bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Xanthomonas translucens Complex Using Draft Genomes, Comparative Genomics, Phylogenetic Analysis, and Diagnostic LAMP Assays
Authors: Langlois Paul A. , Snelling Jacob , Hamilton John P. , Bragard Claude , Koebnik Ralf , Verdier Valérie , Triplett Lindsay R. , Blom Jochen , Tisserat Ned A. , Leach Jan E.
Published: January 2017

Prevalence of Xanthomonas translucens, which causes cereal leaf streak (CLS) in cereal crops and bacterial wilt in forage and turfgrass species, has increased in many regions in recent years. Because the pathogen is seedborne in economically important cereals, it is a concern for international and interstate germplasm exchange and, thus, reliable and robust protocols for its detection in seed are needed. However, historical confusion surrounding the taxonomy within the species has complicated the development of accurate and reliable diagnostic tools for X. translucens. Therefore, we sequenced genomes of 15 X. translucens strains representing six different pathovars and compared them with additional publicly available X. translucens genome sequences to obtain a genome-based phylogeny for robust classification of this species. Our results reveal three main clusters: one consisting of pv. cerealis, one consisting of pvs. undulosa and translucens, and a third consisting of pvs. arrhenatheri, graminis, phlei, and poae. Based on genomic differences, diagnostic loop-mediated isothermal amplification (LAMP) primers were developed that clearly distinguish strains that cause disease on cereals, such as pvs. undulosa, translucens, hordei, and secalis, from strains that cause disease on noncereal hosts, such as pvs. arrhenatheri, cerealis, graminis, phlei, and poae. Additional LAMP assays were developed that selectively amplify strains belonging to pvs. cerealis and poae, distinguishing them from other pathovars. These primers will be instrumental in diagnostics when implementing quarantine regulations to limit further geographic spread of X. translucens pathovars.
Histone deacetylase inhibitors containing a benzamide functional group and a pyridyl cap are preferentially effective human immunodeficiency virus-1 latency-reversing agents in primary resting CD4+ T cells
Authors: Kobayashi Yoshifumi , Gélinas Céline , Dougherty Joseph P
Published: January 2017

Antiretroviral therapy (ART) can control human immunodeficiency virus-1 (HIV-1) replication in infected individuals. Unfortunately, patients remain persistently infected owing to the establishment of latent infection requiring that ART be maintained indefinitely. One strategy being pursued involves the development of latency-reversing agents (LRAs) to eliminate the latent arm of the infection. One class of molecules that has been tested for LRA activity is the epigenetic modulating compounds histone deacetylases inhibitors (HDACis). Previously, initial screening of these molecules typically commenced using established cell models of viral latency, and although certain drugs such as the HDACi suberoylanilide hydroxamic acid demonstrated strong activity in these models, it did not translate to comparable activity with patient samples. Here we developed a primary cell model of viral latency using primary resting CD4+ T cells infected with Vpx-complemented HIV-1 and found that the activation profile using previously described LRAs mimicked that obtained with patient samples. This primary cell model was used to evaluate 94 epigenetic compounds. Not surprisingly, HDACis were found to be the strongest activators. However, within the HDACi class, the most active LRAs with the least pronounced toxicity contained a benzamide functional moiety with a pyridyl cap group, as exemplified by the HDACi chidamide. The results indicate that HDACis with a benzamide moiety and pyridyl cap group should be considered for further drug development in the pursuit of a successful viral clearance strategy.
Monod-Wyman-Changeux Analysis of Ligand-Gated Ion Channel Mutants
Authors: Einav Tal , Phillips Rob
Published: January 2017

We present a framework for computing the gating properties of ligand-gated ion channel mutants using the Monod-Wyman-Changeux (MWC) model of allostery. We derive simple analytic formulas for key functional properties such as the leakiness, dynamic range, half-maximal effective concentration ([EC50]), and effective Hill coefficient, and explore the full spectrum of phenotypes that are accessible through mutations. Specifically, we consider mutations in the channel pore of nicotinic acetylcholine receptor (nAChR) and the ligand binding domain of a cyclic nucleotide-gated (CNG) ion channel, demonstrating how each mutation can be characterized as only affecting a subset of the biophysical parameters. In addition, we show how the unifying perspective offered by the MWC model allows us, perhaps surprisingly, to collapse the plethora of dose-response data from different classes of ion channels into a universal family of curves.
Charge density analysis of metformin chloride, a biguanide anti-hyperglycemic agent
Authors: Niranjana Devi Rajendran , Jelsch Christian , Israel Samuel , Aubert Emmanuel , Anzline Chellam , Hosamani Amar A.
Published: January 2017

