bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin release from eL40 is required for cytoplasmic maturation and function of 60S ribosomal subunits in Saccharomyces cerevisiae
Authors: Martín‐Villanueva Sara , Fernández‐Pevida Antonio , Fernández‐Fernández José , Kressler Dieter , de la Cruz Jesús
Published: July 2019

Ubiquitin is generated by proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a linear polyubiquitin protein of head‐to‐tail monomers, or as a single N‐terminal moiety to one of two ribosomal proteins, eL40 (Ubi1/2 precursors) and eS31 (Ubi3 precursor). It has been proposed that the ubiquitin moiety fused to these ribosomal proteins could act as a chaperone by facilitating their efficient production, folding and ribosome assembly in Saccharomyces cerevisiae. We have previously shown that ubiquitin release from eS31 is required for yeast viability and that noncleaved Ubi3 can get incorporated into translation‐competent 40S subunits. In this study, we have analysed the effects of mutations that partially or totally impair cleavage of the ubiquitin‐eL40A fusion protein. While noncleaved Ubi1 is not able to support growth when it is the sole cellular source of eL40, it can assemble into nascent pre‐60S particles. However, Ubi1‐containing 60S ribosomal subunits are not competent for translation. This is likely due to a steric interference of the unprocessed ubiquitin with the binding and function of factors that interact with the ribosome's GTPase‐associated centre. In agreement with this suggestion, Ubi1‐containing ribosomes affect the efficient recycling of the anti‐association factor Tif6 and have a reduced presence of translation elongation factors. We conclude that the removal of the ubiquitin moiety from ribosomal protein eL40 is an essential prerequisite for both the cytoplasmic maturation and the functionality of 60S ribosomal subunits.
Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment
Authors: Omar Hany A. , El‐Serafi Ahmed T. , Hersi Fatema , Arafa El‐Shaimaa A. , Zaher Dana M. , Madkour Mohamed , Arab Hany H. , Tolba Mai F.
Published: July 2019

Cancer immunotherapy represents a promising new era in cancer management due to the relatively high safety margins and selectivity, compared to the classical cancer chemotherapeutic agents. However, there is an imperative need to overcome tumor resistance in order to improve clinical outcomes and maximize the benefits of cancer immunotherapy. The interaction between the programmed cell death‐1 (PD‐1) receptor and its ligand PD‐L1 is a vital immune checkpoint that is often adopted by cancer cells to undergo immune evasion. PD‐1/PD‐L1 signaling is regulated at multiple levels through the crosstalk with other immune targets or relevant signaling partners involved in the cancer progression. Among the significant epigenetic players that are implicated in modulating the immune system are microRNAs (miRNAs). A complex system of these noncoding RNAs regulates the gene expression at the post‐transcriptional level and plays a significant role in the modulation of both innate and the adaptive immune systems. The expression profile of immune‐modulatory miRNAs might be useful as a predictive biomarker for the response and clinical outcomes in cancer immunotherapy. Therefore, in the current review, we highlighted the role of miRNAs in cancer immune evasion through a critical discussion of their impact on key immune checkpoints as well as the role of miRNAs in cancer progression and resistance.
Optimization research on S‐N curve of ring welding structure based on structural stress method
Authors: Yang Guangwu , Che Chengjian , Yang Bing , Zhu Tao , Wang Feng , Wang Jujin
Published: July 2019

In engineering, △F‐N curves are usually used to predict the fatigue life of ring welding, which is time‐consuming, laborious, and not universal. To improve the above inadequacies, an S‐N curve for evaluating the fatigue life of the ring welded specimen is proposed. The fatigue life of ring welded specimens with different materials, plate thicknesses, and hole diameters is obtained by tensile and shear fatigue tests. Shell elements, CBar beam elements (a kind of beam element in Nastran that can simulate bending), and rigid elements are used to establish the finite element model of ring welding. The stress of the ring welding structure under tensile shear load is calculated according to the structural stress method. The stress range △σs of the welding core is taken as the longitudinal coordinate and the experimental life N as the horizontal coordinate, using two‐parameter log‐log model and the least square method of the fatigue data for linear fitting to obtain the S‐N curve equation of fatigue life evaluation. Most of the data are located within five times of the life span, which proves that the predicted life is close to the actual life of the test, and it can provide a certain reference for design and life prediction of the ring welding structures.
Inter‐specific differences in invader and native fish functional responses illustrate neutral effects on prey but superior invader competitive ability
Authors: Mofu Lubabalo , South Josie , Wasserman Ryan J. , Dalu Tatenda , Woodford Darragh J. , Dick Jaimie T. A. , Weyl Olaf L. F.
Published: July 2019

Inter‐specific interactions are key factors in the structuring and functioning of ecological communities. Therefore, it is necessary to assess species interactions, such as predator–prey dynamics and competitive exclusion, within the context of continuing global species introductions. The aim of the present study was to assess ecological impacts and competitive exclusion dynamics involving co‐occurring introduced and native fish species, using the multiple predator functional response (FR) approach.

