bluuebunny/crossref_metadata_2025 huggingface dataset:
A Rare Case of Triple Positive Metachronous Breast Cancer
Authors: Chhatrala Hardik S. , Khuu John , Zuberi Lara
Published: December 2019

Metachronous contralateral breast cancer (MCBC) is defined as contralateral breast cancer (BC) diagnosed more than 1 year after previous BC diagnosis. More BC survivors are at risk of MCBC given improved life expectancy with the availability of advanced cancer care. Estrogen receptor/progesterone receptor negative and HER-2-positive status of first BC are independent risk factors for the development of MCBC. We present a rare case of triple positive (estrogen receptor, progesterone receptor, HER-2 positive) MCBC patient who eventually developed brain metastasis within 15 months despite a near complete pathologic response of primary tumor. This case highlights that even in this era of antiestrogen and anti-HER-2 therapies, triple positive MCBC can have an aggressive clinical course, especially with brain metastasis as the first sign of metastasis.
Triggering multi-actor change cascades: Non-representational theory and deep disaster risk management co-production
Authors: Hope Max , McCloskey John , Nicbhloscaidh Mairead , Crowley Dominic , Hunt Dom
Published: December 2019

Deep-rooted socio-ecological and technical systems, values and lifestyles, ‘locked in’ by vested interests and flows of power, underpin the interconnected problems of climate change, hazard vulnerability and poverty. A ‘shallow’ approach to co-production, with its focus on knowledge exchange and shared learning between individuals, struggles to gain the ‘purchase’ needed to transform these material structures. In this paper we demonstrate that non-representational theory is a good starting point for an alternative ‘deep’ approach to disaster risk management co-production. We review key aspects of non-representational theory and their application to disaster risk management and build a novel hybrid conceptual framework. We use this to analyse a case study of disaster risk management co-production (an aftershock forecasting approach used by humanitarian agencies during the Nepal 2015 earthquake), how social change occurred in this instance, and the role disaster risk management co-production played. We emphasise how change was the consequence of unexpected shifts in assemblages of human, non-human, virtual and real actors. These created ‘events’ that were opportunities for change that were realised with fidelity. Using this analysis, we develop an alternative deep approach to co-production, as ‘a practical means of going on’, and finish with five precepts to guide transformative disaster risk management based on the concept of multi-actor change cascades.
Quantifying the resolution of spatial and temporal representation in children with 22q11.2 deletion syndrome
Authors: McCabe Kathryn L. , Popa Abbie M. , Durdle Courtney , Amato Michele , Cabaral Margarita H. , Cruz Joshua , Wong Ling M. , Harvey Danielle , Tartaglia Nicole , Simon Tony J.
Published: December 2019

Objectives

Our ability to generate mental representation of magnitude from sensory information affects how we perceive and experience the world. Reduced resolution of the mental representations formed from sensory inputs may generate impairment in the proximal and distal information processes that utilize these representations. Impairment of spatial and temporal information processing likely underpins the non-verbal cognitive impairments observed in 22q11.2 deletion syndrome (22q11DS). The present study builds on prior research by seeking to quantify the resolution of spatial and temporal representation in children with 22q11DS, sex chromosome aneuploidy (SCA), and a typically developing (TD) control group.

Participants and methods

Children (22q11DS = 70, SCA = 49, TD = 46) responded to visual or auditory stimuli with varying difference ratios. The participant’s task was to identify which of two sequentially presented stimuli was of larger magnitude in terms of, size, duration, or auditory frequency. Detection threshold was calculated as the minimum difference ratio between the “standard” and the “target” stimuli required to achieve 75% accuracy in detecting that the two stimuli were different.

Results

Children with 22q11DS required larger magnitude difference betweenspatialstimuli for accurate identification compared with both the SCA and TD groups (% difference from standard: 22q11DS = 14; SCA = 8; TD: 7;F = 8.42,p < 0.001).Temporaldetection threshold was also higher for the 22q11DS group to both visual (% difference from standard: 22q11DS = 14; SCA = 8; TD = 7;F = 8.33,p < 0.001) and auditory (% difference from standard: 22q11DS = 23; SCA = 12; TD: 8;F = 8.99,p < 0.001) stimuli compared with both the SCA and TD groups, while the SCA and TD groups displayed equivalent performance on these measures (p's > 0.05). Pitch detection threshold did not differ among the groups (p's > 0.05).