The experimental charge density analysis of the anti-hyperglycemic agent metformin chloride with high-resolution X-ray diffraction data at low temperature (100 K) has been performed and these experimental results were compared with that derived from the corresponding periodic theoretical calculations at the B3LYP/6-31G** level of theory. The experimental and theoretical multipolar charge-density analyses of metformin chloride have been accomplished in order to understand its structural and electronic properties. The C and N atoms of the molecular backbone adopt a near trigonal geometry due to the occurrence of extensive delocalization/resonance of C—N bonds, as confirmed by topological analysis and also found by Natural Resonance Theory calculations performed in the isolated metformin cation. The molecule contains six C—N bonds and the topological bond order analysis shows that four bonds have bond orders close to 4/3 and two bonds can be considered as single. The analysis of numerical parameters of the valence shell charge concentration reports that the N3 atom, which forms two bonds with C atoms, possesses one non-bonding valence-shell charge concentration (VSCC) in the direction of the electron lone pair. Among the intermolecular interactions of the chloride atom with the H—C and H—N atoms, eight have been found to be shorter than the sum of van der Waals radii. The analysis of contacts on the Hirshfeld surface reveals that the H—N...Cl hydrogen bonds are enriched (over-represented) and act as the driving force in the crystal packing formation. The metformin cations form favorable electrostatic interactions with the chloride anions which have globally a stronger energy than the unfavorable cation/cation interactions.
A new one-dimensional CuIIcomplex with a three-dimensional supramolecular architecture incorporating benzene-1,3-dicarboxylate and 1-[(1H-benzotriazol-1-yl)methyl]-1H-imidazole
Authors: Li Jian-Hua , Zhu Meng-Di , Huang Qiu-Ying
Published: January 2017

Subtle modifications ofN-donor ligands can result in complexes with very different compositions and architectures. In the complexcatena-poly[[bis{1-[(1H-benzotriazol-1-yl)methyl]-1H-imidazole-κN3}copper(II)]-μ-benzene-1,3-dicarboxylato-κ3O1,O1′:O3], {[Cu(C8H4O4)(C10H9N5)2(H2O)]·2H2O}n, each CuIIion is six-coordinated by two N atoms from two crystallographically independent 1-[(1H-benzotriazol-1-yl)methyl]-1H-imidazole (bmi) ligands, by three O atoms from two symmetry-related benzene-1,3-dicarboxylate (bdic2−) ligands and by one water molecule, leading to a distorted CuN2O4octahedral coordination environment. The CuIIions are connected by bridging bdic2−anions to generate a one-dimensional chain. The bmi ligands coordinate to the CuIIions in monodentate modes and are pendant on opposite sides of the main chain. In the crystal, the chains are linked by O—H...O and O—H...N hydrogen bonds, as well as by π–π interactions, into a three-dimensional network. A thermogravimetric analysis was carried out and the fluorescence behaviour of the complex was also investigated.
Failure modes effects analysis (FMEA) for review of a diagnostic genetic laboratory process
Authors: Claxton Karen , Campbell-Allen Nicola Marie
Published: January 2017

Purpose

For any improvement tool to be successfully integrated into an organizations’ quality improvement or risk management programme, it needs to be relatively easy-to-use and proven to provide benefits to the customer and organization. Many healthcare organizations are facing fiscal constraints and increasing complexity of tests, putting strains on resources, particularly for those on “the shop floor” who are “hands on” in the design, delivery and improvement of products or services. Within a laboratory setting, there is often limited time for formal extensive process reviews; with the pressure to meet “turn-around times” for often “clinically urgent” results. Preventative and corrective actions are often identified through audits or root-cause analysis in some cases after an event has occurred. The paper aims to discuss these issues.

Design/methodology/approach

Failure modes effect analysis (FMEA) is a risk management tool, used to identify prospective failures within processes or products, before they occur. Within laboratory healthcare, risk management for prevention of failure (particularly an inaccurate result) is imperative, and underpins the design of all steps of sample handling. FMEA was used to review a laboratory process for a “gene mutation test” initially considered to have few opportunities for improvement. Despite this perception, a previous review of the process, and the time restrictions for review, new improvements were identified with implications to patient management.

Findings

This study shows that FMEA can yield benefits, for prospective risk management and general process improvement, within a laboratory setting where time and team input is restricted, and within a process that was considered to have few “problems”.

Originality/value

The study was undertaken in a large metropolitan public health system laboratory – one of the largest in the country. This laboratory is a significant contributor to the health outcomes of patients in the local region, and through its contribution to national laboratory testing and reporting. This was the first use of FMEA in this laboratory setting.
A critical analysis of supply chain risk management content: a structured literature review
Authors: Prakash Surya , Soni Gunjan , Rathore Ajay Pal Singh
Published: January 2017

Purpose

The research on supply chain risk management (SCRM) is visibly on the rise, although its literature still lacks the state of the art that critically analyzes its content. The SCRM literature seems to require studies that utilize risk typology, sources of risk, etc. for reviewing the topic. The purpose of this paper is to bridge the gap by synthesizing the information obtained from 343 articles across 85 journals. This study also presents a critical analysis of the content of SCRM in a structured manner to identify the directions for future research.

Design/methodology/approach

A systematic literature review (SLR) was devised and adopted, which involved the selection, classification, and evaluation of 343 research articles published over a period of 11 years (2004-2014). The content of extant SCRM literature was critically analyzed and synthesized from the perspective of the risk management process (RMP).

