bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in management of blunt liver trauma and contribution of level of American College of Surgeons Committee on Trauma verification status on mortality
Authors: Tignanelli Christopher J. , Joseph Bellal , Jakubus Jill L. , Iskander Gaby A. , Napolitano Lena M. , Hemmila Mark R.
Published: December 2017

BACKGROUND

Patients who sustain blunt liver trauma and are treated at an American College of Surgeons Committee on Trauma-verified Level I trauma center have an overall lower risk of mortality compared with patients admitted to a level II trauma center. However, elements contributing to these differences are unknown. We hypothesize that practice variation exists between trauma centers in management of blunt liver injury. Our objective is to identify practice variations and their effect on clinical outcomes.

METHODS

Data from a statewide collaborative quality initiative for trauma were used. The data set contains information from 29 American College of Surgeons Committee on Trauma verified Levels I and II trauma centers from 2011 to 2016. Propensity score matching was used to create cohorts of patients treated at Levels I or II trauma centers. The 1:1 matched cohorts were used to compare in-hospital mortality, management strategy, complications, intensive care unit (ICU) and hospital length of stay, and failure to rescue.

RESULTS

Four hundred fifty-four patients with grade 3 or higher blunt liver injury were included. Patients treated at level II trauma centers had higher in-hospital mortality than those treated at Level I trauma centers (15.4% vs 8.8%, p = 0.03). Level II trauma centers used angiography less compared with Level I centers (p = 0.007) and admitted significantly fewer patients to the ICU (p = 0.002). The ICU status was associated with reduced mortality (7.2% vs 23.9%, p < 0.001). Despite a lower rate of overall complications, Level II trauma centers were more likely to fail in rescuing their patients (p = 0.045).

CONCLUSION

Admission with a high-grade liver injury to a Level II trauma center is associated with increased in-hospital mortality. Level II trauma centers were less likely to use angiography or admit high-grade liver injuries to the ICU. This variation in practice may lead to the inability to rescue critically ill patients. Future research should investigate contributors to underutilization of resources for patients with high-grade liver injuries.

Level of Evidence

Care management, level IV
External validation of a smartphone app model to predict the need for massive transfusion using five different definitions
Authors: Hodgman EI , Cripps MW , Mina MJ , Bulger EM , Schreiber MA , Brasel KJ , Cohen MJ , Muskat P , Myers JG , Alarcon LH , Rahbar MH , Holcomb JB , Cotton BA , Fox EE , del Junco DJ , Wade CE , Phelan HA
Published: December 2017

BACKGROUND

Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model’s ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions.

METHODS

The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes.

RESULTS

Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711.

CONCLUSION

Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated (“machine learning”) and thus could improve its predictive capability as additional data are accrued.

LEVEL OF EVIDENCE

Diagnostic test study/Prognostic study, level III.
Growth inhibition by amino acids inSaccharomyces cerevisiae
Authors: Ruiz Stephanie J. , van ’t Klooster Joury S. , Bianchi Frans , Poolman Bert
Published: December 2017

Amino acids are essential metabolites but can also be toxic when present at high levels intracellularly. Substrate-induced down-regulation of amino acid transporters inSaccharomyces cerevisiaeis thought to be a mechanism to avoid this toxicity. It has been shown that unregulated uptake by the general amino acid permease Gap1 causes cells to become sensitive to amino acids. Here, we show that overexpression of eight other amino acid transporters (Agp1, Bap2, Can1, Dip5, Gnp1, Lyp1, Put4 or Tat2) also induces a growth defect when specific single amino acids are present at concentrations of 0.5–5 mM. We can now state that all proteinogenic amino acids, as well as the important metabolite ornithine, are growth inhibitory toS. cerevisiaewhen transported into the cell at high enough levels. Measurements of initial transport rates and cytosolic pH show that toxicity is due to amino acid accumulation and not to the influx of co-transported protons. The amino acid sensitivity phenotype is a useful tool that reports on thein vivoactivity of transporters and has allowed us to identify new transporter-specific substrates.
Engineering a Functional small RNA Negative Autoregulation Network with Model-guided Design
Authors: Hu Chelsea Y. , Takahashi Melissa K. , Zhang Yan , Lucks Julius B.
Published: December 2017

RNA regulators are powerful components of the synthetic biology toolbox. Here, we expand the repertoire of synthetic gene networks built from these regulators by constructing a transcriptional negative autoregulation (NAR) network out of small RNAs (sRNAs). NAR network motifs are core motifs of natural genetic networks, and are known for reducing network response time and steady state signal noise. Here we use cell-free transcription-translation (TX-TL) reactions and a computational model to design and prototype sRNA NAR constructs. Using parameter sensitivity analysis, we design a simple set of experiments that allow us to accurately predict NAR function in TX-TL. We transfer successful network designs in vivo and show that our sRNA transcriptional network reduces both network response time and noise in steady-state gene expression. This work broadens our ability to construct increasingly sophisticated RNA genetic networks with predictable function.
Gene expression effects of lithium and valproic acid in a serotonergic cell line
Authors: Balasubramanian Diana , Pearson John F. , Kennedy Martin A.
Published: December 2017

Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2fold change ≥ 1.0; i.e. odds ratio of ≥ 2, at FDR <5%), but only two genes (Dynlrb2andCdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin),Nts(neurotensin),Maob(monoamine oxidase B) andAp2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix (ECM) remodelling, cell adhesion and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into the therapeutic action of the commonly used mood stabilizer drugs.
Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans
Authors: Steinrücken Matthias , Spence Jeffrey P. , Kamm John A. , Wieczorek Emilia , Song Yun S.
Published: December 2017

Genetic evidence has revealed that the ancestors of modern human populations outside of Africa and their hominin sister groups, notably the Neanderthals, exchanged genetic material in the past. The distribution of these introgressed sequence-tracts along modern-day human genomes provides insight into the ancient structure and migration patterns of these archaic populations. Furthermore, it facilitates studying the selective processes that lead to the accumulation or depletion of introgressed genetic variation. Recent studies have developed methods to localize these introgressed regions, reporting long regions that are depleted of Neanderthal introgression and enriched in genes, suggesting negative selection against the Neanderthal variants. On the other hand, enriched Neanderthal ancestry in hair- and skin-related genes suggests that some introgressed variants facilitated adaptation to new environments. Here, we present a model-based method calleddiCal-admixand apply it to detect tracts of Neanderthal introgression in modern humans. We demonstrate its efficiency and accuracy through extensive simulations. We use our method to detect introgressed regions in modern human individuals from the 1000 Genomes Project, using a high coverage genome from a Neanderthal individual from the Altai mountains as reference. Our introgression detection results and findings concerning their functional implications are largely concordant with previous studies, and are consistent with weak selection against Neanderthal ancestry. We find some evidence that selection against Neanderthal ancestry was due to higher genetic load in Neanderthals, resulting from small effective population size, rather than Dobzhansky-Müller incompatibilities. Finally, we investigate the role of the X-chromosome in the divergence between Neanderthals and modern humans.
Experimental and computational framework for a dynamic protein atlas of human cell division
Authors: Cai Yin , Hossain M. Julius , Hériché Jean-Karim , Politi Antonio Z. , Walther Nike , Koch Birgit , Wachsmuth Malte , Nijmeijer Bianca , Kueblbeck Moritz , Kavur Marina Martinic , Ladurner Rene , Alexander Stephanie , Peters Jan-Michael , Ellenberg Jan
Published: December 2017

Essential biological functions, such as mitosis, require tight coordination of hundreds of proteins in space and time. Localization, timing of interactions and changes in cellular structure are all crucial to ensure correct assembly, function and regulation of protein complexes1-4. Live cell imaging can reveal protein distributions and dynamics but experimental and theoretical challenges prevented its use to produce quantitative data and a model of mitosis that comprehensively integrates information and enables analysis of the dynamic interactions between the molecular parts of the mitotic machinery within changing cellular boundaries.

To address this, we generated a 4D image data-driven, canonical model of the morphological changes during mitotic progression of human cells. We used this model to integrate dynamic 3D concentration data of many fluorescently knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy-calibrated microscopy5. The approach taken here in the context of the MitoSys consortium to generate a dynamic protein atlas of human cell division is generic. It can be applied to systematically map and mine dynamic protein localization networks that drive cell division in different cell types and can be conceptually transferred to other cellular functions.
Whatever Happened to Overloaded Government?
Authors: Moran Michael
Published: December 2017

Anthony King was, among other things, an outstandingly acute public intellectual. His work on overload and policy fiasco exemplifies this. His original diagnosis in his famous paper of 1975 was deeply pessimistic in character, but subsequent adaptations by government solved many of the original problems arising from dependency relations. These adaptations amounted to the creation of a Madisonian system of regulation that insulated policy makers from democratic pressures. But these adaptations in turn created new difficulties that lie at the root of the analysis in King and Crewe's The Blunders of our Governments, published nearly four decades after King's original classic paper.
GRAPHITE: A graphical environment for scalable in situ video tracking of moving insects
Authors: Rossetti Blair J. , Dynes Travis , Brosi Berry , de Roode Jacobus C. , Kong Jun
Published: December 2017

Methods for measuring animal movement are critical for understanding numerous ecological and evolutionary processes. However, few methods are available for small organisms, and even fewer methods offer consistent individual‐level resolution while remaining affordable, scalable and operable in the field.

We describe a low‐cost animal movement tracking method with a user‐friendly graphical interface, called GRAPHITE. Our automated software can quantify motions of insects by offline video analysis of inexpensive and lightweight human‐readable tags attached to individual insects. The integrated graphical editor provides a full‐featured environment for users to review the generated tracking data and make individual‐ or group‐level edits.

GRAPHITE is a novel video analysis and graphical editing software (Matlab v.9.0.0+) that identifies tags in image frames with a minimal false negative rate, links sequences of corresponding tags into “tracks” for each individual insect, infers the tag identifier, and provides a user‐friendly graphical environment for editing tracking data. Users can either batch process raw video data using the full analysis pipeline or execute GRAPHITE modules independently for a tailored analysis.