Conclusions

The observation of higher detection thresholds to spatial and temporal stimuli indicates further evidence for reduced resolution in both spatial and temporal magnitude representation in 22q11DS, that does not extend to frequency magnitude representation (pitch detection), and which is not explained by generalized cognitive impairment alone. These findings generate further support for the hypothesis that spatiotemporal hypergranularity of mental representations contributes to the non-verbal cognitive impairment seen in 22q11DS.
Stone-free rate after semirigid ureteroscopy with holmium laser lithotripsy versus laparoscopic ureterolithotomy for upper ureteral calculi: a multicenter study
Authors: Ali Ahmed Issam , Abdel-Karim Ali M. , Abd El Latif Ahmed A. , Eldakhakhny Amr , Galal Ehab M. , Anwar Ahmed Z. , El-Hawy Mamdouh M. , Fathelbab Tarek K. H. , Elbadry Mohamed S. , Elsharkawy Mostafa S. , Tawfiek Ehab R.
Published: December 2019

Background

Different treatment options were used to treat upper ureteral calculi. The aim of our study is to compare the stone-free rate and postoperative outcomes between semirigid ureteroscope with holmium laser lithotripsy and laparoscopic ureterolithotomy for the management of large solitary upper ureteral stones. Sixty-seven patients with a solitary upper ureteral stone who had LU or semirigid ureteroscopy in the period between January 2014 and March 2017 were included in our study. Out of the sixty-seven patients, 37 patients had semirigid ureteroscopy and holmium laser lithotripsy (Group A) and 30 patients had laparoscopic ureterolithotomy (Group B). Both groups were compared regarding operative time, intraoperative complications, need for auxiliary procedures, hospital stays, postoperative complications and stone-free rate.

Results

The mean stone size was 1.84 ± 0.12 cm in Group A and 1.79 ± 0.17 cm in Group B, P value = 0.2. The mean operative time was 61.5 ± 3.5 min in Group A and 63 ± 4.2 min in Group B, P value = 0.13. Stone migration was recorded in five cases (14%) in Group A while no cases in Group B had stone migration. Flexible ureteroscope was used as an auxiliary measure in five patients (14%) in Group A at the same session. No auxiliary measures were used in the LU group.

Conclusion

The stone-free rates after semirigid URS and laser lithotripsy are comparable to those following LU, especially when flexible URS is used to manage migrating stone fragments at the same session.
Colibri® insecticide induces male reproductive toxicity: alleviating effects of Lannea acida (Anacardiaceae) in rats
Authors: Tetsatsi Aimé Césaire Momo , Nkeng-Effouet Pepin Alango , Alumeti Désiré Munyali , Bonsou Georges Roméo Fozin , Kamanyi Albert , Watcho Pierre
Published: December 2019

Background

Imidacloprid, a neonicotinoid insecticide, has been associated to severe reproductive toxicity in mammals. Although some preventive measures have been reported, curative strategies are yet to be explored. The present study was designed to investigate the alleviating effects ofLannea acidaon the reproductive toxicity of colibri®, a commercial formulation of imidacloprid, in adult male rats.

Materials and methods

Seventy rats were orally administered with colibri® (22.5 mg/kg, 10 mL/kg) for 14 days and treated for other 14 or 28 days with either aqueous or methanol extracts ofL. acida(170 or 340 mg/kg). Control animals were similarly treated with clomiphene citrate or vitamin E. Sexual organ weights, spermatozoa characteristics, sexual hormones, stress markers and testis histology were evaluated at the end of each treatment period.

Results

Colibri® exposition induced reproductive toxicity marked by a decrease in sex organ weights, spermatozoa count, motility and viability. Colibri® also decreased testosterone, luteinizing hormone, follicle stimulating hormone concentrations and increased testicular oxidative stress. Spermatozoa morphology and testis histology were also severely altered. Similar to clomiphene citrate and vitamin E, treatment withL. acidaextracts significantly (p ≤ 0.05–0.001) reversed the above-mentioned damages, especially after 28 days of treatment with aqueous (340 mg/kg) and methanol (170 mg/kg) extracts.

Conclusion

Present results indicate thatL. acidaexerts curative effects against colibri®-induced male reproductive toxicity. These results justify the use of this plant as fertility enhancer and suggest that it could be an alternative in the management of pesticide-derived male infertility.
Fully moderated t-statistic in linear modeling of mixed effects for differential expression analysis
Authors: Yu Lianbo , Zhang Jianying , Brock Guy , Fernandez Soledad
Published: December 2019

Background

Gene expression profiling experiments with few replicates lead to great variability in the estimates of gene variances. Toward this end, several moderated t-test methods have been developed to reduce this variability and to increase power for testing differential expression. Most of these moderated methods are based on linear models with fixed effects where residual variances are smoothed under a hierarchical Bayes framework. However, they are inadequate for designs with complex correlation structures, therefore application of moderated methods to linear models with mixed effects are needed for differential expression analysis.

Results

We demonstrated the implementation of the fully moderated t-statistic method for linear models with mixed effects, where both residual variances and variance estimates of random effects are smoothed under a hierarchical Bayes framework. We compared the proposed method with two current moderated methods and show that the proposed method can control the expected number of false positives at the nominal level, while the two current moderated methods fail.

