bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
Authors: Abidi Syed , Achar Jay , Assao Neino Mourtala Mohamed , Bang Didi , Benedetti Andrea , Brode Sarah , Campbell Jonathon R. , Casas Esther C. , Conradie Francesca , Dravniece Gunta , du Cros Philipp , Falzon Dennis , Jaramillo Ernesto , Kuaban Christopher , Lan Zhiyi , Lange Christoph , Li Pei Zhi , Makhmudova Mavluda , Maug Aung Kya Jai , Menzies Dick , Migliori Giovanni Battista , Miller Ann , Myrzaliev Bakyt , Ndjeka Norbert , Noeske Jürgen , Parpieva Nargiza , Piubello Alberto , Schwoebel Valérie , Sikhondze Welile , Singla Rupak , Souleymane Mahamadou Bassirou , Trébucq Arnaud , Van Deun Armand , Viney Kerri , Weyer Karin , Zhang Betty Jingxuan , Ahmad Khan Faiz
Published: December 2019

We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).

We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.

We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).

In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
Effects of suboptimal adherence of CPAP therapy on symptoms of obstructive sleep apnoea: a randomised, double-blind, controlled trial
Authors: Gaisl Thomas , Rejmer Protazy , Thiel Sira , Haile Sarah R. , Osswald Martin , Roos Malgorzata , Bloch Konrad E. , Stradling John R. , Kohler Malcolm
Published: December 2019

Introduction

Continuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnoea (OSA); however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP usage on objective and subjective sleepiness parameters in patients with OSA.

Material and methods

In this 2-week, parallel, double-blind, randomised controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (Epworth sleepiness scale (ESS) score >10 points) who had suboptimal CPAP adherence over ≥12 months (mean nightly usage time 3–4 h). Patients were allocated through minimisation to either subtherapeutic CPAP (“sham CPAP”) or continuation of CPAP (“therapeutic CPAP”). A Bayesian analysis with historical priors calculated the posterior probability of superiority.

Results

Between May, 2016 and November, 2018, 57 patients (aged 60±8 years, 79% male, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS score increase was 2.4 points (95% CI 0.6–4.2, p=0.01) in the sham-CPAP group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 90.4% for ESS, 90.1% for systolic blood pressure and 80.3% for diastolic blood pressure.

Conclusions

Patients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials.
Biological representation of chemicals using latent target interaction profile
Authors: Ayed Mohamed , Lim Hansaim , Xie Lei
Published: December 2019

Background

Computational prediction of a phenotypic response upon the chemical perturbation on a biological system plays an important role in drug discovery, and many other applications. Chemical fingerprints are a widely used feature to build machine learning models. However, the fingerprints that are derived from chemical structures ignore the biological context, thus, they suffer from several problems such as the activity cliff and curse of dimensionality. Fundamentally, the chemical modulation of biological activities is a multi-scale process. It is the genome-wide chemical-target interactions that modulate chemical phenotypic responses. Thus, the genome-scale chemical-target interaction profile will more directly correlate with in vitro and in vivo activities than the chemical structure. Nevertheless, the scope of direct application of the chemical-target interaction profile is limited due to the severe incompleteness, biasness, and noisiness of bioassay data.

Results

To address the aforementioned problems, we developed a novel chemical representation method: Latent Target Interaction Profile (LTIP). LTIP embeds chemicals into a low dimensional continuous latent space that represents genome-scale chemical-target interactions. Subsequently LTIP can be used as a feature to build machine learning models. Using the drug sensitivity of cancer cell lines as a benchmark, we have shown that the LTIP robustly outperforms chemical fingerprints regardless of machine learning algorithms. Moreover, the LTIP is complementary with the chemical fingerprints. It is possible for us to combine LTIP with other fingerprints to further improve the performance of bioactivity prediction.

Conclusions

Our results demonstrate the potential of LTIP in particular and multi-scale modeling in general in predictive modeling of chemical modulation of biological activities.
DeepShape: estimating isoform-level ribosome abundance and distribution with Ribo-seq data
Authors: Cui Hongfei , Hu Hailin , Zeng Jianyang , Chen Ting
Published: December 2019

Background

Ribosome profiling brings insight to the process of translation. A basic step in profile construction at transcript level is to map Ribo-seq data to transcripts, and then assign a huge number of multiple-mapped reads to similar isoforms. Existing methods either discard the multiple mapped-reads, or allocate them randomly, or assign them proportionally according to transcript abundance estimated from RNA-seq data.

Results

Here we present DeepShape, an RNA-seq free computational method to estimate ribosome abundance of isoforms, and simultaneously compute their ribosome profiles using a deep learning model. Our simulation results demonstrate that DeepShape can provide more accurate estimations on both ribosome abundance and profiles when compared to state-of-the-art methods. We applied DeepShape to a set of Ribo-seq data from PC3 human prostate cancer cells with and without PP242 treatment. In the four cell invasion/metastasis genes that are translationally regulated by PP242 treatment, different isoforms show very different characteristics of translational efficiency and regulation patterns. Transcript level ribosome distributions were analyzed by “Codon Residence Index (CRI)” proposed in this study to investigate the relative speed that a ribosome moves on a codon compared to its synonymous codons. We observe consistent CRI patterns in PC3 cells. We found that the translation of several codons could be regulated by PP242 treatment.