We demonstrate the efficacy of the developed software with a specific application to the movement of honey bees at the entrance of hives. However, this system can be easily modified to track individually marked insects of 3 mm and larger. A notable advantage of this method is its ability to provide easy access to individual‐level tracking data using human‐readable tags.
Reintroduction or natural colonization? Using cost‐distance analysis to inform decisions about Rodrigues Island Fody and Warbler reintroductions
Authors: Davies O. A. M. , Huggins A. E. , Begue J. A. , Groombridge J. J. , Jones C. , Norfolk D. , Steward P. , Tatayah V. , Zuël N. , Ewen J. G.
Published: December 2017

When making decisions about reintroducing a species, practitioners need to consider whether the release site contains habitat suitable for those species, whether past extinction drivers have been remedied and whether reintroduction is the best option for the species to recolonize the release site. These concerns are captured within two paradigms; the habitat and metapopulation paradigms. We use cost‐distance analysis to assess the need for reintroduction of two bird species, Rodrigues Fody and Rodrigues Warbler, to Anse Quitor reserve on Rodrigues Island, testing hypotheses based on these underlying paradigms. Given a lack of detailed field studies of dispersal across the landscape on either species we rely on expert judgment. Our results show that experts believe Rodrigues Fody will naturally colonize Anse Quitor but that Rodrigues Warbler may not, at least within a time frame of 10 years. This information and treatment of expert judgment allows greater justification in reintroduction planning. Our method shows one way to assist in reintroduction decision making in poorly studied systems.
Decidual CD68+HLA‐DR+CD163− M1 macrophages increase in miscarriages with normal fetal chromosome
Authors: Shimada Shigeki , Ebina Yasuhiko , Iijima Norifumi , Deguchi Masashi , Yamada Hideto
Published: December 2017

Problem

Is an abnormal increase or decrease of M1/M2 macrophages observed in the deciduae of miscarriages with normal fetal chromosome (MN)?

Methods of study

Deciduae of 18 MN and 26 miscarriages with abnormal fetal chromosome (MA) were obtained. Additionally, deciduae from 15 women whose pregnancies ended in induced abortions (IA) and endometriums at the mid‐luteal phase from 19 non‐pregnant women endomeriums of mid‐luteal phases (EM) were obtained. Macrophages were analyzed by flow cytometry using monoclonal antibodies for CD68, HLA‐DR, and CD163.

Results

M1 macrophages, defined as CD68+HLA‐DR+CD163− cells, increased in MN compared with MA or IA. M2 macrophages, defined as CD68+HLA‐DR−CD163+ cells, increased in the deciduae of MA and IA compared with EM. However, this increase was not observed in the deciduae of MN.

Conclusion

Our findings of phenotypic characters of decidual macrophages in MN provide additional evidence that M2 polarization is favorable for the maintenance of early stages of pregnancy.
Postoperative outcomes following cardiac surgery in non‐anaemic iron‐replete and iron‐deficient patients – an exploratory study
Authors: Miles L. F. , Kunz S. A. , Na L. H. , Braat S. , Burbury K. , Story D. A.
Published: December 2017

Iron deficiency anaemia is strongly associated with poor outcomes after cardiac surgery. However, pre‐operative non‐anaemic iron deficiency (a probable anaemia precursor) has not been comprehensively examined in patients undergoing cardiac surgery, despite biological plausibility and evidence from other patient populations of negative effect on outcome. This exploratory retrospective cohort study aimed to compare an iron‐deficient group of patients undergoing cardiac surgery with an iron‐replete group. Consecutive non‐anaemic patients undergoing elective coronary artery bypass grafting or single valve replacement in our institution between January 2013 and December 2015 were considered for inclusion. Data from a total of 277 patients were analysed, and were categorised by iron status and blood haemoglobin concentration into iron‐deficient (n = 109) and iron‐replete (n = 168) groups. Compared with the iron‐replete group, patients in the iron‐deficient group were more likely to be female (43% vs. 12%, iron‐replete, respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have a higher pre‐operative EuroSCORE (median IQR [range]) 3 (2–5 [0–10]) vs. 3 (2–4 [0–9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7) g.l−1. Univariate analysis suggested that iron‐deficient patients had a longer hospital length of stay (7 (6–9 [2–40]) vs. 7 (5–8 [4–23]) days; p = 0.013) and fewer days alive and out of hospital at postoperative day 90 (83 (80–84 [0–87]) vs. 83 (81–85 [34–86]), p = 0.009). There was no evidence of an association between iron deficiency and either lower nadir haemoglobin or higher requirement for blood products during inpatient stay. After adjusting the model for pre‐operative age, sex, renal function, EuroSCORE and haemoglobin, the mean increase in hospital length of stay in the iron‐deficient group relative to the iron‐replete group was 0.86 days (bootstrapped 95%CI −0.37 to 2.22, p = 0.098). This exploratory study suggests there is weak evidence of an association between non‐anaemic iron deficiency and outcome after cardiac surgery after controlling for potentially confounding variables.
Determination of the optimal programmed intermittent epidural bolus volume of bupivacaine 0.0625% with fentanyl 2 μg.ml−1 at a fixed interval of forty minutes: a biased coin up‐and‐down sequential allocation trial
Authors: Zakus P. , Arzola C. , Bittencourt R. , Downey K. , Ye X. Y. , Carvalho J. C.
Published: December 2017