We use comparative FR analysis (resource uptake as a function of resource density) to assess inter‐specific interactions between the invasive western mosquitofishGambusia affinisand the native freshwater river gobyGlossogobius callidustowards chironomid larvae. The FR was derived for each fish species as individuals and when in heterospecific pairings. Data from single individuals were used to predict the expected FR of individuals when in heterospecific multiple predator combinations. Expected FRs were then compared to the observed FRs of each predator in combination trials, enumerated using prey items in their gut contents.

Both fish species displayed TypeIIFRs, however, in single fish trials, invasive mosquitofish had significantly higher FRs (curve asymptotes; i.e. shorter handling times and higher maximum feeding rates) than native river gobies. Heterospecific mosquitofish‐river goby combinations revealed that the FR of the river goby was reduced (i.e. longer handling times and lower maximum feeding rates) by the presence of mosquitofish, whereas this combination greatly enhanced mosquitofish FR magnitudes (i.e. shorter handling times and higher maximum feeding rates). The heterospecific treatments resulted in neutral impacts on prey and there were clear inter‐species interference in favour of the non‐native mosquitofish.

This study demonstrates how multiple predators can alter the shape of individualFRs, with neutral effects on prey but superior invader competitive ability. This has implications for predicting the naturalisation success of invasive predators, as predatory and competitive interactions with native predators and prey may facilitate rather than impede establishment.
The effectiveness of aquatic plants as surrogates for wider biodiversity in standing fresh waters
Authors: Law Alan , Baker Ambroise , Sayer Carl , Foster Garth , Gunn Iain D. M. , Taylor Philip , Pattison Zarah , Blaikie James , Willby Nigel J.
Published: July 2019

Freshwaters are among the most globally threatened habitats and their biodiversity is declining at an unparalleled rate. In an attempt to slow this decline, multiple approaches have been used to conserve, restore or enhance waterbodies. However, evaluating their effectiveness is time‐consuming and expensive. Identifying species or assemblages across a range of ecological conditions that can provide a surrogate for wider freshwater biodiversity is therefore of significant value for conservation management and planning.

For lakes and ponds in three contrasting landscapes of Britain (lowland agricultural, eastern England; upland, north‐west England; urban, central Scotland) we examined the link between macrophyte species, macrophyte morpho‐group diversity (an indicator of structural diversity) and the richness of three widespread aquatic macroinvertebrate groups (molluscs, beetles, and odonates) using structural equation modelling. We hypothesised that increased macrophyte richness and, hence, increased vegetation structural complexity, would increase macroinvertebrate richness after accounting for local and landscape conditions.

We found that macrophyte richness, via macrophyte morpho‐group diversity, was an effective surrogate for mollusc, beetle, and odonate richness in ponds after accounting for variation caused by physical variables, water chemistry, and surrounding land use. However, only mollusc richness could be predicted by macrophyte morpho‐group diversity in lakes, with no significant predicted effect on beetles or odonates.

Our results indicate that macrophyte morpho‐group diversity can be viewed as a suitable surrogate of macroinvertebrate biodiversity across diverse landscapes, particularly in ponds and to a lesser extent in lakes. This has important implications for the restoration, conservation, and creation of standing water habitats and for assessing their effectiveness in addressing the decline of global freshwater biodiversity. Management actions prioritising the development of species‐rich and structurally diverse macrophyte assemblages will be likely to benefit wider freshwater biodiversity.
Planned relocation and everyday agency in low‐lying coastal villages in Fiji
Authors: McMichael Celia , Katonivualiku Manasa , Powell Teresia
Published: July 2019

Relocation of communities is widely expected to be an adaptive response to sea‐level rise, albeit a last resort after exhausting other adaptation options. It is a phenomenon, however, from which there are few examples to learn. This paper examines relocation processes underway in three low‐lying coastal villages in Fiji, each affected by coastal erosion and flooding. Drawing on the concept of “everyday agency,” it considers how environmental changes and planned relocation initiatives are resisted, accommodated, or shaped through daily activities and decision‐making. For residents of these three villages, climate change adaptation is not only a matter of adapting to environmental changes, but a process of actively steering a way through unfolding dimensions of planned relocation. The findings respond to increasingly audible calls to recognise the agency of people living in climate‐vulnerable places, and to highlight everyday responses to climate impacts and adaptation initiatives.
Did incentives help municipalities recover from the Great Recession? Evidence from Midwestern cities
Authors: Drucker Joshua , Kim Geon , Weber Rachel
Published: July 2019

This study assesses the impacts of local business incentives in the largest urban areas of Illinois, Michigan, and Wisconsin, three Midwestern states that share similar histories and settings. We assembled a unique dataset combining information on two types of incentives, tax increment financing districts and tax abatements, together with socio‐economic, geographic, fiscal, and spatial competitive characteristics for all of the municipalities in six metropolitan areas. The outcome measures include employment growth, establishment formation, and business relocation. The analysis extends knowledge of the effects of economic development incentives in two ways. First, we improve upon previous research by incorporating key factors in municipal decisions to offer incentives. Second, we add to limited empirical evidence concerning local incentives following the Great Recession. Variation in the use of incentives reflects not only local decision‐making but also differing fiscal capacities and situations of adaptation to adverse economic conditions, with some governments pulling back on incentives and others initiating new approaches to retain or lure businesses.
Interdisciplinary and transdisciplinary research and practice: Balancing expectations of the ‘old’ academy with the future model of universities as ‘problem solvers’
Authors: Fam Dena , Clarke Elizabeth , Freeth Rebecca , Derwort Pim , Klaniecki Kathleen , Kater‐Wettstädt Lydia , Juarez‐Bourke Sadhbh , Hilser Stefan , Peukert Daniela , Meyer Esther , Horcea‐Milcu Andra‐Ioana
Published: July 2019