Conclusion

In summary, we demonstrate that DeepShape can serve as a powerful tool for Ribo-seq data analysis.
SigUNet: signal peptide recognition based on semantic segmentation
Authors: Wu Jhe-Ming , Liu Yu-Chen , Chang Darby Tien-Hao
Published: December 2019

Background

Signal peptides play an important role in protein sorting, which is the mechanism whereby proteins are transported to their destination. Recognition of signal peptides is an important first step in determining the active locations and functions of proteins. Many computational methods have been proposed to facilitate signal peptide recognition. In recent years, the development of deep learning methods has seen significant advances in many research fields. However, most existing models for signal peptide recognition use one-hidden-layer neural networks or hidden Markov models, which are relatively simple in comparison with the deep neural networks that are used in other fields.

Results

This study proposes a convolutional neural network without fully connected layers, which is an important network improvement in computer vision. The proposed network is more complex in comparison with current signal peptide predictors. The experimental results show that the proposed network outperforms current signal peptide predictors on eukaryotic data. This study also demonstrates how model reduction and data augmentation helps the proposed network to predict bacterial data.

Conclusions

The study makes three contributions to this subject: (a) an accurate signal peptide recognizer is developed, (b) the potential to leverage advanced networks from other fields is demonstrated and (c) important modifications are proposed while adopting complex networks on signal peptide recognition.
Association between ALS and retroviruses: evidence from bioinformatics analysis
Authors: Klein Jon P. , Sun Zhifu , Staff Nathan P.
Published: December 2019

Background

Emerging evidence suggests retroviruses play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Specifically, activation of ancient viral genes embedded in the human genome is theorized to lead to motor neuron degeneration. We explore whether connections exist between ALS and retroviruses through protein interaction networks (PIN) and pathway analysis, and consider the potential roles in drug target discovery. Protein database and pathway/network analytical software including Ingenuity Pathway BioProfiler, STRING, and CytoScape were utilized to identify overlapping protein interaction networks and extract core cluster (s) of retroviruses and ALS.

Results

Topological and statistical analysis of the ALS-PIN and retrovirus-PIN identified a shared, essential protein network and a core cluster with significant connections with both networks. The identified core cluster has three interleukin molecules IL10, Il-6 and IL-1B, a central apoptosis regulator TP53, and several major transcription regulators including MAPK1, ANXA5, SQSTM1, SREBF2, and FADD. Pathway enrichment analysis showed that this core cluster is associated with the glucocorticoid receptor singling and neuroinflammation signaling pathways. For confirmation purposes, we applied the same methodology to the West Nile and Polio virus, which demonstrated trivial connectivity with ALS, supporting the unique connection between ALS and retroviruses.

Conclusions

Bioinformatics analysis provides evidence to support pathological links between ALS and retroviral activation. The neuroinflammation and apoptotic regulation pathways are specifically implicated. The continuation and further analysis of large scale genome studies may prove useful in exploring genes important in retroviral activation and ALS, which may help discover new drug targets.
Correction to: Detailed prediction of protein sub-nuclear localization
Authors: Littmann Maria , Goldberg Tatyana , Seitz Sebastian , Bodén Mikael , Rost Burkhard
Published: December 2019

Following publication of the original article [1], the author reported that an incorrect figure has been published as Figure 2. The correct Figure 2 is shown below.
Bigram-PGK: phosphoglycerylation prediction using the technique of bigram probabilities of position specific scoring matrix
Authors: Chandra Abel , Sharma Alok , Dehzangi Abdollah , Shigemizu Daichi , Tsunoda Tatsuhiko
Published: December 2019

Background

The biological process known as post-translational modification (PTM) is a condition whereby proteomes are modified that affects normal cell biology, and hence the pathogenesis. A number of PTMs have been discovered in the recent years and lysine phosphoglycerylation is one of the fairly recent developments. Even with a large number of proteins being sequenced in the post-genomic era, the identification of phosphoglycerylation remains a big challenge due to factors such as cost, time consumption and inefficiency involved in the experimental efforts. To overcome this issue, computational techniques have emerged to accurately identify phosphoglycerylated lysine residues. However, the computational techniques proposed so far hold limitations to correctly predict this covalent modification.

Results

We propose a new predictor in this paper called Bigram-PGK which uses evolutionary information of amino acids to try and predict phosphoglycerylated sites. The benchmark dataset which contains experimentally labelled sites is employed for this purpose and profile bigram occurrences is calculated from position specific scoring matrices of amino acids in the protein sequences. The statistical measures of this work, such as sensitivity, specificity, precision, accuracy, Mathews correlation coefficient and area under ROC curve have been reported to be 0.9642, 0.8973, 0.8253, 0.9193, 0.8330, 0.9306, respectively.

