bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin
Authors: Song Chao , Zhao Jiamin , Zhang Jingcheng , Mao Tingchao , Fu Beibei , Wu Haibo , Zhang Yong
Published: February 2017

Oxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). PGC-1α interacted with the estrogen-related receptor alpha (ERRα) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.
HTSvis: A web app for exploratory data analysis and visualization of arrayed high-throughput screens
Authors: Scheeder Christian , Heigwer Florian , Boutors Michael
Published: February 2017

The analysis and visualization of arrayed high-throughput screens (HTS), such as cell-based RNAi or small-molecule HTS experiments, requires specialized computational methods. Software packages such as the R/Bioconductor package cellHTS have been developed to support the analysis and are broadly used by the high-throughput screening community. However, exploratory data analysis and integration of screening results remains challenging due to the size of produced data tables in multi-channel experiments and the lack of user-friendly tools to integrate and visualize screening results. Here we present HTSvis, an R/Shiny open-source web application for interactive visualization and exploratory analysis of arrayed high-throughput data. Using a light-weight infrastructure suitable for desktop computers, HTSvis can be used to visualize raw data, perform quality control and interactively visualize screening results from single- to multi-channel measurements, such as image-based, screens. Input data can either be a result file obtained upon analysis with cellHTS or a generic table with raw or analyzed data from, e.g. a high-content microscopy screen. HTSvis can be downloaded fromhttp://github.com/boutroslab/HTSvis.
Variability in fitness effects and the limitations of fitness optimization
Authors: Graves Christopher J , Weinreich Daniel M
Published: February 2017

Evolutionary biologists commonly assess the evolutionary advantage of an allele based on its effects on the lifetime survival and reproduction of individuals. However, alleles affecting traits like sex, evolvability, and cooperation can cause fitness effects that depend heavily on differences in the environmental, genetic, and social context of individuals carrying the allele. This variability makes it difficult to summarize the evolutionary fate of an allele based solely on its effects on any one individual. In this review we show how attempts to average over variability in the fitness effects of an allele can sometimes cause misleading results. We then describe a number of intriguing new evolutionary phenomena that have emerged in studies that explicitly model the fate of alleles that influence long-term lineage dynamics. We conclude with prospects for generalizations of population genetics theory and discuss how this theory might be applied to the evolution of infectious diseases.
PhageTerm: a Fast and User-friendly Software to Determine Bacteriophage Termini and Packaging Mode using randomly fragmented NGS data
Authors: Garneau Julian , Depardieu Florence , Fortier Louis-Charles , Bikard David , Monot Marc
Published: February 2017

Bacteriophages are the most abundant viruses on earth and display an impressive genetic as well as morphologic diversity. Among those, the most common order of phages is the Caudovirales, whose viral particles packages linear double stranded DNA (dsDNA). In this study we investigated how the information gathered by high throughput sequencing technologies can be used to determine the DNA termini and packaging mechanisms of dsDNA phages. The wet-lab procedures traditionally used for this purpose rely on the identification and cloning of restriction fragment which can be delicate and cumbersome. Here, we developed a theoretical and statistical framework to analyze DNA termini and phage packaging mechanisms using next-generation sequencing data. Our methods, implemented in the PhageTerm software, work with sequencing reads in fastq format and the corresponding assembled phage genome.

PhageTerm was validated on a set of phages with well-established packaging mechanisms representative of the termini diversity: 5’cos (lambda), 3’cos (HK97), pac (P1), headful without a pac site (T4), DTR (T7) and host fragment (Mu). In addition, we determined the termini of 9Clostridium difficilephages and 6 phages whose sequences where retrieved from the sequence read archive (SRA).

A direct graphical interface is available as a Galaxy wrapper version athttps://galaxy.pasteur.frand a standalone version is accessible athttps://sourceforge.net/projects/phageterm/.
Health quality of seed potato and yield losses in Ecuador
Authors: Navarrete Israel , Panchi Nancy , Kromann Peter , Forbes Gregory A. , Andrade-Piedra Jorge L.
Published: February 2017

Low potato productivity in Ecuador is partly attributed to the use of low quality seed tubers. However, seed health quality in Ecuador, and its interaction with altitude and yield has been poorly investigated. We surveyed 11 farmers’ fields in Ecuador in 2010 to determine incidence and severity of pathogens and pests affecting foliage and seed tubers, and to determine the influence of altitude and seed sources over seed health quality (pathogen and pest diversity in/on the seed tuber). Additionally, a field experiment was planted in CIP-Quito using assessed seed tubers collected from surveyed farmers’ fields, during 2010 and 2011, to determine yield responses to seed health quality. Results show that foliage was mainly affected by late blight and flea beetle damages while seed tubers were predominantly affected by black scurf, andean weevil damages, potato virus S and potato virus X. We found that seed health quality was similar among farmers’ seed sources, and detected that increase in altitude decreased seed-borne virus diversity. Only seed-borne pathogens and presence of mechanical damages were found to explain yield variation. Seed-borne pathogens affecting yield variation were black scurf on seed tubers, potato virus S, and potato yellow vein virus. However, these factors changed when regressions were performed per seed source or variety. The yield responses to seed health quality of each variety should be considered to fine-tune integrated pest management strategies.
Frequency-specific directed interactions in the human brain network for language
Authors: Schoffelen J. M. , Hultén A. , Lam N. , Marquand A. , Uddén J. , Hagoort P.
Published: February 2017