Conclusions

We proposed an approach for testing differential expression under complex correlation structures while providing variance shrinkage. The proposed method is able to improve power by moderation and controls the expected number of false positives properly at the nominal level.
BISR-RNAseq: an efficient and scalable RNAseq analysis workflow with interactive report generation
Authors: Gadepalli Venkat Sundar , Ozer Hatice Gulcin , Yilmaz Ayse Selen , Pietrzak Maciej , Webb Amy
Published: December 2019

Background

RNA sequencing has become an increasingly affordable way to profile gene expression patterns. Here we introduce a workflow implementing several open-source softwares that can be run on a high performance computing environment.

Results

Developed as a tool by the Bioinformatics Shared Resource Group (BISR) at the Ohio State University, we have applied the pipeline to a few publicly available RNAseq datasets downloaded from GEO in order to demonstrate the feasibility of this workflow. Source code is available here: workflow: https://code.bmi.osumc.edu/gadepalli.3/BISR-RNAseq-ICIBM2019 and shiny: https://code.bmi.osumc.edu/gadepalli.3/BISR_RNASeq_ICIBM19. Example dataset is demonstrated here: https://dataportal.bmi.osumc.edu/RNA_Seq/.

Conclusion

The workflow allows for the analysis (alignment, QC, gene-wise counts generation) of raw RNAseq data and seamless integration of quality analysis and differential expression results into a configurable R shiny web application.
Prediction of novel mouse TLR9 agonists using a random forest approach
Authors: Khanna Varun , Li Lei , Fung Johnson , Ranganathan Shoba , Petrovsky Nikolai
Published: December 2019

Background

Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-sampling.

Results

Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test samples was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity.

Conclusion

We combined repeated random down-sampling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.
A hybrid and scalable error correction algorithm for indel and substitution errors of long reads
Authors: Das Arghya Kusum , Goswami Sayan , Lee Kisung , Park Seung-Jong
Published: December 2019

Background

Long-read sequencing has shown the promises to overcome the short length limitations of second-generation sequencing by providing more complete assembly. However, the computation of the long sequencing reads is challenged by their higher error rates (e.g., 13% vs. 1%) and higher cost ($0.3 vs. $0.03 per Mbp) compared to the short reads.

Methods

In this paper, we present a new hybrid error correction tool, called ParLECH (Parallel Long-read Error Correction using Hybrid methodology). The error correction algorithm of ParLECH is distributed in nature and efficiently utilizes thek-mer coverage information of high throughput Illumina short-read sequences to rectify the PacBio long-read sequences.ParLECH first constructs a de Bruijn graph from the short reads, and then replaces the indel error regions of the long reads with their corresponding widest path (or maximum min-coverage path) in the short read-based de Bruijn graph. ParLECH then utilizes thek-mer coverage information of the short reads to divide each long read into a sequence of low and high coverage regions, followed by a majority voting to rectify each substituted error base.

Results

ParLECH outperforms latest state-of-the-art hybrid error correction methods on real PacBio datasets. Our experimental evaluation results demonstrate that ParLECH can correct large-scale real-world datasets in an accurate and scalable manner. ParLECH can correct the indel errors of human genome PacBio long reads (312 GB) with Illumina short reads (452 GB) in less than 29 h using 128 compute nodes. ParLECH can align more than 92% bases of anE. coliPacBio dataset with the reference genome, proving its accuracy.

Conclusion

ParLECH can scale to over terabytes of sequencing data using hundreds of computing nodes. The proposed hybrid error correction methodology is novel and rectifies both indel and substitution errors present in the original long reads or newly introduced by the short reads.
Chondroitinase ABC reduces dopaminergic nigral cell death and striatal terminal loss in a 6-hydroxydopamine partial lesion mouse model of Parkinson’s disease
Authors: Fletcher Edward J. R. , Moon Lawrence D. F. , Duty Susan
Published: December 2019

Background

Parkinson’s disease (PD) is characterised by dopaminergic cell loss within the substantia nigra pars compacta (SNc) that leads to reduced striatal dopamine content and resulting motor deficits. Identifying new strategies to protect these cells from degeneration and retain striatal dopaminergic innervation is therefore of great importance. Chondroitin sulphate proteoglycans (CSPGs) are recognised contributors to the inhibitory extracellular milieu known to hinder tissue recovery following CNS damage. Digestion of these molecules by the bacterial lyase chondroitinase ABC (ChABC) has been shown to promote functional recovery in animal models of neurological injury. Although ChABC has been shown to promote sprouting of dopaminergic axons following transection of the nigrostriatal pathway, its ability to protect against nigrostriatal degeneration in a toxin-based module with better construct validity for PD has yet to be explored. Here we examined the neuroprotective efficacy of ChABC treatment in the full and partial 6-hydroxydopamine (6-OHDA) lesion mouse models of PD.

Results

In mice bearing a full 6-OHDA lesion, ChABC treatment failed to protect against the loss of either nigral cells or striatal terminals. In contrast, in mice bearing a partial 6-OHDA lesion, ChABC treatment significantly protected cells of the rostral SNc, which remained at more than double the numbers seen in vehicle-treated animals. In the partial lesion model, ChABC treatment also significantly preserved dopaminergic fibres of the rostral dorsal striatum which increased from 15.3 ± 3.5% of the intact hemisphere in saline-treated animals to 36.3 ± 6.5% in the ChABC-treated group. These protective effects of ChABC treatment were not accompanied by improvements in either the cylinder or amphetamine-induced rotations tests of motor function.

