bluuebunny/crossref_metadata_2025 huggingface dataset:
Why cultural safety rather than cultural competency is required to achieve health equity: a literature review and recommended definition
Authors: Curtis Elana , Jones Rhys , Tipene-Leach David , Walker Curtis , Loring Belinda , Paine Sarah-Jane , Reid Papaarangi
Published: November 2019

Background

Eliminating indigenous and ethnic health inequities requires addressing the determinants of health inequities which includes institutionalised racism, and ensuring a health care system that delivers appropriate and equitable care. There is growing recognition of the importance of cultural competency and cultural safety at both individual health practitioner and organisational levels to achieve equitable health care. Some jurisdictions have included cultural competency in health professional licensing legislation, health professional accreditation standards, and pre-service and in-service training programmes. However, there are mixed definitions and understandings of cultural competency and cultural safety, and how best to achieve them.

Methods

A literature review of 59 international articles on the definitions of cultural competency and cultural safety was undertaken. Findings were contextualised to the cultural competency legislation, statements and initiatives present within Aotearoa New Zealand, a national Symposium on Cultural Competence and Māori Health, convened by the Medical Council of New Zealand and Te Ohu Rata o Aotearoa – Māori Medical Practitioners Association (Te ORA) and consultation with Māori medical practitioners via Te ORA.

Results

Health practitioners, healthcare organisations and health systems need to be engaged in working towards cultural safety and critical consciousness. To do this, they must be prepared to critique the ‘taken for granted’ power structures and be prepared to challenge their own culture and cultural systems rather than prioritise becoming ‘competent’ in the cultures of others. The objective of cultural safety activities also needs to be clearly linked to achieving health equity. Healthcare organisations and authorities need to be held accountable for providing culturally safe care, as defined by patients and their communities, and as measured through progress towards achieving health equity.

Conclusions

A move to cultural safety rather than cultural competency is recommended. We propose a definition for cultural safety that we believe to be more fit for purpose in achieving health equity, and clarify the essential principles and practical steps to operationalise this approach in healthcare organisations and workforce development. The unintended consequences of a narrow or limited understanding of cultural competency are discussed, along with recommendations for how a broader conceptualisation of these terms is important.
circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer
Authors: Wang Sen , Tang Dong , Wang Wei , Yang Yining , Wu Xiaoqing , Wang Liuhua , Wang Daorong
Published: November 2019

Background

As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis.

Methods

circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.

Results

circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis.

Conclusion

Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.
m6A modification suppresses ocular melanoma through modulating HINT2 mRNA translation
Authors: Jia Ruobing , Chai Peiwei , Wang Shanzheng , Sun Baofa , Xu Yangfan , Yang Ying , Ge Shengfang , Jia Renbing , Yang Yun-Gui , Fan Xianqun
Published: November 2019

Background

Dynamic N6-methyladenosine (m6A) RNA modification generated and erased by N6-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of m6A modification in ocular melanoma remains unclear.

Methods

m6A assays and survival analysis were used to explore decreased global m6A levels, indicating a late stage of ocular melanoma and a poor prognosis. Multiomic analysis of miCLIP-seq, RNA-seq and Label-free MS data revealed that m6A RNA modification posttranscriptionally promoted HINT2 expression. RNA immunoprecipitation (RIP)-qPCR and dual luciferase assays revealed thatHINT2mRNA specifically interacted with YTHDF1. Furthermore, polysome profiling analysis indicated a greater amount ofHINT2mRNA in the translation pool in ocular melanoma cells with higher m6A methylation.

Results

Here, we show that RNA methylation significantly inhibits the progression of UM and CM. Ocular melanoma samples showed decreased m6A levels, indicating a poor prognosis. Changes in global m6A modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylatedHINT2mRNA, a tumor suppressor in ocular melanoma.

Conclusions

Our work uncovers a critical function for m6A methylation in ocular melanoma and provides additional insight into the understanding of m6A modification.
Analysis of miRNA signatures in CSF identifies upregulation of miR-21 and miR-146a/b in patients with multiple sclerosis and active lesions
Authors: Muñoz-San Martín María , Reverter Gemma , Robles-Cedeño Rene , Buxò Maria , Ortega Francisco José , Gómez Imma , Tomàs-Roig Jordi , Celarain Naiara , Villar Luisa María , Perkal Hector , Fernández-Real José Manuel , Quintana Ester , Ramió-Torrentà Lluís
Published: November 2019

Background

MicroRNAs (miRNAs) have been reported as deregulated in active brain lesions derived from patients with multiple sclerosis (MS). In there, these post-transcriptional regulators may elicit very important effects but proper identification of miRNA candidates as potential biomarkers and/or therapeutic targets is scarcely available.

Objective

The aim of the study was to detect the presence of a set of candidate miRNAs in cell-free cerebrospinal fluid (CSF) and to determine their association with gadolinium-enhancing (Gd+) lesions in order to assess their value as biomarkers of MS activity.

