bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient
Authors: Chapuis Aude G. , Lee Sylvia M. , Thompson John A. , Roberts Ilana M. , Margolin Kim A. , Bhatia Shailender , Sloan Heather L. , Lai Ivy , Wagener Felecia , Shibuya Kendall , Cao Jianhong , Wolchok Jedd D. , Greenberg Philip D. , Yee Cassian
Published: May 2016

Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8+ cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21–primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4. Long-term persistence and sustained anti-tumor activity of transferred CTL, as well as responses to nontargeted antigens, confirmed mutually beneficial effects of the combined treatment. In this first-in-human study, Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually.
The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1
Authors: Bahia Parmvir K. , Parks Thomas A. , Stanford Katherine R. , Mitchell David A. , Varma Sameer , Stevens Stanley M. , Taylor-Clark Thomas E.
Published: May 2016

Activation of the sensory nerve ion channel TRPA1 by electrophiles is the key mechanism that initiates nociceptive signaling, and leads to defensive reflexes and avoidance behaviors, during oxidative stress in mammals. TRPA1 is rapidly activated by subtoxic levels of electrophiles, but it is unclear how TRPA1 outcompetes cellular antioxidants that protect cytosolic proteins from electrophiles. Here, using physiologically relevant exposures, we demonstrate that electrophiles react with cysteine residues on mammalian TRPA1 at rates that exceed the reactivity of typical cysteines by 6,000-fold and that also exceed the reactivity of antioxidant enzymes. We show that TRPA1 possesses a complex reactive cysteine profile in which C621 is necessary for electrophile-induced binding and activation. Modeling of deprotonation energies suggests that K620 contributes to C621 reactivity and mutation of K620 alone greatly reduces the effect of electrophiles on TRPA1. Nevertheless, binding of electrophiles to C621 is not sufficient for activation, which also depends on the function of another reactive cysteine (C665). Together, our results demonstrate that TRPA1 acts as an effective electrophilic sensor because of the exceptionally high reactivity of C621.
A novel Nrf2 activator from microbial transformation inhibits radiation-induced dermatitis in mice
Authors: Nakagami Yasuhiro , Masuda Kayoko
Published: May 2016

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that regulates many antioxidants, and we have recently succeeded in obtaining a novel Nrf2 activator, RS9, from microbial transformation. RS9 is categorized as a triterpenoid, and well-known triterpenoids such as RTA 402 (bardoxolone methyl) and RTA 408 have been tested in clinical trials. RTA 408 lotion is currently being tested in patients at risk for radiation dermatitis. This prompted us to study the profiles of RS9 in the skin. All the above triterpenoids increased the level of an Nrf2-targeted gene, NADPH:quinone oxidoreductase-1, in normal human epidermal keratinocytes. Among them, the activity of RS9 was prominent; furthermore, the cellular toxicity was less compared with RTA compounds. BALB/c mice were irradiated with 30 Gy/day on Day 0, and compounds were topically applied on the back once daily from Day 1 to Day 30. Dermatitis scores peaked on Day 18, with a score of 2.6 in vehicle-treated mice, and topical applications of 0.1% RTA 402, RTA 408 and RS9 reduced the scores to 1.8, 2.0 and 1.4, respectively. Moreover, the percentage of animals with scores ≥2 was analyzed, and 0.1% RS9 suppressed the percentage from 100% to 47%. These results imply that RS9 has potential efficacy for treating radiation dermatitis.
Is Disuse Osteopenia a Favorable Prognostic Sign After Femoral Neck Fracture?
Authors: Ting Beverlie L. , Heng Marilyn , Vrahas Mark S. , Rodriguez Edward K. , Harris Mitchel B. , Weaver Michael J.
Published: May 2016

Objectives:

Avascular necrosis (AVN) of the femoral head is a devastating complication following fixation of femoral neck fractures in younger adults. In this study, we investigate the prognostic utility of disuse osteopenia.

Design:

Retrospective study.

Setting:

Three academic Level 1 trauma centers.

Patients:

One hundred twenty patients younger than 60 years treated for a femoral neck fracture.

Intervention:

N/A.

Main Outcome Measures:

The presence of sclerosis or osteopenia, compared to the contralateral femoral head, was measured 6 weeks from injury both subjectively and using a novel radiographic measure, the relative density ratio (RDR). The outcome measure was radiographic development of AVN.

Results:

The presence of relative sclerosis was associated with AVN and overall treatment failure. Patients with subjective relative sclerosis had a 12.6 (95% confidence interval, 2.9–61.3; P < 0.001) times higher odds of developing AVN. Multiple logistic regression showed that for every 0.10 increase in the RDR, there was a 5.2 increase in the odds (95% confidence interval, 2.1–26.9; P = 0.009) of developing AVN. Patients with an RDR of ≥1.2 have an 80% probability of AVN, whereas those with an RDR ≤0.8 have a <1% probability of developing AVN.

Conclusions:

Disuse osteopenia detected on 6-week radiographs is a favorable prognostic sign following fixation of femoral neck fractures. Patients who have relative sclerosis of the femoral head at 6-week follow-up are at a higher risk of developing AVN.