The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2 μg.ml−1 as part of a programmed intermittent epidural bolus regimen has been found to be 40 min. This regimen was shown to be effective without the use of supplementary patient‐controlled epidural analgesia boluses in 90% of women during the first stage of labour, although with a rate of sensory block to ice above T6 in 34% of women. We aimed to determine the optimum programmed intermittent epidural bolus volume at a 40 min interval to provide effective analgesia in 90% of women (EV90) during the first stage of labour, without the use of patient‐controlled epidural analgesia. We performed a prospective double‐blind dose‐finding study using the biased coin up‐and‐down sequential allocation method in 40 women. The estimated EV90 was 11.0 (95%CI 10.0–11.7) ml with the isotonic regression method and 10.7 (95%CI 10.3–11.0) ml with the truncated Dixon and Mood method. Overall, 18 women had a sensory block above T6, and 37 women exhibited no motor block. No women required treatment for hypotension. In conclusion, it is not possible to reduce the programmed intermittent epidural bolus volume from 10 ml, used in our current regimen, without compromising the quality of analgesia. Using this regimen, a high proportion of women will develop a sensory block above T6.
Is myocardial repolarization duration associated with repolarization heterogeneity?
Authors: Marill Keith A. , Dorsey Pat , Holmes Anthony , Muthal Ketaki , Miller Emily S. , Xue Joel
Published: December 2017

Background

Dispersion of repolarization is theorized as one mechanism by which myocardial repolarization prolongation causes lethal torsades de pointes, (TdP). Our primary purpose was to determine whether prolongation of myocardial repolarization as measured by the heart rate‐corrected J‐to‐T peak interval (JTpkc), is associated with repolarization heterogeneity as measured by transmural dispersion, defined as the median duration from the peak to the end of the T wave (TpTe).

Methods

A retrospective cohort study was performed at a single urban tertiary ED from July 2011–September 2012. Inclusion criteria included all consecutive ED patients with ECG based on QTc and QRS intervals. Automated measurements of all intervals were performed. The association of JTpkc with the dependent variable TpTe was assessed after adjustment for QRS and RR interval durations with a multiple linear regression model. A secondary analysis included a similar adjusted assessment of the association of JTpkc with QT dispersion, QTd. Finally, we constructed two multiple regression models to assess the association of clinical causative factors of TdP with TpTe and JTpkc.

Results

Eight hundred seventy‐four cases were included: 186 with QTc <500 ms, 118 with QTc ≥500 and QRS ≥120 ms, and 570 with QTc ≥500 and QRS <120 ms. The coefficient for association of JTpkc with TpTe was −0.10 (95%CI −0.15 to −0.05), and for JTpkc with QTd was 0.03 (95% CI −0.01 to 0.06). Clinical causative TdP factors were associated more with JTpkc than TpTe.

Conclusion

Repolarization duration as measured by JTpkc is not positively associated with dispersion of repolarization as measured by TpTe or QTd. Dispersion of repolarization may not be a critical mechanistic link between QTc prolongation and TdP.
Application of the ISNT rules on retinal nerve fibre layer thickness and neuroretinal rim area in healthy myopic eyes
Authors: Qiu Kunliang , Wang Geng , Lu Xuehui , Zhang Riping , Sun Lixia , Zhang Mingzhi
Published: December 2017

Purpose

We determined the applicability of inferior > superior > nasal > temporal (ISNT) rules on retinal nerve fibre layer (RNFL) thickness and rim area and evaluated the impact of various ocular factors on the performance of the ISNT rules in healthy myopic eyes.

Methods

A total of 138 eyes from 138 healthy myopic subjects were included in this cross‐sectional observational study. The peripapillary RNFL and optic disc in each eye were imaged with Cirrus HD optical coherence tomography (OCT) and Heidelberg Retina Tomograph II (HRT2), respectively. The performance of the inferior > superior (IS), inferior > superior > nasal > temporal (IST) and ISNT rules on RNFL thickness and rim area was determined and compared between low‐to‐moderate myopia and high myopia. The effects of ocular factors [including axial length, disc area, disc tilt, disc torsion, disc‐fovea angle (DFA) and retina artery angle] on the performance of ISNT rules were evaluated with logistic regression analysis.

Results

The mean axial length and refractive error were 25.57 ± 1.09 mm (range, 22.52–28.77 mm) and −5.12 ± 2.30 D [range, −9.63 to −0.50 dioptres (D)], respectively. Sixty‐three per cent of the healthy eyes were compliant with the ISNT rule on rim area, while ISNT rule on RNFL thickness was followed in only 11.6% of the included eyes. For rim area, smaller disc area was significantly associated with increased compliance of the IS rule (odds ratio: 0.46, p = 0.039), IST rule (odds ratio: 0.46, p = 0.037) and ISNT rule (odds ratio: 0.44, p = 0.030). For RNFL thickness, greater DFA was significantly associated with increased compliance of the IS and IST rules (odds ratio: 1.30, p < 0.001; odds ratio: 1.19, p = 0.006, respectively).

