iii) verify correlation between sperm motility, morphology and viability withTUNELandSCSA® parameters.

Materials and methods

Men attending a fertility clinic were recruited and grouped according to their sperm parameters (n = 9/group): normozoospermia, oligoasthenoteratozoospermia and teratozoospermia. Each semen sample was processed as follow: (i) directly frozen at −80 °C; (ii) diluted in Sperm Maintenance Medium, cooled for 30 min at 4 °C and frozen at −80 °C; (iii) diluted in Sperm Maintenance Medium; or (iv) in SpermFreeze. Each mixture from method (iii) and (iv) was then suspended for 30 min in liquid nitrogen vapor and plunged into liquid nitrogen. After at least two months of storage, samples were thawed at room temperature and analyzed for motility and viability,TUNELandSCSA® assays.

Results

Progressive motility and viability decreased after freeze‐thawing.TUNELscores increased significantly in all samples after freezing‐thawing while no significant change in theDNAfragmentation index (DFI) fromSCSA® was observed. No change in the percentage highDNAstainability (HDS) was observed in normozoospermic samples; however it was significantly increased in all the methods in oligoasthenoteratozoospermic and in the methods (ii)–(iv) in teratozoospermic samples. TheDFIandTUNELscores correlated significantly with each other and inversely with sperm motility, viability and morphology.

Discussion and conclusion

Cryopreservation seems to be deleterious for the integrity of human spermDNAand compaction. However, the spermDFIwas not affected during cryopreservation under the various methods of storage tested. Clinicians and investigators should take this information into consideration when using cryopreserved sperm for assisted reproduction.
RCEP or TPP? An Empirical Analysis Based on Global Experience
Authors: Yamamoto Rosenbaum Chika
Published: September 2018

The Trans‐Pacific Partnership (TPP) and the Regional Comprehensive Economic Partnership (RCEP) are two of the most discussed preferential trade agreements (PTAs) in the 21st century. However, the future of these PTAs—whether they will be implemented—still remains mired in debate. This paper empirically explores various factors contributing to the development of the agreements based on the recent patterns of multilateral PTAs across the globe. It also discusses the Comprehensive and Progressive Trans‐Pacific Partnership (CPTPP), for which negotiations have just begun among the TPP members, without the United States. The analysis reveals both political and economic factors that affect the complex situation surrounding these PTAs. In addition, a trilateral PTA among China, Japan, and South Korea may help promote the implementation of the RCEP. The chances of the CPTPP forming are higher than that of the TPP, which means the TPP is likely to form without the United States.
Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device
Authors: Zwart Tom C. , Gokoel Sumit R.M. , van der Boog Paul J.M. , de Fijter Johan W. , Kweekel Dina M. , Swen Jesse J. , Guchelaar Henk‐Jan , Moes Dirk Jan A.R.
Published: September 2018

Aims

Tacrolimus and mycophenolic acid dosing after renal transplantation is individualized through therapeutic drug monitoring (TDM). Home‐based dried blood spot (DBS) sampling has the potential to replace conventional TDM sampling at the clinic. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay was developed to quantify tacrolimus and mycophenolic acid in DBS and clinically validated for abbreviated area under the concentration–time curve (AUC) monitoring using an innovative volumetric DBS sampling device.

Methods

Clinical validation was performed by direct comparison of paired DBS and whole blood (WB) (tacrolimus) and plasma (mycophenolic acid) concentrations and AUCs. Agreement was evaluated using Passing–Bablok regression, Bland–Altman analysis and DBS‐to‐WB predictive performance. TDM dosing recommendations based on both methods were compared to assess clinical impact.

Results

Paired tacrolimus (n = 200) and mycophenolic acid (n = 192) DBS and WB samples were collected from 65 kidney(–pancreas) transplant recipients. Differences for tacrolimus and mycophenolic acid were within ±20% for 84.5% and 76.6% of concentrations and 90.5% and 90.7% of AUCs, respectively. Tacrolimus and mycophenolic acid dosing recommendation differences occurred on 44.4% and 4.7% of occasions. Tacrolimus DBS dosing recommendations were 0.35 ± 0.14 mg higher than for WB and 8 ± 3% of the initial dose. Mycophenolic acid DBS dosing recommendations were 23.3 ± 31.9 mg lower than for plasma and 2 ± 3.5% of the initial dose.