Findings

The analysis of extant literature shows that there is a marked rise in research in the SCRM area, especially after the year 2005. It was observed that not only risk but also different forms of uncertainties make supply chain (SC) operations difficult to manage. The SCRM actions yielded most benefits when their implementation was at chain or network level and managed strategically. The analysis also reveals that the manufacturing sector is most affected by risks and highly investigated by researchers.

Practical implications

A complete process for SCRM based on risk stratification, objectives of risk management, and RMP will be a guiding model for firms to manage risks. The research gaps identified and future directions provided here will encourage researchers and managers to devise new methods, tools, and techniques to address the risks in modern SC operations.

Originality/value

An SLR and risk-based content classification of SCRM literature were performed. To identify, locate, select, and analyze the SCRM literature, a structured and systematic process was adopted with some very rarely used methods such as two levels of search keywords, and strings were formulated to locate the most relevant articles in major academic databases.
Selection of broad‐spectrum cephalosporin‐resistant Escherichia coli in the feces of healthy dogs after administration of first‐generation cephalosporins
Authors: Kimura Ayako , Yossapol Montira , Shibata Sanae , Asai Tetsuo
Published: January 2017

Although antimicrobial products are essential for treating diseases caused by bacteria, antimicrobial treatment selects for antimicrobial‐resistant (AMR) bacteria. The aim of this study was to determine the effects of administration of first‐generation cephalosporins on development of resistant Escherichia coli in dog feces. The proportions of cephalexin (LEX)‐resistant E. coli in fecal samples of three healthy dogs treated i.v. with cefazolin before castration and then orally with LEX for 3 days post‐operation (PO) were examined using DHL agar with or without LEX (50 µg/mL). LEX‐resistant E. coli were found within 3 days PO, accounted for 100% of all identified E. coli 3–5 days PO in all dogs, and were predominantly found until 12 days PO. LEX‐resistant E. coli isolates on DHL agar containing LEX were subjected to antimicrobial susceptibility testing, pulsed‐field gel electrophoresis (PFGE) genotyping, β‐lactamase typing and plasmid profiling. All isolates tested exhibited cefotaxime (CTX) resistance (CTX minimal inhibitory concentration ≥4 µg/mL). Seven PFGE profiles were classified into five groups and three β‐lactamase combinations (blaCMY‐4‐blaTEM‐1, blaTEM‐1‐blaCTX‐M‐15 and blaTEM‐1‐blaCTX‐M‐15‐blaCMY‐4). All isolates exhibited identical PFGE profiles in all dogs on four days PO and subsequently showed divergent PFGE profiles. Our results indicate there are two selection periods for AMR bacteria resulting from the use of antimicrobials. Thus, continuing hygiene practices are necessary to prevent AMR bacteria transfer via dog feces after antimicrobial administration.
Every restoration is unique: testing year effects and site effects as drivers of initial restoration trajectories
Authors: Stuble Katharine L. , Fick Stephen E. , Young Truman P.
Published: January 2017

The outcomes of restoration efforts are contingent on the specifics of the restoration practices utilized, but also on uncontrolled contingencies such as site effects and year effects. Although restoration practitioners have long been aware that the successes of their projects vary from site to site and from year to year, there have been few direct experimental tests of these contingencies.

We established grassland restoration plots identically across three sites in northern California, in each of four establishment years (for 12 site‐year combinations).

The resulting plant communities differed significantly across sites and across establishment years. As a consequence of these community differences, there were ‘forb years’ and ‘grass years’, although these sometimes differed among sites. Multivariate analysis identified mean annual temperature and total precipitation as likely drivers of some of these differences.

Synthesis and applications. Our results not only confirm the idiosyncratic nature of the results of restoration efforts (and ecological experiments in general) but also demonstrate that some of this variation can potentially be related to measurable environmental conditions. Understanding the drivers of this variability can ultimately aid restoration practitioners by allowing them to focus restoration efforts on years and sites most likely to yield desired outcomes.
Individual variation in children's reading comprehension across digital text types
Authors: Fesel Sabine S. , Segers Eliane , Verhoeven Ludo
Published: January 2017

The present study examined children's digital text comprehension of digital text types linear digital text vs hypertext, with or without graphical navigable overviews. We investigated to what extent individual variation in children's comprehension could be explained by lexical quality (word reading efficiency and vocabulary knowledge), cognitive load factors (prior knowledge and working memory), text type and graphical overview. Participants were 93 sixth graders in a within‐subject design. Word reading efficiency, vocabulary knowledge and prior knowledge predicted children's digital comprehension scores, while working memory did not. Reading comprehension was equal for linear text or hypertext. However, the presence of an overview facilitated reading comprehension for readers with lower prior knowledge. It can be concluded that hypertexts with basic digital text features and accompanying comprehension questions are not more difficult for children than linear digital texts, that similar individual factors predict reading comprehension of linear text and hypertext, and that a graphical overview helps when prior knowledge is low.
Whole genome sequence study of cannabis dependence in two independent cohorts
Authors: Gizer Ian R. , Bizon Chris , Gilder David A. , Ehlers Cindy L. , Wilhelmsen Kirk C.
Published: January 2017