Academics are increasingly required to balance the expectations of the ‘old’ academy with a future model of universities as interdisciplinary and transdisciplinary ‘problem solvers’. This paper highlights changing expectations of academics in producing alternative research outcomes in collaborative, practice‐based research. Through a series of workshops with 20 researchers, preferred research outcomes and tensions in achieving these outcomes were identified. The tensions identified are presented as three dichotomies comprising the tension between: (a) ‘I versus We’ ‐ individual versus team expectations & outcomes. (b) Disciplinary outcomes versus inter‐/transdisciplinary outcomes. (c) Learning versus research objectives for the students and academics involved. These tensions reflect the authors' experiences of working in three international sustainability projects, drawing on lessons learned from these projects, with recommendations for universities seeking to implement interdisciplinary and transdisciplinary doctoral and postdoctoral programmes. Recommendations include the need for formal and informal leadership models, strong communication skills, empathy and willingness to learn from each other. A need for more systemic changes within university administration to better reward and value the breadth and depth of collaborative work, while facilitating open learning cultures and practice‐oriented learning opportunities and curricula across faculties was also identified.
Dextran modulates physical properties of rennet‐induced milk gels
Authors: Mende Susann , Jaros Doris , Rohm Harald
Published: July 2019

Physical properties of rennet‐induced milk gels as core intermediates of cheese production are mainly affected by milk composition, type and amount of coagulation enzyme and starter culture activity. We investigated model systems of reconstituted milk and dextran, which triggers effects on milk gels similar to exopolysaccharides from lactic acid bacteria. Furthermore, clotting activity (0.02 or 0.04 IMCU mL−1) and milk pH adjusted prior to renneting (6.5–5.7) were studied. A lower pH at renneting resulted in an earlier gelation onset, a higher gelation velocity and gel stiffness. The addition of dextran stabilised the gels especially at higher pH, and microstructural analysis revealed larger, more interconnected protein aggregates. However, at pH 5.7, a reverse effect was observed, indicating a destabilisation of the casein network. The current study indicates that altering milk pH and addition of polysaccharides gives the potential to change textural properties of cheese by affecting rennet‐induced gelation.
Long‐term safety and efficacy of trifarotene 50 μg/g cream, a first‐in‐class RAR‐γ selective topical retinoid, in patients with moderate facial and truncal acne
Authors: Blume‐Peytavi U. , Fowler J. , Kemény L. , Draelos Z. , Cook‐Bolden F. , Dirschka T. , Eichenfield L. , Graeber M. , Ahmad F. , Alió Saenz A. , Rich P. , Tanghetti E.
Published: July 2019

Background

Treatment for both facial and truncal acne has not sufficiently been studied.

Objectives

To evaluate the long‐term safety and efficacy of trifarotene in both facial and truncal acne.

Methods

In a multicentre, open‐label, 52‐week study, patients with moderate facial and truncal acne received trifarotene 50 μg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET.

Results

Of 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene‐related treatment‐emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter.

At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52.

At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit.

Conclusion

In this 52‐week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne.
Can multidisciplinary team meetings reduce burnout?
Authors: Gorbenko Ksenia , Mendelev Eliezer , Keefer Laurie
Published: July 2019

Burnout is an epidemic affecting between a third and two‐thirds of health care providers in the US. The prevalence and impact of burnout in the health care workforce is increasing, and most interventions thus far have shown limited efficacy. In an ongoing mixed‐methods study of establishing a specialty medical home, providers reported gaining interprofessional learning and collegiate support through a patient‐centered weekly team meeting that they believed was protective of burnout. Further research is needed into whether medical home models can improve not only patient, but also provider wellbeing.
Kinetics and mathematical modeling of thin layer drying of osmo‐treated Aloe vera (Aloe barbadensis) gel slices
Authors: Moradi Mehdi , Niakousari Mehrdad , Mousavi Khaneghah Amin
Published: July 2019

In the present work, the drying kinetics of osmo‐pretreated Aloe vera gel slices (AVGS) was investigated. AVGS with an initial moisture content of 98.29% (wet basis) were subjected to 5 hr of osmosis process (10% NaCl solution, at 40°C, NaCl solution to A. vera ratio = 5:1), prior to atmospheric thin layer drying at air temperatures of 55, 70, and 85°C and air volumetric air flow rates of 0.015, 0.036, and 0.054 m3/s for the duration of 160 min. Results showed the mean values of the moisture ratio in air temperatures of 55, 70, and 85°C were categorized into three levels (p < .01) of 0.551, 0.429, and 0.336, respectively, while the corresponding values for the osmo‐convective method were 0.561, 0.418, and 0.321, respectively. Similarly, the mean values of the moisture ratio in air flow rates of 0.015, 0.036, and 0.054 m3/s for the convective and osmo‐convective method assigned to different levels (p < .01) of 0.511, 0.417, 0.385 and 0.510, 0.416, 0.372, respectively. Superposition technique was utilized to propose a new model for each drying method. The predicted moisture ratios evaluated by the superposition technique were in a good agreement with experimental values of moisture ratio.