Conclusions

Tacrolimus and mycophenolic acid TDM for outpatient renal transplant recipients, based on abbreviated AUC collected with a DBS sampling device, is comparable to conventional TDM based on WB sampling. Patient training and guidance on good blood‐spotting practices is essential to ensure method feasibility.
Long‐term outcomes and mutation profiling of patients with mantle cell lymphoma (MCL) who discontinued ibrutinib
Authors: Jain Preetesh , Kanagal‐Shamanna Rashmi , Zhang Shaojun , Ahmed Makhdum , Ghorab Ahmad , Zhang Liang , Ok Chi Young , Li Shaoying , Hagemeister Frederick , Zeng Dongfeng , Gong Tiejun , Chen Wendy , Badillo Maria , Nomie Krystle , Fayad Luis , Medeiros Leonard J. , Neelapu Sattva , Fowler Nathan , Romaguera Jorge , Champlin Richard , Wang Linghua , Wang Michael L.
Published: September 2018

Long term outcomes and mutations in patients with mantle cell lymphoma (MCL) who discontinued ibrutinib have not been described. Using deep targeted next generation sequencing, we performed somatic mutation profiling from 15 MCL patients (including 5 patients with paired samples; before and after progression on ibrutinib). We identified 80 patients with MCL who discontinued ibrutinib therapy for various reasons. Median follow‐up after ibrutinib discontinuation was 38 months. The median duration on ibrutinib was 7·6 months. Forty‐one (51%) patients discontinued ibrutinib due to disease progression/transformation, 20 (25%) for intolerance, 7 (9%) due to patient choice, 5 (6%) for stem cell transplant, 4 (5%) due to second cancers and 3 (4%) other causes. The median survival after ibrutinib was 10 and 6 months for disease progression and transformation, respectively, and 25 months for patients with ibrutinib intolerance. Overall, BTK mutations were observed in 17% patients after progression on ibrutinib. Notably, TP53 alterations were observed after progression in 75% patients. Among the 4 patients with blastoid transformation, 3 (75%) had NSD2 mutations (co‐existing with TP53). Ibrutinib‐refractory MCL patients had a short survival. Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib‐refractory MCL.
Elevational changes in the avian community of a Mesoamerican cloud forest park
Authors: Neate‐Clegg Montague H. C. , Jones Samuel E. I. , Burdekin Oliver , Jocque Merlijn , Şekercioğlu Çağan Hakkı
Published: September 2018

Harboring many range‐restricted and specialized species, high elevation tropical cloud forests are diverse habitats represented in many protected areas. Despite this, many such areas receive little practical protection from deforestation and land conversion. Moreover, montane species may be more sensitive to climate change owing to various factors affecting community assembly across elevational gradients. Few studies have used annual monitoring to assess how biological communities in cloud forests may be shifting in response to habitat or climate change or assessed the efficacy of protected areas in buffering these effects. We analyzed avifaunal community trends in a 10‐yr dataset of constant‐effort bird point‐count data in a cloud forest national park in Honduras, Central America. We found that species richness and diversity increased at higher elevations, but decreased at lower elevations. Abundances of most dietary and forest‐dependency groups exhibited similar trends, and many key cloud forest species shifted upslope and/or increased in abundance. Taken together, our results suggest that the avian community is moving upslope and species composition is changing. Results for species richness and diversity were similar when only nondegraded transects were considered, suggesting the role of climate change as an important driver. At lower elevations, however, many species may be negatively affected by increased habitat degradation, favoring species with low forest dependency. Continued habitat conversion and climate change could push the cloud forest bird community further upslope, potentially resulting in increased competition, mortality, and even extirpation of some species. Increased protection is unlikely to mitigate the effects of climate change.