bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke Volume Reserve Is an Independent Predictor of Survival and Need for Advanced Therapies in Systolic Heart Failure Patients
Authors: Selevany Ibrahim , Vaida Florin , Adler Eric D. , Kim Paul J. , Morris Timothy
Published: December 2019

Background

Current predictors of clinical deterioration in patients with heart-failure with reduced ejection fraction (HFrEF) have limited accuracy. We investigated whether stroke volume reserve index (SVRI) would predict 1-year mortality and need for advanced therapies in HFrEF patients.

Methods

We retrospectively studied a consecutive series of 104 ambulatory HFrEF patients (59±11 years, 89% men) at our center who underwent cardiopulmonary exercise testing (CPET) from January 2017 to September 2018. The primary outcome was defined as heart-transplantation, urgent left ventricular assist device (LVAD) implantation or death within 1 year of evaluation. SVRI was estimated at rest and at anaerobic threshold (AT) by VO2 (oxygen consumption)/pulse and previously validated estimates of C[a-v]O2 (arteriovenous difference in oxygen content). Multivariate regression selected the optimal predictors from clinical, CPET and right heart catheterization data.

Results

Among HFrEF patients studied, 39 (37.5%) deteriorated: 16 required heart-transplantation, 8 required LVADs and 15 died. SVRI 128% or less was the best predictor (OR 6.69, p=0.001), followed by an invasively determined resting cardiac index 2 L/min/m2 or less (OR 3.18, p=0.02), and peak VO2 below the International Society for Heart and Lung Transplantation (ISHLT) cut-off (OR 4.15, p=0.01). A scoring system derived from the SVRI (less than 128%: 2 points), peak VO2 (below the ISHLT cut-off: 1 point), and cardiac index (less than 2 L/min/m2: 1 point) predicted clinical deterioration with a sensitivity of 64% and specificity of 81%.

Conclusions

SVRI is a non-invasive measurement that may predict deterioration in HFrEF patients more accurately than currently recommended predictors.
Recellularization of bronchial extracellular matrix with primary bronchial smooth muscle cells
Authors: Hamouda Selma Ben , Vargas Amandine , Boivin Roxane , Miglino Maria Angelica , da Palma Renata Kelly , Lavoie Jean-Pierre
Published: December 2019

Severe asthma is associated with an increased airway smooth muscle (ASM) mass and an altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment. Our goal was to obtain acellular bronchial matrices and then develop a recellularization protocol with ASM cells. We studied equine bronchi as horses spontaneously develop a human asthma-like disease. The bronchi were decellularized using Triton/Sodium Deoxycholate. The obtained scaffolds retained their anatomical and histological properties. Using immunohistochemistry and a semi-quantitative score to compare native bronchi to scaffolds revealed no significant variation for matrixial proteins. A DNA quantification and electrophoresis indicated that most of DNA was 29.6 ng/mg of tissue ± 5.6 with remaining fragments of less than 100 bp. Primary ASM cells were seeded on the scaffolds. Histological analysis after recellularization showed that ASM cells migrated and proliferated primarily in the decellularized smooth muscle matrix, suggesting a chemotactic effect of the scaffolds. This is the first report of primary ASM cells preferentially repopulating the smooth muscle matrix layer in bronchial matrices. This protocol is now being used to study the molecular interactions occurring between the asthmatic ECMs and ASM to identify effectors of asthmatic bronchial remodeling.
Sources of predictive information in dynamical neural networks
Authors: Candadai Madhavun , Izquierdo Eduardo J.
Published: December 2019

Behavior involves the ongoing interaction between an organism and its environment. One of the prevailing theories of adaptive behavior is that organisms are constantly making predictions about their future environmental stimuli. However, how they acquire that predictive information is still poorly understood. Two complementary mechanisms have been proposed: predictions are generated from an agent’s internal model of the world or predictions are extracted directly from the environmental stimulus. In this work, we demonstrate that predictive information, measured using mutual information, cannot distinguish between these two kinds of systems. Furthermore, we show that predictive information cannot distinguish between organisms that are adapted to their environments and random dynamical systems exposed to the same environment. To understand the role of predictive information in adaptive behavior, we need to be able to identify where it is generated. To do this, we decompose information transfer across the different components of the organism-environment system and track the flow of information in the system over time. To validate the proposed framework, we examined it on a set of computational models of idealized agent-environment systems. Analysis of the systems revealed three key insights. First, predictive information, when sourced from the environment, can be reflected in any agent irrespective of its ability to perform a task. Second, predictive information, when sourced from the nervous system, requires special dynamics acquired during the process of adapting to the environment. Third, the magnitude of predictive information in a system can be different for the same task if the environmental structure changes.