Practical Applications

In the current investigation, a superposition technique was utilized to propose a new model for two drying methods (osmo‐convective and convective). Subsequently, an equation describing the drying process for each method was derived. This technique while being a simple model, delivers high accuracy data for all influencing parameters in the drying process.
The role of miR156 in rejuvenation in Arabidopsis thaliana
Authors: Ye Bin‐Bin , Zhang Ke , Wang Jia‐Wei
Published: July 2019

Rejuvenation refers to the process enabling plants to regain physiological and molecular characteristics lost after entering the adult phase. The underlying molecular mechanism is poorly understood. Previous studies have revealed that microRNA156 (miR156) is highly accumulated at juvenile stage and maintains juvenile traits by repressing a group of SQUAMOSA PROMOTER BINDING PROTEIN‐LIKE (SPL) transcription factors. Here, we found that induction of miR156 expression in adult leaves can only restore some aspects of juvenile traits, such as loss of epidermal leaf hairs on the lower side of leaves and absence of serration at the leaf edges, but is incapable of delaying flowering and promoting adventitious root production.
Application of ‘no‐touch’ hysteroscopy (vaginoscopy) for the treatment of abnormal uterine bleeding in adolescence
Authors: Jin Lin , Yi Shuijing , Wang Xiaoxia , Xu Yimin
Published: July 2019

Aim

This article retrospectively analyzed the efficacy and safety of vaginoscopy in the treatment of adolescent abnormal uterine bleeding (AUB) in 204 cases of AUB.

Method

From January 1, 2007 to December 31, 2017, 204 patients with intact hymen who were admitted to our hospital due to AUB received vaginoscopy, and vaginoscopy did not damage the hymen. In this study, 4.5 mm and 6.5 mm hysteroscopy were used with a pumping fluid pressure of 100–120 mm Hg and a flow rate of 400 mL/min. All 204 vaginoscopy was successfully completed in intravenous anesthesia.

Results

Postoperative pathological examination confirmed that of the 204 patients, 53 patients had simple hyperplasia. There were 53 cases of polyps, 50 cases of endometrial gland hyperplasia and disordered arrangement, 35 cases of proliferative phase endometrium, five cases of bleeding phase endometrium, partial glandular secretion, three cases of complex hyperplasia and one case of decidua like change. Follow‐up data from 64 patients showed that 34 patients were effective after treatment. Stepwise logistic regression analysis suggested that endometrial thickness was associated with treatment outcome (HR, 0.875, 95% CI, 0.786–0.974, P = 0.014). There was no significant difference in drug use between patients with effective and ineffective treatment.

Conclusion

‘No‐touch’ vaginoscopy is feasible for the diagnosis and treatment of adolescent AUB without destroying the intact hymen.
Effect of fire regimes on the demographic parameters of the perennial tussock grasses of a humid savanna
Authors: Koffi Kouamé Fulgence , N'Dri Aya Brigitte , Lata Jean‐Christophe , Konaté Souleymane , Srikanthasamy Tharaniya , Konaré Sarah , Konan Marcel , Barot Sébastien
Published: July 2019

Questions

Perennial tussock grasses represent the principal fuel source for savanna fires; however, basic information about the impact of fire on their demography remains scarce. Do dominant perennial grass species differ in their demographic parameters? What is the overall impact of tussock circumference and fire regimes on grass demographic parameters? Do grass species differ in the sensitivity of their demographic parameters to fire regimes and tussock circumference?

Location

The study site is located in the savanna of the Lamto reserve, in the center of Ivory Coast (6°9′ to 6°18′ N, 5°15′ to 4°57′ E).

Methods

Data on the nine dominant species of tussock grasses were sampled over one year under four fire treatments (early fire, mid‐season fire, late fire and no fire). We studied the impact of these fire treatments and tussock circumference on five demographic parameters: mortality, fragmentation (the division of a tussock into several smaller ones), growth, retrogression (the decrease in tussock size) and fecundity.

Results

All demographic parameters varied among species and across the fire regimes. Late fire had the largest negative effect on all parameters except fecundity. Schizachyrium platyphyllum was the most disadvantaged species by fire in terms of mortality, retrogression and growth, whilst Andropogon ascinodis was the most prone to fragmentation. Hyparrhenia smithiana and Sorghastrum bipennatum produced the most seeds and Brachiaria brachylopha produced the most new tussocks. The circumference of perennial grasses impacted all demographic parameters. Small individuals had the highest mortality and growth rates, while large individuals showed the highest fragmentation and retrogression rates, and produced the most seeds.