Conclusions

The proposed predictor, based on the feature of evolutionary information and support vector machine classifier, has shown great potential to effectively predict phosphoglycerylated and non-phosphoglycerylated lysine residues when compared against the existing predictors. The data and software of this work can be acquired from https://github.com/abelavit/Bigram-PGK.
Effects of different doses of magnesium sulfate on pneumoperitoneum-related hemodynamic changes in patients undergoing gastrointestinal laparoscopy: a randomized, double-blind, controlled trial
Authors: Tan Wei , Qian Dong-chen , Zheng Meng-meng , Lu Xuan , Han Yuan , Qi Dun-yi
Published: December 2019

Background

The infusion of magnesium sulfate is well known to reduce arterial pressure and attenuate hemodynamic response to pneumoperitoneum. This study aimed to investigate whether different doses of magnesium sulfate can effectively attenuate the pneumoperitoneum-related hemodynamic changes and the release of vasopressin in patients undergoing laparoscopic gastrointestinal surgery.

Methods

Sixty-nine patients undergoing laparoscopic partial gastrectomy were randomized into three groups: group L received magnesium sulfate 30 mg/kg loading dose and 15 mg/kg/h continuous maintenance infusion for 1 h; group H received magnesium sulfate 50 mg/kg followed by 30 mg/kg/h for 1 h; and group S (control group) received same volume 0.9% saline infusion, immediately before the induction of pneumoperitoneum. Systemic vascular resistance (SVR), cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum vasopressin and magnesium concentrations were measured. The extubation time, visual analogue scale were also assessed. The primary outcome is the difference in SVR between different groups. The secondary outcome is the differences of other indicators between groups, such as CO, MAP, HR, CVP, vasopressin and postoperative pain score.

Results

Pneumoperitoneum instantly resulted in a significant reduction of cardiac output and an increase in mean arterial pressure, systemic vascular resistance, central venous pressure and heart rate in the control group (P <  0.01). The mean arterial pressure (T2 – T4),systemic vascular resistance (T2 – T3), central venous pressure(T3-T5) and the level of serum vasopressin were significantly lower (P <  0.05) and the cardiac output (T2 – T3) was significantly higher (P <  0.05) in group H than those in the control group. The mean arterial pressure (T4), systemic vascular resistance (T2), and central venous pressure(T3-T4) were significantly lower in group H than those in group L (P <  0.05). Furthermore, the visual analog scales at 5 min and 20 min, the level of vasopressin, and the dose of remifentanil were significantly decreased in group H compared to the control group and group L (P <  0.01).

Conclusion

Magnesium sulfate could safely and effectively attenuate the pneumoperitoneum-related hemodynamic instability during gastrointestinal laparoscopy and improve postoperative pain at serum magnesium concentrations above 2 mmol/L.

Trial registration

The study was retrospectively registered at Chinese Clinical Trial Registry; the registration number isChiCTR-IPD-17011145, principal investigator: D.Y. Q., date of registration: April 13, 2017.
What rationale do GPs use to choose a particular antibiotic for a specific clinical situation?
Authors: Krishnakumar Jegatha , Tsopra Rosy
Published: December 2019

Background

Many studies have investigated the ways in which physicians decide whether to prescribe antibiotics, but very few studies have focused on the reasons for which general practitioners (GPs) choose to prescribe a particular antibiotic in a specific clinical situation. Improvements in our understanding of the rationale behind GPs’ decisions would provide insight into the reasons for which GPs do not always prescribe the antibiotic recommended in clinical practice guidelines and facilitate the development of appropriate interventions to improve antibiotic prescription.

The objective of the study was to understand the rationale used by GPs to decide which antibiotic to prescribe in a specific clinical situation, and to propose a model representing this rationale.

Methods

We used a three-step process. First, data were collected from interviews with 20 GPs, and analysed according to the grounded theory approach. Second, data were collected from publications exploring the factors used by GPs to choose an antibiotic. Third, data were used to develop a comprehensive model of the rationale used by GPs to decide which antibiotic to prescribe.

Results

The GPs considered various factors when choosing antibiotics: factors relating to microbiology (bacterial resistance), pharmacology (adverse effects, efficacy, practicality of the administration protocol, antibiotic class, drug cost), clinical conditions (patient profile and comorbid conditions, symptoms, progression of infection, history of antibiotic treatment, preference), and personal factors (GP’s experience, knowledge, emotion, preference).