Methods

Assessment of 28 miRNA candidates in cell-free CSF collected from 46 patients with MS (26 Gd+ and 20 Gd− patients) was performed by TaqMan assays and qPCR. Variations in their relative abundance were analyzed by the Mann-Whitney U test and further evaluated by receiver operating characteristic (ROC) analysis. Signaling pathways and biological functions of miRNAs were analyzed using bioinformatic tools (miRTarBase, Enrichr, REVIGO, and Cytoscape softwares).

Results

Seven out of 28 miRNA candidates were detected in at least 75% of CSF samples. Consistent increase of miR-21 and miR-146a/b was found in Gd+ MS patients. This increase was in parallel to the number of Gd+ lesions and neurofilament light chain (NF-L) levels. Gene Ontology enrichment analysis revealed that the target genes of these miRNAs are involved in biological processes of key relevance such as apoptosis, cell migration and proliferation, and in cytokine-mediated signaling pathways.

Conclusion

Levels of miR-21 and miR-146a/b in cell-free CSF may represent valuable biomarkers to identify patients with active MS lesions.
Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases
Authors: Lepennetier Gildas , Hracsko Zsuzsanna , Unger Marina , Van Griensven Martijn , Grummel Verena , Krumbholz Markus , Berthele Achim , Hemmer Bernhard , Kowarik Markus C.
Published: November 2019

Background

Cytokines play multiple roles during neuro-inflammatory processes and several cytokines have been studied in the context of specific diseases. This study provides a comprehensive picture of cerebrospinal fluid (CSF) changes during neuro-inflammation by analyzing multiple cytokines in combination with immune cell subsets and standard CSF parameters.

Methods

Using multiplex assays, we simultaneously measured 36 cytokines (CCL1–3, CCL7, CCL8, CCL11, CCL13, CCL19, CCL20, CCL22–27, CXCL1, CXCL2, CXCL5, CXCL6, CXCL8, CXCL9, CXCL11–13, CXCL16, CX3CL1, IL2, IL4, IL6, IL10, IL16, GM-CSF, IFNγ, MIF, TNFα, and MIB1β) in the CSF and serum of 75 subjects. Diagnoses included clinically isolated syndrome and relapsing-remitting multiple sclerosis (MS, n = 18), secondary progressive MS (n = 8), neuro-syphilis (n = 6), Lyme neuro-borreliosis (n = 13), bacterial and viral meningitis (n = 20), and patients with non-inflammatory neurological diseases (NIND, n = 10). Cytokine concentrations were correlated with CSF standard parameters and CSF immune cell subsets (CD4 and CD8 T cells, B cells, plasmablasts, monocytes, and NK cells) quantified by flow cytometry.

Results

We observed increased levels of multiple cytokines (26/36) in patients with neuro-inflammatory diseases when compared to NIND that consistently correlated with CSF cell count and QAlbumin. Most CSF cytokine concentrations correlated with each other, but correlations between CSF and serum values were scarce (3/36). Within the CSF compartment, CXCL13 showed a strong association with B cells when analyzing all patients, as well as patients with an intact blood-brain barrier (BBB). NK cells positively correlated with CSF concentrations of multiple cytokines (22/36) when analyzing all patients. These correlations were maintained when looking at patients with a disrupted BBB but not detectable in patients with an intact BBB.

Conclusions

Under conditions of neuro-inflammation, multiple CSF cytokines are regulated in parallel and most likely produced locally. A combined increase of CSF CXCL13 levels and B cells occurs under conditions of an intact BBB. Under conditions of a disrupted BBB, CSF NK cells show significantly increased values and seem to have a major contribution to overall inflammatory processes, reflected by a strong correlation with multiple cytokines. Future studies are necessary to address the exact kinetics of these cytokines during neuro-inflammation and their relation to specific diseases phenotypes.
Correction to: Does transcranial direct current stimulation improve functional locomotion in people with Parkinson’s disease? A systematic review and meta-analysis
Authors: Lee Hyo Keun , Ahn Se Ji , Shin Yang Mi , Kang Nyeonju , Cauraugh James H.
Published: November 2019

In the original article [1], we mentioned that some study characteristics of the article by Dagan and colleagues [2] were unavailable.
Improving bimanual interaction with a prosthesis using semi-autonomous control
Authors: Volkmar Robin , Dosen Strahinja , Gonzalez-Vargas Jose , Baum Marcus , Markovic Marko
Published: November 2019

Background

The loss of a hand is a traumatic experience that substantially compromises an individual’s capability to interact with his environment. The myoelectric prostheses are state-of-the-art (SoA) functional replacements for the lost limbs. Their overall mechanical design and dexterity have improved over the last few decades, but the users have not been able to fully exploit these advances because of the lack of effective and intuitive control. Bimanual tasks are particularly challenging for an amputee since prosthesis control needs to be coordinated with the movement of the sound limb. So far, the bimanual activities have been often neglected by the prosthetic research community.