Conclusions

This study showed that perennial grass species differed in their sensitivity to fire treatments. Nevertheless, the mid‐season fire could be advised to managers for the sustainable management of the Lamto savanna.
The evolution of polycyclic aromatic hydrocarbons under simulated inner asteroid conditions
Authors: Giese Claudia‐Corina , Ten Kate Inge Loes , Plümper Oliver , King Helen E. , Lenting Christoph , Liu Yang , Tielens Alexander G. G. M.
Published: July 2019

Large polycyclic aromatic hydrocarbons (PAHs) are an important component of the interstellar medium. PAHs have been identified in the soluble and insoluble matter of carbonaceous chondrites (CCs). Here, we study the evolution of PAHs under conditions relevant to the interiors of asteroids and compare our results to PAHs observed in CCs. We have performed long‐term and short‐term hydrothermal experiments, in which we exposed PAH‐mineral mixture analogs of meteorites to temperature conditions representative of those predicted for asteroids interiors. Our results show that small PAHs with melting points within the aqueous alteration temperature of CCs form carbonaceous spherules in the presence of water. In this work, we describe the microstructure and morphology of these spherules. We discuss the similarities and differences compared to globules isolated from CCs.
The All‐Seeing: Fraternity and Vision of God in Nicholas of Cusa
Authors: Falque Emmanuel
Published: July 2019

“I am because you look upon me.” This phrase from Nicholas of Cusa’s De visione Dei sive De icona is enough to sum up the stakes and originality of this treatise sent in 1453 to the Tegernsee monks. “Speaking in order to see,” “seeing in order to speak,” and “hearing in order to believe” chart the different stages of this unique experience, at once aesthetic, philosophical, spiritual, and mystical. Whereas one might have believed that the mere call to transcendence would be enough to justify gathering together before God, the collective contemplation of Rogier van der Weyden’s painting by the community of monks instead allows one to see and even hear that “the revelation of the witness” (and thus “the revelation of the brother”) validates the truth of this communally shared experience. Reaching the “wall of paradise” does not so much mean “escaping through the wall” or “getting over the wall” as it does “inhabiting the boundary” where opposites “coincide” and man and God meet within a human community.
The plant hypersensitive response: concepts, control and consequences
Authors: Balint‐Kurti Peter
Published: July 2019

The hypersensitive defence response is found in all higher plants and is characterized by a rapid cell death at the point of pathogen ingress. It is usually associated with pathogen resistance, though, in specific situations, it may have other consequences such as pathogen susceptibility, growth retardation and, over evolutionary timescales, speciation. Due to the potentially severe costs of inappropriate activation, plants employ multiple mechanisms to suppress inappropriate activation of HR and to constrain it after activation. The ubiquity of this response among higher plants despite its costs suggests that it is an extremely effective component of the plant immune system.
Understanding what matters to patients in critical care: An exploratory evaluation
Authors: Connelly Christine , Jarvie Lyndsey , Daniel Malcolm , Monachello Emma , Quasim Tara , Dunn Lelia , McPeake Joanne
Published: July 2019

Background

The delivery of person‐centred care is a key priority for managers, policy makers, and clinicians in health care. The delivery person‐centred care in critical care is challenging because of competing demands.

Aims and objectives

The aim of this quality improvement project was to understand what mattered to patients on a daily basis within the critical care environment. It aimed to understand personal goals and what patients needed to improve their experience. This paper reports on the outputs from this quality improvement project.

Design and Data Analysis

During each daily ward round, patients were asked “what matters to you today?” Outputs from this were entered into the Daily Goals Sheet, which is utilized for every patient in our critical care unit or in the nursing notes. Using Framework Analysis, prevalent themes were extracted from the patient statements documented.

Results

A total of 196 unique patients were included in this analysis alongside 592 patient statements. Four broad themes were generated: medical outcomes and information, the critical care environment, personal care, and family and caregivers.

Conclusion

The analysis of the data from this quality improvement project has demonstrated that, by asking a simple question within the context of a ward round, care can be enhanced and personalized and long‐term outcomes potentially improved. More research is required to understand what the optimal methods are of implementing these requests.

Relevance to clinical practice

Two main recommendations from practice emerged from this quality improvement project: asking patients “what matters to you?” on a daily basis may help support the humanization of the critical care environment, and visiting and access by families must be discussed with patients to ensure this is appropriate for their needs.
Being a woman in an ICT job: an analysis of the gender pay gap and discrimination in Spain
Authors: Segovia‐Pérez Mónica , Castro Núñez Rosa Belén , Santero Sánchez Rosa , Laguna Sánchez Pilar
Published: July 2019

Despite policy initiatives aimed at promoting female access to jobs, the information and communication technology (ICT) professions have traditionally been largely monopolised by men. Segregation, gendered stereotypes and environmental factors have a clear impact on educational and professional choices, as well as on working conditions. The spread of ICT to all economic activities has meant that ICT specialists are now to be found everywhere, not only in the ICT sector where many stereotypes related to technical jobs persist. This work aims to analyse the gender wage gap and discrimination in ICT professions, with the emphasis on how working in an ICT‐intensive industry might affect that situation. The study uses the Spanish Earning Structure Survey data for 2014, and applies wage decomposition techniques to the wage distribution. The results show that female ICT professionals face unfavorable working conditions, especially in highly qualified jobs and in ICT‐intensive industries.
Morphological and physiological traits in relation to carbon balance in a diverse clade of dryland mosses
Authors: Coe Kirsten K. , Howard Nora B. , Slate Mandy L. , Bowker Matthew A. , Mishler Brent D. , Butler Riley , Greenwood Joshua , Stark Lloyd R.
Published: July 2019