Conclusions

Various interventions, targeting all the factors underlying antibiotic choice, are required to improve antibiotic prescription. GP-related factors could be improved through interventions aiming to improve the GPs’ knowledge of antibiotics (e.g. continuing medical education). Factors relating to microbiology, pharmacology and clinical conditions could be targeted through the use of clinical decision support systems in everyday clinical practice.
Correction to: Upregulation of FOXM1 leads to diminished drug sensitivity in myeloma
Authors: Gu Chunyan , Jing Xuefang , Holman Carol , Sompallae Ramakrishna , Zhan Fenghuang , Tricot Guido , Yang Ye , Janz Siegfried
Published: December 2019

As a result of an author oversight in the original article [1], the legend of Figure 5A and C is inaccurate and one panel in Figure 5C (FOXM1N H929 cells shown in the top row, left) is wrong.
Correction to: Hepatitis B virus perceptions and health seeking behaviors among pregnant women in Uganda: implications for prevention and policy
Authors: Nankya-Mutyoba Joan , Aizire Jim , Makumbi Fredrick , Ocama Ponsiano , Kirk Gregory D.
Published: December 2019

In the original publication of this article [1], some values are missing in the Figure 1, Figure 2 and Figure 3. These errors were introduced during typesetting; thus the publisher apologizes for this error. Additionally, the original manuscript has also been updated to amend this error. The correct figures are shown below:
Improved cell composition deconvolution method of bulk gene expression profiles to quantify subsets of immune cells
Authors: Chiu Yen-Jung , Hsieh Yi-Hsuan , Huang Yen-Hua
Published: December 2019

Background

To facilitate the investigation of the pathogenic roles played by various immune cells in complex tissues such as tumors, a few computational methods for deconvoluting bulk gene expression profiles to predict cell composition have been created. However, available methods were usually developed along with a set of reference gene expression profiles consisting of imbalanced replicates across different cell types. Therefore, the objective of this study was to create a new deconvolution method equipped with a new set of reference gene expression profiles that incorporate more microarray replicates of the immune cells that have been frequently implicated in the poor prognosis of cancers, such as T helper cells, regulatory T cells and macrophage M1/M2 cells.

Methods

Our deconvolution method was developed by choosing ε-support vector regression (ε-SVR) as the core algorithm assigned with a loss function subject to the L1-norm penalty. To construct the reference gene expression signature matrix for regression, a subset of differentially expressed genes were chosen from 148 microarray-based gene expression profiles for 9 types of immune cells by using ANOVA and minimizing condition number. Agreement analyses including mean absolute percentage errors and Bland-Altman plots were carried out to compare the performances of our method and CIBERSORT.

Results

In silico cell mixtures, simulated bulk tissues, and real human samples with known immune-cell fractions were used as the test datasets for benchmarking. Our method outperformed CIBERSORT in the benchmarks using in silico breast tissue-immune cell mixtures in the proportions of 30:70 and 50:50, and in the benchmark using 164 human PBMC samples. Our results suggest that the performance of our method was at least comparable to that of a state-of-the-art tool, CIBERSORT.

Conclusions

We developed a new cell composition deconvolution method and the implementation was entirely based on the publicly available R and Python packages. In addition, we compiled a new set of reference gene expression profiles, which might allow for a more robust prediction of the immune cell fractions from the expression profiles of cell mixtures. The source code of our method could be downloaded from https://github.com/holiday01/deconvolution-to-estimate-immune-cell-subsets.
GTX.Digest.VCF: an online NGS data interpretation system based on intelligent gene ranking and large-scale text mining
Authors: Jiang Yanhuang , Wu Chengkun , Zhang Yanghui , Zhang Shaowei , Yu Shuojun , Lei Peng , Lu Qin , Xi Yanwei , Wang Hua , Song Zhuo
Published: December 2019

Background

An important task in the interpretation of sequencing data is to highlight pathogenic genes (or detrimental variants) in the field of Mendelian diseases. It is still challenging despite the recent rapid development of genomics and bioinformatics. A typical interpretation workflow includes annotation, filtration, manual inspection and literature review. Those steps are time-consuming and error-prone in the absence of systematic support. Therefore, we developed GTX.Digest.VCF, an online DNA sequencing interpretation system, which prioritizes genes and variants for novel disease-gene relation discovery and integrates text mining results to provide literature evidence for the discovery. Its phenotype-driven ranking and biological data mining approach significantly speed up the whole interpretation process.

Results

The GTX.Digest.VCF system is freely available as a web portal at http://vcf.gtxlab.com for academic research. Evaluation on the DDD project dataset demonstrates an accuracy of 77% (235 out of 305 cases) for top-50 genes and an accuracy of 41.6% (127 out of 305 cases) for top-5 genes.

Conclusions

GTX.Digest.VCF provides an intelligent web portal for genomics data interpretation via the integration of bioinformatics tools, distributed parallel computing, biomedical text mining. It can facilitate the application of genomic analytics in clinical research and practices.
BrightFocus Alzheimer’s Fast Track 2019
Authors: Whitaker Keith W. , LaFerla Frank M. , Steinbusch Harry W. M. , Lemere Cynthia A. , Bovenkamp Diane E.
Published: December 2019