Conclusion

In healthy myopic subjects, 88.4% and 37% of eyes did not comply with the ISNT rule on RNFL thickness and rim area, respectively. Due to significant low compliance in healthy eyes, the ISNT rule and its variants have limited potential utility in diagnosing glaucoma in myopic subjects.
The treatment of postoperative endophthalmitis: should we still follow the endophthalmitis vitrectomy study more than two decades after its publication?
Authors: Grzybowski Andrzej , Turczynowska Magdalena , Kuhn Ferenc
Published: December 2017

Conducted in the early 1990s Endophthalmitis Vitrectomy Study (EVS) have helped in establishing reasonable guidelines for the management of infectious postoperative endophthalmitis. However at present, more than 20 years after its publication, tremendous progress has been introduced in vitrectomy technology, which now permits the vitreoretinal surgeon to perform surgery more safely, and with better outcomes. Moerover, performing a complete vitreous removal, along with the moving up of the surgical intervention to as early as possible allows the prevention of complications that would limit the functional improvement postoperatively. Thus, it is now highly needed to re‐evaluate the conclusions of the EVS study.
Evaluation of a computerized cognitive behavioural therapy programme, MindWise (2.0), for adults with mild‐to‐moderate depression and anxiety
Authors: Collins Sarah , Byrne Michael , Hawe James , O'Reilly Gary
Published: December 2017

Objectives

To investigate the acceptability and utility of a newly developed computerized cognitive behavioural therapy (cCBT) programme, MindWise (2.0), for adults attending Irish primary care psychology services.

Method

Adult primary care psychology service users across four rural locations in Ireland were invited to participate in this study. A total of 60 service users participated in the MindWise (2.0) treatment group and compared to 22 people in a comparison waiting list control group. Participants completed pre‐ and post‐intervention outcome measures of anxiety, depression, and work/social functioning.

Results

At post‐intervention, 25 of 60 people in the MindWise (2.0) condition had fully completed the programme and 19 of 22 people in the waiting list condition provided time 2 data. Relative to those in the control group, the MindWise (2.0) participants reported significantly reduced symptoms of anxiety and no change in depression or work/social functioning.

Conclusions

The newly developed cCBT programme, MindWise (2.0), resulted in significant improvements on a measure of anxiety and may address some barriers to accessing more traditional face‐to‐face mental health services for adults in a primary care setting. Further programme development and related research appears both warranted and needed to lower programme drop‐out, establish if gains in anxiety management are maintained over time, and support people in a primary care context with depression.

Practitioner points

There is a growing evidence base that computerized self‐help programmes can assist in a stepped‐care approach to adult mental health service provision.

These programmes require further development to address issues such as high dropout, the development of equally effective transdiagnostic content, and greater effectiveness in the country of origin.

This study evaluated the acceptability and utility of a brief online CBT programme for adults referred due to anxiety or low mood to primary care psychology services in the national health service in Ireland.

Results indicate that 42% of people completed the programme and experienced a significant reduction in anxiety but not depression and no improvement in work or social adjustment compared to similar adults on a waiting list for services.

This study suggests the programme warrants further development and research and may in time become a useful and suitable intervention within the national health service in Ireland.
Induction of mast cell accumulation by chymase via an enzymatic activity‐ and intercellular adhesion molecule‐1‐dependent mechanism
Authors: Zhang Huiyun , Wang Junling , Wang Ling , Zhan Mengmeng , Li Shigang , Fang Zeman , Xu Ciyan , Zheng Yanshan , He Shaoheng
Published: December 2017

Background and Purpose

Chymase is a unique, abundant secretory product of mast cells and a potent chemoattractant for eosinophils, monocytes and neutrophils, but little is known of its influence on mast cell accumulation.

Experimental Approach

A mouse peritoneal inflammation model, cell migration assay and flowcytometry analysis, were used to investigate the role of chymase in recruiting mast cells.

Key Results

Chymase increased, by up to 5.4‐fold, mast cell numbers in mouse peritoneum. Inhibitors of chymase, heat‐inactivation of the enzyme, sodium cromoglycate and terfenadine, and pretreatment of mice with anti‐intercellular adhesion molecule 1, anti‐L‐selectin, anti‐CD11a and anti‐CD18 antibodies dramatically diminished the chymase‐induced increase in mast cell accumulation. These findings indicate that this effect of chymase is dependent on its enzymatic activity and activation of adhesion molecules. In addition, chymase provoked a significant increase in 5‐HT and eotaxin release (up to 1.8‐ and 2.2‐fold, respectively) in mouse peritoneum. Since 5‐HT, eotaxin and RANTES can induce marked mast cell accumulation, these indirect mechanisms may also contribute to chymase‐induced mast cell accumulation. Moreover, chymase increased the trans‐endothelium migration of mast cells in vitro indicating it also acts as a chemoattractant.