Plant functional trait analyses have focused almost exclusively on vascular plants, but bryophytes comprise ancient and diverse plant lineages that have widespread global distributions and important ecological functions in terrestrial ecosystems. We examined a diverse clade of dryland mosses, Syntrichia, and studied carbon balance during a precipitation event (C‐balance), a functional trait related to physiological functioning, desiccation tolerance, survival, and ecosystem carbon and nitrogen cycling. We examined variability in C‐balance among 14 genotypes of Syntrichia and measured an additional 10 physiological and 13 morphological traits at the cell, leaf, shoot, and clump level. C‐balance varied 20‐fold among genotypes, and highest C‐balances were associated with long, narrow leaves with awns, and small cells with thick cell walls, traits that may influence water uptake and retention during a precipitation event. Ordination analyses revealed that the axis most strongly correlated with C‐balance included the maximum chlorophyll fluorescence, Fm, indicating the importance of photosystem II health for C exchange. C‐balance represents a key functional trait in bryophytes, but its measurement is time intensive and not feasible to measure on large scales. We propose two models (using physiological and morphological traits) to predict C‐balance, whereby identifying simpler to measure traits for trait databases.
Translational approach to apathy‐like behavior in mice: From the practical point of view
Authors: Tanaka Kenji F. , Hamaguchi Takuya
Published: July 2019

Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre‐clinical levels. To study apathy‐like behavior in mice, we relied on an operational definition of apathy: the quantitative reduction of voluntary, goal‐directed behaviors. We recently found that the chronic loss of function of a specific cell type (striatal dopamine receptor type 2‐expressing medium spiny neurons, D2‐MSN) in a restricted region (the ventrolateral striatum, VLS) was sufficient to induce apathy‐like behavior in a food‐seeking operant task. We further showed that VLS D2‐MSN are activated at the preparatory period, and that optogenetic inhibition of VLS D2‐MSN during that period resulted in transient decreases in instrumental motivation, strengthening the hypothesis that VLS D2‐MSN mediate apathy‐like behavior in mice. Mice bearing VLS D2‐MSN dysfunction can thus be regarded as an apathy model for future translational studies.
State attachment variability across distressing situations in middle childhood
Authors: Verhees Martine W. F. T. , Ceulemans Eva , van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J. , Bosmans Guy
Published: July 2019

Contemporary research suggests that attachment has both a trait‐like, stable component, and a state‐like component that varies across contexts. In the current study, we assessed state attachment variability across comparably distressing situations in middle childhood. In two samples, children reported their expectations of maternal support in each situation. Additionally, we administered trait attachment and psychological well‐being measures. Results indicated that, overall, children varied in their expectations across situations: more than half of the variance was explained by intra‐individual differences across situations. Results revealed two components underlying variability: a Signal‐and‐Support component reflecting expectations of support‐seeking and receiving, and a Back‐on‐Track component reflecting expectations of stress reduction and comfort. State attachment variability was related to individual differences in trait attachment: children who are more securely attached at the trait level, overall appear to vary less in their state attachment, likely due to their high mean state attachment scores across situations. When the mean state attachment scores are accounted for, more securely attached children seem to vary more, suggesting that their state attachment expectations are more sensitive to contextual fluctuations. Importantly, degree of state attachment variability explained psychological well‐being over and above trait attachment.
Reactive oxygen species and reactive carbonyl species constitute a feed‐forward loop in auxin signaling for lateral root formation
Authors: Biswas Md. Sanaullah , Fukaki Hidehiro , Mori Izumi C. , Nakahara Kazuha , Mano Jun'ichi
Published: July 2019

In auxin‐stimulated roots, production of reactive oxygen species (ROS) via the hormone‐induced activation of respiratory burst oxidase homologous NADPH oxidases facilitates lateral root (LR) formation. In this study, in order to verify that ROS can modulate auxin signaling, we examined the involvement of the lipid peroxide‐derived agents known as reactive carbonyl species (RCS) in LR formation. When auxin was added to Arabidopsis thaliana roots, the levels of RCS, for example acrolein, 4‐hydroxynonenal and crotonaldehyde, were increased prior to LR formation. Addition of the carbonyl scavenger carnosine suppressed auxin‐induced LR formation. Addition of RCS to the roots induced the expression of the auxin‐responsive DR5 promoter and the TIR1, IAA14, ARF7, LBD16 and PUCHI genes and facilitated LR formation without increasing the endogenous auxin level. DR5 and LBD16 were activated in the LR primordia. The auxin signaling‐deficient mutants arf7 arf19 and slr‐1 did not respond – and tir1 afb2 appeared to show a poor response – to RCS. When given to the roots RCS promoted the disappearance of the AXR3NT–GUS fusion protein, i.e. the degradation of the auxin/indole‐3‐acetic acid protein, as did auxin. These results indicate that the auxin‐induced production of ROS and their downstream products RCS modulate the auxin signaling pathway in a feed‐forward manner. RCS are key agents that connect the ROS signaling and the auxin signaling pathways.
A comparison of three data mining time series models in prediction of monthly brucellosis surveillance data
Authors: Shirmohammadi‐Khorram Nasrin , Tapak Leili , Hamidi Omid , Maryanaji Zohreh
Published: July 2019