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Chronic Cervicitis: Presenting Features and Response to Therapy
Authors: Mattson Shawn K. , Polk Julia P. , Nyirjesy Paul
Published: May 2016

Objectives

Chronic nongonococcal nonchlamydial cervicitis is a condition of unknown etiology. Data about treatment options are limited. Our goal was to review a single center's experience in managing women with chronic NGNCC.

Methods

We evaluated all encounters at a tertiary care center with ICD-9 code for cervicitis between April 2008 and March 2014. Cases were defined by having two of the following 3 diagnostic criteria: mucopurulent discharge noted by (1) patient or (2) practitioner, and (3) cervical bleeding upon gentle probing. All women had negative nucleic acid amplification testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Information regarding patient demographics, symptoms, findings, treatment, and outcomes were analyzed. Cure was defined as resolution of patient-specific diagnostic criteria.

Results

Sixty-one women were identified. The mean age was 31 years; 73.7% were white, and 59% were nulliparous. The mean duration of symptoms was 25.2 months. Initially, all 61 patients received one of 3 antibiotic treatments. The cure rate after initial antibiotic treatment was 65.6%. Nineteen patients required at least one further treatment. Additional treatments included secondary antibiotics, hormonal treatments, vaginal hydrocortisone, silver nitrate, cryotherapy, and loop excision electrosurgical procedure. Cure rates were as follows: 57.9% with antibiotics, 50% with hormone treatment, 0% with hydrocortisone, 100% with silver nitrate, 0% with cryotherapy, and 100% with loop electrosurgical excisional procedure. Of the initial 61 women, 93.4% were eventually cured.

Conclusions

Nongonococcal nonchlamydial cervicitis is a condition that can cause unremitting symptoms. Most patients will respond to antibiotics, although other treatments including surgery may be necessary.
Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study
Authors: Roberts Sarah T. , Haberer Jessica , Celum Connie , Mugo Nelly , Ware Norma C. , Cohen Craig R. , Tappero Jordan W. , Kiarie James , Ronald Allan , Mujugira Andrew , Tumwesigye Elioda , Were Edwin , Irungu Elizabeth , Baeten Jared M. ,   for the Partners PrEP Study Team
Published: May 2016

Background:

Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP).

Methods:

We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence.

Results:

Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0–35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away.

Conclusions:

Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated.
Functions of phytoliths in vascular plants: an evolutionary perspective
Authors: Strömberg Caroline A. E. , Di Stilio Verónica S. , Song Zhaoliang
Published: May 2016

Solid biosilica (phytoliths) deposited in plant tissues is thought to function as structural support, as a cost‐effective alternative to lignin, and in herbivore defence, by limiting nutrient access/extraction and abrading herbivore mouthparts. It has been assumed that active phytolith accumulation evolved for these purposes, but these hypotheses remain untested. For example, an influential idea holds that grasses became so silica‐rich through antagonistic co‐evolution with mammalian grazers during the Cenozoic.

We examine whether phytoliths fulfil criteria established for adaptations, focusing on three aspects. First, we evaluate the recent debate concerning whether plant silica wears herbivore mouthparts/teeth. Secondly, we test whether the evolutionary pattern of phytolith accumulation is consistent with adaptive hypotheses by mapping silica content onto time‐calibrated land plant and grass phylogenies. Thirdly, we compare with palaeontological evidence for the timing of the ‘demand’ for the hypothesized function (structural support, herbivore defence).

Our survey demonstrates that phytoliths meet several criteria for adaptations, but key aspects require further study. For example, phytoliths wear teeth but are likely less important than dietary grit, suggesting that silica deterrence is ineffective against large mammalian grazers.

Mapping analysis indicates that active silica accumulation evolved numerous times, rather than being ancestral in land plants. However, a clear temporal link between these events and hypothesized functional ‘demands’ is still missing. For example, we find no convincing evidence for Cenozoic grass‐grazer co‐evolution.

Synthesis. Phytoliths help support and defend plants today, but the adaptive origin of this trait requires further testing. Such tests should integrate the phylogenetic distributions of phytoliths with ecology and biomechanics and use fossil evidence to evaluate the correlation between functional ‘demand’ and plant evolution.
Below‐ground biological responses to pyrogenic organic matter and litter inputs in grasslands
Authors: Soong Jennifer L. , Dam Marie , Wall Diana H. , Cotrufo M. Francesca
Published: May 2016

Terrestrial ecosystems are often burned by both managed and wildfires. During a fire, the above‐ground biomass that would typically accumulate and be decomposed as litter on the soil surface is combusted. Pyrogenic organic matter (PyOM) remaining after a fire is a considerably more recalcitrant organic input to the soil than fresh litter. The activity and community composition of soil organisms responsible for decomposition of organic matter and nutrient recycling in the soil could thus be affected by altered resource availability caused by frequent fires.

We examined the effect of PyOMvs. fresh litter inputs to soil biota at both an annually burned and an infrequently burned tallgrass prairie site by tracing13C‐ and15N‐labelled litter and PyOMinto growing plant roots, microbial phospholipid fatty acids (PLFAs) and soil nematodes for 1 year.