Recent advances in genome wide sequencing techniques and analytical methods allow for more comprehensive examinations of the genome than microarray‐based genome‐wide association studies (GWAS). The present report provides the first application of whole genome sequencing (WGS) to identify low frequency variants involved in cannabis dependence across two independent cohorts. The present study used low‐coverage whole genome sequence data to conduct set‐based association and enrichment analyses of low frequency variation in protein‐coding regions as well as regulatory regions in relation to cannabis dependence. Two cohorts were studied: a population‐based Native American tribal community consisting of 697 participants nested within large multi‐generational pedigrees and a family‐based sample of 1832 predominantly European ancestry participants largely nested within nuclear families. Participants in both samples were assessed for Diagnostic and Statistical Manual of Mental Disorders‐IV (DSM‐IV) lifetime cannabis dependence, with 168 and 241 participants receiving a positive diagnosis in each sample, respectively. Sequence kernel association tests identified one protein‐coding region, C1orf110 and one regulatory region in the MEF2B gene that achieved significance in a meta‐analysis of both samples. A regulatory region within the PCCB gene, a gene previously associated with schizophrenia, exhibited a suggestive association. Finally, a significant enrichment of regions within or near genes with multiple splice variants or involved in cell adhesion or potassium channel activity were associated with cannabis dependence. This initial study demonstrates the potential utility of low pass whole genome sequencing for identifying genetic variants involved in the etiology of cannabis use disorders.
No association of goal‐directed and habitual control with alcohol consumption in young adults
Authors: Nebe Stephan , Kroemer Nils B. , Schad Daniel J. , Bernhardt Nadine , Sebold Miriam , Müller Dirk K. , Scholl Lucie , Kuitunen‐Paul Sören , Heinz Andreas , Rapp Michael A. , Huys Quentin J.M. , Smolka Michael N.
Published: January 2017

Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model‐free habitual over model‐based goal‐directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model‐based goal‐directed and model‐free habitual control in 188 18‐year‐old social drinkers in a two‐step sequential decision‐making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model‐free and model‐based decision‐making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model‐free nor model‐based decision weights nor the trade‐off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model‐free or model‐based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole‐brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model‐free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model‐based goal‐directed and model‐free habitual control might rather not be a trait marker of alcohol intake per se.
Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia
Authors: Tan V. P. Y. , Liu K. S. H. , Lam F. Y. F. , Hung I. F. N. , Yuen M. F. , Leung W. K.
Published: January 2017

Background

Gut dysbiosis may contribute to pain and bloating in patients with functional gastrointestinal disease.

Aims

To determine if treatment with rifaximin would improve the symptoms of functional dyspepsia in Chinese patients in a double‐blinded, randomised, placebo‐controlled trial.

Methods

Consecutive subjects with a diagnosis of functional dyspepsia as per the Rome III criteria were randomised to receive rifaximin 400 mg or placebo, all taken three times daily for 2 weeks. The investigators and study subjects were blinded to the treatment allocation. Subjects were followed up for 8 weeks. The primary end point was adequate relief of global dyspeptic symptoms (GDS). Secondary endpoints were relief of individual dyspeptic symptoms.

Results

Eighty‐six subjects were recruited. At week 8, there were significantly more subjects in the rifaximin than in the placebo group who experienced adequate relief of GDS (78% vs. 52%, P = 0.02). A trend favouring rifaximin group was also noted in the preceding 4 weeks. Rifaximin was also superior to placebo in providing adequate relief of belching and post‐prandial fullness/bloating (PPF) in subjects at week 4. Subgroup analysis revealed that female subjects had more significant response to rifaximin treatment (adequate relief of GDS at week 4: 76% vs. 42%, P = 0.006; week 8: 79% vs. 47%, P = 0.008), as well as improvements in their belching and PPF at week 4. The incidences of adverse effects were similar in both groups.

Conclusions

Treatment with 2 weeks of rifaximin led to adequate relief of global dyspeptic symptoms, belching and post‐prandial fullness/bloating in subjects with functional dyspepsia. The difference was more marked in females. (clinicaltrials.org NCT01643083).
A Dirichlet-Tree Multinomial Regression Model for Associating Dietary Nutrients with Gut Microorganisms
Authors: Wang Tao , Zhao Hongyu
Published: January 2017

Understanding the factors that alter the composition of the human microbiota may help personalized healthcare strategies and therapeutic drug targets. In many sequencing studies, microbial communities are characterized by a list of taxa, their counts, and their evolutionary relationships represented by a phylogenetic tree. In this article, we consider an extension of the Dirichlet multinomial distribution, called the Dirichlet-tree multinomial distribution, for multivariate, over-dispersed, and tree-structured count data. To address the relationships between these counts and a set of covariates, we propose the Dirichlet-tree multinomial regression model for which we develop a penalized likelihood method for estimating parameters and selecting covariates. For efficient optimization, we adopt the accelerated proximal gradient approach. Simulation studies are presented to demonstrate the good performance of the proposed procedure. An analysis of a data set relating dietary nutrients with bacterial counts is used to show that the incorporation of the tree structure into the model helps increase the prediction power.
Cultural safety and belonging for refugee background women attending group pregnancy care: An Australian qualitative study
Authors: Riggs Elisha , Muyeen Sumaiya , Brown Stephanie , Dawson Wendy , Petschel Pauline , Tardiff Waan , Norman Fiona , Vanpraag Dannielle , Szwarc Jo , Yelland Jane
Published: January 2017

Background

Refugee women experience higher incidence of childbirth complications and poor pregnancy outcomes. Resettled refugee women often face multiple barriers accessing pregnancy care and navigating health systems in high income countries.