The brain’s remarkable capacity for language requires bidirectional interactions between functionally specialized brain regions. We used magnetoencephalography to investigate interregional interactions in the brain network for language, while 102 participants were reading sentences. Using Granger causality analysis, we identified inferior frontal cortex and anterior temporal regions to receive widespread input, and middle temporal regions to send widespread output. This fits well with the notion that these regions play a central role in language processing. Characterization of the functional topology of this network, using data-driven matrix factorization, which allowed for partitioning into a set of subnetworks, revealed directed connections at distinct frequencies of interaction. Connections originating from temporal regions peaked at alpha frequency, whereas connections originating from frontal and parietal regions peaked at beta frequency. These findings indicate that processing different types of linguistic information may depend on the contributions of distinct brain rhythms.

One Sentence Summary

Communication between language relevant areas in the brain is supported by rhythmic synchronization, where different rhythms reflect the direction of information flow.
Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens
Authors: Amberg-Johnson Katherine , Hari Sanjay B. , Ganesan Suresh M. , Lorenzi Hernan A. , Sauer Robert T. , Niles Jacquin C. , Yeh Ellen
Published: February 2017

The malaria parasitePlasmodium falciparumand related apicomplexan pathogens contain an essential plastid organelle, the apicoplast, which is a key anti-parasitic target. Derived from secondary endosymbiosis, the apicoplast depends on novel, but largely cryptic, mechanisms for protein/lipid import and organelle inheritance during parasite replication. These critical biogenesis pathways present untapped opportunities to discover new parasite-specific drug targets. We used an innovative screen to identify actinonin as having a novel mechanism-of-action inhibiting apicoplast biogenesis. Resistant mutation, chemical-genetic interaction, and biochemical inhibition demonstrate that the unexpected target of actinonin inP. falciparumandToxoplasma gondiiis FtsH1, a homolog of a bacterial membrane AAA+ metalloprotease.PfFtsH1 is the first novel factor required for apicoplast biogenesis identified in a phenotypic screen. Our findings demonstrate that FtsH1 is a novel and, importantly, druggable antimalarial target. Development of FtsH1 inhibitors will have significant advantages with improved drug kinetics and multistage efficacy against multiple human parasites.
Incidental context information increases recollection
Authors: Ameen-Ali Kamar E. , Norman Liam J. , Eacott Madeline J. , Easton Alexander
Published: February 2017

The current study describes a receiver-operating characteristic (ROC) task for human participants based on the spontaneous recognition memory paradigms typically used with rodents. Recollection was significantly higher when an object was in the same location and background as at encoding, a combination used to assess episodic-like memory in animals, but not when only one of these task-irrelevant cues was present. The results show that incidentally encoded cue information can determine the degree of recollection, and opens up the possibility of assessing recollection across species in a single experimental paradigm, allowing better understanding of the cognitive and biological mechanisms at play.
Ultra-short and ultra-intense X-ray free-electron laser single pulse in one-dimensional photonic crystals
Authors: André Jean-Michel , Jonnard Philippe
Published: February 2017

The propagation within a one-dimensional photonic crystal of a single ultra-short and ultra-intense pulse delivered by an X-ray free-electron laser is analysed with the framework of the time-dependent coupled-wave theory in non-linear media. It is shown that the reflection and the transmission of an ultra-short pulse present a transient period conditioned by the extinction length and also the thickness of the structure for transmission. For ultra-intense pulses, non-linear effects are expected: they could give rise to numerous phenomena, bi-stability, self-induced transparency, gap solitons, switching, etc., which have been previously shown in the optical domain.
5-Methylbenzo[d][2,1,3]selenadiazole
Authors: Ouahine Halima , Ait Ali Mustapha , El Firdoussi Larbi , Spannenberg Anke
Published: February 2017

In the crystal of the title compound, C7H6N2Se, the molecules are arranged in rods along theb-axis direction and form dimeric units due to intermolecular Se...N contacts of 2.982 (2) Å. The molecules are further linked by weak π–π stacking interactions between the 2,1,3-selenadiazole and six-membered aromatic rings [centroid–centroid distance = 3.8509 (11) Å and ring slippage = 1.539 (3) Å].
China's Emergent City‐Region Governance: A New Form of State Spatial Selectivity through State‐orchestrated Rescaling
Authors: Wu Fulong
Published: February 2017