Litter‐derived C or N was incorporated into microbes, nematodes and roots, while PyOMcontributed minimally to soil microbes and plant roots and was not detectable in nematodes. Soil microbial and nematode abundances in the PyOMamended plots did not significantly differ from the bare soil plots, but nematodes were more abundant and microbialPLFAs less abundant in litter‐amended plots. The annually burned site had less predator and omnivore nematodes, with increased abundance of microbial feeders and greater microbial uptake of litter C.

An alteration of the soil food web structure caused by burning and the removal of the litter layer, along with the accumulation of non‐microbially decomposed PyOMin the soil, contributes to the limitation of N cycling in frequently burned ecosystems.

ALay Summaryis available for this article.
The Impact of Investor Horizon on Say‐on‐Pay Voting
Authors: Stathopoulos Konstantinos , Voulgaris Georgios
Published: May 2016

Shareholder investment horizons have a significant impact on say‐on‐pay voting patterns. Short‐term investors are more likely to avoid expressing opinion on executive pay proposals by casting an abstaining vote. They vote against board proposals on pay only in cases where the CEO already receives excessive pay levels. In contrast, long‐term investors typically cast favourable votes. According to our findings, this is due to effective monitoring rather than collusion with the management. Overall, investor heterogeneity in terms of investment horizons helps explain say‐on‐pay voting, in particular the low levels of say‐on‐pay dissent, which have recently raised questions over the efficiency of this corporate governance mechanism.
Social class tensions, habitus and the advertising of Guinness
Authors: Connolly John , Dolan Paddy
Published: May 2016

Drawing from an Eliasian perspective we examine how an ‘advertising subjectivity’ became more firmly embedded within the bourgeois habitus. We explain how and why advertising slowly developed and expanded within a commercial organization despite initial opposition, ambivalence and even hostility from some of its bourgeois senior management towards the practice – the very social class sometimes identified with advertising’s origins and advance. Our empirical case is based on Arthur Guinness & Sons Ltd, the Irish company which came to be renowned for the alcohol beverage which carried its name – Guinness stout. We explain how the development of advertising was impelled by a series of processes that increasingly interlocked; a widening and intensification of competitive commercial interdependencies; a shift in the power balance between the bourgeoisie and aristocracy in favour of the former in Britain; and by a changing consumer habitus in several different nation-states. Central though, as we illustrate, was a process involving the changing power relation between various social classes in Britain – principally the increasing power chances of bourgeoisie in relation to the aristocracy – a process that had advanced considerably by the turn of the twentieth century.
Choice of primary outcomes evaluating treatment for heavy menstrual bleeding
Authors: Herman MC , Penninx JPM , Geomini PM , Mol BW , Bongers MY
Published: May 2016

Background

Heavy menstrual bleeding (HMB) is a common problem with a variety of treatment options and many studies have been performed evaluating treatment effects. Consistency in the choice and definition of primary and secondary outcomes is important for the interpretation of data and for the synthesis of data in systematic reviews or individual patient data meta‐analysis (IPDMA).

Objective

To give insight into the primary endpoints and outcome measures chosen in randomised controlled trials (RCTs) and systematic reviews regarding the treatment of HMB.

Search strategy

Published systematic reviews and RCTs.

Selection criteria

Full reports of RCTs or systematic reviews.

Data collection and analysis

For RCTs, we used the primary outcomes, as they were used for the sample size calculation. For systematic reviews, all outcomes listed as primary were included. Four authors selected the studies.

Results

Twelve different primary outcomes were reported by 66 RCTs, most blood loss‐ related (44/66 studies). Amenorrhoea was the most common blood loss primary outcome (16/44 studies) and the Pictorial Blood Loss Assessment Chart (PBAC) was the most used measurement tool (27/44 studies). Satisfaction was the second most prevalent primary outcome measure (13/66 studies). In all, 14/26 (54%) systematic reviews prespecified a single primary outcome, whereas all other reviews used composite primary outcomes. Blood loss was the most studied outcome (12/26 reviews).

Conclusions

The most used primary outcomes in HMB studies relate to blood loss but there is no consistency regarding the endpoints chosen or measurement tools used to describe blood loss. Standardising outcomes will aid valid comparison and interpretation of data pertaining to the treatment of HMB.

Tweetable abstract

A standardised collection of outcomes in heavy menstrual bleeding research is urgently needed.
Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta‐analysis
Authors: Eke AC , Saccone G , Berghella V
Published: May 2016

Background

Depression is a prevalent condition in pregnancy affecting about 10% of women. Maternal depression has been associated with an increase in preterm births (PTB), low birthweight and fetal growth restriction, and postnatal complications. Available treatments for depressive disorders are psychotherapeutic interventions and antidepressant medications including selective serotonin inhibitors (SSRIs). SSRI use during pregnancy has been associated with several fetal and neonatal complications; so far, however, the risk of PTB in women using SSRIs during pregnancy is still a subject of debate.