Methods

A community‐based model of group pregnancy care for Karen women from Burma was co‐designed by health services in consultation with Karen families in Melbourne, Australia. Focus groups were conducted with women who had participated to explore their experiences of using the program, and whether it had helped them feel prepared for childbirth and going home with a new baby.

Results

Nineteen women (average time in Australia 4.3 years) participated in two focus groups. Women reported feeling empowered and confident through learning about pregnancy and childbirth in the group setting. The collective sharing of stories in the facilitated environment allowed women to feel prepared, confident and reassured, with the greatest benefits coming from storytelling with peers, and developing trusting relationships with a team of professionals, with whom women were able to communicate in their own language. Women also discussed the pivotal role of the bicultural worker in the multidisciplinary care team. Challenges in the hospital during labor and birth were reported and included lack of professional interpreters and a lack of privacy.

Conclusion

Group pregnancy care has the potential to increase refugee background women's access to pregnancy care and information, sense of belonging, cultural safety using services, preparation for labor and birth, and care of a newborn.
Jean Laplanche: The Unconscious, The Id and the Other
Authors: Fletcher John
Published: January 2017

This paper is an attempt to present Jean Laplanche's interpretation of the Freudian field as one that is driven and shaped by opposing gravitational pulls. These he represents by developing Freud's analogy of the Copernican and psychoanalytic revolutions to demonstrate the successive decentrings and recentrings of the human subject in relation to a primal and formative other at the level of a psychoanalytic theory that is itself alternately both ‘Copernican’ and ‘Ptolemaic’. In doing so, he replicates those movements at work at the level of the formation of human subjectivity. Focusing on Freud's shifting conceptions of the unconscious, the drive and the id, this paper seeks to show how Laplanche radicalizes certain ‘Copernican’ elements of Freud's metapsychology to establish the primacy of the other and the dimension of ‘primal seduction’ in concepts intended by Freud to decentre the narcissistic illusions of the ego, but which are captured by regressive movements of thought, retreating to ‘Ptolemaic’ conceptions of an endogenous, biologically grounded development of subjectivity.
Structural improvement of new thiazolidinones compounds with antinociceptive activity in experimental chemotherapy‐induced painful neuropathy
Authors: Moreira Diogo Rodrigo Magalhaes , Santos Dourivaldo Silva , Espírito Santo Renan Fernandes do , Santos Flávia Evangelista dos , de Oliveira Filho Gevanio Bezerra , Leite Ana Cristina Lima , Soares Milena Botelho Pereira , Villarreal Cristiane Flora
Published: January 2017

Chemotherapy‐induced neuropathy is a disabling pain condition resulting from chemotherapy for cancers. Up to now, no drug is available to cure chemotherapy‐induced neuropathy. In the present study, we describe the structural design, synthesis, chemical and pharmacological characterization of 15 thiazolidinones, a class of potential analgesic compounds. The synthesis of new thiazolidinones was achieved by using the thiazolidinone heterocyclic as main structural pharmacophoric group and varying the substituents attached to the phenyl near to the iminic bond. The analgesic potential of the compounds was investigated in a mice model of oxaliplatin‐induced neuropathic pain, using von Frey, rota‐rod and open‐field tests. Except for compound 14, these thiazolidinones exhibited antinociceptive property without causing motor impairment. Thiazolidinones 12, 15 and 16 displayed a dose‐dependent antinociceptive effect, with similar efficacy and enhanced potency than gabapentin, the gold standard drug used for neuropathic pain. In addition, the antinociceptive activity of 16 lasted longer than gabapentin. The antinociceptive effect of thiazolidinones was prevented by GW9662, a PPARγ antagonist. The main antinociceptive compounds exhibited positive Lipinski's index, predicting their oral bioavailability. In conclusion, the structural design performed here led to the identification of new compounds endowed with potent antinociceptive activity, potentially useful to treat chemotherapy‐induced neuropathic pain.
Preoperative weight loss program targeting women with overweight and hypertrophy of the breast – a pilot study
Authors: Geiker N. R. W. , Horn J. , Astrup A.
Published: January 2017