The 3 day workshop “Alzheimer’s Fast Track” is a unique opportunity for graduate students, postdoctoral fellows, or other early-career scientists, focused on Alzheimer’s disease research, to gain new knowledge and become an expert in where this emerging scientific field is moving. In addition, it is not only about receiving a good overview, but also learning to write and defend a successful application for securing funding for Alzheimer’s disease research projects.
PIRCh-seq: functional classification of non-coding RNAs associated with distinct histone modifications
Authors: Fang Jingwen , Ma Qing , Chu Ci , Huang Beibei , Li Lingjie , Cai Pengfei , Batista Pedro J. , Tolentino Karen Erisse Martin , Xu Jin , Li Rui , Du Pengcheng , Qu Kun , Chang Howard Y.
Published: December 2019

We develop PIRCh-seq, a method which enables a comprehensive survey of chromatin-associated RNAs in a histone modification-specific manner. We identify hundreds of chromatin-associated RNAs in several cell types with substantially less contamination by nascent transcripts. Non-coding RNAs are found enriched on chromatin and are classified into functional groups based on the patterns of their association with specific histone modifications. We find single-stranded RNA bases are more chromatin-associated, and we discover hundreds of allele-specific RNA-chromatin interactions. These results provide a unique resource to globally study the functions of chromatin-associated lncRNAs and elucidate the basic mechanisms of chromatin-RNA interactions.
Neck paraganglioma and follicular lymphoma: a case report
Authors: Marchetti Lara , Perrucci Luca , D’Ercole Francesca , Zatelli Maria Chiara , Ambrosio Maria Rosaria , Giganti Melchiore , Carnevale Aldo
Published: December 2019

Background

Paragangliomas and pheochromocytomas are sympathetic or parasympathetic tumors derived from the paraganglia and the adrenal medulla, respectively. Paragangliomas and pheochromocytomas can be sporadic or familial, the latter frequently being multifocal and possibly due to succinate dehydrogenase complex genes mutations. In addition, 12% of sporadic paragangliomas are related to covered succinate dehydrogenase complex mutations. The importance of identifying succinate dehydrogenase complex mutations is related to the risk for these patients of developing multiple tumors, including non-endocrine ones, showing an aggressive clinical presentation.

Case presentation

We report the case of a 45-year-old Caucasian man with an indolent mass in his neck. Ultrasound of his neck, magnetic resonance imaging, and 1,4,7,10-tetraazacyclododecane-N(I),N(II),N(III),N(IIII)-tetraacetic acid(D)-Phe(1)-thy(3)-octreotide (68Ga-DOTATOC) positron emission tomography-computed tomography and endocrine work-up were consistent with a carotid body paraganglioma with concomitant nodal enlargement in several body regions, which turned out to be a follicular lymphoma at histology. He was found to carry a germline Succinate dehydrogenase subunit B gene (SDHB) mutation.

Conclusion

It is crucial to look for a second malignancy in the case of a paraganglioma demonstrating succinate dehydrogenase complex germline mutations.
Correction to: miR199a-3p regulates P53 by targeting CABLES1 in mouse cardiac c-kit+ cells to promote proliferation and inhibit apoptosis through a negative feedback loop
Authors: Liu Jingjin , Wang Yongshun , Cui Jinjin , Sun Meng , Pu Zhongyue , Wang Chao , Du Wenjuan , Liu Xinxin , Wu Jian , Hou Jingbo , Zhang Shuo , Yu Bo
Published: December 2019

After publication of our article [1] we became aware that there were errors in Fig. 5b and Fig. 6c, namely that the immunofluorescence of EDU-positive cells of the CABLES1 transfection group in Fig. 5b (panel 2) and the cell cycle distribution of the combination group (treatment with the antimiR199a-3p and shRNA-CABLES1) in Fig. 6c (panel 3) were incorrectly presented.
Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype
Authors: Hesse Raphael , Hurtado Maica Llavero , Jackson Rosemary J. , Eaton Samantha L. , Herrmann Abigail G. , Colom-Cadena Marti , Tzioras Makis , King Declan , Rose Jamie , Tulloch Jane , McKenzie Chris-Anne , Smith Colin , Henstridge Christopher M. , Lamont Douglas , Wishart Thomas M. , Spires-Jones Tara L.
Published: December 2019

Degeneration of synapses in Alzheimer’s disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently observed that the strongest genetic risk factor for sporadic AD, apolipoprotein E epsilon 4 (APOE4), is associated with exacerbated synapse loss and synaptic accumulation of oligomeric amyloid beta in human AD brain. To begin to understand the molecular cascades involved in synapse loss in AD and how this is mediated by APOE, and to generate a resource of knowledge of changes in the synaptic proteome in AD, we conducted a proteomic screen and systematic in silico analysis of synaptoneurosome preparations from temporal and occipital cortices of human AD and control subjects with known APOE gene status. We examined brain tissue from 33 subjects (7–10 per group). We pooled tissue from all subjects in each group for unbiased proteomic analyses followed by validation with individual case samples. Our analysis identified over 5500 proteins in human synaptoneurosomes and highlighted disease, brain region, and APOE-associated changes in multiple molecular pathways including a decreased abundance in AD of proteins important for synaptic and mitochondrial function and an increased abundance of proteins involved in neuroimmune interactions and intracellular signaling.
Using stakeholder input to inform scenario content: an example from physiotherapy
Authors: Edwards Sandy , Tuttle Neil
Published: December 2019

Background

Simulated learning environments (SLEs) are being embraced as effective, though potentially costly tools, by health educators in a variety of contexts. The selection of scenarios, however, can be arbitrary and idiosyncratic.