Objective

To evaluate the risk of preterm birth (PTB) in cases of exposure to SSRIs during pregnancy.

Search strategy

Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE and the Cochrane Central Register of Controlled Trials) were searched from their inception until May 2015 with the use of a combination of the following text words ‘depression’, ‘pregnancy’, ‘exposure’, ‘antidepressant’, ‘SSRI’, ‘selective serotonin reuptake inhibitor’, ‘preterm birth’, ‘small for gestational age’ and ‘prematurity’.

Selection criteria

We included studies evaluating the effect of SSRIs exposure in utero and pregnancy outcomes. All cohort and case‐control studies were eligible to be included if they reported the incidence of PTB after any exposure to SSRIs and had a comparison group of unexposed pregnant women. Studies without a control group were excluded.

Data collection and analysis

The primary outcome was the incidence of PTB <37 weeks. Subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy were planned.

Main results

Eight studies (1 237 669 women) were included: 93 982 in the exposure group and 1 143 687 in the control group. After adjusting for confounders, the incidence of PTB was significantly higher in the group of women treated with SSRIs compared with controls (i.e. both women with depression but without SSRI exposure and women without depression) (adjusted OR (aOR) 1.24, 95% CI 1.09–1.41). In the subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy, an increased risk of PTB (6.8 versus 5.8%; OR 1.17, 95% CI 1.10–1.25) in the SSRI group was found compared with controls (i.e. depressed women treated with psychotherapy alone).

Conclusions

Women who received SSRIs during pregnancy had a significantly higher risk of developing PTB compared with controls. This higher risk remained significant even when comparing depressed women on SSRI with women not on SSRI.

Tweetable abstract

Selective serotonin reuptake inhibitors may be associated with preterm birth.
Determination of Nicotine, Cotinine and Trans‐3′‐Hydroxycotinine using LC/MS/MS in Forensic Samples of a Nicotine Fatal Case by Oral Ingestion of e‐cigarette Liquid,
Authors: You Gundong , Rhee Jongsook , Park Yuran , Park Sunhye
Published: May 2016

Nicotine is a potent neurotoxin alkaloid and is used in e‐cigarette liquid. The LC/MS/MS method was linear over 0.01–1.0 mg/L (r2 = 0.992–0.995). Limit of detection and limit of quantitation were 0.001 mg/L (S/N = 3) and 0.003 (S/N = 10). The inaccuracy and imprecision were <13.2%. The recoveries were >99.3%. A 39‐year‐old dentist was found dead lying on the floor under the couch in his dental clinic. The concentration of nicotine, cotinine, and trans‐3′‐hydroxycotinine (heart blood/peripheral blood) was analyzed as follows: 87.2/85.2 mg/L (ratio 1.0), 1.4/1.1 mg/L (ratio 1.3), and 0.012/0.0089 mg/L (ratio 1.3), respectively. The concentration of nicotine was determined to be 6734.8 mg/kg in gastric contents and 7262.0 mg/L in remaining e‐liquid. Only, high concentration of nicotine was detected in the gastric contents as well as the two pieces of evidence collected from the death scene. This fatal case resulted from oral ingestion of e‐cigarette liquid. It is estimated that at least 714 mg of nicotine was orally ingested.
Extraction and Purification of Quercitrin, Hyperoside, Rutin, and Afzelin from Zanthoxylum Bungeanum Maxim Leaves Using an Aqueous Two‐Phase System
Authors: He Fengyuan , Li Dengwu , Wang Dongmei , Deng Ming
Published: May 2016

In this study, an aqueous two‐phase system (ATPS) based on ethanol/NaH2PO4 was developed for the extraction and purification of quercitrin, hyperoside, rutin, and afzelin from Zanthoxylum bungeanum Maxim leaves. These 4 flavonoids were 1st extracted from dried Z. bungeanum leaves using a 60% ethanol solution and subsequently added to the ATPS for further purification. The partition behavior of the 4 flavonoids in ATPS was investigated. The optimal ATPS conditions were: 29% (w/w) NaH2PO4, 25% (w/w) ethanol concentration, 1% (w/w) added amount of leaf extracts, no pH adjustment, and repeated 1 h extractions at 25 °C. Under the optimal conditions for the 10 g ATPS, the absolute recovery of quercitrin, hyperoside, rutin, and afzelin reached 90.3%, 83.5%, 92.3%, and 89.1%, respectively. Compared to the 60% ethanol extracts, the content of quercitrin (44.8 mg/g), hyperoside (65.6 mg/g), rutin (56.4 mg/g), and afzelin (6.84 mg/g) in the extracts increased by 49.9%, 38.8%, 45.6%, and 36.8% respectively. The extracts after ATPS also exhibited stronger antioxidant activities, the 2,2‐diphenyl‐1‐picrylhydrazyl IC50 value (10.5 μg/mL) decreased by 41.8%, and the 2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt value (966 μmol Trolox/g) and ferric reducing power value (619 μmol Trolox/g) increased by 29.8% and 53.7%, respectively. Furthermore, scale‐up experiments indicated that a larger scale experiment was feasible for the purification of the 4 flavonoids.
Identification of novel microRNA genes in freshwater and marine ecotypes of the three‐spined stickleback (Gasterosteus aculeatus)
Authors: Rastorguev S. M. , Nedoluzhko A. V. , Sharko F. S. , Boulygina E. S. , Sokolov A. S. , Gruzdeva N. M. , Skryabin K. G. , Prokhortchouk E. B.
Published: May 2016