Conclusions

ChABC treatment provided significant protection against a partial 6-OHDA lesion of the nigrostriatal tract although the degree of protection was not sufficient to improve motor outcomes. These results support further investigations into the benefits of ChABC treatment for providing neuroprotection in PD.
Analysis of factors influencing hospital-acquired infection in postoperative patients with intracranial aneurysm
Authors: Wang Jun , Ji Yuanyuan , Jiang Lidan , Zhao Xia , Guan Shaochen , Yang Piao , Yu Jie , Liu Yunyun , Zhang Hongqi
Published: December 2019

Background

Hospital-acquired infection (HAI) is a serious complication of neurosurgery. In recent years, the medical body has paid increasing attention to this issue.

Aim

We investigated the status of HAIs in patients who had undergone surgery for intracranial aneurysms and analysed their risk factors.

Methods

A retrospective analysis was carried out on the medical records of 542 patients with intracranial aneurysms after they were admitted for neurosurgery at Xuanwu Hospital of Capital Medical University between January and December 2016. Cases studied were divided into an infection group and a control group. Logistic regression analysis of the data was carried out.

Findings

Of the 542 patients with intracranial aneurysms who underwent surgery, 77 HAIs occurred in 64 patients, with an infection prevalence of 11.8% and prevalence of infection cases of 14.2%. Logistic regression showed that an admission Glasgow Coma Scale (GCS) score of less than 8 points (odds ratio = 4.261, 95% confidence interval 1.102–16.476), hyperglycaemia (2.759, 1.159–6.564), hypothermia treatment (6.557, 2.244–19.159), and central venous catheterisation (CVC) (8.853, 2.860–27.398) were independent risk factors for HAIs in patients with intracranial aneurysm who underwent surgery.

Conclusion

Being comatose upon hospital admission, having hyperglycaemia or hypothermia, and indwelling CVC are major risk factors for HAIs in patients undergoing surgery for intracranial aneurysms.
Prepregnancy obesity is associated with cognitive outcomes in boys in a low-income, multiethnic birth cohort
Authors: Widen Elizabeth M. , Nichols Amy R. , Kahn Linda G. , Factor-Litvak Pam , Insel Beverly J. , Hoepner Lori , Dube Sara M. , Rauh Virginia , Perera Frederica , Rundle Andrew
Published: December 2019

Background

Maternal obesity and high gestational weight gain (GWG) disproportionally affect low-income populations and may be associated with child neurodevelopment in a sex-specific manner. We examined sex-specific associations between prepregnancy BMI, GWG, and child neurodevelopment at age 7.

Methods

Data are from a prospective low-income cohort of African American and Dominican women (n = 368; 44.8% male offspring) enrolled during the second half of pregnancy from 1998 to 2006. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children (WISC-IV) at approximately child age 7. Linear regression estimated associations between prepregnancy BMI, GWG, and child outcomes, adjusting for race/ethnicity, marital status, gestational age at delivery, maternal education, maternal IQ and child age.

Results

Overweight affected 23.9% of mothers and obesity affected 22.6%. At age 7, full-scale IQ was higher among girls (99.7 ± 11.6) compared to boys (96.9 ± 13.3). Among boys, but not girls, prepregnancy overweight and obesity were associated with lower full-scale IQ scores [overweight β: − 7.1, 95% CI: (− 12.1, − 2.0); obesity β: − 5.7, 95% CI: (− 10.7, − 0.7)]. GWG was not associated with full-scale IQ in either sex.

Conclusions

Prepregnancy overweight and obesity were associated with lower IQ among boys, but not girls, at 7 years. These findings are important considering overweight and obesity prevalence and the long-term implications of early cognitive development.
Architecture of the Short External Rotator Muscles of the Hip
Authors: Parvaresh Kevin C. , Chang Charles , Patel Ankur , Lieber Richard L. , Ball Scott T. , Ward Samuel R.
Published: December 2019

Background

Muscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles.

Methods

Eight muscles from 10 independent human cadaver hips were used in this study (n = 80 muscles). Architectural measurements were made on pectineus, piriformis, gemelli, obturators, quadratus femoris, and gluteus minimus. Muscle mass, fiber length, sarcomere length, and pennation angle were used to calculate the normalized muscle fiber length, which defines excursion, and physiological cross-sectional area (PCSA), which defines force-producing capacity.

Results

Gluteus minimus had the largest PCSA (8.29 cm2) followed by obturator externus (4.54 cm2), whereas superior gemellus had the smallest PCSA (0.68 cm2). Fiber lengths clustered into long (pectineus - 10.38 cm and gluteus minimus - 10.30 cm), moderate (obturator internus - 8.77 cm and externus - 8.04 cm), or short (inferior gemellus - 5.64 and superior gemellus - 4.85). There were no significant differences among muscles in pennation angle which were all nearly zero. When the gemelli and obturators were considered as a single functional unit, their collective PCSA (10.00 cm2) exceeded that of gluteus minimus as a substantial force-producing group.