Methods

We conducted a stakeholder audit to determine priorities for student learning which would inform scenario design. The process consisted of (1) the identification of stakeholders, (2) consultation with stakeholders to identify their priorities, (3) determination of priorities that could be addressed in the SLE being developed, and (4) incorporating these priorities into scenarios.

Results

The identified stakeholders were the funding body, educational institution and discipline, regulatory agency, accreditation agency, external clinical placement providers, employers of new graduates, patients, and learners. Stakeholder input included a combination of surveys, consultation of online resources, and semi-structured interviews. Identified areas where student learning could be improved included (1) all students not having experience of all populations or ‘essential’ conditions, (2) situations where adverse events had occurred, (3) working with people from diverse backgrounds or those with psychosocial issues including those in chronic pain, (4) communication, (5) situation awareness, and (6) ethical issues.

Conclusions

Ten scenarios were developed considering the stakeholder input. Facilitator notes were written to ensure all facilitators addressed the areas that had been identified. Where possible, simulated patients, with diverse backgrounds, were hired to portray roles even though such areas of diversity were not explicitly written into the scenarios. Whilst the example concerns physiotherapy students within Australia, the principles may be applicable across a range of health disciplines.
Interprofessional simulation in a student community clinic: insights from an educational framework and contact theory
Authors: Waller Susan , Nestel Debra
Published: December 2019

Introduction

Simulation in community care is a relatively understudied area. In this paper, we report a qualitative evaluation of the Simulated Client Interprofessional Education (SCIPE) program in a community clinic for undergraduate health and social care students in a rural setting. We sought to explore the stakeholders’ perceptions and experiences of training for, and conduct of, a simulated client-based activity to support the development of collaborative practice of students. We used an educational framework (presage, process, product–3P) and contact theory to analyse the evaluation data and suggest improvement strategies.

Methods

Data on professional characteristics was collected from facilitators, simulated client and students. Facilitators and simulated clients received training. Written evaluations were collected after training and after the simulated clinics. Purposively sampled facilitators, students and community partner agencies participated in individual semi-structured interviews to gain deeper insights into experiences.

Results

Fourteen clinics involved 5 facilitators, 12 simulated clients and 40 students. Fifteen interviews were conducted. The SCIPE program led to perceived improvements in students’ communication and awareness of interprofessional collaboration. Participation in the program enabled students to experience a holistic approach to client interviewing and development of competency in collaborative goal setting. Further attention to presage and ability of facilitators to build positive contact conditions was identified. Coordination from a central site facilitated exchange and quality assurance for all elements of the program. Scoping of conditions of positive contact enabled a greater understanding of students’ and facilitators’ evaluation of the experience and constraints which would be modifiable for future improvement and sustainability.

Discussion

Although the SCIPE program benefited students, the need for more explicit organisational engagement and support was revealed in interviews. The use of 3P and contact theory was helpful in identifying elements of the program for maintenance and development. Future research could follow students into practice to see if the behaviours are sustained and translated. Strengths included broad stakeholder involvement and immediate feedback. The key limitation was that the activity lacked explicit institutional support, facilitators required further training in briefing and the outcomes largely refer to participants’ perceptions and may not translate to practice.
Online teaching in response to student protests and campus shutdowns: academics’ perspectives
Authors: Czerniewicz Laura , Trotter Henry , Haupt Genevieve
Published: December 2019

During the period 2015–2017, student protests and university shutdowns rocked the higher education sector in South Africa, with key issues being raised regarding student exclusion based on financial, epistemological and cultural grounds. In this highly politicised and contested environment, some universities decided to use blended and online delivery as a strategy to enable the academic year to be completed and all curriculum to be covered, despite the disruptions. This was a controversial decision politically and a challenging one practically. From the perspective of the academics at the University of Cape Town (UCT), this paper draws on interviews with educators in three broad disciplinary areas to explore their views, practices, and experiences regarding the use of online materials in these unique circumstances. Activity Theory provides a framework to consider the issues systemically and to identify the tensions and contradictions in the system.
Local meanings for supra-local change: Perceptions of TRAP backing in Kansas1
Authors: Villarreal Dan , Kohn Mary
Published: December 2019