The three‐spined stickleback (Gasterosteus aculeatus L.) is an important model organism for studying the molecular mechanisms of speciation and adaptation to salinity. Despite increased interest to microRNA discovery and recent publication on microRNA prediction in the three‐spined stickleback using bioinformatics approaches, there is still a lack of experimental support for these data. In this paper, high‐throughput sequencing technology was applied to identify microRNA genes in gills of the three‐spined stickleback. In total, 595 miRNA genes were discovered; half of them were predicted in previous computational studies and were confirmed here as microRNAs expressed in gill tissue. Moreover, 298 novel microRNA genes were identified. The presence of miRNA genes in selected ‘divergence islands’ was analysed and 10 miRNA genes were identified as not randomly located in ‘divergence islands’. Regulatory regions of miRNA genes were found enriched with selective SNPs that may play a role in freshwater adaptation.
metaBIT, an integrative and automated metagenomic pipeline for analysing microbial profiles from high‐throughput sequencing shotgun data
Authors: Louvel Guillaume , Der Sarkissian Clio , Hanghøj Kristian , Orlando Ludovic
Published: May 2016

Micro‐organisms account for most of the Earth's biodiversity and yet remain largely unknown. The complexity and diversity of microbial communities present in clinical and environmental samples can now be robustly investigated in record times and prices thanks to recent advances in high‐throughput DNA sequencing (HTS). Here, we develop metaBIT, an open‐source computational pipeline automatizing routine microbial profiling of shotgun HTS data. Customizable by the user at different stringency levels, it performs robust taxonomy‐based assignment and relative abundance calculation of microbial taxa, as well as cross‐sample statistical analyses of microbial diversity distributions. We demonstrate the versatility of metaBIT within a range of published HTS data sets sampled from the environment (soil and seawater) and the human body (skin and gut), but also from archaeological specimens. We present the diversity of outputs provided by the pipeline for the visualization of microbial profiles (barplots, heatmaps) and for their characterization and comparison (diversity indices, hierarchical clustering and principal coordinates analyses). We show that metaBIT allows an automatic, fast and user‐friendly profiling of the microbial DNA present in HTS shotgun data sets. The applications of metaBIT are vast, from monitoring of laboratory errors and contaminations, to the reconstruction of past and present microbiota, and the detection of candidate species, including pathogens.
Determination of Nursing Diagnoses in Children of Agricultural Laborer Families in South Eastern Regions of Turkey
Authors: Karatas Hulya , Müller‐Staub Maria , Erdemir Firdevs
Published: May 2016

PURPOSE

Identifying functional health patterns and nursing diagnoses of migrant agricultural laborer families.

METHODS

Interpretative—qualitative study based on interviews with 162 mothers of 0‐ to 2‐year‐old children in two Turkish provinces.

FINDINGS

Health perception‐health management: growth and development, risk for being delayed; health maintenance, ineffective; health behavior, risk‐prone; risk for contamination; risk for sudden infant death syndrome; and risk for injury. Nutritional‐metabolic: Risk for infection; and breastfeeding, interrupted. Self‐perception: risk for chronic low self‐esteem, disturbed self‐esteem; and powerlessness. Role‐relationship: impaired parenting; and dysfunctional family process. Coping‐stress tolerance: coping, disabled family; violence, risk for other‐directed. Cognitive‐perceptive: knowledge deficit

CONCLUSIONS

Nursing diagnoses of this population were reported for the first time.

IMPLICATIONS

Addressing agricultural laborer families’ diagnoses will positively affect maternal—child health.
Decadal changes in mean annual rainfall drive long‐term changes in bush‐encroached southern African savannas
Authors: Shekede Munyaradzi D. , Murwira Amon , Masocha Mhosisi , Zengeya Fadzai M.
Published: May 2016

Bush encroachment can have profound effects on the ability of savanna ecosystems to provide goods and services to society. It is therefore crucial to understand the key drivers of bush encroachment in savannas. In this study, we test whether decadal changes in mean annual rainfall significantly explain changes in the dominant patch size as well as the density of bush patches at six protected savanna sites located along a rainfall gradient in Zimbabwe. We first performed Maximal Overlap Discrete Wavelet transform within the intensity‐dominant scale theoretical framework on multi‐temporal aerial photographs and high spatial resolution satellite imagery to objectively detect changes in the dominant patch dimension as well as the intensity of bush cover over a 40‐year period at six test sites. We then pooled the data and performed regression analysis relating changes in dominant scale and intensity to decadal changes in mean annual rainfall in order to deduce a possible connection between dynamics of bush encroachment and rainfall variability. Our results indicate a significant nonlinear relationship between changes in the dominant scale and decadal changes in mean annual rainfall (R2 = 0.85, F13 = 35.96, P < 0.01). In contrast, the relationship between decadal changes in mean annual rainfall and changes in intensity was weak and not significant (R2 = 0.29, F13 = 2.69, P = 0.106). These results imply the importance of annual rainfall in explaining long‐term changes in the dominant scale of woody patches. However, mechanisms other than rainfall probably explain changes in the intensity of bush cover, and this needs further investigation.
Microbiome and its impact on gastrointestinal atopy
Authors: Muir A. B. , Benitez A. J. , Dods K. , Spergel J. M. , Fillon S. A.
Published: May 2016