Methods

We present a novel method to prosthesis control, which uses a semi-autonomous approach in order to simplify bimanual interactions. The approach supplements the commercial SoA two-channel myoelectric control with two additional sensors. Two inertial measurement units were attached to the prosthesis and the sound hand to detect the movement of both limbs. Once a bimanual interaction is detected, the system mimics the coordination strategies of able-bodied subjects to automatically adjust the prosthesis wrist rotation (pronation, supination) and grip type (lateral, palmar) to assist the sound hand during a bimanual task. The system has been evaluated in eight able-bodied subjects performing functional uni- and bi-manual tasks using the novel method and SoA two-channel myocontrol. The outcome measures were time to accomplish the task, semi-autonomous system misclassification rate, subjective rating of intuitiveness, and perceived workload (NASA TLX).

Results

The results demonstrated that the novel control interface substantially outperformed the SoA myoelectric control. While using the semi-autonomous control the time to accomplish the task and the perceived workload decreased for 25 and 27%, respectively, while the subjects rated the system as more intuitive then SoA myocontrol.

Conclusions

The novel system uses minimal additional hardware (two inertial sensors) and simple processing and it is therefore convenient for practical implementation. By using the proposed control scheme, the prosthesis assists the user’s sound hand in performing bimanual interactions while decreasing cognitive burden.
Effect of blood contamination of cerebrospinal fluid on amino acids, biogenic amines, pterins and vitamins
Authors: Batllori Marta , Casado Mercedes , Sierra Cristina , Salgado Maria del Carmen , Marti-Sanchez Laura , Maynou Joan , Fernandez Guerau , Garcia-Cazorla Angels , Ormazabal Aida , Molero-Luis Marta , Artuch Rafael
Published: November 2019

Background

Cerebrospinal fluid (CSF) metabolomic investigations are a powerful tool for studying neurometabolic diseases. We aimed to assess the effect of CSF contamination with blood on the concentrations of selected biomarkers.

Methods

CSF samples were spiked in duplicate with increasing volumes of whole blood under two conditions: (A) pooled CSF spiked with fresh whole blood and frozen to cause red blood cell (RBC) lysis; (B) pooled CSF spiked with fresh blood and centrifuged (the supernatant with no RBCs was frozen until the moment of analysis). CSF concentrations of amino acids, biogenic amines, pterins, and vitamins were analysed by HPLC coupled with tandem mass spectrometry, electrochemical and fluorescence detection.

Results

Aspartate, glutamate, taurine, ornithine, glycine, citrulline, pyridoxal 5´-phosphate, 5-methyltetrahydrofolate, and thiamine showed higher values when RBCs were lysed when compared with those of CSF with no RBC, while arginine, 5-hydroxyindoleacetic and homovanillic acids showed lower values. When RBCs were removed from CSF, only some amino acids, thiamine and pyridoxal 5´-phosphate showed moderately higher values when compared with the non-spiked CSF sample.

Conclusions

CSF-targeted metabolomic analysis is feasible even when substantial RBC contamination of CSF has occurred since CSF centrifugation to remove RBC prior to freezing eliminated most of the interferences observed.
Early detection of subclinical left ventricular dysfunction after breast cancer radiation therapy using speckle-tracking echocardiography: association between cardiac exposure and longitudinal strain reduction (BACCARAT study)
Authors: Walker Valentin , Lairez Olivier , Fondard Olivier , Pathak Atul , Pinel Baptiste , Chevelle Christian , Franck Denis , Jimenez Gaëlle , Camilleri Jérémy , Panh Loïc , Broggio David , Derreumaux Sylvie , Bernier Marie-Odile , Laurier Dominique , Ferrières Jean , Jacob Sophie
Published: November 2019

Background

Breast cancer (BC) radiotherapy (RT) can induce cardiotoxicity, with adverse events often observed many years after BC RT. Subclinical left ventricular (LV) dysfunction can be detected early after BC RT with global longitudinal strain (GLS) measurement based on 2D speckle-tracking echocardiography. This 6-month follow-up analysis from the BACCARAT prospective study aimed to investigate the association between cardiac radiation doses and subclinical LV dysfunction based on GLS reduction.

Methods

The patient study group consisted of 79 BC patients (64 left-sided BC, 15 right-sided BC) treated with RT without chemotherapy. Echocardiographic parameters, including GLS, were measured before RT and 6 months post-RT. The association between subclinical LV dysfunction, defined as GLS reduction > 10%, and radiation doses to whole heart and the LV were performed based on logistic regressions. Non-radiation factors associated with subclinical LV dysfunction including age, BMI, hypertension, hypercholesterolemia and endocrine therapy were considered for multivariate analyses.

Results

A mean decrease of 6% in GLS was observed (− 15.1% ± 3.2% at 6 months vs. − 16.1% ± 2.7% before RT, p = 0.01). For left-sided patients, mean heart and LV doses were 3.1 ± 1.3 Gy and 6.7 ± 3.4 Gy respectively. For right-sided patients, mean heart dose was 0.7 ± 0.5 Gy and median LV dose was 0.1 Gy. Associations between GLS reduction > 10% (37 patients) and mean doses to the heart and the LV as well as the V20 were observed in univariate analysis (Odds Ratio = 1.37[1.01–1.86], p = 0.04 for Dmean Heart; OR = 1.14 [1.01–1.28], p = 0.03 for Dmean LV; OR = 1.08 [1.01–1.14], p = 0.02 for LV V20). In multivariate analysis, these associations did not remain significant after adjustment for non-radiation factors. Further exploratory analysis allowed identifying a subgroup of patients (LV V20 > 15%) for whom a significant association with subclinical LV dysfunction was found (adjusted OR = 3.97 [1.01–15.70], p = 0.048).