The early and accurately detection of brucellosis incidence change is of great importance for implementing brucellosis prevention strategic health planning. The present study investigated and compared the performance of the three data mining techniques, random forest (RF), support vector machine (SVM) and multivariate adaptive regression splines (MARSs), in time series modelling and predicting of monthly brucellosis data from 2005 (March/April) to 2017 (February/March) extracted from a national public health surveillance system in Hamadan located in west of Iran. The performances were compared based on the root mean square errors, mean absolute errors, determination coefficient (R2) and intraclass correlation coefficient criteria. Results indicated that the RF model outperformed the SVM and MARS models in modeling used data and it can be utilized successfully utilized to diagnose the behaviour of brucellosis over time. Further research with application of such novel time series models in practice provides the most appropriate method in the control and prevention of future outbreaks for the epidemiologist.
Deep Generative Design: Integration of Topology Optimization and Generative Models
Authors: Oh Sangeun , Jung Yongsu , Kim Seongsin , Lee Ikjin , Kang Namwoo
Published: July 2019

Deep learning has recently been applied to various research areas of design optimization. This study presents the need and effectiveness of adopting deep learning for generative design (or design exploration) research area. This work proposes an artificial intelligent (AI)-based deep generative design framework that is capable of generating numerous design options which are not only aesthetic but also optimized for engineering performance. The proposed framework integrates topology optimization and generative models (e.g., generative adversarial networks (GANs)) in an iterative manner to explore new design options, thus generating a large number of designs starting from limited previous design data. In addition, anomaly detection can evaluate the novelty of generated designs, thus helping designers choose among design options. The 2D wheel design problem is applied as a case study for validation of the proposed framework. The framework manifests better aesthetics, diversity, and robustness of generated designs than previous generative design methods.
Lack of the Major Multifunctional Catalase KatA in Pseudomonas aeruginosa Accelerates Evolution of Antibiotic Resistance in Ciprofloxacin-Treated Biofilms
Authors: Ahmed Marwa N. , Porse Andreas , Abdelsamad Ahmed , Sommer Morten , Høiby Niels , Ciofu Oana
Published: July 2019

During chronic biofilm infections,
Pseudomonas aeruginosa
bacteria are exposed to increased oxidative stress as a result of the inflammatory response. As reactive oxygen species (ROS) are mutagenic, the evolution of resistance to ciprofloxacin (CIP) in biofilms under oxidative stress conditions was investigated.
Toxoplasma
GRA15 Activates the NF-κB Pathway through Interactions with TNF Receptor-Associated Factors
Authors: Sangaré Lamba Omar , Yang Ninghan , Konstantinou Eleni K. , Lu Diana , Mukhopadhyay Debanjan , Young Lucy H. , Saeij Jeroen P. J.
Published: July 2019

The parasite
Toxoplasma
can cause birth defects and severe disease in immunosuppressed patients. Strain differences in pathogenicity exist, and these differences are due to polymorphic effector proteins that
Toxoplasma
secretes into the host cell to coopt host cell functions. The effector protein GRA15 of some
Toxoplasma
strains activates the nuclear factor kappa B (NF-κB) pathway, which plays an important role in cell death, innate immunity, and inflammation. We show that GRA15 interacts with TNF receptor-associated factors (TRAFs), which are adaptor proteins functioning upstream of the NF-κB transcription factor. Deletion of TRAF-binding sites in GRA15 greatly reduces its ability to activate the NF-κB pathway, and TRAF2 knockout cells have impaired GRA15-mediated NF-κB activation. Thus, we determined the mechanism for GRA15-dependent NF-κB activation.
Dissecting Colistin Resistance Mechanisms in Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates
Authors: Trebosc Vincent , Gartenmann Sarah , Tötzl Marcus , Lucchini Valentina , Schellhorn Birgit , Pieren Michel , Lociuro Sergio , Gitzinger Marc , Tigges Marcel , Bumann Dirk , Kemmer Christian
Published: July 2019