While the retraction of TRAP is found throughout the American West (Fridland et al. 2016), it is associated with California and supposed Californian values in both the popular media (Pratt and D’Onofrio 2017) and the ears of Californian listeners (Villarreal 2018). This study investigates the local construction of meaning for a supra-local sound change by examining perceptions of TRAP backing in Kansas, a locale that has undergone front lax vowel retraction (Kohn and Stithem 2015). Thirty-five college students heard matched-guise stimuli differing only by TRAP F2, guessed speakers’ regional origin, and rated speakers on 14 affective scales. Listeners associated TRAP backing with California (despite local participation in the sound shift) and general prestige. We suggest that that this association with general prestige may help to explain the presence of this vowel shift in Kansas despite considerable ideological differences with California. We argue that these results highlight the interaction between local construction of meaning and broader national discourses for a sound change: While stereotypical associations with a sound change can spread rapidly through means like popular media, stance and identity associations are constructed at the local level.
Writing Working-Class History from the Bottom Up and Beyond
Authors: LeFlouria Talitha L.
Published: December 2019

This essay recognizes the important role the Working Class in American History book series has played in shaping our understanding of the historical experiences of African American and women workers in the United States. It outlines the advancements historians have made in the field of working-class labor history and challenges scholars to incorporate the stories of informal, enslaved, and incarcerated workers.
Pre-activation affects the effect of stretch-shortening cycle by modulating fascicle behavior
Authors: Fukutani Atsuki , Shimoho Kento , Isaka Tadao
Published: December 2019

The torque attained during active shortening is enhanced after an active stretch (stretch-shortening cycle, SSC). This study examined the influence of pre-activation on fascicle behavior and the SSC effect. Subjects exhibited the following three conditions by electrically induced plantar flexions. In the isometric-concentric (ISO-CON) condition, subjects exhibited active shortening from dorsiflexion of 15° to 0° after isometric pre-activation. In the eccentric-concentric (ECC-CON) condition, subjects exhibited the above active shortening immediately after the eccentric pre-activation. In the isometric-eccentric-concentric (ISO-ECC-CON) condition, isometric pre-activation was conducted before exhibiting the ECC-CON maneuver. Joint torque and fascicle length of the medial gastrocnemius were compared. The joint torque at the onset and end of shortening was larger in the ISO-ECC-CON than in the ISO-CON or ECC-CON conditions, while no differences were found between ISO-CON and ECC-CON conditions. The magnitude of fascicle elongation attained during the active stretch was larger in the ISO-ECC-CON than in the ECC-CON condition. This could be caused by the shorter fascicle length at the onset of active stretch due to isometric pre-activation. This shorter fascicle length could lead to larger fascicle elongation during the subsequent active stretch, which should emphasize the effect of active stretch-induced force enhancement mechanism.
Norovirus genogroup correlation with acute diarrhea severity in Indonesian pediatric patients aged 1-60 months: a cross-sectional study
Authors: Fardah Athiyyah Alpha , Shigemura Katsumi , Kitagawa Koichi , Agustina Nazara , Darma Andy , Ranuh Reza , Raharjo Dadik , Shirakawa Toshiro , Fujisawa Masato , Marto Sudarmo Subijanto
Published: December 2019

Background: The objective of this study was to investigate the correlation between norovirus genogroup and severity of acute diarrhea in pediatric patients at the Dr. Soetomo Hospital, Surabaya, Indonesia.

Methods: This cross-sectional study involved 31 participants aged 1-60 months admitted to the hospital with acute diarrhea from April 2012 to March 2013. Norovirus genogroups (GI and II) were identified from patient stool using reverse transcription polymerase chain reaction (RT-PCR). Severity was measured using the Ruuska and Vesikari scoring system.

Results: In total, 91 stool samples were obtained, of which 31 (19%) were norovirus positive. Norovirus GI was found in one sample with mild diarrhea. Norovirus GII was found in 30 samples (96.8%); one sample with mild diarrhea (3.3%), 20 samples with moderate diarrhea (66.7%), and nine samples with severe diarrhea (30%).

Conclusion: Norovirus GII was the most prevalent cause of acute diarrhea and 30% of the cases manifested as severe diarrhea.
Mobilized peripheral blood: an updated perspective
Authors: Karpova Darja , Rettig Michael P. , DiPersio John F.
Published: December 2019

Enforced egress of hematopoietic stem cells (HSCs) out of the bone marrow (BM) into the peripheral circulation, termed mobilization, has come a long way since its discovery over four decades ago. Mobilization research continues to be driven by the need to optimize the regimen currently available in the clinic with regard to pharmacokinetic and pharmacodynamic profile, costs, and donor convenience. In this review, we describe the most recent findings in the field and how we anticipate them to affect the development of mobilization strategies in the future. Furthermore, the significance of mobilization beyond HSC collection, i.e. for chemosensitization, conditioning, and gene therapy as well as a means to study the interactions between HSCs and their BM microenvironment, is reviewed. Open questions, controversies, and the potential impact of recent technical progress on mobilization research are also highlighted.
Rectal gonorrhoea and chlamydia among men who have sex with men in coastal Kenya
Authors: Ngetsa Caroline J. , Heymann Marc W. , Thiong'o Alex , Wahome Elizabeth , Mwambi John , Karani Clara , Menza Nelson C. , Mwashigadi Grace , Muturi Margaret W. , Graham Susan M. , Mugo Peter M. , Sanders Eduard J.
Published: December 2019

Background: Men who have sex with men (MSM) have a higher prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections compared to the rest of the population, often remaining undiagnosed. In Kenya, prevalence of rectal CT and NG infection and NG antimicrobial sensitivity are poorly described.