Conclusion and Implications

The finding that mast cells accumulate in response to chymase implies further that chymase is a major pro‐inflammatory mediator of mast cells. This effect of chymase, a major product of mast cell granules, suggests a novel self‐amplification mechanism for mast cell accumulation in allergic inflammation. Mast cell stabilizers and inhibitors of chymase may have potential as a treatment of allergic disorders.
Design, synthesis, and cytotoxic evaluation of novel furo[2,3‐b]quinoline derivatives
Authors: Wang Bing , Li Qiangqiang , Shi Wei , Chen Li , Sun Jianbo
Published: December 2017

A number of novel furo[2,3‐b]quinoline derivatives were designed and synthesized by introducing benzyl ether, benzoate, and benzenesulfonate to 6‐position of furo[2,3‐b]quinoline and their chemical structures were confirmed by ESI‐MS, 1H NMR, and 13C NMR spectra. All target compounds were evaluated in vitro against four human cancer cell lines (HCT‐116, MCF‐7, U2OS, and A549) by MTT method. Cytotoxic assay showed that compounds 8a, 8e, 10a, 10b, and 10c exhibited more potent cytotoxicities compared to 2‐bromine‐6‐hydroxy‐furo‐[2,3‐b]quinoline (7). Compound 10c exhibited higher antiproliferative activity (IC50 values ranging from 4.32 to 24.96 μm) against four human cancer cell lines (HCT‐116, MCF‐7, U2OS, and A549) and weak cytotoxicity on normal cell HL‐7702, which suggested that 10c might be an ideal anticancer candidate. Compounds 8a, 10a, 10b showed good selectivities to MCF‐7 and HCT‐116, which could be considered as ideal selective candidates for further study. The SARs showed that the introduction of the benzyl ether and benzenesulfonate could significantly improve cytotoxicities, while the benzoate failed to enhance potency obviously.
Impact of Austropuccinia psidii in New Caledonia, a biodiversity hotspot
Authors: Soewarto J. , Carriconde F. , Hugot N. , Bocs S. , Hamelin C. , Maggia L.
Published: December 2017

Myrtle rust, caused by the fungus Austropuccinia psidii, infects a wide range of host species within the Myrtaceae family worldwide. Since its first report in 2013 from New Caledonia, the extent of the host range, geographical distribution and genetic diversity of A. psidii in this territory have been unknown. This study reports 67 new host species distributed in 13 different Myrtaceae genera, including five new genera. The pathogen was found in various types of plant communities, where Myrtaceae species are the dominant or codominant species, as well as in several nurseries. It is now considered a significant threat to the biodiversity of ecosystems and the Myrtaceae‐related economy. A 3‐year disease monitoring trial with 35 cultivated Myrtaceae species showed variations in disease severity at the species and individual scales. This suggests that some level of genetic resistance to myrtle rust may possibly exist among the endemic Myrtaceae of New Caledonia. A population genetic investigation revealed that only one single genotype of A. psidii occurs across its entire host range in New Caledonia. Therefore, it is essential to carry out population genetic surveillance to identify the appearance of mutations or the introduction of potentially more virulent genotypes of A. psidii. The outcomes from this study will assist with the ongoing management of the disease in New Caledonia.
A double point mutation at residues Ile14 and Val15 of Bcl‐2 uncovers a role for the BH4 domain in both protein stability and function
Authors: Monaco Giovanni , La Rovere Rita , Karamanou Spyridoula , Welkenhuyzen Kirsten , Ivanova Hristina , Vandermarliere Elien , Di Martile Marta , Del Bufalo Donatella , De Smedt Humbert , Parys Jan B. , Economou Anastassios , Bultynck Geert
Published: December 2017

B‐cell lymphoma 2 (Bcl‐2) protein is the archetype apoptosis suppressor protein. The N‐terminal Bcl‐2‐homology 4 (BH4) domain of Bcl‐2 is required for the antiapoptotic function of this protein at the mitochondria and endoplasmic reticulum (ER). The involvement of the BH4 domain in Bcl‐2′s antiapoptotic functions has been proposed based on Gly‐based substitutions of the Ile14/Val15 amino acids, two hydrophobic residues located in the center of Bcl‐2′s BH4 domain. Following this strategy, we recently showed that a BH4‐domain‐derived peptide in which Ile14 and Val15 have been replaced by Gly residues, was unable to dampen proapoptotic Ca2+‐release events from the ER. Here, we investigated the impact of these mutations on the overall structure, stability, and function of full‐length Bcl‐2 as a regulator of Ca2+ signaling and cell death. Our results indicate that full‐length Bcl‐2 Ile14Gly/Val15Gly, in contrast to wild‐type Bcl‐2, (a) displayed severely reduced structural stability and a shortened protein half‐life; (b) failed to interact with Bcl‐2‐associated X protein (BAX), to inhibit the inositol 1,4,5‐trisphosphate receptor (IP3R) and to protect against Ca2+‐mediated apoptosis. We conclude that the hydrophobic face of Bcl‐2′s BH4 domain (Ile14, Val15) is an important structural regulatory element by affecting protein stability and turnover, thereby likely reducing Bcl‐2′s ability to modulate the function of its targets, like IP3R and BAX. Therefore, Bcl‐2 structure/function studies require pre‐emptive and reliable determination of protein stability upon introduction of point mutations at the level of the BH4 domain.
Protection of macrophages from intracellular pathogens by miR‐182‐5p mimic—a gene expression meta‐analysis approach
Authors: Gregory David J. , Kramnik Igor , Kobzik Lester
Published: December 2017