This article examines the emergence of city‐region governance as a specific state spatial selectivity in post‐reform China. The process has been driven by the state in response to the crisis of economic decentralization, and to vicious inter‐city competition and uncoordinated development. As part of the recentralization of state power, the development of urban clusters (chengshiqun) as interconnected city‐regions is now a salient feature of ‘new urbanization' policy. I argue in this article that the Chinese city‐region corresponds to specific logics of scale production. Economic globalization has led to the development of local economies and further created the need to foster ‘regional competitiveness'. To cope with regulatory deficit at the regional level, three mechanisms have been orchestrated by the state: administrative annexation, spatial plan preparation and regional institution building, which reflect recent upscaling in post‐reform governance.
Justice As Subject and Object of Planning
Authors: Lake Robert W.
Published: February 2017

Considerations of justice have moved to a central place in planning theory following Susan Fainstein's (2010) eloquent plea to elevate justice to the principal criterion for the evaluation of planning practice. Justice based on this understanding is the object of planning—the normative end that planning practice should strive to achieve. In this essay I explore the implications for planning theory and practice of making justice the subject rather than the object of planning. This formulation places justice at the center of rather than regarding it as the outcome of practice: what is of concern here is planning as the practice of justice rather than the justice of planning practice. The question for planning in this mode shifts from ‘Is this a just outcome?' to ‘What is justice in this situation?'. Based on John Dewey's pragmatist philosophy, this question transcends the dualisms between subject and object, and process and outcome, by understanding outcomes as already formulated (what Dewey called ends‐in‐view) in the process of their production. A planning process that takes justice as its subject is anti‐foundational and contextual rather than universal, anticipatory rather than retrospective, generative of solutions rather than evaluative of outcomes, culturally encompassing rather than project‐delimited, and inclusively democratic rather than expert‐driven. Examples from a variety of sources illustrate the practice of justice as the subject of planning.
Factors affecting uptake of postmortem examination in the prenatal, perinatal and paediatric setting
Authors: Lewis C , Hill M , Arthurs OJ , Hutchinson C , Chitty LS , Sebire NJ
Published: February 2017

Background

Postmortem examination is the single most useful investigation in providing information to parents about why their baby or child died. Despite this, uptake remains well below the recommended 75%.

Objective

To address the question ‘what are the barriers and motivators to perinatal, prenatal and paediatric PM examination?’

Search strategy

Key databases including Pubmed and CINAHL; Cochrane library, websites of relevant patient organisations, hand search of key journals, first and last authors and references.

Selection criteria

Peer‐reviewed qualitative, quantitative or mixed methods research examining factors affecting uptake or decline of perinatal or paediatric postmortem examination.

Data collection and analysis

Narrative synthesis; findings were compared across studies to examine interrelations.

Main results

Seven major themes describing barriers to postmortem uptake were identified: dislike of invasiveness, practicalities of the procedure, organ retention issues, protective parenting, communication and understanding, religion and culture and professional or organisational barriers. Six major themes related to factors which facilitated parental consent were identified: desire for information, contributing to research, coping and well‐being, respectful care, minimally invasive options, and policy and practice. There were a number of themes in the literature that reflected best practice.

Conclusion

Findings highlight the need for better health professional education and the fact some concerns may be mitigated if less invasive methods of postmortem were routinely available. New consent packages and codes of practice may have a positive impact on perception of examination after death. The landscape is changing; further research is necessary to assess the impact on postmortem uptake rates.

Tweetable abstract

Systematic review to explore the barriers and motivators to perinatal, prenatal and paediatric postmortem examination.
Efficacy of salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer: a systematic review
Authors: Darelius A , Lycke M , Kindblom JM , Kristjansdottir B , Sundfeldt K , Strandell A
Published: February 2017

Background

It has been argued that salpingectomy would reduce the risk of epithelial ovarian cancer (EOC), based on the theory of the tube being the site of origin.

Objectives

To conduct a systematic review of ‘salpingectomy’ associated with ovarian cancer risk and ‘salpingectomy with concomitant hysterectomy’ on outcomes of complications including endocrine function.

Search strategy

A comprehensive search was conducted in PubMed, Embase, and the Cochrane library.

Selection criteria

Original studies and systematic reviews were eligible.

Data collection and analysis

Each article was quality assessed. Data were extracted and, when possible, pooled in meta‐analyses. The certainty of evidence across studies was evaluated using GRADE.