Conclusions

This analysis indicated that subclinical LV dysfunction defined as a GLS decrease > 10% is associated with cardiac doses, but adjustment for non-radiation factors such as endocrine therapy lead to no longer statistically significant relationships. However, LV dosimetry may be promising to identify high-risk subpopulations. Larger and longer follow-up studies are required to further investigate these associations.

Trial registration

ClinicalTrials.gov: NCT02605512, Registered 6 November 2015 - Retrospectively registered
Biomechanical analysis of a novel height-adjustable nano-hydroxyapatite/polyamide-66 vertebral body: a finite element study
Authors: Chen Guanghui , Xin Baoquan , Yin Mengchen , Fan Tianqi , Wang Jing , Wang Ting , Bai Guangjian , Xiao Jianru , Liu Tielong
Published: November 2019

Background

To compare the biomechanical properties of a novel height-adjustable nano-hydroxyapatite/polyamide-66 vertebral body (HAVB) with the titanium mesh cage (TMC) and artificial vertebral body (AVB), and evaluate its biomechanical efficacy in spinal stability reconstruction.

Methods

A 3D nonliner FE model of the intact L1-sacrum was established and validated. Three FE models which instrumented HAVB, TMC, and AVB were constructed for surgical simulation. A pure moment of 7.5 Nm and a 400-N preload were applied to the three FE models in 3D motion. The peak von Mises stress upon each prosthesis and the interfaced endplate was recorded for analysis. In addition, the overall and intersegmental range of motion (ROM) of each model was investigated to assess the efficacy of each model in spinal stability reconstruction.

Results

AVB had the greatest stress concentration compared with TMC and HAVB in all motions (25.6–101.8 times of HAVB, 0.8–8.1 times of TMC). The peak stress on HAVB was 3.1–10.3% of TMC and 1.6–3.9% of AVB. The maximum stress values on L2 caudal and L4 cranial endplates are different between the three FE models: 0.9–1.9, 1.3–12.1, and 31.3–117.9 times of the intact model on L2 caudal endplates and 0.9–3.5, 7.2–31.5, and 10.3–56.4 times of the intact model on L4 cranial endplates in HAVB, TMC, and AVB, respectively, while the overall and segmental ROM reduction was similar between the three models, with AVB providing a relatively higher ROM reduction in all loading conditions (88.1–84.7% of intact model for overall ROM and 69.5–82.1% for L1/2, 87.0–91.7% for L2/4, and 71.1–87.2% for L4/5, respectively).

Conclusions

HAVB had similar biomechanical efficacy in spinal stability reconstruction as compared with TMC and AVB. The material used and the anatomic design of HAVB can help avoid stress concentration and the stress shielding effect, thus greatly reducing the implant-associated complications. HAVB exhibited some advantageous biomechanical properties over TMC and AVB and may prove to be a potentially viable option for spinal stability reconstruction. Further in vivo and vitro studies are still required to validate our findings and conclusions.
Obesity in achondroplasia patients: from evidence to medical monitoring
Authors: Saint-Laurent Celine , Garde-Etayo Laura , Gouze Elvire
Published: November 2019

Achondroplasia is a rare genetic disease representing the most common form of short-limb dwarfism. It is characterized by bone growth abnormalities that are well characterized and by a strong predisposition to abdominal obesity for which causes are unknown. Despite having aroused interest at the end of the 20 h century, there are still only very little data available on this aspect of the pathology. Today, interest is rising again, and some studies are now proposing mechanistic hypotheses and guidance for patient management. These data confirm that obesity is a major health problem in achondroplasia necessitating an early yet complex clinical management. Anticipatory care should be directed at identifying children who are at high risk to develop obesity and intervening to prevent the metabolic complications in adults. In this review, we are regrouping available data characterizing obesity in achondroplasia and we are identifying the current tools used to monitor obesity in these patients.
What drives mortality among HIV patients in a conflict setting? A prospective cohort study in the Central African Republic
Authors: Crellen Thomas , Ssonko Charles , Piening Turid , Simaleko Marcel Mbeko , Geiger Karen , Siddiqui M. Ruby
Published: November 2019

Background

Provision of antiretroviral therapy (ART) in conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 110,000 people living with HIV and 5000 AIDS-related deaths in 2018. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in a 2010 survey), and was subject to repeated attacks by armed groups on civilians during the observed period.

Methods

Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determined patient-level risk factors for mortality and how the risk of mortality varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using logistic regression with terms accounting for temporal autocorrelation.