The goals of this study were to (a) define which host genes are of particular importance during the interactions between macrophages and intracellular pathogens, and (b) use this knowledge to gain fresh, experimental understanding of how macrophage activities may be manipulated during host defense. We designed an in silico method for meta‐analysis of microarray gene expression data, and used this to combine data from 16 different studies of cells in the monocyte–macrophage lineage infected with seven different pathogens. Three thousand four hundred ninety‐eight genes were identified, which we call the macrophage intracellular pathogen response (macIPR) gene set. As expected, the macIPR gene set showed a strong bias toward genes previously associated with the immune response. Predicted target sites for miR‐182‐5p (miR‐182) were strongly over‐represented among macIPR genes, indicating an unexpected role for miR‐182‐regulatable genes during intracellular pathogenesis. We therefore transfected primary human alveolar macrophage‐like monocyte‐derived macrophages from multiple different donors with synthetic miR‐182, and found that miR‐182 overexpression (a) increases proinflammatory gene induction during infection with Francisella tularensis live vaccine strain (LVS), (b) primes macrophages for increased autophagy, and (c) enhances macrophage control of both gram negative F. tularensisLVS and gram positive Bacillus anthracisANR‐1 spores. These data therefore suggest a new application for miR‐182 in promoting resistance to intracellular pathogens.
Genipin alleviates high‐fat diet‐induced hyperlipidemia and hepatic lipid accumulation in mice via miR‐142a‐5p/SREBP‐1c axis
Authors: Zhong Hong , Chen Ke , Feng Mengyang , Shao Wei , Wu Jun , Chen Kun , Liang Tingming , Liu Chang
Published: December 2017

Hyperlipidemia is a chronic disorder which plays an important role in the development of cardiovascular diseases, type 2 diabetes, atherosclerosis, hypertension, and nonalcoholic fatty liver disease. Genipin (GNP) is a metabolite from genipioside, which is an active component of the traditional Chinese medicine Gardenia jasminoides Ellis, and has been recognized as a beneficial compound against metabolic disorders. However, whether it can correct overnutrition‐induced dyslipidemia is still unknown. In this study, the effects of GNP on attenuating hyperlipidemia and hepatic lipid accumulation were investigated using normal and obese mice induced with a high‐fat diet (HFD) and primary hepatocytes treated with free fatty acids. We also sought to identify potential targets of GNP to mediate its effects in the liver. We found that obese mice treated with GNP showed a decrease in the body weight, serum lipid levels, as well as hepatic lipid accumulation. Besides, GNP regulated hepatic expression levels of lipid metabolic genes, which are important in maintaining systemic lipid homeostasis. At the molecular level, GNP increased the expression levels of miR‐142a‐5p, which bound to 3′ untranslated region of Srebp‐1c, an important regulator of lipogenesis, which thus led to the inhibition of lipogenesis. Collectively, our data demonstrated that GNP effectively antagonized HFD‐induced hyperlipidemia and hepatic lipid accumulation in mice. Such effects were achieved by regulating miR‐142a‐5p/SREBP‐1c axis.
Observations on the origin of ovarian cortical inclusion cysts in women undergoing risk‐reducing salpingo‐oophorectomy
Authors: Park Kay J , Patel Prusha , Linkov Irina , Jotwani Anjali , Kauff Noah , Pike Malcolm C
Published: December 2017

Aims

Evidence suggests that up to 70% of high‐grade serous ovarian carcinomas (HGSCs) arise potentially from fallopian tube fimbriae, and that many of the remaining cases arise from within the ovary in cortical inclusion cysts (CICs) with a Müllerian phenotype (Müllerian‐CICs). It has been proposed that Müllerian‐CICs arise either from metaplasia of mesothelial ovarian surface epithelium (OSE) entrapped within the ovary after ovulation or from normal tubal cells entrapped postovulation. However, this proposal is controversial. We therefore conducted a study of CICs in women, most of them BRCA1/2 mutation carriers, undergoing risk‐reducing salpingo‐oophorectomy at our institution from 2000 to 2014.

Methods and results

We used immunohistochemistry for PAX8, a Müllerian marker, and calretinin, a mesothelial marker to classify CIC cells. In 499 CICs from 59 women, 72.3% were positive for PAX8 (PAX8+): ≥10% of CIC cells positive; 43.5% positive for calretinin (calretinin+). The proportion of PAX8+ CICs increased from 62.9% in premenopausal to 80.5% in postmenopausal patients. The proportion of calretinin+ CICs decreased from 52.6% to 35.6%, respectively. There was significant overlap of PAX8 and calretinin positivity: 82 (16.4%) CICs were PAX8+/calretinin+; 43 (40.2%) of these 82 demonstrated PAX8+/calretinin+ in the same cells.