Conclusions

The key findings are that these muscles have relatively small individual PCSAs, short fiber lengths, and low pennation angles. The large collective PCSA and short fiber lengths of the gemelli and obturators suggest that they primarily play a stabilizing role rather than a joint rotating role.
Phylogeography of higher Diptera in glacial and postglacial grasslands in western North America
Authors: Solecki Anna M. , Skevington Jeffrey H. , Buddle Christopher M. , Wheeler Terry A.
Published: December 2019

Background

Pleistocene glaciations have had an important impact on the species distribution and community composition of the North American biota. Species survived these glacial cycles south of the ice sheets and/or in other refugia, such as Beringia. In this study, we assessed, using mitochondrial DNA from three Diptera species, whether flies currently found in Beringian grasslands (1) survived glaciation as disjunct populations in Beringia and in the southern refugium; (2) dispersed northward postglacially from the southern refugium; or (3) arose by a combination of the two. Samples were collected in grasslands in western Canada: Prairies in Alberta and Manitoba; the Peace River region (Alberta); and the southern Yukon Territory. We sequenced two gene regions (658 bp of cytochrome c oxidase subunit I, 510 bp of cytochrome b) from three species of higher Diptera: one with a continuous distribution across grassland regions, and two with disjunct populations between the regions. We used a Bayesian approach to determine population groupings without a priori assumptions and performed analysis of molecular variance (AMOVA) and exact tests of population differentiation (ETPD) to examine their validity. Molecular dating was used to establish divergence times.

Results

Two geographically structured populations were found for all species: a southern Prairie and Peace River population, and a Yukon population. Although AMOVA did not show significant differentiation between populations, ETPD did. Divergence time between Yukon and southern populations predated the Holocene for two species; the species with an ambiguous divergence time had high haplotype diversity, which could suggest survival in a Beringian refugium.

Conclusions

Populations of Diptera in Yukon grasslands could have persisted in steppe habitats in Beringia through Pleistocene glaciations. Current populations in the region appear to be a mix of Beringian relict populations and, to a lesser extent, postglacial dispersal northward from southern prairie grasslands.
A deep neural network approach to predicting clinical outcomes of neuroblastoma patients
Authors: Tranchevent Léon-Charles , Azuaje Francisco , Rajapakse Jagath C.
Published: December 2019

Background

The availability of high-throughput omics datasets from large patient cohorts has allowed the development of methods that aim at predicting patient clinical outcomes, such as survival and disease recurrence. Such methods are also important to better understand the biological mechanisms underlying disease etiology and development, as well as treatment responses. Recently, different predictive models, relying on distinct algorithms (including Support Vector Machines and Random Forests) have been investigated. In this context, deep learning strategies are of special interest due to their demonstrated superior performance over a wide range of problems and datasets. One of the main challenges of such strategies is the “small n large p” problem. Indeed, omics datasets typically consist of small numbers of samples and large numbers of features relative to typical deep learning datasets. Neural networks usually tackle this problem through feature selection or by including additional constraints during the learning process.

Methods

We propose to tackle this problem with a novel strategy that relies on a graph-based method for feature extraction, coupled with a deep neural network for clinical outcome prediction. The omics data are first represented as graphs whose nodes represent patients, and edges represent correlations between the patients’ omics profiles. Topological features, such as centralities, are then extracted from these graphs for every node. Lastly, these features are used as input to train and test various classifiers.

Results

We apply this strategy to four neuroblastoma datasets and observe that models based on neural networks are more accurate than state of the art models (DNN: 85%-87%, SVM/RF: 75%-82%). We explore how different parameters and configurations are selected in order to overcome the effects of the small data problem as well as the curse of dimensionality.

Conclusions

Our results indicate that the deep neural networks capture complex features in the data that help predicting patient clinical outcomes.
Private expenditures on healthcare: determinants, patterns and progressivity aspects
Authors: Achdut Leah
Published: December 2019

Background

The mixture of public vs. private financing of the healthcare system has important fiscal and economic welfare implications. The consequences of this mixture for access to health services and for equity have become highly debated policy issues. In the first decade of 2000s, Israel experienced a continuous upward trend in the proportion of private financing, reaching a peak of 37–38%, which has subsequently leveled off. The 38% level is significantly higher than the 26% average across the Organization for Economic Co-operation and Development (OECD) countries.

Main text

A recent paper by Tur-Sinai et al. in this journal shows that private spending by Israelis on health care is positively related to the income of individuals and to the socioeconomic status of their place of residence. This commentary draws attention to studies that integrate into one model both demand-side and supply-side determinants of private expenditures on healthcare. It also discusses inequity.