The prevalence of allergic conditions has continuously increased in the last few decades in Westernized countries. A dysbiotic gut microbiome may play an important role in the development of allergic diseases. Genetic, environmental, and dietary factors may alter the commensal microbiota leading to inflammatory dysregulation of homeostasis. Murine and human studies have begun to elucidate the role of the microbiota in the pathogenesis of atopic diseases including asthma, atopic dermatitis, and food allergies. However, the role of the microbiome in most eosinophilic gastrointestinal diseases (EGIDs) is not yet known. This review provides an overview of what is currently known about the development of tolerance from both molecular and clinical standpoints. We also look at the gut‐specific microbiome and its role in atopic conditions with the hope of applying this knowledge to the understanding, prevention, and treatment of EGIDs, particularly EoE.
Longitudinal evaluation of computerized cardiotocographic parameters throughout pregnancy in normal fetuses: a prospective cohort study
Authors: Amorim‐Costa Célia , Costa‐Santos Cristina , Ayres‐de‐Campos Diogo , Bernardes João
Published: May 2016

Introduction

The longitudinal cardiotocographic (CTG) changes throughout pregnancy in normal fetuses have never been fully described. We aimed at characterizing the evolution of CTG parameters in healthy fetuses, from 24 to 41 weeks of gestation.

Material and methods

A prospective cohort study was conducted in singleton fetuses without structural abnormalities on second‐trimester ultrasound. At least one CTG was performed in each of the following intervals: 24–26 weeks+6d, 27–29 weeks+6d, 30–32 weeks+6d, 33–35 weeks+6d, 36–38 weeks+6d and ≥39 weeks; tracings were analyzed by the OMNIVIEW‐SISPORTO 3.6 system. Cases of preterm delivery, fetal death, birthweight under the 10th percentile, low five‐minute Apgar, umbilical artery acidemia or neonatal intensive care unit admission were subsequently excluded.

Results

A total of 1049 eligible tracings were obtained from 145 fetuses. There was a significant increase over time in average long‐term variability (LTV), average short‐term variability (STV), number of accelerations and uterine contractions. Conversely, fetal heart rate (FHR) baseline and number of decelerations decreased. A high inter‐fetal variability was observed, but there was considerable intra‐fetal consistency. Fetuses showing a marked decrease in FHR baseline and those with a marked increase in average LTV had a significantly lower birthweight. Cesarean section rate was significantly higher in cases with a decrease in average STV throughout gestation.

Conclusions

This prospective longitudinal study shows an evolution in computerized CTG parameters during pregnancy, indicating the need to adapt interpretation criteria based on gestational age. The high inter‐fetal variability and considerable intra‐fetal consistency suggests the possible value of using each fetus as its own reference in serial assessments.
Epidemiologic characteristics of retinal detachment surgery at a specialized unit in Denmark
Authors: Poulsen Christina Doefler , Peto Tunde , Grauslund Jakob , Green Anders
Published: May 2016

Purpose

To examine the incidence of retinal detachments and to evaluate patient profiles and surgical characteristics.

Methods

Retrospective review of patients operated for primary retinal detachment (RD) and redetachment between 2010 and 2012 at the Department of Ophthalmology, Odense University Hospital, Denmark. We included all RD such as rhegmatogenous retinal detachment (RRD), tractional retinal detachment (TRD) and exudative retinal detachment (ERD).

Results

In total, 779 RD surgeries were performed: 83.7% (n = 652) primary operations and 16.3% (n = 127) reoperation. For primary operation, pars plana vitrectomy (PPV), scleral buckling and combined operations were performed in 95.1% (n = 620), 4.6% (n = 30) and 0.3% (n = 2) respectively. Over time there was less use of silicone oil and greater use of gas tamponade (p = <0.001), less simultaneous cataract operations (p = <0.001), less use of cryotherapy (p = 0.045) and more use of peeling procedures (p = <0.001) in primary operations. The annual incidence of surgery for primary RD was 22.0 [95% confidence interval (CI) 20.4–23.8] per 100 000 inhabitants aged >15 years. Retinal detachment (RD) was more common in males than females (1.8:1), and mean age at presentation was 61.8 years (standard deviations ± 12.3). The annual incidence for RRD and TRD operation was 20.72 (95% CI 19.11–22.43) and 1.25 (95% CI 0.9–1.7) per 100 000 inhabitants >15 years.