Significance Statement

An organism’s ability to predict the consequences of its actions on future stimuli is considered a strong indicator of its environmental adaptation. However, in highly structured natural environments, to what extent does an agent have to develop specialized mechanisms to generate predictions? To study this, we present an information theoretic framework to infer the source of predictive information in an organism: extrinsically from the environment or intrinsically from the agent. We find that predictive information extracted from the environment can be reflected in any agent and is therefore not a good indicator of behavioral performance. Studying the flow of predictive information over time across the organism-environment system enables us to better understand its role in behavior.
Deciphering the many maps of the Xingu – an assessment of land cover classifications at multiple scales
Authors: Kalacska M , Arroyo-Mora J.P , Lucanus O , Sousa L , Pereira T , Vieira T
Published: December 2019

Remote sensing is an invaluable tool to objectively illustrate the rapid decline in habitat extents worldwide. The many operational Earth Observation platforms provide options for the generation of land cover maps, each with unique characteristics, as well as considerable semantic differences in the definition of classes. As a result, differences in baseline estimates are inevitable. Here we compare forest cover and surface water estimates over four time periods spanning three decades (1989–2018) for ∼1.3 million km2encompassing the Xingu river basin, Brazil, from published, freely accessible remotely sensed classifications. While all datasets showed a decrease in forest extent over time, we found a large range in the total area reported by each product for all time periods. The greatest differences ranged from 9% (year 2000) to 17% of the total area (2014-2018 period). We also show the high sensitivity of forest fragmentation metrics (entropy and foreground area density) to data quality and spatial resolution, with cloud cover and sensor artefacts resulting in errors. We further show the importance of choosing surface water datasets carefully because they differ greatly in location and amount of surface water mapped between sources. In several of the datasets illustrating the land cover following operationalization of the Belo Monte dam, the large reservoirs are notably absent. Freshwater ecosystem health is influenced by the land cover surrounding water bodies (e.g. Riparian zones). Understanding differences between the many remotely sensed baselines is fundamentally important to avoid information misuse, and to objectively choose the most appropriate dataset for conservation, taxonomy or policy-making. The differences in forest cover between the datasets examined here are not a failure of the technology, but due to different interpretations of ‘forest’ and characteristics of the input data (e.g. spatial resolution). Our findings demonstrate the importance of transparency in the generation of remotely sensed datasets and the need for users to familiarize themselves with the characteristics and limitations of each chosen data set.
Cytoplasmic streaming drifts the polarity cue and specifies the cell polarity inCaenorhabditis eleganszygotes
Authors: Kimura Kenji , Kimura Akatsuki
Published: December 2019

Cell polarisation is required to define body axes during development. The position of spatial cues for polarisation is critical to direct the body axes. InCaenorhabditis eleganszygotes, the sperm-derived pronucleus/centrosome complex (SPCC) serves as the spatial cue to specify the anterior–posterior axis. Approximately 30 minutes after fertilisation, the contractility of the cell cortex is relaxed near the SPCC, which is the earliest sign of polarisation and called symmetry breaking (SB). It is unclear how the position of SPCC at SB is determined after fertilisation. Here, we show that SPCC drifts dynamically through the cell-wide flow of the cytoplasm, called meiotic cytoplasmic streaming. This flow occasionally brings SPCC to the opposite side of the sperm entry site before SB. Our results demonstrate that cytoplasmic flow determines stochastically the position of the spatial cue of the body axis, even in an organism likeC. elegansfor which development is stereotyped.
Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein
Authors: Kobayashi Kazuhiro , Shihoya Wataru , Nishizawa Tomohiro , Kadji Francois Marie Ngako , Aoki Junken , Inoue Asuka , Nureki Osamu
Published: December 2019

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide hormone functioning in the central nervous system and peripheral tissues. The PACAP receptor PAC1R, which belongs to the class B G-protein-coupled receptors (GPCRs), is a drug target for mental disorders and dry eye syndrome. Here we present a cryo-electron microscopy structure of human PAC1R bound to PACAP and an engineered Gs heterotrimer. The structure revealed that TM1 plays an essential role in PACAP recognition. The ECD (extracellular domain) of PAC1R tilts by ~40° as compared to that of the glucagon-like peptide-1 receptor (GLP1R), and thus does not cover the peptide ligand. A functional analysis demonstrated that the PAC1R-ECD functions as an affinity trap and is not required for receptor activation, whereas the GLP1R-ECD plays an indispensable role in receptor activation, illuminating the functional diversity of the ECDs in the class B GPCRs. Our structural information will facilitate the design and improvement of better PAC1R agonists for clinical applications.