Main results

Of 844 articles found, 11 were included. No study evaluated risk reduction for EOC after salpingectomy in conjunction with hysterectomy. Two retrospective studies reported a reduced ovarian cancer risk after indicated salpingectomy, compared with no surgery: adjusted hazard ratio 0.65 (95% confidence interval, 95% CI 0.52–0.81) and adjusted odds ratio 0.58 (95% CI 0.36–0.95). Complications did not differ between groups with or without salpingectomy, but were non‐systematically reported. Ovarian endocrine function, measured with surrogate outcomes, did not differ at short‐term follow‐up in randomised or observational studies. The certainty of evidence was very low or low for all outcomes.

Conclusions

There is currently insufficient evidence to state that opportunistic salpingectomy reduces the risk of EOC. The impact on long‐term endocrine function is unknown. The heterogeneity in results and identified knowledge gaps stress the need for a prospective trial.

Tweetable abstract

Insufficient evidence for prophylactic removal of the fallopian tubes for risk reduction of ovarian cancer.
Testing for a Debt‐Threshold Effect on Output Growth
Authors: Lee Sokbae , Park Hyunmin , Seo Myung Hwan , Shin Youngki
Published: February 2017

Using the Reinhart–Rogoff dataset, we find a debt threshold not around 90 per cent but around 30 per cent, above which the median real gross domestic product (GDP) growth falls abruptly. Our work is the first to formally test for threshold effects in the relationship between public debt and median real GDP growth. The null hypothesis of no threshold effect is rejected at the 5 per cent significance level for most cases. While we find no evidence of a threshold around 90 per cent, our findings from the post‐war sample suggest that the debt threshold for economic growth may exist around a relatively small debt‐to‐GDP ratio of 30 per cent. Furthermore, countries with debt‐to‐GDP ratios above 30 per cent have GDP growth that is 1 percentage point lower at the median.
Protest Responses and Willingness to Accept: Ecosystem Services Providers’ Preferences towards Incentive‐Based Schemes
Authors: Villanueva Anastasio J. , Glenk Klaus , Rodríguez‐Entrena Macario
Published: February 2017

The identification and treatment of protest responses in stated preference surveys has long been subject to debate. We analyse protest responses while investigating ecosystem services providers’ preferences for incentive‐based schemes. We use a choice experiment for olive farmers’ preferences for agri‐environmental scheme participation in southern Spain. Our two main objectives are: first, to identify and discuss a range of possible motives for protest responses that emerge in a WTA context; second, we analyse the impact on WTA estimates of censoring serial non‐participation linked to protest or high compensation requirements (very high takers). Using a random parameter logit model in WTA space, we find that the inclusion or exclusion of serial non‐participants in the analysis can have a significant impact on marginal and total WTA estimates. Based on the findings, the paper makes recommendations on how to reduce the incidence of protest responses through survey design, regarding the identification of protesters as opposed to very high takers, and regarding the treatment of both groups of respondents for WTA estimation.
Forensic Identification of Bipartite Patella Misdiagnosed as Patella Fracture
Authors: Ma Jingyuan , Shi Fang , Huang Chongya , Gu Shanzhi
Published: February 2017

Bipartite patella is recognized as a developmental anomaly of ossification. Most of them are asymptomatic and are discovered incidentally. Bipartite patella is sometimes misdiagnosed as a patella fracture, because the x‐ray images of both these conditions may appear very similar. In this case, the patient complained of left knee pain after x‐ray films revealed a fracture‐like line in the left patella. The patient was then diagnosed as having a patella fracture. In China, the injury degree is categorized as serious injury, minor injury, and trivial injury. As the injury degree of patellar fracture is identified as minor injury, the defendant who injured the patient will be sentenced to prison for ≤3 years. However, the defendant objected to this judgment and applied for the second evaluation of injury degree. On the basis of the site of injury, clinical manifestations, and imaging findings, we diagnosed the patient with bipartite patella which belongs to normal anatomic variant. Therefore, the injury degree of the patient was not minor injury.
Using Cluster Analysis and ICP‐MS to Identify Groups of Ecstasy Tablets in Sao Paulo State, Brazil
Authors: Maione Camila , de Oliveira Souza Vanessa Cristina , Togni Loraine Rezende , da Costa José Luiz , Campiglia Andres Dobal , Barbosa Fernando , Barbosa Rommel Melgaço
Published: February 2017

The variations found in the elemental composition in ecstasy samples result in spectral profiles with useful information for data analysis, and cluster analysis of these profiles can help uncover different categories of the drug. We provide a cluster analysis of ecstasy tablets based on their elemental composition. Twenty‐five elements were determined by ICP‐MS in tablets apprehended by Sao Paulo's State Police, Brazil. We employ the K‐means clustering algorithm along with C4.5 decision tree to help us interpret the clustering results. We found a better number of two clusters within the data, which can refer to the approximated number of sources of the drug which supply the cities of seizures. The C4.5 model was capable of differentiating the ecstasy samples from the two clusters with high prediction accuracy using the leave‐one‐out cross‐validation. The model used only Nd, Ni, and Pb concentration values in the classification of the samples.
Organisational consequences of asymmetries in task dependence: the moderating role of HR practices
Authors: De Jong Simon B. , Kunze Florian , Bruch Heike
Published: February 2017