Conclusions

Overall, the financing of national health expenditures in Israel is slightly regressive, but the progressivity of public financing is almost enough to offset the regressive effect of out-of-pocket payments and payments for voluntary complementary insurance.
The Systematic Review Data Repository (SRDR): descriptive characteristics of publicly available data and opportunities for research
Authors: Saldanha Ian J. , Smith Bryant T. , Ntzani Evangelia , Jap Jens , Balk Ethan M. , Lau Joseph
Published: December 2019

Background

Conducting systematic reviews (“reviews”) requires a great deal of effort and resources. Making data extracted during reviews available publicly could offer many benefits, including reducing unnecessary duplication of effort, standardizing data, supporting analyses to address secondary research questions, and facilitating methodologic research. Funded by the US Agency for Healthcare Research and Quality (AHRQ), the Systematic Review Data Repository (SRDR) is a free, web-based, open-source, data management and archival platform for reviews. Our specific objectives in this paper are to describe (1) the current extent of usage of SRDR and (2) the characteristics of all projects with publicly available data on the SRDR website.

Methods

We examined all projects with data made publicly available through SRDR as of November 12, 2019. We extracted information about the characteristics of these projects. Two investigators extracted and verified the data.

Results

SRDR has had 2552 individual user accounts belonging to users from 80 countries. Since SRDR’s launch in 2012, data have been made available publicly for 152 of the 735 projects in SRDR (21%), at a rate of 24.5 projects per year, on average. Most projects are in clinical fields (144/152 projects; 95%); most have evaluated interventions (therapeutic or preventive) (109/152; 72%). The most frequent health areas addressed are mental and behavioral disorders (31/152; 20%) and diseases of the eye and ocular adnexa (23/152; 15%). Two-thirds of the projects (104/152; 67%) were funded by AHRQ, and one-sixth (23/152; 15%) are Cochrane reviews. The 152 projects each address a median of 3 research questions (IQR 1–5) and include a median of 70 studies (IQR 20–130).

Conclusions

Until we arrive at a future in which the systematic review and broader research communities are comfortable with the accuracy of automated data extraction, re-use of data extracted by humans has the potential to help reduce redundancy and costs. The 152 projects with publicly available data through SRDR, and the more than 15,000 studies therein, are freely available to researchers and the general public who might be working on similar reviews or updates of reviews or who want access to the data for decision-making, meta-research, or other purposes.
Truncated-exponential-based Frobenius–Euler polynomials
Authors: Kumam Wiyada , Srivastava Hari Mohan , Wani Shahid Ahmad , Araci Serkan , Kumam Poom
Published: December 2019

In this paper, we first introduce a new family of polynomials, which are called the truncated-exponential based Frobenius–Euler polynomials, based upon an exponential generating function. By making use of this exponential generating function, we obtain their several new properties and explicit summation formulas. Finally, we consider the truncated-exponential based Apostol-type Frobenius–Euler polynomials and their quasi-monomial properties.
Effects of the Income Stabilization Tool on farm income level, variability and concentration in Italian agriculture
Authors: Severini Simone , Di Tommaso Giuliano , Finger Robert
Published: December 2019

This paper provides an ex ante assessment of the effects of the Income Stabilization Tool (IST), a new risk management tool proposed in the Common Agricultural Policy of the European Union. We investigate the effects of IST on income variability and levels as well as on income inequality in the farming population. We take Italian agriculture as an example as the introduction of IST is currently under discussion there. A rich panel of 2777 farms was studied over a period of 7 years. We use stochastic simulation to derive different income inequality estimates and apply Gini decomposition approaches to assess the distributional implications of IST. We compare the current income situation with that resulting from a hypothetical implementation of IST under different policy scenarios, also accounting for reduced levels of CAP direct payments. We find that IST not only stabilizes farm income but also enhances its level and reduces income inequality in Italian agriculture. IST is more effective in reducing income inequality when farmers pay contributions to mutual funds that are proportional to their income compared to the case of flat rate contributions. Finally, results do not support the hypothesis that the impact of IST will differ if the level of direct payments were to be reduced. Thus, results seem robust enough to accommodate future policy conditions.
Self-objectification and eating disorder pathology in an ethnically diverse sample of adult women: cross-sectional and short-term longitudinal associations
Authors: Kilpela Lisa Smith , Calogero Rachel , Wilfred Salomé A. , Verzijl Christina L. , Hale Willie J. , Becker Carolyn Black
Published: December 2019

Background

Extensive support exists for objectification theory’s original aim of explaining patterns of women’s mental health risk through a sociocultural lens. One pathway in objectification theory proposes a mediational role of body shame in the relationship between self-objectification and eating disorder (ED) pathology. Robust past cross-sectional research supports this proposed pathway, but largely in non-Hispanic Caucasian, college-aged samples; this pathway has yet to be empirically demonstrated longitudinally. Given previously documented concerns regarding direct measurement of body shame, we tested two measures of body shame as mediators in both cross-sectional and longitudinal models in a diverse sample of adult women.