This article is a preprint version and has not been certified by peer review.
Enhancement of gene expression noise due to nonspecific transcription factor binding
Authors: Dey Supravat , Soltani Mohammad , Singh Abhyudai
Published: December 2019

The genome contains several high-affinity non-functional binding sites for transcription factors (TFs) creating a hidden and unexplored layer of gene regulation. We investigate the role of such “decoy sites” in controlling noise (random fluctuations) in the level of a TF that is synthesized in stochastic bursts. Prior studies have assumed that decoy-bound TFs are protected from degradation, and in this case decoys function to buffer noise. Relaxing this assumption to consider arbitrary degradation rates for both bound/unbound TF states, we find rich noise behaviors. For low-affinity decoys, noise in the level of unbound TF always monotonically decreases to the Poisson limit with increasing decoy numbers. In contrast, for high affinity decoys, noise levels first increase with increasing decoy numbers, before decreasing back to the Poisson limit. Interestingly, while protection of bound TFs from degradation slows the time-scale of fluctuations in the unbound TF levels, decay of bounds TFs leads to faster fluctuations and smaller noise propagation to downstream target proteins. In summary, our analysis reveals stochastic dynamics emerging from nonspecific binding of TFs, and highlight the dual role of decoys as attenuators or amplifiers of gene expression noise depending on their binding affinity and stability of the bound TF.
The Drosophila MLR COMPASS-like complex regulatesbantammiRNA expression differentially in the context of cell fate
Authors: Ford David J. , Zraly Claudia B. , Perez John Hertenstein , Dingwall Andrew K.
Published: December 2019

The conserved MLR COMPASS-like complexes are histone modifiers that are recruited by a variety of transcription factors to enhancer regions where they act as necessary epigenetic tools for enhancer establishment and function. A criticalin vivotarget of the Drosophila MLR complex is thebantammiRNA that regulates cell survival and functions in feedback regulation of cellular signaling pathways during development. We determine that loss of Drosophila MLR complex function in developing wing and eye imaginal discs results in growth and patterning defects that are sensitive tobantamlevels. Consistent with an essential regulatory role in modulatingbantamtranscription, the MLR complex binds to tissue-specificbantamenhancers and contributes to fine-tuning expression levels during larval tissue development. In wing imaginal discs, the MLR complex attenuatesbantamenhancer activity by negatively regulating expression; whereas, in differentiating eye discs, the complex exerts either positive or negative regulatory activity onbantamtranscription depending on cell fate. Furthermore, while the MLR complex is not required to controlbantamlevels in undifferentiated eye cells anterior to the morphogenetic furrow, it serves to prepare critical enhancer control ofbantamtranscription for later regulation upon differentiation. Our investigation into the transcriptional regulation of a single target in a developmental context has provided novel insights as to how the MLR complex contributes to the precise timing of gene expression, and how the complex functions to help orchestrate the regulatory output of conserved signaling pathways during animal development.
Targeted mutagenesis using CRISPR-Cas9 in the chelicerate herbivoreTetranychus urticae
Authors: Dermauw Wannes , Jonckheere Wim , Riga Maria , Livadaras Ioannis , Vontas John , Van Leeuwen Thomas
Published: December 2019

The use of CRISPR-Cas9 has revolutionized functional genetic work in many organisms, including more and more insect species. However, successful gene editing or genetic transformation has not yet been reported for chelicerates, the second largest group of terrestrial animals. Within this group, some mite and tick species are economically very important for agriculture and human health, and the availability of a gene-editing tool would be a significant advancement for the field. Here, we report on the use of CRISPR-Cas9 to create gene knock-outs in the spider miteTetranychus urticae. The ovary of virgin adult females was injected with a mix of Cas9 and sgRNAs targeting the phytoene desaturase gene. Natural mutants of this gene have previously shown an easy-to-score albino phenotype. Albino sons of injected virgin females were mated with wild-type females, and two independent transformed lines where created and further characterized. Albinism inherited as a recessive monogenic trait. Sequencing of the complete target-gene of both lines revealed two different lesions at expected locations near the PAM site in the target-gene. Both lines did not genetically complement each other in dedicated crosses, nor when crossed to a reference albino line with a known genetic defect in the same gene. In conclusion, two independent mutagenesis events were induced in the spider miteT. urticaeusing CRISPR-Cas9, providing an impetus for genetic transformation in chelicerates and paving the way for functional studies using CRISPR-Cas9 inT. urticae.
Single cell transcriptome analysis reveals RGS1 as a new marker and promoting factor for T cell exhaustion in multiple cancers
Authors: Bai Yunmeng , Hu Meiling , Chen Zixi , Wei Jinfen , Du Hongli
Published: December 2019

T cell exhaustion is one of the main reasons of tumor immune escape. Using single cell transcriptome data of CD8+ T cells in multiple cancers, we identified different cell types, in which Pre_exhaust and exhausted T cells participated in negative regulation of immune system process. By analyzing the co-expression network patterns and differentially expressed genes of Pre_exhaust, exhausted and effector T cells, we identified 35 genes related to T cell exhaustion, which high GSVA scores were associated with significantly poor prognosis in various cancers. In the differentially expressed genes,RGS1showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression ofRGS1was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore,RGS1displayed positive correlation with the 35 genes, especially highly correlated withPDCD1, CTLA4, HAVCR2andTNFRSF9in CD8+ T cells and cancer tissues, indicating important roles ofRGS1in CD8+ T cell exhaustion. Considering the GTP-hydrolysis activity ofRGS1and significantly high mRNA and protein expression in cancer tissues, we speculated thatRGS1potentially mediate the T cell retention to lead to the persistent antigen stimulation, resulting in T cell exhaustion. In conclusion, our findings suggest that RGS1 is a new marker and promoting factor for CD8+ T cell exhaustion, and provide theoretical basis for research and immunotherapy of exhausted cells.
Development of pre‐service teachers' self‐efficacy beliefs and attitudes towards inclusive education through first teaching experiences
Authors: Weber Kira E. , Greiner Franziska
Published: December 2019