Among women with hypertrophic breasts, the clear majority are overweight or obese. Owing to increased risk of complications, women with a body mass index (BMI) above 25 kg m
−2
are precluded from reduction mammaplasty. The primary aim was to investigate if intensive weight loss could ready women with overweight for breast reduction surgery. Six women, all overweight [BMI 30.9 {28.5; 35.8} kg m
−2
] with symptomatic hypertrophy of the breast, were included a 12‐week weight loss program. All women desired reduction mammaplasty and were motivated for preoperational weight loss. The first 8 weeks consisted of a formula‐based diet supplying 800 kcal daily, in the subsequent 4 weeks regular foods were reintroduced increasing the intake to 1200 kcal daily. Five women completed the trial, and achieved a median (range) weight loss of 10.2 (6.5; 19) kg. Initial breast volume was 1100–2500 mL per breast, this was reduced by 300 (200; 500) mL after the intervention; equivalent to approximately 19%. Waist, hip, upper arm and thorax circumference were significantly reduced following weight loss. At end of study, all the women still suffered from symptomatic breast hypertrophy to substantiate reduction mammaplasty. Surgeries were performed 2 months thereafter. A 12‐week intensive preoperative weight loss program enabled women with obesity for breast reduction surgery. Breast size was reduced proportionally more than total weight loss among women with hypertrophy.
Squamous cell carcinoma with enteric adenocarcinomatous differentiation
Authors: Emanuel Patrick O. , Desman Garrett , Tallon Ben
Published: January 2017

We report a highly unusual case of a primary cutaneous squamous cell carcinoma (SCC) with intermixed enteric‐type adenocarcinomatous dedifferentiation and a small component of undifferentiated mesenchymal differentiation. We believe this is the first time this form of phenotypic plasticity has been described in cutaneous SCC.
Responses of insect herbivores and herbivory to habitat fragmentation: a hierarchical meta‐analysis
Authors: Rossetti María Rosa , Tscharntke Teja , Aguilar Ramiro , Batáry Péter
Published: January 2017

Loss and fragmentation of natural habitats can lead to alterations of plant–animal interactions and ecosystems functioning. Insect herbivory, an important antagonistic interaction is expected to be influenced by habitat fragmentation through direct negative effects on herbivore community richness and indirect positive effects due to losses of natural enemies. Plant community changes with habitat fragmentation added to the indirect effects but with little predictable impact. Here, we evaluated habitat fragmentation effects on both herbivory and herbivore diversity, using novel hierarchical meta‐analyses. Across 89 studies, we found a negative effect of habitat fragmentation on abundance and species richness of herbivores, but only a non‐significant trend on herbivory. Reduced area and increased isolation of remaining fragments yielded the strongest effect on abundance and species richness, while specialist herbivores were the most vulnerable to habitat fragmentation. These fragmentation effects were more pronounced in studies with large spatial extent. The strong reduction in herbivore diversity, but not herbivory, indicates how important common generalist species can be in maintaining herbivory as a major ecosystem process.
Progress report on new antiepileptic drugs: A summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII)
Authors: Bialer Meir , Johannessen Svein I. , Levy René H. , Perucca Emilio , Tomson Torbjörn , White H. Steve
Published: January 2017

The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26–29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include anAEDapproved in 2016 (brivaracetam), 12 drugs in phase I–IIIclinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2‐deoxy‐d‐glucose, everolimus, fenfluramine, huperzine A, minocycline,SAGE‐217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives,sec‐butylpropylacetamide,FV‐082, 1OP‐2198,NAX810‐2, andSAGE‐689). Overall, the results presented at the Conference show that considerable efforts are ongoing into discovery and development ofAEDs with potentially improved therapeutic profiles compared with existing agents. Many of the drugs discussed in this report show innovative mechanisms of action and many have shown promising results in patients with pharmacoresistant epilepsies, including previously neglected rare and severe epilepsy syndromes.
Harmonizing the regulation of invertebrate biological control agents in the EPPO region: using the NAPPO region as a model
Authors: Mason P. G. , Everatt M. J. , Loomans A. J. M. , Collatz J.
Published: January 2017

Harmonized regulation of invertebrate biological control agents (IBCAs) is a major challenge for the 51 countries of the European and Mediterranean Plant Protection Organization (EPPO). Although some of these member countries in the EPPO region have well‐defined regulations and follow a common approach, others do not. The North American Plant Protection Organization (NAPPO) has achieved a common approach in North America through the development of Regional Standards for Phytosanitary Measures specific to IBCAs that outline the information required for submission of a request to release an agent. NAPPO has also developed a process to ensure that submissions are reviewed by experts and regulatory officials in all three member countries. It is proposed that EPPO takes advantage of the experience of NAPPO in developing a harmonized approach for regulating IBCAs.
Unique mouse monoclonal antibodies reactive with maturation‐related epitopes on type VII collagen
Authors: Hayakawa Taihei , Hirako Yoshiaki , Teye Kwesi , Tsuchisaka Atsunari , Koga Hiroshi , Ishii Norito , Karashima Tadashi , Kaneda Minori , Oyu Yuka , Tateishi Chiharu , Sugawara Koji , Yonamine Ayano , Shinkuma Satoru , Shimizu Hiroshi , Fukano Hideo , Shimozato Kazuo , Nguyen Ngon T. , Marinkovich M. Peter , Tsuruta Daisuke , Hashimoto Takashi
Published: January 2017