Results

Patients were recruited and observed in the HIV treatment program from October 2011 to May 2017. Overall 1631 patients were enrolled and 1628 were included in the analysis giving 48,430 person-months at risk and 145 deaths. The crude survival rate after 12 months was 0.92 (95% CI 0.90, 0.93). Our model showed that patient mortality did not increase during periods of heightened conflict; the odds ratios (OR) 95% credible interval (CrI) for i) civilian fatalities and injuries, and ii) civilian abductions on patient mortality both spanned unity. The risk of mortality for individual patients was highest in the second month after entering the cohort, and declined seven-fold over the first 12 months. Male sex was associated with a higher mortality (odds ratio 1.70 [95% CrI 1.20, 2.33]) along with the severity of opportunistic infections (OIs) at baseline (OR 2.52; 95% CrI 2.01, 3.23 for stage 2 OIs compared with stage 1).

Conclusions

Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient-specific risk factors. The risk of mortality and recovery of CD4 T-cell counts observed in this conflict setting are comparable to those in stable resource poor settings, suggesting that conflict should not be a barrier in access to ART.
Evaluating nanopore sequencing data processing pipelines for structural variation identification
Authors: Zhou Anbo , Lin Timothy , Xing Jinchuan
Published: November 2019

Background

Structural variations (SVs) account for about 1% of the differences among human genomes and play a significant role in phenotypic variation and disease susceptibility. The emerging nanopore sequencing technology can generate long sequence reads and can potentially provide accurate SV identification. However, the tools for aligning long-read data and detecting SVs have not been thoroughly evaluated.

Results

Using four nanopore datasets, including both empirical and simulated reads, we evaluate four alignment tools and three SV detection tools. We also evaluate the impact of sequencing depth on SV detection. Finally, we develop a machine learning approach to integrate call sets from multiple pipelines. Overall SV callers’ performance varies depending on the SV types. For an initial data assessment, we recommend using aligner minimap2 in combination with SV caller Sniffles because of their speed and relatively balanced performance. For detailed analysis, we recommend incorporating information from multiple call sets to improve the SV call performance.

Conclusions

We present a workflow for evaluating aligners and SV callers for nanopore sequencing data and approaches for integrating multiple call sets. Our results indicate that additional optimizations are needed to improve SV detection accuracy and sensitivity, and an integrated call set can provide enhanced performance. The nanopore technology is improving, and the sequencing community is likely to grow accordingly. In turn, better benchmark call sets will be available to more accurately assess the performance of available tools and facilitate further tool development.
Evaluation of commonly used analysis strategies for epigenome- and transcriptome-wide association studies through replication of large-scale population studies
Authors:   BIOS consortium, van Rooij Jeroen , Mandaviya Pooja R. , Claringbould Annique , Felix Janine F. , van Dongen Jenny , Jansen Rick , Franke Lude , ’t Hoen Peter A. C. , Heijmans Bas , van Meurs Joyce B. J.
Published: November 2019

Background

A large number of analysis strategies are available for DNA methylation (DNAm) array and RNA-seq datasets, but it is unclear which strategies are best to use. We compare commonly used strategies and report how they influence results in large cohort studies.

Results

We tested the associations of DNAm and RNA expression with age, BMI, and smoking in four different cohorts (n = ~ 2900). By comparing strategies against the base model on the number and percentage of replicated CpGs for DNAm analyses or genes for RNA-seq analyses in a leave-one-out cohort replication approach, we find the choice of the normalization method and statistical test does not strongly influence the results for DNAm array data. However, adjusting for cell counts or hidden confounders substantially decreases the number of replicated CpGs for age and increases the number of replicated CpGs for BMI and smoking. For RNA-seq data, the choice of the normalization method, gene expression inclusion threshold, and statistical test does not strongly influence the results. Including five principal components or excluding correction of technical covariates or cell counts decreases the number of replicated genes.

Conclusions

Results were not influenced by the normalization method or statistical test. However, the correction method for cell counts, technical covariates, principal components, and/or hidden confounders does influence the results.
Novel insights into the potential role of ion transport in sensory perception in Acanthamoeba
Authors: Siddiqui Ruqaiyyah , Roberts Stephen K. , Ong Timothy Yu Yee , Mungroo Mohammad Ridwane , Anwar Areeba , Khan Naveed Ahmed
Published: November 2019

Background

Acanthamoeba is well known to produce a blinding keratitis and serious brain infection known as encephalitis. Effective treatment is problematic, and can continue up to a year, and even then, recurrence can ensue. Partly, this is due to the capability of vegetative amoebae to convert into resistant cysts. Cysts can persist in an inactive form for decades while retaining their pathogenicity. It is not clear how Acanthamoeba cysts monitor environmental changes, and determine favourable conditions leading to their emergence as viable trophozoites.

Methods

The role of ion transporters in the encystation and excystation of Acanthamoeba remains unclear. Here, we investigated the role of sodium, potassium and calcium ion transporters as well as proton pump inhibitors on A. castellanii encystation and excystation and their effects on trophozoites.