We examined the development of pre‐service teachers' self‐efficacy beliefs and attitudes towards inclusive education through first teaching experiences during a 4‐week practicum. Additionally, we assessed the burnout‐related variables (job‐related satisfaction and exhaustion and perceived competence support during the practicum). Whereast‐tests for paired samples showed that self‐efficacy increased significantly, attitudes remained the same except for a decrease regarding attitudes towards the effects of inclusive education. However, 97% of the pre‐service teachers in our study reported positive to neutral experiences with inclusive teaching during the teaching practicum and correlational analysis revealed a low, but significant positive relationship between positive experiences and self‐efficacy and attitudes. Moreover, multiple regression analyses showed that positive experiences in inclusive classrooms predicted self‐efficacy regarding the arrangements of inclusive education, while perceived competence support from university supervisors was a significant predictor of attitudes towards the effects of inclusive education. High self‐efficacy correlated significantly with satisfaction of career choice, whereas attitudes were significantly negatively correlated with exhaustion. The implications of these findings and the importance of a sufficiently scaffolded teaching practicum in order to increase attitudes and self‐efficacy beliefs towards inclusive education are discussed.
Resurrecting immortal‐time bias in the study of readmissions
Authors: Hugar Lee A. , Borza Tudor , Oerline Mary K. , Hollenbeck Brent K. , Skolarus Ted A. , Jacobs Bruce L.
Published: December 2019

Objective

To compare readmission rates as measured by the Centers for Medicare and Medicaid Services and the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) methods.

Data Sources

20 percent sample of national Medicare data for patients undergoing cystectomy, colectomy, abdominal aortic aneurysm (AAA) repair, and total knee arthroplasty (TKA) between 2010 and 2014.

Study Design

Retrospective cohort study comparing 30‐day readmission rates.

Data Collection/Extraction Methods

Patients undergoing cystectomy, colectomy, abdominal aortic aneurysm repair, and total knee arthroplasty between 2010 and 2014 were identified.

Principal Findings

Cystectomy had the highest and total knee arthroplasty had the lowest readmission rate. The NSQIP measure reported significantly lower rates for all procedures compared to the CMS measure, which reflects an immortal‐time bias.

Conclusions

We found significantly different readmission rates across all surgical procedures when comparing CMS and NSQIP measures. Longer length of stay exacerbated these differences. Uniform outcome measures are needed to eliminate ambiguity and synergize research and policy efforts.
Plant–herbivorous insect networks: who is eating what revealed by long barcodes using high‐throughput sequencing and Trinity assembly
Authors: Zhang Xiao‐Man , Shi Zhi‐Yong , Zhang Shao‐Qian , Zhang Peng , Wilson John‐James , Shih Chungkun , Li Jing , Li Xue‐Dong , Yu Guo‐Yue , Zhang Ai‐Bing
Published: December 2019

Interactions between plants and insects are among the most important life functions for all organism at a particular natural community. Usually a large number of samples are required to identify insect diets in food web studies. Previously, Sanger sequencing and next generation sequencing (NGS) with short DNA barcodes were used, resulting in low species‐level identification; meanwhile the costs of Sanger sequencing are expensive for metabarcoding together with more samples. Here, we present a fast and effective sequencing strategy to identify larvae of Lepidoptera and their diets at the same time without increasing the cost on Illumina platform in a single HiSeq run, with long‐multiplex‐metabarcoding (COI for insects, rbcL, matK, ITS and trnL for plants) obtained by Trinity assembly (SHMMT). Meanwhile, Sanger sequencing (for single individuals) and NGS (for polyphagous) were used to verify the reliability of the SHMMT approach. Furthermore, we show that SHMMT approach is fast and reliable, with most high‐quality sequences of five DNA barcodes of 63 larvae individuals (54 species) recovered (full length of 100% of the COI gene and 98.3% of plant DNA barcodes) using Trinity assembly (up‐sized to 1015 bp). For larvae diets identification, 95% are reliable; the other 5% failed because their guts were empty. The diets identified by SHMMT approach are 100% consistent with the host plants that the larvae were feeding on during our collection. Our study demonstrates that SHMMT approach is reliable and cost‐effective for insect‐plants network studies. This will facilitate insect‐host plant studies that generally contain a huge number of samples.
Effect of ultra‐fine friction grinding on the physical and chemical properties of curcuma (Curcuma longa L.) suspensions
Authors: Serpa Guerra A. M. , Gómez Hoyos C. , Velásquez‐Cock J. A. , Vélez Penagos L. , Gañán Rojo P. , Vélez Acosta L. , Pereira M. A. , Zuluaga R.
Published: December 2019