In this study, we generated a new set of monoclonal antibodies (mAbs) to bovine and human type VII collagen (COL7) by immunizing mice with bovine cornea‐derived basement membrane zone (BMZ) fraction. The four mAbs, tentatively named as COL7‐like mAbs, showed speckled subepidermal staining in addition to linear BMZ staining of normal human skin and bovine cornea, a characteristic immunofluorescence feature of COL7, but showed no reactivity with COL7 by in vitro biochemical analyses. Taking advantage of the phenomenon that COL7‐like mAbs did not react with mouse BMZ, we compared immunofluorescence reactivity between wild‐type and COL7‐rescued humanized mice and found that COL7‐like mAbs reacted with BMZ of COL7‐rescued humanized mice. In ELISAs, COL7‐like mAbs reacted with intact triple‐helical mammalian recombinant protein (RP) of COL7 but not with bacterial RP. Furthermore, COL7‐like mAbs did not react with COL7 within either cultured DJM‐1 cells or basal cells of skin of a bullous dermolysis of the newborn patient. These results confirmed that COL7‐like mAbs reacted with human and bovine COL7. The epitopes for COL7‐like mAbs were considered to be present only on mature COL7 after secretion from keratinocytes and deposition to BMZ and to be easily destroyed during immunoblotting procedure. Additional studies indicated association of the speckled subepidermal staining with both type IV collagen and elastin. These unique anti‐COL7 mAbs should be useful in studies of both normal and diseased conditions, particularly dystrophic epidermolysis bullosa, which produces only immature COL7.
Multifunctional benefits of sainfoin mixtures: Effects of partner species, sowing density and cutting regime
Authors: Malisch C. S. , Suter D. , Studer B. , Lüscher A.
Published: January 2017

Grass–legume mixtures have proven successful at improving the sustainability of grasslands. Their ability to suppress unsown species is particularly important for sainfoin (Onobrychis viciifolia), a forage crop with valuable bioactive compounds, yet low competitiveness. In this 3‐year study, the suitability of six partner species cultivated in mixtures with sainfoin at different annual numbers of cuts and partner sowing densities were evaluated. Mixture yields outperformed average monoculture yields by 31%, reduced the ratio of unsown species by 65% and increased the symbiotic N2 fixation up to 158 kg ha−1. A key finding of the study was the highly differential patterns of development of the partner grass species over the 3 years. These patterns of development had a large effect on the persistency of the proportion of sainfoin in the mixtures, which varied in the third year between 17% (when grown with Dactylis glomerata) and 38% (with Lolium perenne). These findings contribute to the further development of sustainable grass–legume systems, as evidence for the successful cultivation of sainfoin as an alternative legume species can help diversification, and knowledge of mixture development supports more persistent legume proportions.
Wonders of Nature in each Quarter of the World: a nineteenth century geological game
Authors: Dove Jane
Published: January 2017

Wonders of Nature in each Quarter of the World was an early nineteenth century educational board game designed to teach children about some of the natural wonders of the world, such as volcanoes. The game was produced at a time of advances in geological thinking and geographical expeditions and this study places such changes and events within the context of the pastime, and presents an interesting window on the way geology was perceived almost two centuries ago.
Autophagy‐related genes in Helicobacter pylori infection
Authors: Tanaka Shingo , Nagashima Hiroyuki , Uotani Takahiro , Graham David Y. , Yamaoka Yoshio
Published: January 2017

Background

In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy‐related genes in H. pylori infection are not yet fully understood.

Materials and Methods

We analyzed autophagy‐related gene expression in H. pylori‐infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy‐related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection.

Results

Microarray analysis of 226 autophagy‐related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori‐positive specimens (n=86) were significantly less than those in H. pylori‐negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori‐positive and 77 H. pylori‐negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18‐0.91) relative to the AA/AG genotypes.

Conclusions

Autophagy‐related gene expression profiling using high‐throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells.
Effects of UV‐B on vitamin C, phenolics, flavonoids and their related enzyme activities in mung bean sprouts (Vigna radiata)
Authors: Wang Hanbo , Gui Mengyuan , Tian Xue , Xin Xin , Wang Taixia , li Jingyuan
Published: January 2017

In this study, ultraviolet‐B radiation (UV‐B) was used to effect the accumulation of vitamin C, phenolics and flavonoids in mung bean sprouts. Results indicate that the content of vitamin C and flavonoids increased during the initial period, and after a brief decline, reached peak levels of 25.29 ± 1.02 mg/100 g FW and 726.67 ± 7.35 mg/100 g DW, respectively, at 2.5 h (1.845 kJ m−2), while the peak levels of the phenolics were 10741.33 ± 68.04 mg/100 g DW. The thiobarbituric acid reactive substances (TBARS) content decreases with the increase in irradiation time. The activities of the related enzymes, including phenylalanine ammonia‐lyase (PAL), L‐galactono‐1, 4‐lactone dehydrogenase (GalLDH), peroxidase (POD), polyphenol oxidase (PPO) and chalcone isomerase (CHI) were determined, which showed strong correlations with the change in the content of vitamin C, phenolics and flavonoids. In conclusion, the accumulation of vitamin C, phenolics and flavonoids in mung bean sprouts can be promoted by a low‐dose UV‐B irradiation.
Sweetened beverage intake in association to energy and sugar consumption and cardiometabolic markers in children
Authors: Seferidi P. , Millett C. , Laverty A. A.
Published: January 2017