This study integrates recent advances in interdependence theory with the literature on commitment‐based HR practices. New research on interdependence theory suggests that differences, or asymmetries, in task dependence among organisational members can cause interests to diverge. Prior research has shown that this can negatively affect interpersonal relations, individual outcomes and team processes. However, these insights gained on the dyadic, individual and team levels of analysis have not yet been explored at the organisational level and, until now, no research had yet connected these advances in interdependence theory to the field of HRM research. Hence, the current study investigates (a) whether asymmetries in task dependence do (or do not) matter at the organisational level and affect organisational effectiveness, (b) why this relationship may work by assessing a key mediator, namely, trust climate and (c) if and how these relationships can be altered by commitment‐based HR practices. Our moderated‐mediation model was tested and fully supported by a multi‐source data set of 8,390 employees from 67 organisations.
Strategic human resource management, human capital and competitive advantage: is the field going in circles?
Authors: Delery John E. , Roumpi Dorothea
Published: February 2017

The resource‐based view (RBV) of the firm has been consistently used as a backdrop in strategic human resource management (SHRM) research and has the potential to bridge the ‘micro–macro’ divide. The tension between the SHRM and the strategic human capital literature, however, signifies that RBV has not reached its potential. In this paper, we begin with a brief review of the conceptual logic linking human resource management (HRM) practices and firm outcomes that aim at highlighting the different treatment of RBV in the SHRM and strategic human capital literatures. We then propose a conceptual model that suggests that HRM practices are not simple levers that enable firms to create sustainable competitive advantage, as most of the strategic human capital research postulates. On the contrary, we argue that HRM practices can contribute to a firm's sustainable competitive advantage not only by enhancing employees' ability, and offering motivation and opportunities, but also by shaping supply‐side and demand‐side mobility constraints.
Longitudinal study of clinical prognostic factors in patients with early rheumatoid arthritis: the PREDICT study
Authors: Bird Paul , Nicholls Dave , Barrett Rina , de Jager Julien , Griffiths Hedley , Roberts Lynden , Tymms Kathleen , McCloud Philip , Littlejohn Geoffrey ,   the OPAL consortium
Published: February 2017

Aim

To assess the association between baseline clinical prognostic factors and subsequent Disease Activity Score of 28 joints (DAS28) remission in early rheumatoid arthritis (RA).

Methods

Data were collected using point of care clinical software from participating rheumatology centres. Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12–24 months, who had at least 6 months of follow‐up data and a DAS28‐ESR (erythrocyte sedimentation rate) score recorded between 12 and 24 months from first being seen for RA were included. Data collected included baseline demographics, mode of disease onset, pattern of joint involvement at onset, smoking status, DAS28, rheumatoid factor (RF), anti‐citrullinated peptide antibodies (ACPA), time from symptom onset to presentation and disease activity at baseline. Univariate and multivariate logistic regression of DAS28‐ESR remission between 12 and 24 months after first assessment were performed.

Results

Data from 1017 patients were analyzed: 70% female; mean age 60 years (SD: 14.7); 70% RF‐positive, 58% ACPA‐positive. The strongest age and sex adjusted baseline predictors of DAS28‐ESR remission at 12–24 months were remission at baseline (odds ratio [OR]: 4.49, 95% CI: 2.17–9.29, P < 0.001), being male (OR: 2.42, 95% CI: 1.46–4.01, P < 0.001), abstaining from alcohol (P < 0.001) and being lower weight (OR: 0.98, 95% CI: 0.97–1.00, P = 0.015). There was no statistically significant association between joint onset patterns, mode of onset, RF, ACPA or smoking status.

Conclusion

In this observational study, patients with early RA at risk of not achieving remission include those with high disease activity at baseline, women, those who drink alcohol and those with higher body weight.
Alcohol Mixed with Energy Drinks: Daily Context of Use
Authors: Linden‐Carmichael Ashley N. , Lau‐Barraco Cathy
Published: February 2017

Background

The link between use of alcohol mixed with energy drinks (AmEDs) and alcohol‐related harms is well established, but limited research has examined the context in which AmEDs are consumed. Identifying the social and environmental characteristics of use may illuminate whether AmEDs are used in settings that could increase the likelihood of engaging in risky behaviors or experiencing harms. This study used a 2‐week daily diary assessment to compare days in which AmEDs were consumed (“AmED days”) and days where other types of alcohol were used (“non‐AmED days”) on where, when, and with whom drinking occurred.