Curcuma longa is a rhizome used for the extraction of curcumin, a yellow colorant that only represents 3 wt% of the dried rhizome. To increase the possibility of using the entire rhizome as a food colorant, in the present investigation, the effect of ultra‐fine friction grinding (supermasscolloider) to obtain turmeric suspensions was evaluated. To achieve this goal, two distances between the grinding stones or Gap were evaluated (G of –1 and –1.5), and the obtained suspensions were characterized by infrared spectroscopy and through the determination of curcumin content, color, particle size, sedimentation index, serum cloudiness, and microstructure. The results establish that a lower G contributes to an increase in the release of curcumin in the suspension up to 21%, which is related to a greater tendency for yellow coloration, observed in the increase of the *b coordinate of color (from 61.588 to 66.497). Additionally, it was found that a lower G generates smaller particle sizes, which is related to a lower turbidity.

Practical Application

This research shows that ultra‐fine friction grinding (UFFG) has great potential for the development of turmeric suspensions. The results have applications in the food industry sector, because UFFG could be used to produce different types of vegetable suspensions.
Visible and eco‐friendly immunoassays for the detection of cyclopiazonic acid in maize and rice
Authors: Li Yue , Liu Liqiang , Kuang Hua , Xu Chuanlai
Published: December 2019

Cyclopiazonic acid (CPA) is an indole‐tetramine mycotoxin commonly produced by Penicillium and Aspergillus and is widely found in agricultural products, fermented food, and feed. Food contaminated with CPA poses a substantial health risk to consumers. Therefore, eco‐friendly immunoassays, including an indirect competitive enzyme‐linked immunosorbent assay (ic‐ELISA) and a lateral flow immunochromatographic strip (LFICS), were developed to monitor CPA in maize and rice samples. For this purpose, a monoclonal antibody (3H12) posed highly resistant to pH (5.6 to 9.6) and ethanol (≤50%) was generated by mouse immunization. Negative maize and rice samples or samples spiked with CPA were extracted with ethanol/0.01 M sodium borate buffer (4/1, v/v, pH 8.4). For ic–ELISA analysis, the limits of detection (LODs) were 0.48 and 0.28 ng/g for maize and rice samples, respectively. The recovery for spiked maize was 76.9% to 83.5% with the highest variable coefficient (CVmax) being 9.32%. For spiked rice, the recovery was 85.3% to 105.1% with a CVmax of 8.56%. For LFICS analysis, the visible LODs were 2.5 and 1 ng/g and cutoff values were 5 and 2.5 ng/g for maize and rice samples, respectively. The LFICS method gave results within 5 to 10 min, providing an auxiliary analytical tool for the rapid, sensitive, and portable screening of the massive samples onsite.
Unraveling the genetic diversity of Belgian Milk Sheep using medium‐density SNP genotypes
Authors: Meyermans R. , Gorssen W. , Wijnrocx K. , Lenstra J. A. , Vellema P. , Buys N. , Janssens S.
Published: December 2019

The present study focuses on the Belgian Milk Sheep in Flanders (Belgium) and compares its genetic diversity and relationship with the Flemish Sheep, the Friesian Milk Sheep, the French Lacaune dairy sheep and other Northern European breeds. For this study, 94 Belgian Milk Sheep, 23 Flemish Sheep and 22 Friesian Milk Sheep were genotyped with the OvineSNP50 array. In addition, 29 unregistered animals phenotypically similar to Belgian Milk Sheep were genotyped using the 15K ISGC chip. Both Belgian and Friesian Milk Sheep as well as the East Friesian Sheep were found to be less diverse than the other seven breeds included in this study. Genomic inbreeding coefficients based on runs of homozygosity (ROH) were estimated at 14.5, 12.4 and 10.2% for Belgian Milk Sheep, Flemish Sheep and Friesian Milk Sheep respectively. Out of 29 unregistered Belgian Milk Sheep, 28 mapped in the registered Belgian Milk Sheep population. Ancestry analysis, PCA and FST calculations showed that Belgian Milk Sheep are more related to Friesian Milk Sheep than to Flemish Sheep, which was contrary to the breeders' expectations. Consequently, breeders may prefer to crossbreed Belgian Milk Sheep with Friesian sheep populations (Friesian Milk Sheep or East Friesian Sheep) in order to increase diversity. This research underlines the usefulness of SNP chip genotyping and ROH analyses for monitoring genetic diversity and studying genetic links in small livestock populations, profiting from internationally available genotypes. As assessment of genetic diversity is vital for long‐term breed survival, these results will aid flockbooks to preserve genetic diversity.
Critical care burden of skin and soft tissue infection in Central Australia: More than skin deep
Authors: Secombe Paul , Planche Yannick , Athan Eugene , Ollapallil Jacob
Published: December 2019

Objective

To describe the epidemiology, critical care resource use of and outcomes from an intensive care admission for a skin or soft tissue infection in Central Australia.

Design

Retrospective database review of prospectively collected data identifying all patients requiring admission for a life‐threatening illness related to a skin or soft tissue infection.