Method

Utilizing snowball sampling via email, we recruited age and racially/ethnically diverse women predominantly within the United States. Participants completed online surveys assessing self-objectification (operationalized as body surveillance), body shame, and ED pathology at baseline, 3-months and 6-months.

Results

Racial/ethnic minority (n = 139) and non-Hispanic Caucasian (n = 181) adult women completed the measures. Cross-sectional moderated mediation models indicated that racial/ethnic status did not moderate relationships, and that body shame significantly mediated the relation between body surveillance and ED pathology at each time point. The longitudinal model, analyzed using cross-lagged panel analyses, was nonsignificant, as body surveillance failed to predict future body shame when controlling for past body shame.

Conclusions

Racial/ethnic status did not moderate relations at any time point. Cross-sectional findings replicated past research; the longitudinal model did not support a core mediation pathway linking self-objectification to ED pathology through body shame. Because self-objectification putatively develops earlier in life, future research also should examine these relations in younger diverse samples over a longer time period.
Exploring the feasibility and acceptability of a mixed-methods pilot randomized controlled trial testing a 12-week physical activity intervention with adolescent and young adult cancer survivors
Authors: Wurz Amanda , Brunet Jennifer
Published: December 2019

Background

Adolescent and young adult (AYA) cancer survivors (i.e. individuals diagnosed with cancer between 15 and 39 years and who completed treatment) may benefit from physical activity. Yet, few researchers have explored the effects of physical activity on physical and psychological outcomes among AYA cancer survivors. A pilot study exploring the feasibility and acceptability of a physical activity intervention and proposed trial methods to inform a definitive randomized controlled trial (RCT) is therefore necessary to fill this gap.

Methods

A two-arm, mixed-methods pilot RCT was conducted. Participants were randomized to a wait-list control group or a 12-week physical activity intervention comprised of 4 weekly aerobic and strength training sessions (intervention group). Feasibility measures included: number of AYA cancer survivors referred/self-referred, eligible, and recruited, retention to the trial (i.e. assessment completion), adherence to the physical activity intervention, and percentage of missing data for baseline (week 0), mid- (week 6), and post-intervention assessments (week 12). The acceptability of trial methods (all participants) and the intervention (intervention group only) was assessed via qualitative interviews post-intervention.

Results

Over a 12-month period, 31 AYA cancer survivors were referred/self-referred and 16 were eligible and consented to participate. Retention to the trial was 94% and adherence to the physical activity intervention ranged from 50 to 92%. With the exception of the assessment of aerobic capacity and directly measured physical activity behaviour, there were no missing data. Participants generally reported being satisfied with the trial methods and intervention; however, issues related to delivery of the physical activity intervention were identified.

Conclusions

The methods and intervention piloted require modification and further pilot testing in advance of a definitive RCT. Recruitment strategies identifying a greater number of younger AYA cancer survivors who have different types of cancers and who lack motivation to participate in physical activity-based studies should be explored. Refining the assessments of directly measured physical activity behaviour and aerobic capacity and incorporating behavioural support into the intervention may improve feasibility and acceptability. This study highlights the value of doing pilot work and provides critically useful data that can be used to refine studies seeking to assess causation and optimize physical activity interventions for AYA cancer survivors.

Trial registration

clinicaltrials.gov, NCT03016728. Registered January 11, 2017.
The effect of replacing 1 week of content teaching with an intensive simulation-based learning activity on physiotherapy student clinical placement performance
Authors: Tuttle Neil , Horan Sean A.
Published: December 2019

Background

Simulation-based learning (SBL) activities are increasingly used to replace or supplement clinical placements for physiotherapy students. There is limited literature evaluating SBL activities that replace on-campus teaching, and to our knowledge, no studies evaluate the role of SBL in counteracting the negative impact of delay between content teaching and clinical placements. The aims of this study were to (i) determine the effect on clinical placement performance of replacing 1 week of content teaching with a SBL activity and (ii) determine if a delay between content teaching and clinical placement impacted clinical placement performance.

Methods

This study is a retrospective cohort study. Participants included students in the first two clinical placements of a graduate-entry, masters-level program. Six hundred twenty-nine student placements were analysed—285 clinical placements where students undertook a 20-h SBL activity immediately prior to clinical placement were compared with 344 placements where students received traditional content. Of the placements where students received the SBL, 147 occurred immediately following content teaching and 138 had a delay of at least 5 weeks. Performance on clinical placement was assessed using the Assessment of Physiotherapy Practice (APP).

Results

There was a significant main effect of SBL with higher APP marks for the experimental group (3.12/4, SD = 0.25 vs 3.01/4, SD = 0.22), and post hoc analysis indicated marks were significantly higher for all seven areas of assessment. Students whose placements immediately followed content teaching performed better on mid-placement APP marks in two areas of assessment (analysis and planning, and intervention) compared to students for whom there was a delay. There were no statistically significant differences in relation to delay for end of placement APP marks.