Methods

Participants were 122 (90 women) heavy drinking college students who reported mixing caffeine with alcohol at least once in the past week. Data were collected across 389 drinking days; 40 of these days involved AmED use.

Results

Multilevel modeling findings revealed that odds of drinking AmEDs were higher on days where individuals drank at a bar or club and drank at home relative to other locations. In addition, odds of pregaming were higher on AmED days as compared to non‐AmED days. AmED use was linked with lower odds of drinking game behavior.

Conclusions

Overall, AmEDs appear to be consumed in potentially risky contexts. In combination with prior findings that AmED days are linked with heavier alcohol use and more harms experienced, these findings support the unique nature of AmED consumption in terms of the factors that may predict or maintain potentially hazardous drinking patterns.
A systematic review of visual processing and associated treatments in body dysmorphic disorder
Authors: Beilharz F. , Castle D. J. , Grace S. , Rossell S. L.
Published: February 2017

Objective

Recent advances in body dysmorphic disorder (BDD) have explored abnormal visual processing, yet it is unclear how this relates to treatment. The aim of this study was to summarize our current understanding of visual processing in BDD and review associated treatments.

Method

The literature was collected through PsycInfo and PubMed. Visual processing articles were included if written in English after 1970, had a specific BDD group compared to healthy controls and were not case studies. Due to the lack of research regarding treatments associated with visual processing, case studies were included.

Results

A number of visual processing abnormalities are present in BDD, including face recognition, emotion identification, aesthetics, object recognition and gestalt processing. Differences to healthy controls include a dominance of detailed local processing over global processing and associated changes in brain activation in visual regions. Perceptual mirror retraining and some forms of self‐exposure have demonstrated improved treatment outcomes, but have not been examined in isolation from broader treatments.

Conclusion

Despite these abnormalities in perception, particularly concerning face and emotion recognition, few BDD treatments attempt to specifically remediate this. The development of a novel visual training programme which addresses these widespread abnormalities may provide an effective treatment modality.
Anticonvulsants and suicide attempts in bipolar I disorders
Authors: Bellivier F. , Belzeaux R. , Scott J. , Courtet P. , Golmard J.‐L. , Azorin J.‐M.
Published: February 2017

Objective

To identify risk factors for suicide attempts (SA) in individuals commencing treatment for a manic or mixed episode.

Method

A total of 3390 manic or mixed cases with bipolar disorder (BD) type I recruited from 14 European countries were included in a prospective, 2‐year observational study. Poisson regression models were used to identify individual and treatment factors associated with new SA events. Two multivariate models were built, stratified for the presence or absence of prior SA.

Results

A total of 302 SA were recorded prospectively; the peak incidence was 0–12 weeks after commencing treatment. In cases with a prior history of SA, risk of SA repetition was associated with younger age of first manic episode (P = 0.03), rapid cycling (P < 0.001), history of alcohol and/or substance use disorder (P < 0.001), number of psychotropic drugs prescribed (P < 0.001) and initiation of an anticonvulsant at study entry (P < 0.001). In cases with no previous SA, the first SA event was associated with rapid cycling (P = 0.02), lifetime history of alcohol use disorder (P = 0.02) and initiation of an anticonvulsant at study entry (P = 0.002).

Conclusion

The introduction of anticonvulsants for a recent‐onset manic or mixed episode may be associated with an increased risk of SA. Further BD studies must determine whether this link is causal.
Attenuated airway hyperresponsiveness and mucus secretion in HDM‐exposed Igf1r‐deficient mice
Authors: Piñeiro‐Hermida S. , Gregory J. A. , López I. P. , Torrens R. , Ruíz‐Martínez C. , Adner M. , Pichel J. G.
Published: February 2017

Background

Asthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR), and airway inflammation. IGFs have been reported to play a role in asthma, but little is known about how the insulin‐like growth factor 1 receptor (IGF1R) affects asthma pathobiology.

Methods

Female Igf1r‐deficient and control mice were intranasally challenged with house dust mite (HDM) extract or PBS five days per week for four weeks. Lung function measurements, and bronchoalveolar lavage fluid (BALF), serum, and lungs were collected on day 28 for further cellular, histological, and molecular analysis.

Results

Following HDM exposure, the control mice responded with a marked AHR and airway inflammation. The Igf1r‐deficient mice exhibited an increased expression of the IGF system and surfactant genes, which were decreased in a similar manner for control and Igf1r‐deficient mice after HDM exposure. On the other hand, the Igf1r‐deficient mice exhibited no AHR, and a selective decrease in blood and BALF eosinophils, lung Il13 levels, collagen, and smooth muscle, as well as a significant depletion of goblet cell metaplasia and mucus secretion markers after HDM exposure. The Igf1r‐deficient mice displayed a distinctly thinner epithelial layer than control mice, but this was not altered by HDM.