Setting

Intensive care unit Alice Springs Hospital.

Participants

All patients admitted with a primary diagnosis of skin or soft tissue infection between 2010 and 2016.

Main outcome measure

Annualised incidence of skin or soft tissue infection requiring intensive care. Secondary outcomes examined resource use (length of stay, mechanical ventilation) and a description of the microbiology of skin or soft tissue infection in Central Australia.

Results

There were 80 admissions to the intensive care unit over the sampling period, yielding an annualised incidence of 24.2 intensive care unit admissions per 100 000 population. Eighty‐five per cent were Indigenous with high rates of co‐morbid disease including poorly controlled type 2 diabetes, haemodialysis‐dependent chronic kidney disease and co‐infection with human T‐cell lymphocytic virus. The predominant type of skin or soft tissue infection was abscess, predominantly below the waist. Gram‐positive cocci comprised 50% of the organisms cultured, and 20% of organisms were multi‐resistant. Mortality was 0% and 1.3% at 28 and 90 days respectively.

Conclusion

The annualised incidence of skin or soft tissue infection requiring intensive care support in Central Australia is higher than expected. This probably reflects the high burden of chronic disease and poor living conditions. While there is no mortality burden associated with skin or soft tissue infection in Central Australia, there is substantial morbidity. The data from this study adds weight to the call for improved primary health resources for this group.
Laser‐facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation
Authors: Korotchenko Evgeniia , Moya Raquel , Scheiblhofer Sandra , Joubert Isabella A , Horejs‐Hoeck Jutta , Hauser Michael , Calzada David , Iraola Víctor , Carnés Jerónimo , Weiss Richard
Published: December 2019

Background

Skin‐based immunotherapy of type 1 allergies has recently been re‐investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)‐induced lung inflammation to explore the potential of laser‐facilitated epicutaneous allergen‐specific treatment.

Methods

Mice were sensitized against native Dermatophagoides pteronyssinus extract and repeatedly treated by application of depigmented D pteronyssinus extract via laser‐generated skin micropores or by subcutaneous injection with or without alum. Following aerosol challenges, lung function was determined by whole‐body plethysmography and bronchoalveolar lavage fluid was analyzed for cellular composition and cytokine levels. HDM‐specific IgG subclass antibodies were determined by ELISA. Serum as well as cell‐bound IgE was measured by ELISA, rat basophil leukemia cell assay, and ex vivo using a basophil activation test, respectively. Cultured lymphocytes were analyzed for cytokine secretion profiles and cellular polarization by flow cytometry.

Results

Immunization of mice by subcutaneous injection or epicutaneous laser microporation induced comparable IgG antibody levels, but the latter preferentially induced regulatory T cells and in general downregulated T cell cytokine production. This effect was found to be a result of the laser treatment itself, independent from extract application. Epicutaneous treatment of sensitized animals led to induction of blocking IgG, and improvement of lung function, superior compared to the effects of subcutaneous therapy. During the whole therapy schedule, no local or systemic side effects occurred.

Conclusion

Allergen‐specific immunotherapy with depigmented HDM extract via laser‐generated skin micropores offers a safe and effective treatment option for HDM‐induced allergy and lung inflammation.
Letter: is tenofovir superior to entecavir for hepatocellular carcinoma prevention in chronic hepatitis B?
Authors: Yuan Bao‐Hong , Zhu Yan‐Kun , Li Ru‐Hong
Published: December 2019

LINKED CONTENT

This article is linked to Brancaccio et al and Yip and Wong papers. To view these articles, visit https://doi.org/10.1111/apt.15188 and https://doi.org/10.1111/apt.15614.
Letter: the Shock Index and predicting outcomes in patients with upper gastrointestinal bleeding
Authors: McPherson Simon J , Hammond Christopher J
Published: December 2019

LINKED CONTENT

This article is linked to Saffouri et al and Stanley papers. To view these articles, visit https://doi.org/10.1111/apt.15541 and https://doi.org/10.1111/apt.15615.
Letter: the Shock Index and predicting outcomes in patients with upper gastrointestinal bleeding. Author’s reply
Authors: Stanley Adrian
Published: December 2019

LINKED CONTENT

This article is linked to Saffouri et al and McPherson and Hammond papers. To view these articles, visit https://doi.org/10.1111/apt.15541 and https://doi.org/10.1111/apt.15605.
Cross‐national assessment of the effects of income level, socialization process, and social conditions on employees’ ethics
Authors: Tuliao Kristine Velasquez , Chen Chung‐wen , Yeh Ying‐Jung
Published: December 2019