Results

Remarkably 3′,4′-dichlorobenzamil hydrochloride a sodium–calcium exchange inhibitor, completely abolished excystation of Acanthamoeba. Furthermore, lanthanum oxide and stevioside hydrate, both potassium transport inhibitors, resulted in the partial inhibition of Acanthamoeba excystation. Conversely, none of the ion transport inhibitors affected encystation or had any effects on Acanthamoeba trophozoites viability.

Conclusions

The present study indicates that ion transporters are involved in sensory perception of A. castellanii suggesting their value as potential therapeutic targets to block cellular differentiation that presents a significant challenge in the successful prognosis of Acanthamoeba infections.
Open source 3D printable replacement parts for the WHO insecticide susceptibility bioassay system
Authors: Tomlinson Sean , Carrington Yates Henrietta , Oruni Ambrose , Njoroge Harun , Weetman David , Donnelly Martin J. , Hof Arjen E Van’t
Published: November 2019

Background

Malaria vector control and research rely heavily on monitoring mosquito populations for the development of resistance to public health insecticides. One standard method for determining resistance in adult mosquito populations is the World Health Organization test (WHO bioassay). The WHO bioassay kit consists of several acrylic pieces that are assembled into a unit. Parts of the kit commonly break, reducing the capacity of insectaries to carry out resistance profiling. Since there is at present only a single supplier for the test kits, replacement parts can be hard to procure in a timely fashion.

Methods

Using computer-aided design software and widely available polylactic acid (PLA) filament as a printing material, we 3D designed and printed replacement parts for the WHO bioassay system. We conducted a comparison experiment between original WHO bioassay kits and 3D printed kits to assess congruence between results. The comparison experiment was performed on two Kenyan laboratory strains of Anopheles gambiae (s.s.), Kilifi and Mbita. Studentʼs t-tests were used to assess significant differences between tube types. Finally, we exposed the PLA filament to common solutions used with the bioassay kit.

Results

We were able to design and print functional replacements for each piece of the WHO bioassay kit. Replacement parts are functionally identical to and interchangeable with original WHO bioassay parts. We note no significant difference in mortality results obtained from PLA printed tubes and WHO acrylic tubes. Additionally, we observed no degradation of PLA in response to prolonged exposure times of commonly used cleaning solutions.

Conclusions

Our designs can be used to produce replacement parts for the WHO bioassay kit in any facility with a 3D printer, which are becoming increasingly widespread. 3D printing technologies can affordably and rapidly address equipment shortages and be used to develop bespoke equipment in laboratories.
Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension
Authors: Zhu Na , Pauciulo Michael W. , Welch Carrie L. , Lutz Katie A. , Coleman Anna W. , Gonzaga-Jauregui Claudia , Wang Jiayao , Grimes Joseph M. , Martin Lisa J. , He Hua ,   PAH Biobank Enrolling Centers’ Investigators, Hirsch Russel , White R. James , Simon Marc , Badesch David , Rosenzweig Erika , Burger Charles , Chakinala Murali , Thenappan Thenappan , Elliott Greg , Simms Robert , Farber Harrison , Frantz Robert , Elwing Jean , Hill Nicholas , Ivy Dunbar , Klinger James , Nathan Steven , Oudiz Ronald , Robbins Ivan , Schilz Robert , Fortin Terry , Wilt Jeffrey , Yung Delphine , Austin Eric , Ahmad Ferhaan , Bhatt Nitin , Lahm Tim , Frost Adaani , Safdar Zeenat , Rehman Zia , Walter Robert , Torres Fernando , Bakshi Sahil , Archer Stephen , Argula Rahul , Barnett Christopher , Benza Raymond , Desai Ankit , Maddipati Veeranna , Shen Yufeng , Chung Wendy K. , Nichols William C.
Published: November 2019

Background

Group 1 pulmonary arterial hypertension (PAH) is a rare disease with high mortality despite recent therapeutic advances. Pathogenic remodeling of pulmonary arterioles leads to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. Mutations in bone morphogenetic protein receptor type 2 and other risk genes predispose to disease, but the vast majority of non-familial cases remain genetically undefined.

Methods

To identify new risk genes, we performed exome sequencing in a large cohort from the National Biological Sample and Data Repository for PAH (PAH Biobank,n = 2572). We then carried out rare deleterious variant identification followed by case-control gene-based association analyses. To control for population structure, only unrelated European cases (n = 1832) and controls (n = 12,771) were used in association tests. Empiricalpvalues were determined by permutation analyses, and the threshold for significance defined by Bonferroni’s correction for multiple testing.

Results

Tissue kallikrein 1 (KLK1) and gamma glutamyl carboxylase (GGCX) were identified as new candidate risk genes for idiopathic PAH (IPAH) with genome-wide significance. We note that variant carriers had later mean age of onset and relatively moderate disease phenotypes compared to bone morphogenetic receptor type 2 variant carriers. We also confirmed the genome-wide association of recently reported growth differentiation factor (GDF2) with IPAH and further implicate T-box 4 (TBX4) with child-onset PAH.