Conclusion

This study presents the first overall incidence for RD in Denmark. The highest incidence of RRD was among males aged 60 to 79 years, whereas TRD was among females at same age. Pars plana vitrectomy (PPV) was the preferred surgical technique, and during 2012 all RD patients were treated with PPV, independent of lens status and age.
Three‐year visual outcomes of intravitreal ranibizumab with or without photodynamic therapy for polypoidal choroidal vasculopathy
Authors: Sakai Tsutomu , Okano Kiichiro , Kohno Hideo , Tsuneoka Hiroshi
Published: May 2016

Purpose

To compare 3‐year visual outcomes after intravitreal ranibizumab (IVR) monotherapy and combination therapy of photodynamic therapy (PDT) with IVR for polypoidal choroidal vasculopathy (PCV).

Methods

Medical records for 45 eyes in 45 patients (34 men, 11 women; mean age, 73.8 years old; range, 62–86 years old) with treatment‐naïve PCV were reviewed retrospectively. Of the 45 eyes, 20 were treated with IVR monotherapy and 25 with combination therapy. Mean change in best‐corrected visual acuity, numbers of injections of IVR and length of treatment‐free period from baseline at month 36 were observed. Adverse events were monitored.

Results

The change in visual acuity after combination therapy was significantly better than that after IVR monotherapy (p = 0.0399). At 36 months, improvement in visual acuity was seen in five eyes (25.0%) in the IVR monotherapy group and 13 eyes (52.0%) in the combination therapy group. The treatment‐free period was significantly longer in the combination therapy group (p = 0.0008). Additional IVR therapy was required significantly more frequently in the IVR monotherapy group (p = 0.0026). Post‐treatment subretinal haemorrhage or retinal pigment epithelium tear occurred only in the IVR monotherapy group, in one eye (5.0%) and one eye (5.0%), respectively.

Conclusion

Initial therapy consisting of a single session of PDT combined with IVR improves vision in treatment‐naïve PCV. Compared with IVR monotherapy, this combination therapy may be more effective for PCV.
Hydrocortisone use in ventilated extremely preterm infants decreased bronchopulmonary dysplasia with no effects on neurodevelopment after two years
Authors: Renault Anaïs , Patkaï Juliana , Dassieu Gilles , El Ayoubi Mayass , Canouï‐Poitrine Florence , Durrmeyer Xavier
Published: May 2016

Aim

We assessed the outcomes of ventilated extremely premature infants treated with late postnatal corticosteroids from 2005–2008, according to permissive or restrictive policies in two centres.

Methods

This retrospective study included inborn infants below 27 weeks of gestational age who were ventilator dependent after 14 days. Centre P permitted postnatal corticosteroids but centre R restricted their use. The effects on infants were assessed in hospital and after two years using multivariable analysis.

Results

We compared 62 infants from centre P, including 92% who received hydrocortisone, and 48 infants from centre R, including 13% who received betamethasone. Infants from both centres had comparable baseline characteristics and perinatal management, but bronchopulmonary dysplasia (BPD) rates were significantly lower in centre P (30% versus 71%, p < 0.001) and this centre was significantly associated with a younger post‐conceptional age at oxygen weaning, with an adjusted hazard ratio (aHR) of 0.45 and an aHR of 0.51at discharge. At two years of corrected age, 18% of centre P infants and 30% of centre R infants showed poor neurodevelopmental outcome (p = 0.18).

Conclusion

Using hydrocortisone after 14 days on ventilated extremely preterm infants was associated with decreased BPD, with no apparent effects on neurodevelopment at two years of corrected age.
Adenine‐induced chronic renal failure in rats decreases aortic relaxation rate and alters expression of proteins involved in vascular smooth muscle calcium handling
Authors: Nguy L. , Shubbar E. , Jernås M. , Nookaew I. , Lundgren J. , Olsson B. , Nilsson H. , Guron G.
Published: May 2016

Aim

Rats with adenine‐induced chronic renal failure (A‐CRF) develop a reduced rate of relaxation of the thoracic aorta. The aim of this study was to elucidate the mechanisms underlying this abnormality.

Methods

Male Sprague Dawley rats received either chow containing adenine or were pair‐fed with normal chow (controls). After 8–14 weeks, arterial function was analysed ex vivo using wire myography and the expression of proteins involved in vascular smooth muscle excitation–contraction coupling in the thoracic aorta was analysed.

Results

The rate of relaxation following washout of KCl was reduced in A‐CRF rats vs. controls in the thoracic aorta (P < 0.01), abdominal aorta (P < 0.05), and common carotid artery (P < 0.05), but not in the common femoral artery. Relaxation rates of thoracic aortas increased (P < 0.01), but were not normalized, in response to washout of KCl with Ca2+‐free buffer. Microarray and qRT‐PCR analyses of genes involved in excitation–contraction coupling identified 10 genes, which showed significantly altered expression in A‐CRF thoracic aortas. At the protein level, the α2 subunit of the Na,K‐ATPase (P < 0.001) and SERCA2 (P < 0.05) was significantly downregulated, whereas stromal interaction molecule 1 and calsequestrin‐1 and calsequestrin‐2 were significantly upregulated (P < 0.05).