Conclusions

Herein, we demonstrate by the first time that the Igf1r plays an important role in murine asthma, mediating both AHR and mucus secretion after HDM exposure. Thus, our study identifies IGF1R as a potential therapeutic target, not only for asthma but also for hypersecretory airway diseases.
Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non‐invasive hormonal male contraception: a randomized clinical trial
Authors: Zitzmann M. , Rohayem J. , Raidt J. , Kliesch S. , Kumar N. , Sitruk‐Ware R. , Nieschlag E.
Published: February 2017

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2‐week progestin‐only treatment, transdermal T was added for further 4 weeks and was followed by a 3‐week recovery period. Progestin‐dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 μg/day absorbed, NETA 5 mg/10 mg, LNG 120 μg/240 μg. From an andrology outpatient clinic, 56 healthy men aged 18–50 years, with body mass index ≤33 kg × m−2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end‐point should be conducted to determine the lowest effective dose for hormonal male contraception.
Assessing oxygen saturation in retinal vessels in high myopia patients pre‐ and post‐implantable collamer lens implantation surgery
Authors: Chen Pei , Cai Xiaoxiao , Xu Lijun , Zhang Jing , Yang Ying , Gao Qianying , Ge Jian , Yu Keming , Zhuang Jing
Published: February 2017

Purpose

To determine whether posterior chamber phakic implantable collamer lens (ICL) surgery in high myopia patients impedes oxygen saturation of retinal vessels.

Methods

Mean oxygen saturation and diameter in retinal blood vessels were measured before and after ICL implantation surgery to correct high myopia refractive errors (i.e. −6.00 to −20.25 dioptres [D]), using an Oxymap T1 retinal oximeter.

Results

In 17 eyes of 17 patients, the Oxymap T1 retinal oximeter detected a small but significant decrease in oxygen saturation of retinal venules, 1‐week postoperatively (compared to preoperative measurements). Moreover, at 1 week after ICL implantation, the diameter of patient retinal vessels had consistently contracted, compared to preoperative measurements. By 1 month after ICL surgery, however, both the oxygen saturation and retinal vessel diameter had returned to preoperative levels. Otherwise, no statistically significant difference in oxygen saturation and diameter of retinal arterioles was found when comparing their measurements before and 1 week after implantation.

Conclusion

Stable levels of oxygen saturation in retinal vessels, as detected by the Oxymap T1 oximeter, show ICL implantation would not leave lasting impact or adverse effects to retina oxygen saturation in high myopia patients.
Ophthalmologic wax models as an educational tool for 18th‐century vision scientists
Authors: Zampieri Fabio , Comacchio Francesco , Zanatta Alberto
Published: February 2017

The Medical Faculties of the University of Padua (Italy) and the University of Vienna (Austria) preserved two series of wax models, made by the Austrian Johann Nepomuk Hoffmayr at the beginning of the 19th century. These models were created in a period of evolution of both medical specialties and organ pathology, which brought morbid organs at the centre of medical investigation. Ceroplastic was considered a useful tool for didactic and research, as it provided a three‐dimensional realistically coloured reproduction of organic lesions. The models represent the typical eye diseases of the period, in particular those affecting external parts, which could be investigated without the need for specific instruments devised for the observation of the inner and posterior anatomy of the eye, at that time not yet available. Even if the nosological categories then employed by Hoffmayr were different from those currently used, it has been possible to find a correspondence thanks to the ophthalmological literature of his period. Ceroplastic started to decline at the end of 19th century, substituted by the much less expensive method of preservation of morbid organs in formalin and by new techniques of investigation of the inner body, such as X‐ray.
Systematic review with meta‐analysis: the impact of Clostridium difficile infection on the short‐ and long‐term risks of colectomy in inflammatory bowel disease
Authors: Law C. C. Y. , Tariq R. , Khanna S. , Murthy S. , McCurdy J. D.
Published: February 2017

Background

Clostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied.

Aim

To perform a systematic review and meta‐analysis to assess the impact of CDI on colectomy risk in IBD.

Methods

Multiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow‐up (short term 3 months, and long term at least 1 year). Weighted summary estimates were calculated using generalised inverse variance with random‐effects model. Study quality was assessed using the Newcastle–Ottawa scale.

Results

Twelve observational studies were identified and included 35 057 IBD patients with CDI, and 929 259 without CDI. CDI did not increase the short‐term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68–2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39–3.76). In contrast, CDI was associated with higher long‐term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18–4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19–7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti‐microbial therapy.