Conclusions

We report robust association of novel genesKLK1andGGCXwith IPAH, accounting for ~ 0.4% and 0.9% of PAH Biobank cases, respectively. Both genes play important roles in vascular hemodynamics and inflammation but have not been implicated in PAH previously. These data suggest new genes, pathogenic mechanisms, and therapeutic targets for this lethal vasculopathy.
Developing a high-performance liquid chromatography fast and accurate method for quantification of silibinin
Authors: Bakhshi Faezeh , Molavi Ommoleila , Rashidi Mohammad Reza , Shayanfar Ali , Amini Hassan
Published: November 2019

Objective

Silibinin is an antioxidant agent and is shown to have anticancer effects in different cancers including lung, breast, colorectal, liver, prostate, and kidney. There are challenges in the clinical use of silibinin. The main limitation is low solubility, poor oral absorption, and extensive hepatic metabolism. We aim to develop a High-Performance Liquid Chromatography (HPLC) sensitive method for quantification of silibinin in aqueous samples to quantify its concentration in new formulations. A reverse-phase high-performance liquid chromatography (RP-HPLC) composed of C18 column as stationary phase and the mixture of methanol (90%) and water (10%) as mobile phase. The developed method was validated based on the established guidelines.

Results

The retention time for silibinin was seen in 2.97 min after injection. The calibration curve was drawn and the established method demonstrated a linear ranged from 10 to 100 µg/ml, with a correlation coefficient of 0.996. The sensitivity of the developed method was 10 µg/ml. The accuracy calculated in the range of 88–105.9% and the precision (as relative standard deviation) was between 2.7 and 10.9%. These results demonstrate that the developed method can be a fast and accurate method for quantification of silibinin in aqueous samples.
New delay-dependent observer-based control for uncertain stochastic time-delay systems
Authors: Miao Xiu-feng , Li Long-suo
Published: November 2019

This paper considers the problem of estimating the state vector of uncertain stochastic time-delay systems, while the system states are unmeasured. The system under study involves parameter uncertainties, noise disturbances and time delay, and they are dependent on the state. Based on the Lyapunov–Krasovskii functional approach, we present a delay-dependent condition for the existence of a state observer in terms of a linear matrix inequality. A numerical example is exploited to show the validity of the results obtained.
Spectral analysis of the matrix Sturm–Liouville operator
Authors: Bondarenko Natalia P.
Published: November 2019

The self-adjoint matrix Sturm–Liouville operator on a finite interval with a boundary condition in general form is studied. We obtain asymptotic formulas for the eigenvalues and the weight matrices of the considered operator. These spectral characteristics play an important role in the inverse spectral theory. Our technique is based on an analysis of analytic functions and on the contour integration in the complex plane of the spectral parameter. In addition, we adapt the obtained asymptotic formulas to the Sturm–Liouville operators on a star-shaped graph with two different types of matching conditions.
Positive solutions of beam equations under nonlocal boundary value conditions
Authors: Wang Shenglin , Chai Jialong , Zhang Guowei
Published: November 2019

In this article, we study the fourth-order problem with the first and second derivatives in nonlinearity under nonlocal boundary value conditions
$$\begin{aligned}& \left \{ \textstyle\begin{array}{l}u^{(4)}(t)=h(t)f(t,u(t),u'(t),u''(t)),\quad t\in(0,1),\\ u(0)=u(1)=\beta_{1}[u],\qquad u''(0)+\beta_{2}[u]=0,\qquad u''(1)+\beta_{3}[u]=0, \end{array}\displaystyle \right . \end{aligned}$$ {u(4)(t)=h(t)f(t,u(t),u′(t),u″(t)),t∈(0,1),u(0)=u(1)=β1[u],u″(0)+β2[u]=0,u″(1)+β3[u]=0, where $f: [0,1]\times\mathbb{R}_{+}\times\mathbb{R}\times\mathbb{R}_{-}\to \mathbb{R}_{+}$f:[0,1]×R+×R×R−→R+ is continuous, $h\in L^{1}(0,1)$h∈L1(0,1) and $\beta_{i}[u]$βi[u] is Stieltjes integral ($i=1,2,3$i=1,2,3). This equation describes the deflection of an elastic beam. Some inequality conditions on nonlinearity f are presented that guarantee the existence of positive solutions to the problem by the theory of fixed point index on a special cone in $C^{2}[0,1]$C2[0,1]. Two examples are provided to support the main results under mixed boundary conditions involving multi-point with sign-changing coefficients and integral with sign-changing kernel.
Investigation of the trends of electricity demands in Jordan and its susceptibility to the ambient air temperature towards sustainable electricity generation
Authors: Almuhtady Ahmad , Alshwawra Ahmad , Alfaouri Marwa , Al-Kouz Wael , Al-Hinti Ismael
Published: November 2019

Background

Efficient production and reliable availability of electricity requires comprehensive understanding of load demand trends to plan and match production with consumption. Although electricity demand depends on a combination of cultural and economic conditions, weather conditions remain as the major driver. With increased capabilities of accurate predictions of weather, the importance of investigating and quantifying its impact on electricity demand becomes obvious. The electrical system in Jordan has been facing several challenges including the failure to respond to increased demands induced by extreme temperatures. This paper covers a clear gap in literature through presenting a detailed investigation of the electricity consumption trends and in identifying the susceptibility of these trends to weather.