Methods: MSM who reported receptive anal intercourse (RAI) were recruited from an ongoing human immunodeficiency virus acquisition and treatment study in coastal Kenya in 2016-2017. Rectal swabs were collected at two time points 6 months apart to estimate prevalence and incidence of CT/NG infection using a molecular point-of-care assay. Participants positive for CT or NG were treated according to national guidelines. NG culture and antimicrobial susceptibility testing was performed. Participant and risk behaviour characteristics were collected and association with baseline CT/NG prevalence assessed by multivariable regression analysis.

Results: Prevalence of CT/NG in 104 MSM was 21.2% (CT 13.5%, NG 9.6%, dual infection 1.9%) at baseline and 25.9% in 81 MSM at follow-up (CT 14.8%, NG 14.8%, dual infection 3.7%). CT/NG incidence was estimated at 53.0 (95% CI, 34.5-81.3) per 100 person-years. Most CT/NG positive participants were asymptomatic: 95.5% at baseline and 100% at follow-up. CT/NG infection was associated with being paid for sex [adjusted odds ratio (aOR)=6.2, 95% CI (1.7-22.9)] and being in formal employment [aOR=7.5, 95% CI (1.1-49.2)]. Six NG isolates were obtained at follow-up; all were susceptible to ceftriaxone and cefixime and all were resistant to penicillin, tetracycline and ciprofloxacin.

Conclusions: There is a high prevalence and incidence of asymptomatic rectal CT and NG in MSM reporting RAI in coastal Kenya. MSM who were paid for sex or had formal employment were more likely to be infected with CT/NG suggesting increased risk behaviour during transactional sex. Antimicrobial susceptibility results suggest that current antibiotic choices in Kenya are appropriate for NG treatment.
Aplicación tópica de crema con nanopartículas con vitamina E para prevenir radiodermatitis en cáncer de mama: protocolo de ensayo clínico
Authors: Schmidt Fernanda Mateus Queiróz , González Carol V. Serna , Mattar Rodrigo Calixto , Lopes Luciana Biagini , Santos Marinilce Fagundes dos , de Gouveia Santos Vera L.C.
Published: December 2019

Sinopsis:

Objetivo:

Poco se conoce sobre la eficacia de productos para la prevención de radiodermatitis, que afecta al 90–95% de las mujeres con cáncer de mama. El uso de antioxidantes es promisorio, sin embargo, poco estudiado. Los autores desarrollaron un protocolo de ensayo clínico para evaluar el efecto potencial de la aplicación de crema con nanopartículas con vitamina E para prevenir radiodermatitis aguda en mujeres con cáncer de mama.

Método:

El protocolo sugiere que 108 mujeres adultas con cáncer de mama, que estén recibiendo radioterapia, sean incluidas en este ensayo clínico, controlado, aleatorizado y triple ciego, en un hospital oncológico. Se prevé la distribución de pacientes en tres grupos de 36 personas: el grupo A recibirá una crema con nanopartículas lipídicas con vitamina E, el grupo B obtendrá una crema sin nanopartículas ni vitamina E, y el grupo C usará una crema con nanopartículas sin vitamina E. Los resultados primarios evaluarán la incidencia, el grado y el tiempo de surgimiento de la radiodermatitis. Los resultados secundarios se centrarán en la calidad de vida, los síntomas y la temperatura local. Las pacientes serán evaluadas tres veces por semana, desde el inicio de la radioterapia hasta dos semanas después de la última sesión. El presente proyecto fue aprobado por el comité de ética en investigación de las instituciones involucradas.
Supportive technology in collaborative research: proposing the STiCR framework
Authors: Kwasnicki RM , Cato LD , Geoghegan L , Stanley G , Pancholi J , Jain A , Gardiner MD
Published: December 2019

Introduction

Achieving a standard of clinical research at the pinnacle of the evidence pyramid is historically expensive and logistically challenging. Research collaboratives have delivered high-impact prospective multicentre audits and clinical trials by using trainee networks with a range of enabling technology. This review outlines such use of technology in the UK and provides a framework of recommended technologies for future studies.

Methods

A review of the literature identified technology used in collaborative projects. Additional technologies were identified through web searches. Technologies were grouped into themes including access (networking and engagement), collaboration and event organisation. The technologies available to support each theme were studied further to outline relative benefits and limitations.

Findings

Thirty-three articles from trainee research collaboratives were identified. The most frequently documented technologies were social media applications, website platforms and research databases. The Supportive Technologies in Collaborative Research framework is proposed, providing a structure for using the technologies available to support multicentre collaboration. Such technologies are often overlooked in the literature by established and start-up collaborative project groups. If used correctly, they might help to overcome the physical, logistical and financial barriers of multicentre clinical trials.