Employees often experience ethical dilemmas throughout their service in an organization. This study utilized a multilevel standpoint to address employees’ differences in ethical reasoning. Hierarchical linear modeling was used to analyze responses from 40,485 full‐time employees across 54 countries. Drawing from Durkheim's concepts of the homo duplex, socialization process, and social conditions, this study found a positive relationship between employees’ income level and unethical reasoning. Furthermore, the results indicate that modern social regulation, technological advancement, economic development, and economic change moderate the relationship between income and ethical judgment. The study findings contribute to the Durkheimian model by validating the effects of individual‐ and country‐level factors on employees’ ethicality. Considering that the results contradict Durkheim's initial propositions, another concept and theory are proposed, which may complement Durkheim's arguments. Practical implications for organizations and society are further discussed to reinforce employees’ ethics.
Mind‐wandering in children with and without ADHD
Authors: Frick Matilda A. , Asherson Philip , Brocki Karin C.
Published: December 2019

Objectives

Mind‐wandering (MW) is a commonly experienced phenomenon, characterized by focus of attention drifting away from the present situation to intrinsically originated thoughts. Studies in adults show that MW is related to ADHD symptoms, but this association is understudied in children. We set out to investigate the associations of MW in children with and without ADHD and to simultaneously validate the self‐report Mind Excessively Wandering Scale (MEWS) in children.

Design

We used a cross‐sectional, correlational, design to examine the research questions.

Methods

The sample consisted of 82 children (61 boys) aged 8–13 years (m = 10.46), of which 35 had a diagnosis of ADHD. Children rated MW; parents and teachers rated ADHD symptoms, emotion regulation and academic achievement. Working memory was assessed with Digit Span.

Results

MW was positively related to ADHD symptoms, and the MEWS could differentiate between cases and controls with a sensitivity of 0.71 and specificity of 0.81. Psychometric properties of the MEWS were satisfactory. In addition, MW contributed independently to working memory (R2Δ = .05, p = .01) and emotion regulation (R2Δ = .04, p = .04) beyond ADHD symptoms.

Conclusions

MW is elevated in children with ADHD and contributes to functional domains. The MEWS is a valid tool for assessing MW in children, and the results are mostly comparable to that of adults (Mowlem et al., 2016, Journal of Attention Disorders, 23, 624), suggesting a similar relationship of MW to ADHD across the lifespan.

Practitioner points

Spontaneous mind‐wandering is elevated in children with ADHD compared to children without a diagnosis.

Elevated spontaneous mind‐wandering predicts lower working memory, emotion regulation and academic achievement beyond ADHD symptoms, IQ and socio‐economic status.

Clinicians should consider evaluating excessive spontaneous mind‐wandering and targeting it as an important outcome when treating children with ADHD.

The MEWS is a valid tool for assessing excessive mind‐wandering in children.
Muscle and fat aftereffects and the role of gender: Implications for body image disturbance
Authors: Brooks Kevin R. , Keen Edwina , Sturman Daniel , Mond Jonathan , Stevenson Richard J. , Stephen Ian D.
Published: December 2019

Body image disturbance – a cause of distress amongst the general population and those diagnosed with various disorders – is often attributed to the media’s unrealistic depiction of ideal bodies. These ideals are strongly gendered, leading to pronounced fat concern amongst females, and a male preoccupation with muscularity. Recent research suggests that visual aftereffects may be fundamental to the misperception of body fat and muscle mass – the perceptual component of body image disturbance. This study sought to establish the influence of gender on these body aftereffects. Male and female observers were randomly assigned to one of four adaptation conditions (low‐fat, high‐fat, low‐muscle, and high‐muscle bodies) and were asked to adjust the apparent fat and muscle levels of male and female bodies to make them appear as ‘normal’ as possible both before adaptation and after adaptation. While neither the gender of observers nor of body stimuli had a direct effect, aftereffect magnitude was significantly larger when observers viewed own‐gender (compared with other‐gender) stimuli. This effect, which may be due to attentional factors, could have implications for the development of body image disturbance, given the preponderance of idealized own‐gender bodies in media marketed to male and female consumers.
A Cross‐Dimension Annotations Method for 3D Structural Facial Landmark Extraction
Authors: Gong Xun , Chen Ping , Zhang Zhemin , Chen Ke , Xiang Yue , Li Xin
Published: December 2019

Recent methods for 2D facial landmark localization perform well on close‐to‐frontal faces, but 2D landmarks are insufficient to represent 3D structure of a facial shape. For applications that require better accuracy, such as facial motion capture and 3D shape recovery, 3DA‐2D (2D Projections of 3D Facial Annotations) is preferred. Inferring the 3D structure from a single image is an ill‐posed problem whose accuracy and robustness are not always guaranteed. This paper aims to solve accurate 2D facial landmark localization and the transformation between 2D and 3DA‐2D landmarks. One way to increase the accuracy is to input more precisely annotated facial images. The traditional cascaded regressions cannot effectively handle large or noisy training data sets. In this paper, we propose a Mini‐Batch Cascaded Regressions (MBCR) method that can iteratively train a robust model from a large data set. Benefiting from the incremental learning strategy and a small learning rate, MBCR is robust to noise in training data. We also propose a new Cross‐Dimension Annotations Conversion (CDAC) method to map facial landmarks from 2D to 3DA‐2D coordinates and vice versa. The experimental results showed that CDAC combined with MBCR outperforms the‐state‐of‐the‐art methods in 3DA‐2D facial landmark localization. Moreover, CDAC can run efficiently at up to 110 fps on a 3.4 GHz‐CPU workstation. Thus, CDAC provides a solution to transform existing 2D alignment methods into 3DA‐2D ones without slowing down the speed. Training and testing code as well as the data set can be downloaded from https://github.com/SWJTU‐3DVision/CDAC.
Retrospective clinical analysis of risk factors associated with failed short implants
Authors: Chen Li , Yang Tao , Yang Guangwen , Zhou Na , Dong Heng , Mou Yongbin
Published: December 2019