Methods

This study relies on the statistical processing and analysis, through modeling of hourly electricity demands in Jordan in the period of 10 years between 2007 and 2016. Actual weather data was used employing the degree-day approach. The monthly, daily, and hourly seasonal variation indices were determined. Optimally formulated piecewise functions were used to track the thermal comfort zone and rate of increase in electricity demand for temperatures beyond it for each year. Moreover, the elasticity of polynomial functions was adopted to identify saturation points to thermally map the electricity consumption.

Results

The developed models successfully described the relationship between the daily electricity demand and the mean daily ambient temperature. The average comfort zone width was 4 °C and the average mean base temperature was 17.9 °C. The sensitivity of electricity demand to both high and low temperatures has increased on average, with 11% and 16.4% to hot and cold weather, respectively. Finally, the electricity demand in cooling was found to saturate at 32.9 °C, whereas it saturates for heating at 4.7 °C.

Conclusions

The electricity demand in Jordan observes seasonal trends in a consistent and predictable manner. An optimally formulated piecewise function successfully tracked the thermal comfort zone and the rate of increase in electricity demand for temperatures beyond it for each year of the study period. Finally, saturation heating and cooling temperatures were acquired from the elasticity of the daily electricity demands modeled against daily HDD and CDD.
Production, characterization, and cross-reactivity of a polyclonal antibody against Arabidopsis TARGET OF RAPAMYCIN
Authors: Shin Gyeong-Im , Moon Sun Young , Jeong Song Yi , Ji Myung Geun , Cha Joon-Yung , Kim Woe-Yeon
Published: November 2019

TARGET OF RAPAMYCIN (TOR), a member of the phosphatidylinositol 3-kinase-related family of protein kinases, is encoded by a single, large gene and is evolutionarily conserved in all eukaryotes. TOR plays a role as a master regulator that integrates nutrient, energy, and stress signaling to orchestrate development. TOR was first identified in yeast mutant screens, as its mutants conferred resistance to rapamycin, an antibiotic with immunosuppressive and anticancer activities. In Arabidopsis thaliana, the loss-of-function tor mutant displays embryo lethality, but the precise mechanisms of TOR function are still unknown. Moreover, a lack of reliable molecular and biochemical assay tools limits our ability to explore TOR functions in plants. Here, we produced a polyclonal α-TOR antibody using two truncated variants of TOR (1–200 and 1113–1304 amino acids) as antigens because recombinant full-length TOR is challenging to express in Escherichia coli. Recombinant His-TOR1−200 and His-TOR1113−1304 proteins were individually expressed in E. coli, and a mixture of proteins (at a 1:1 ratio) was used for immunizing rabbits. Antiserum was purified by an antigen-specific purification method, and the purified polyclonal α-TOR antibody successfully detected endogenous TOR proteins in wild-type Arabidopsis and TOR orthologous in major crop plants, including tomato, maize, and alfalfa. Moreover, our α-TOR antibody is useful for coimmunoprecipitation assays. In summary, we generated a polyclonal α-TOR antibody that detects endogenous TOR in various plant species. Our antibody could be used in future studies to determine the precise molecular mechanisms of TOR, which has largely unknown multifunctional roles in plants.
Analysis of households’ vulnerability to food insecurity and its influencing factors in East Hararghe, Ethiopia
Authors: Sileshi Million , Kadigi Reuben , Mutabazi Khamaldin , Sieber Stefan
Published: November 2019

Previous studies on food insecurity in many developing countries, including Ethiopia, have mainly focused on current food insecurity, lacking theex-anteanalysis. An understanding of household vulnerability to food insecurity is critically important to inform the formulation of policies and strategies to enhance food security and reduce vulnerability to food insecurity among smallholder farmers. This paper analyses vulnerability to food insecurity of farming households using the vulnerability as expected poverty (VEP) approach. The paper is based on cross-section data collected from a sample of 408 households in East Hararghe, Ethiopia, selected using a multi-stage sampling procedure. The factors which influenced vulnerability to food insecurity were analyzed using the Feasible General Least Squares regression model. The results of analysis indicate that vulnerability to food insecurity increased with the age of household head (P < 0.1), and family size (P < 0.01). It decreased with access to improved seeds (P < 0.01), adoption of soil and water conservation (P < 0.01), size of cultivated land (P < 0.1), and access to credits (P < 0.1). Based on the intensity of their vulnerability, households were grouped as chronic food insecure (24.27%), transient food insecure (11.77%), highly vulnerable-food secure (18.38%), and low vulnerable-food secure (45.59%). Overall, about 54% of households were categorized as vulnerable to food insecurity. These included households who were food insecure at the time of the survey (36.02%) and those who were categorized as transient food secure group (18.38%). These findings imply that food insecurity policies and interventions in developing countries should focus not only on households that are currently food insecure, but also on those categorized as transient food insecure or households that are more likely to be food insecure in the near future.