Conclusion

Based on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long‐ but not short‐ term.
Emergence of TNIK inhibitors in cancer therapeutics
Authors: Yamada Tesshi , Masuda Mari
Published: February 2017

The outcome of patients with metastatic colorectal cancer remains unsatisfactory. To improve patient prognosis, it will be necessary to identify new drug targets based on molecules that are essential for colorectal carcinogenesis, and to develop therapeutics that target such molecules. The great majority of colorectal cancers (>90%) have mutations in at least one Wnt signaling pathway gene. Aberrant activation of Wnt signaling is a major force driving colorectal carcinogenesis. Several therapeutics targeting Wnt pathway molecules, including porcupine, frizzled receptors and tankyrases, have been developed, but none of them have yet been incorporated into clinical practice. Wnt signaling is most frequently activated by loss of function of the adenomatous polyposis coli (APC) tumor suppressor gene. Restoration of APC gene function does not seem to be a realistic therapeutic approach, and, therefore, only Wnt signaling molecules downstream of the APC gene product can be considered as targets for pharmacological intervention. Traf2 and Nck‐interacting protein kinase (TNIK) was identified as a regulatory component of the β‐catenin and T‐cell factor‐4 (TCF‐4) transcriptional complex. Several small‐molecule compounds targeting this protein kinase have been shown to have anti‐tumor effects against various cancers. An anthelmintic agent, mebendazole, was recently identified as a selective inhibitor of TNIK and is under clinical evaluation. TNIK regulates Wnt signaling in the most downstream part of the pathway, and its pharmacological inhibition seems to be a promising therapeutic approach. We demonstrated the feasibility of this approach by developing a small‐molecule TNIK inhibitor, NCB‐0846.
Nardilysin promotes hepatocellular carcinoma through activation of signal transducer and activator of transcription 3
Authors: Kasai Yosuke , Toriguchi Kan , Hatano Etsuro , Nishi Kiyoto , Ohno Mikiko , Yoh Tomoaki , Fukuyama Keita , Nishio Takahiro , Okuno Masayuki , Iwaisako Keiko , Seo Satoru , Taura Kojiro , Kurokawa Masato , Kunichika Makoto , Uemoto Shinji , Nishi Eiichiro
Published: February 2017

Nardilysin (NRDC) is a metalloendopeptidase of the M16 family. We previously showed that NRDC activates inflammatory cytokine signaling, including interleukin‐6‐signal transducer and activator of transcription 3 (STAT3) signaling. NRDC has been implicated in the promotion of breast, gastric and esophageal cancer, as well as the development of liver fibrosis. In this study, we investigated the role of NRDC in the promotion of hepatocellular carcinoma (HCC), both clinically and experimentally. We found that NRDC expression was upregulated threefold in HCC tissue compared to the adjacent non‐tumor liver tissue, which was confirmed by immunohistochemistry and western blotting. We also found that high serum NRDC was associated with large tumor size (>3 cm, P = 0.016) and poor prognosis after hepatectomy (median survival time 32.0 vs 73.9 months, P = 0.003) in patients with hepatitis C (n = 120). Diethylnitrosamine‐induced hepatocarcinogenesis was suppressed in heterozygous NRDC‐deficient mice compared to their wild‐type littermates. Gene silencing of NRDC with miRNA diminished the growth of Huh‐7 and Hep3B spheroids in vitro. Notably, phosphorylation of STAT3 was decreased in NRDC‐depleted Huh‐7 spheroids compared to control spheroids. The effect of a STAT3 inhibitor (S3I‐201) on the growth of Huh‐7 spheroids was reduced in NRDC‐depleted cells relative to controls. Our results show that NRDC is a promising prognostic marker for HCC in patients with hepatitis C, and that NRDC promotes tumor growth through activation of STAT3.
Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers
Authors: Martinez De Pinillos Bayona Alejandra , Mroz Pawel , Thunshelle Connor , Hamblin Michael R.
Published: February 2017

Photodynamic therapy (PDT) uses non‐toxic dyes called photosensitizers (PS) and harmless visible light that combine to form highly toxic reactive oxygen species that kill cells. Originally, a cancer therapy, PDT, now includes applications for infections. The most widely studied PS are tetrapyrrole macrocycles including porphyrins, chlorins, bacteriochlorins, and phthalocyanines. The present review covers the design features in PS that can work together to maximize the PDT activity for various disease targets. Photophysical and photochemical properties include the wavelength and size of the long‐wavelength absorption peak (for good light penetration into tissue), the triplet quantum yield and lifetime, and the propensity to undergo type I (electron transfer) or type II (energy transfer) photochemical mechanisms. The central metal in the tetrapyrrole macrocycle has a strong influence on the PDT activity. Hydrophobicity and charge are important factors that govern interactions with various types of cells (cancer and microbial) in vitro and the pharmacokinetics and biodistribution in vivo. Hydrophobic structures tend to be water insoluble and require a drug delivery vehicle for maximal activity. Molecular asymmetry and amphiphilicity are also important for high activity. In vivo some structures possess the ability to selectively accumulate in tumors and to localize in the tumor microvasculature producing vascular shutdown after illumination.