Background

With advanced technology, short implants are more commonly used and have proven to have a relatively reliable curable efficacy. A consensus has not been reached regarding potential risk factors related to the loss of short implants.

Purpose

This large‐sample retrospective study concentrated not only on patient characteristics and medical procedures but also on the features of implants in order to uncover the risk factors associated with short implants.

Methods

Between 2014 and 2017, a total of 7001 implants were inserted at Nanjing Stomatological Hospital, Medical School of Nanjing University. Among the all, 1236 short implants were included after being evaluated according to the inclusion and exclusion criteria. In organizing the detailed information, seven variables including bone grafting procedure, age, gender, diameter of the implant, implant position, surface treatment, and definitive restorations were taken into consideration. The χ2 test, Kaplan‐Meier test, logistic regression, and multifactorial Cox regression analysis were employed to explore the risk factors.

Results

The cumulative survival rate of short implants was 96.36%, slightly lower than that of the standard implants (98.16%, P < .001). Most of the short implants (84.44%) were lost at the early stage, mainly because of infection. Based on the results, male gender, implants treated by titanium anodizing and single‐crown restoration increased the loss rate of short implants. Comparison of the short implants inserted into the maxillary and mandibular posterior area alone showed that the maxillary molar area was a risk factor for prognosis.

Conclusions

Male gender, TA surface treatment, and the presence of a single crown were associated with an increasing rate of short implants loss. Examination of the implant location focused on the posterior area revealed the maxillary posterior area to be a risk factor.
Comparison of Efficacy of Dipeptidyl Peptidase‐4 Inhibitors and Sodium‐Glucose Co‐Transporter 2 Inhibitors Between Japanese and Non‐Japanese Patients: A Meta‐Analysis
Authors: Ito Yuka , Ambe Kaori , Hayase Toshiki , Kobayashi Mayu , Tohkin Masahiro
Published: December 2019

We explored efficacy of dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and sodium‐glucose co‐transporter 2 inhibitors (SGLT2is) between Japanese and non‐Japanese patients with type 2 diabetes mellitus by conducting a systematic review and meta‐analysis. A literature search of public databases before May 2017 identified 91 (DPP‐4i) and 63 (SGLT2i) randomized placebo‐controlled trials (> 12‐week treatment). Multivariate meta‐regression analysis identified baseline hemoglobin A1c (HbA1c) levels and placebo responses as covariates affecting efficacy of two agent classes independently of study region (Japanese/non‐Japanese). When accounted for covariates, DPP‐4i caused more pronounced HbA1c reduction in Japanese studies than in non‐Japanese studies by 0.18% difference (P < 0.05) while causing no difference in fasting plasma glucose reduction between regions. On the other hand, when adjusted by baseline HbA1c levels and placebo responses, efficacy of SGLT2i were comparable between regions. The contrasting results for two agent classes indicate that drug efficacy is affected by different pathophysiology at its therapeutic action point.
Participation of children with disabilities across the life course: using socio‐ecological perspectives to guide research and practice
Authors: Rosenfeld Lindsay
Published: December 2019

This commentary is on the original article by Arakelyan et al. on pages 445–453 of this issue.
Current and future treatments of spinal muscular atrophy
Authors: Smith Martin
Published: December 2019

This commentary is on the original article by Aragon‐Gawinska et al. on pages 310–314 of this issue.
Global and mitosis‐specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging
Authors: Saldanha Gerald , Ali Rokiah , Bakshi Arti , Basiouni Ahmed , Bishop Rachael , Colloby Peter , Craig Paul , Da Forno Philip , Edward Sara , Espinosa de los Monteros Olivia , Evans Alan , Jamieson Lynne , Rytina Ed , Bamford Mark
Published: December 2019

Aims

Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual was removal of mitotic count. We explore the extent to which this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions.

Methods and results

In a cohort of 476 patients with melanoma ≤1.0 mm, a mitotic count of 0 versus 1 was significant for metastasis‐free survival, but not melanoma‐specific or overall survival. In 10 melanomas that were 0.9–1.0 mm thick, the mitotic count intraclass correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists among cases (P = 0.04). Every case had a range that crossed the AJCC8 0.8‐mm pT1a/pT1b staging boundary. Ulceration was only identified in two of the 10 cases. For ulceration, kappa agreement score was 0.31 (fair).

Conclusion

This study supports the removal of mitotic count from staging, but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value.