Background

Artificially sweetened beverages (ASBs) are promoted as healthy alternatives to sugar‐sweetened beverages (SSBs) in order to reduce sugar intake, but their effects on weight control and glycaemia have been debated. This study examines associations of SSBs and ASBs with energy and sugar intake and cardiometabolic measures.

Methods

One thousand six hundred eighty‐seven children aged 4–18 participated in the National Diet and Nutrition Survey Rolling Programme (2008/9–2011/12) in the UK. Linear regression was used to examine associations between SSBs and ASBs and energy and sugar, overall and from solid foods and beverages, and body mass index, waist‐to‐hip ratio and blood analytes. Fixed effects linear regression examined within‐person associations with energy and sugar.

Results

Compared with non‐consumption, SSB consumption was associated with higher sugar intake overall (6.1%; 4.2, 8.1) and ASB consumption with higher sugar intake from solid foods (1.7%; 0.5, 2.9) but not overall, mainly among boys. On SSB consumption days, energy and sugar intakes were higher (216 kcal; 163, 269 and 7.0%; 6.2, 7.8), and on ASB consumption days, sugar intake was lower (−1.0%; −1.8, −0.1) compared with those on non‐consumption days. SSB and ASB intakes were associated with higher levels of blood glucose (SSB: 0.30 mmol L−1; 0.11, 0.49 and ASB: 0.24 mmol L−1; 0.06, 0.43) and SSB intake with higher triglycerides (0.29 mmol L−1; 0.13, 0.46). No associations were found with other outcomes.

Conclusion

Sugar‐sweetened beverage intake was associated with higher sugar intake and both SSBs and ASBs with a less healthy cardiometabolic profile. These findings add to evidence that health policy should discourage all sweetened beverage consumption.
The impact of ‘free choice’: Family reforms of France and Belgium, a synthetic control analysis
Authors: Podestà Federico
Published: January 2017

Between the 1980s and the late 1990s, France and Belgium introduced two long‐leave schemes and several measures to support childcare at home. Although this change was presented under the umbrella of the ‘free‐choice‐for‐women’ rhetoric, it moved both countries towards a more familistic model. To evaluate the impact of this reform phase on female labour force participation, the present study employed the synthetic control method. This approach made it possible to contrast the evolution of the French and Belgian female labour force participation rates, observed in consequence of the implementation of the policies under investigation, with the corresponding evolution of the same rates reconstructed in the absence of such family programmes. The results of this exercise suggest that if France and Belgium had not undergone this policy treatment, their female labour market participation rates would have been higher than those actually measured.

Key Practitioner Message: • Combining long‐leave schemes with low incentives to support employment of a childminder obstructs female labour force participation.
Secukinumab administration by autoinjector maintains reduction of plaque psoriasis severity over 52 weeks: results of the randomized controlled JUNCTURE trial
Authors: Lacour J.‐P. , Paul C. , Jazayeri S. , Papanastasiou P. , Xu C. , Nyirady J. , Fox T. , Papavassilis C.
Published: January 2017

Background

User satisfaction is an important factor associated with treatment adherence in chronic diseases including moderate‐to‐severe psoriasis.

Objective

To evaluate the efficacy, safety and patient acceptability of 300 and 150 mg secukinumab – a fully human anti‐interleukin‐17A monoclonal antibody that has demonstrated efficacy in the treatment of patients with moderate‐to‐severe plaque psoriasis – self‐administered by autoinjection.

Methods

Patients with moderate‐to‐severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg or placebo self‐administered by autoinjection at baseline, Weeks 1, 2 and 3 and then every 4 weeks from Week 4 to Week 48. Efficacy responses [≥75/90/100% improvement in Psoriasis Area and Severity Index (PASI 75/90/100) and clear/almost clear skin by Investigator's Global Assessment 2011 modified version (IGA mod 2011 0/1)] were measured at Week 52. Patient‐reported usability of the autoinjector was evaluated by the self‐injection assessment questionnaire to Week 48.

Results

At Week 52 with secukinumab 300 mg, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 81.4/64.1/38.8% and 69.6% of patients, respectively, by multiple imputation. At Week 52 with secukinumab 150 mg, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 75.2/57.4/33.1% and 60.2% of patients, respectively, by multiple imputation. Patient‐assessed acceptability of the autoinjector remained high to Week 48. The proportion of patients experiencing adverse events was greater with secukinumab 300 mg (88.6%) than with secukinumab 150 mg (78.7%).

Conclusion

Self‐administration of secukinumab using an autoinjector was associated with robust and sustained efficacy, a good safety profile and high acceptability.