Conclusion

Replacing 1 week of classroom teaching with a targeted, SBL activity immediately before placement significantly improved student performance on that clinical placement. A negative impact of delay was found on mid-placement, but not the end of placement APPs. Findings of improved performance when replacing a week of content teaching with a targeted SBL activity, and poorer performance on mid-placement marks with a delay between content teaching and clinical placement, may have implications for curriculum design.
Developing preclinical models of neuroblastoma: driving therapeutic testing
Authors: Ornell Kimberly J. , Coburn Jeannine M.
Published: December 2019

Despite advances in cancer therapeutics, particularly in the area of immuno-oncology, successful treatment of neuroblastoma (NB) remains a challenge. NB is the most common cancer in infants under 1 year of age, and accounts for approximately 10% of all pediatric cancers. Currently, children with high-risk NB exhibit a survival rate of 40–50%. The heterogeneous nature of NB makes development of effective therapeutic strategies challenging. Many preclinical models attempt to mimic the tumor phenotype and tumor microenvironment. In vivo mouse models, in the form of genetic, syngeneic, and xenograft mice, are advantageous as they replicated the complex tumor-stroma interactions and represent the gold standard for preclinical therapeutic testing. Traditional in vitro models, while high throughput, exhibit many limitations. The emergence of new tissue engineered models has the potential to bridge the gap between in vitro and in vivo models for therapeutic testing. Therapeutics continue to evolve from traditional cytotoxic chemotherapies to biologically targeted therapies. These therapeutics act on both the tumor cells and other cells within the tumor microenvironment, making development of preclinical models that accurately reflect tumor heterogeneity more important than ever. In this review, we will discuss current in vitro and in vivo preclinical testing models, and their potential applications to therapeutic development.
CT arthrography for demonstration of various articular injuries in post-sprained ankle pain
Authors: El-Sherif Ashraf Mohamed Hassan , Mohamed Mohamed Ali Ahmed , El-Ameen Nadia Farouk Mohamed , Samra Manal Fayez Abu , Abdel-Naby Alkawthar Ezedin Saied
Published: December 2019

Background

Post-sprained ankles may sustain ligamentous tear, chondral defect, or osteochondral lesions (OCL). Being widely available and does not depend on high-end machine, the aim of this study was to assess the value of high resolution multi-detector CT arthrography (CTA) in detection of various ligamentous tears, chondral defects, and osteochondral lesions in case of sprain-related persistent ankle pain.

Results

There were 34 (68%) cases of ligamentous injury, most of which had single ligament affection whereas some cases demonstrated multi-ligamentous injury, and the total number of individual injured ligaments was 42 ligaments. There were 36 cases (72%) which had either chondral or osteochondral defects; the total number of OCL was 21 lesions and the total number of segmental cartilage defects was 20.

Conclusion

This study emphasized the diagnostic importance of multi-detector CTA in sprain-related ankle pain. In persistent post-sprained ankle pain, multi-detector CTA is a helpful imaging modality which could be utilized for detection of OCL, chondral defects, and various ligamentous tears.
Expanding Coverage of Oncology Drugs in an Aging, Upper-Middle-Income Country: Analyses of Public and Private Expenditures in Chile
Authors: Vargas Veronica , Leopold Christine , Castillo-Riquelme Marianela , Darrow Jonathan J.
Published: December 2019

PURPOSE

The population of Chile has aged, and in 2017, cancer became the leading cause of death. Since 2005, a national health program has expanded coverage of drugs for 13 types of cancer and related palliative care. We describe the trends in public and private oncology drug expenditures in Chile and consider how increasing expenditures might be addressed.

METHODS

We analyzed total quarterly drug expenditures for 131 oncology drugs from quarter (Q)3 2012 until Q1 2017, including public and private insurance payments and patient out-of-pocket spending. The data were analyzed by drug-mix, sources of funding, growth, and intellectual property status. The Laspeyres Price Index was used to analyze expenditure growth.

RESULTS

We found 131 oncology drugs associated with 87,129 observations. Spending on drugs rose 120% from the first period, spanning from the first 3 quarters (Q3, Q4, Q1 2012-2013) to the last period (Q3, Q4, Q1 2016-2017), corresponding to an annualized rate of 19.2% and totaling US$398 million (in 2017 dollars). The public sector accounted for 84.2% of spending, which included 50 drugs in the official treatment protocols, whereas private insurance accounted for 7.3% in on-protocol drugs. The remaining 8.5% was paid out of pocket. In the public sector, more than 90% of growth resulted from increased use. Seven drugs, including 3 with nonexpired patents, accounted for 50% of total expenditures.

CONCLUSION

Increased use and access enabled by expanded public expenditures drove most of the growth in oncology drug expenditures. However, the rate of public expenditure growth may be fiscally unsustainable. Policies are urgently needed to promote the use of generic drugs, the appropriate mix of on-protocol versus off-protocol drugs, and the curbing of off-label prescribing.