The discovery of antibiotics revolutionized modern medicine and enabled us to cure previously deadly bacterial infections. However, a progressive increase in antibiotic resistance rates is a major and global threat for our health care system. Colistin represents one of our last-resort antibiotics that is still active against most Gram-negative bacterial pathogens, but increasing resistance is reported worldwide, in particular due to the plasmid-encoded protein MCR-1 present in pathogens such as
Escherichia coli
and
Klebsiella pneumoniae
. Here, we showed that colistin resistance in
A. baumannii
, a top-priority pathogen causing deadly nosocomial infections, is mediated through different avenues that result in increased activity of homologous phosphoethanolamine (PetN) transferases. Considering that MCR-1 is also a PetN transferase, our findings indicate that PetN transferases might be the Achilles heel of superbugs and that direct targeting of them may have the potential to preserve the activity of polymyxin antibiotics.
Identification of Pathogen Genomic Differences That Impact Human Immune Response and Disease during Cryptococcus neoformans Infection
Authors: Gerstein Aleeza C. , Jackson Katrina M. , McDonald Tami R. , Wang Yina , Lueck Benjamin D. , Bohjanen Sara , Smith Kyle D. , Akampurira Andrew , Meya David B. , Xue Chaoyang , Boulware David R. , Nielsen Kirsten
Published: July 2019

Even with the best available care, mortality rates in cryptococcal meningitis range from 20% to 60%. Disease is often due to infection by the fungus
Cryptococcus neoformans
and involves a complex interaction between the human host and the fungal pathogen. Although previous studies have suggested genetic differences in the pathogen impact human disease, it has proven quite difficult to identify the specific
C. neoformans
genes that impact the outcome of the human infection. Here, we take advantage of a Ugandan patient cohort infected with closely related
C. neoformans
strains to examine the role of pathogen genetic variants on several human disease characteristics. Using a pathogen whole-genome sequencing approach, we showed that 40 
C. neoformans
genes are associated with human disease. Surprisingly, many of these genes are specific to
Cryptococcus
and have unknown functions. We also show deletion of some of these genes alters disease in a mouse model of infection, confirming their role in disease. These findings are particularly important because they are the first to identify
C. neoformans
genes associated with human cryptococcal meningitis and lay the foundation for future studies that may lead to new treatment strategies aimed at reducing patient mortality.
Bilateral congenital eventration of diaphragm: keep in mind, the other side
Authors: Joshi Avadhesh , Kumar Manish , Acharya Abhilipsa
Published: July 2019

Eventration of diaphragm is an uncommon disorder in which diaphragmatic muscle is replaced by fibroelastic tissue, either partially or completely. Bilateral eventration is even rarer. We present a case of bilateral eventration of diaphragm in newborn with a fibroelastic sac on left side and diaphragmatic eventration with good muscular lips on right side. The right-sided diaphragmatic eventration was not evident initially, but manifested after surgical repair of the left-sided eventration.
Cyclosporine-induced pericarditis: an elusive cause of chest pain in Behçet’s disease
Authors: Jain Siddharth , Singh Parminder , Naidu Shankar , Sharma Aman
Published: July 2019

Behçet’s disease (BD) is a variable-vessel vasculitis which commonly presents with recurrent orogenital ulceration, skin lesions, visual disturbances and neurodeficits. Arterial involvement is seen variably in 8%–18% cases of BD, with common affliction of the carotid, pulmonary, aortic and iliofemoral arteries. Cardiac involvement in the form of myocarditis, myocardial infarction, pericarditis, cardiac dysrhythmias or valvular disease is also known in BD, although rarely. Sudden-onset chest pain in BD is a medical emergency, with acute coronary syndrome, pulmonary thromboembolism and rupture of aortic or pulmonary artery aneurysms being the commonly implicated causes. Here, we report a rare case of BD who presented with sudden-onset severe chest pain, the cause of which remained elusive despite extensive evaluation for the abovementioned causes. To the best of our knowledge, this is the first reported case of cyclosporine-induced pericarditis in BD in available literature and should be considered in patients on cyclosporine presenting with chest pain.
First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants
Authors: Sessa Ben , Sakal Chloe , O’Brien Steve , Nutt David
Published: July 2019

We present the preliminary data in an ongoing open-label safety and tolerability proof of concept study exploring the potential role for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in treating patients with alcohol use disorder. At this stage, seven participants have completed the full 8-week MDMA-assisted psychotherapy course, including two therapy sessions each with MDMA. This paper focuses on the safety and tolerability of the therapeutic course for the first four participants to complete treatment. Longer-term outcomes of drinking behaviour will be presented later when the full project data are published. Results show all four participants have successfully tolerated the treatment. There have been no serious adverse events related to MDMA, no unexpected physiological responses to the MDMA sessions or changes to blood results or electrocardiograms, measured before and after the 8-week course. We conclude that the treatment is well- tolerated and are making plans to expand the project into a randomised placebo-controlled study.
De novo X-linked Alport syndrome in a 3-year-old girl
Authors: Komatsu Hiroshi , Goda Takeshi , Nozu Kandai
Published: July 2019

Alport syndrome (AS) is an inherited kidney disease that may lead to end-stage renal disease in early adult life. It is a clinically and genetically heterogeneous nephropathy. The possibility of a patient with haematuria or proteinuria being diagnosed as having AS cannot be excluded even if the patient is female or if the family history is unknown. We report a 3-year-old girl with a de novo frameshift mutation, c.3906delA p.(Gly1303Aspfs*17), in theCOL4A5gene. The significance of the electron microscopic study on the glomerular basement membrane must be emphasised because it is the first step towards the diagnosis of AS. Genetic analysis provides the only conclusive diagnosis of AS, by determining the mode of inheritance and prognosis.