Conclusions

These results, and the increased ratio of PAX8+ to calretinin+ CICs from premenopausal to postmenopausal, show that many PAX8+ CICs probably arise from metaplasia of OSE‐derived CICs. The proportion of PAX+/calretinin− CICs arising from OSE‐derived CICs is unclear, but our results strongly support the proposal that many Müllerian‐CICs arise from OSE via metaplasia.
Bullous pemphigoid complicated by cytomegalovirus disease as a manifestation of immune reconstitution inflammatory syndrome: retrospective analyses of our institutional cases and literature review
Authors: Narita Yoko M. , Horie Chiho , Hirahara Kazuhisa , Kano Yoko , Shiohara Tetsuo , Mizukawa Yoshiko
Published: December 2017

Background

Cytomegalovirus (CMV) disease induced by reactivation of latent CMV is a fatal viral infection that may develop in a setting of therapy with immunosuppressive agents. There is a clear need to clarify any clinical features and markers of CMV disease.

Objective

We investigated which clinical markers usually available in a clinical setting can predict CMV disease occurring in bullous pemphigoid (BP) patients receiving corticosteroids.

Method

We described a BP patient with CMV disease complicated by gastrointestinal hemorrhage and liver dysfunction. Prompted by this patient, we retrospectively analyzed clinical features and laboratory findings in our institutional four BP patients and previously reported nine BP patients with CMV disease. We also compared these patients with our institutional 42 BP patients not complicated by CMV disease.

Results

High levels of anti‐BP180 antibody titers associated with resistance to corticosteroids are a risk factor for the development of CMV disease. A reduction in platelet (PLT) and white blood cell (WBC) counts and an increase in alanine aminotransferase (ALT) levels 3–4 weeks after the initiation of corticosteroids are useful predictive markers for the onset of CMV disease.

Conclusions

Frequent WBC, PLT, and ALT measurements may identify BP patients at a risk of subsequently developing CMV disease. Careful monitoring of CMV disease in BP refractory to systemic corticosteroids may reduce the risk of fatal outcomes.
Cardiopulmonary anomalies in incontinentia pigmenti patients
Authors: Onnis Giuliana , Diociaiuti Andrea , Zangari Paola , D'Argenio Patrizia , Cancrini Caterina , Iughetti Lorenzo , El Hachem May
Published: December 2017

Background

Incontinentia pigmenti (IP) is a rare inherited genodermatosis that usually involves the skin, and also teeth, oral cavity, central nervous system, eyes, blood with eosinophilia, and rarely skeletal system, breast, heart, and lungs. Skin lesions usually appear early, at birth or within the first 2 weeks of life, with four different phases tending to follow Blaschko lines that may overlap.

Case report

We report a rare case of a neonate with transient reversible pulmonary hypertension that presented at day 9 of life. She manifested increasing dyspnea and deterioration of respiratory dynamics with a serious pulmonary hypertension without a primary pulmonary disease. Hence, oxygen therapy at high flows and nitric oxide have been administered with an initial response, but, subsequently, because of the worsening of the respiratory activity, she underwent sildenafil and bosentan treatment with respiratory dynamics improvement and progressive decrease of the pulmonary pressures.

Conclusion

In literature only a few cases of cardiopulmonary anomalies in IP have been described with different outcomes, and these rare complications are probably underestimated by physicians. We could suppose that microangiopathic damages may have a critical role in endothelial alterations, and these processes are probably shared by multiple organs involved in IP and rarely by lungs and heart.
Impact of high‐pressure processing on chemical constituents and nutritional properties in aquatic foods: a review
Authors: Aubourg Santiago P.
Published: December 2017

Among the recent advanced technologies, high‐pressure processing (HPP) has emerged as an attractive tool for inactivating microbial populations and endogenous enzymes activity, while retaining the sensory and nutritional properties. This review covers information concerning the research carried out on the changes undergone by the different chemical constituents of aquatic foods as a result of HPP, including modifications produced in nutritional value parameters. Such description includes changes produced just after the HPP as well as those resulting from a combination of HPP and further storage (i.e. refrigerated and frozen storages) or processing (thermal treatment, ready‐to‐eat products elaboration, etc.) corresponding to common commercial procedures employed nowadays by the food industry. The impact of constituent modifications on the formation of molecules related to quality parameters is also reviewed. Finally, the needs for complementary research on constituent changes by HPP and the possibilities for widening the application of this advanced technology are discussed.
Statistical mechanical model of bonding in mixed modifier glasses
Authors: Goyal Sushmit , Mauro John C.
Published: December 2017

Oxide glasses often consist of multiple network formers that create the backbone of the glass network and modifiers that serve as either charge compensators or creators of non‐bridging oxygens. The variety of bonding preferences results in very rich composition‐property relationships. In this work, we present a statistical description of the glass structure governed by the relative enthalpic and entropic contributions to the bonding preferences in a glassy system. Using the proposed model, we derive an analytical expression to represent the bonding in mixed modifier glasses and explain the role of composition and fictive temperature on glass structure. The model provides the criteria for nonlinearity in bonding preference and reveals regions where high fluctuations in local structure are predicted.