Conclusions

Rats with A‐CRF show a marked alteration in relaxation of larger conduit arteries localized proximal to the common femoral artery. This abnormality may be caused by reduced cytosolic Ca2+ clearance in vascular smooth muscle cells secondary to dysregulation of proteins crucially involved in this process.
Short‐term dynamics of submerged aquatic vegetation diversity and abundance in deep lakes
Authors: Bolpagni Rossano , Laini Alex , Azzella Mattia M.
Published: May 2016

Question

What are the short‐term trends of submerged aquatic vegetation (SAV) in deep lakes? Is it possible to measure significant changes in SAV distribution in deep lakes characterized by different trophic states and stable water physico‐chemical conditions using standard procedures over a 3‐yr period (2010–2013), as defined by the Water Framework Directive?

Location

We collected data from four deep lakes belonging to the Italian volcanic lake system (central Italy), which is one of the most important reserves of freshwater in Mediterranean Italy as well as one of the main hotspots of stonewort diversity in the Mediterranean area.

Methods

Macrophytes were sampled along five transects in each lake in 2010 and 2013. Data on aquatic plant diversity, composition and abundance were collected from each 1‐m depth intervals down to the maximum colonization depth. Simultaneously, the water quality and climate were assessed by standard procedures. Data were analysed with PCA, ANOVA, PROTEST and rank abundance curves.

Results

The sampling revealed a significant rearrangement of SAV. Increased species diversity in the first meters of depth (0–5 m) was due to the migration of mid‐depth species to lower depths. A reduction in the maximum growing depth of macrophytes was observed within the deepest stonewort communities (below 5 m). No significant changes emerged in water quality or climate.

Conclusions

Over 3 yr, SAV displayed significant changes that appear to be independent of summer nutrient conditions and climate drivers. In particular, vascular and stonewort species underwent a distinct spatial rearrangement according to specific behaviours. The present data point to the need for more rigorous analyses of the intra‐annual dynamics of macrophytes in deep lakes. An influence of the significant increase in spring precipitation (which is in keeping with local climate variability) recorded in central Italy in the last decade cannot be ruled out a priori, nor can the possibility of stochastic fluctuations be excluded. All these considerations further highlight the critical role of aquatic plants as bioindicators.
Hippocampal subfield volumes in short‐ and long‐term lithium‐treated patients with bipolar I disorder
Authors: Simonetti Alessio , Sani Gabriele , Dacquino Claudia , Piras Fabrizio , De Rossi Pietro , Caltagirone Carlo , Coryell William , Spalletta Gianfranco
Published: May 2016

Objectives

Patients diagnosed with bipolar disorder (BP) may experience hippocampal atrophy. Lithium exposure has been associated with increased hippocampal volumes. However, its effects on hippocampal subfields remain to be clarified.

Methods

We investigated the effects of short‐ and long‐term lithium exposure on the hippocampus and its subfields in patients affected by bipolar I disorder (BP‐I). Hippocampal subfields and total hippocampal volumes were measured in 60 subjects divided into four groups: 15 patients with BP‐I who were never exposed to lithium [no‐exposure group (NE)], 15 patients with BP‐I exposed to lithium for < 24 months [short‐exposure group (SE)], 15 patients with BP‐I exposed to lithium for > 24 months [long‐exposure group (LE)], and 15 healthy control subjects (HC).

Results

The SE and NE groups showed smaller total hippocampal volumes and smaller bilateral cornu ammonis CA2‐3, CA4‐dentate gyrus (DG), presubiculum, and subiculum volumes compared with HC. The LE group showed larger total hippocampal volumes and bilateral CA2‐3, left CA4‐DG, left presubiculum, and right subiculum volumes compared with the NE group, and larger volumes of the right CA2‐3, left CA4‐DG, left presubiculum, and right subiculum compared with the SE group. No differences were found between the LE group and HC or between the SE and NE groups.

Conclusions

Long‐term, but not short‐term, exposure to lithium treatment may exert neuroprotective effects on specific hippocampal subfields linked to disease progression.
Essential features of serious games design in higher education: Linking learning attributes to game mechanics
Authors: Lameras Petros , Arnab Sylvester , Dunwell Ian , Stewart Craig , Clarke Samantha , Petridis Panagiotis
Published: May 2016

This paper consolidates evidence and material from a range of specialist and disciplinary fields to provide an evidence‐based review and synthesis on the design and use of serious games in higher education. Search terms identified 165 papers reporting conceptual and empirical evidence on how learning attributes and game mechanics may be planned, designed and implemented by university teachers interested in using games, which are integrated into lesson plans and orchestrated as part of a learning sequence at any scale. The findings outline the potential of classifying the links between learning attributes and game mechanics as a means to scaffold teachers’ understanding of how to perpetuate learning in optimal ways while enhancing the in‐game learning experience. The findings of this paper provide a foundation for describing methods, frames and discourse around experiences of design and use of serious games, linked to methodological limitations and recommendations for further research in this area.