bluuebunny/crossref_metadata_2025 huggingface dataset:
Immobilized pH in culture reveals an optimal condition for somatic cell reprogramming and differentiation of pluripotent stem cells
Authors: Kim Narae , Minami Naojiro , Yamada Masayasu , Imai Hiroshi
Published: January 2017

Aim

One of the parameters that greatly affects homeostasis in the body is the pH. Regarding reproductive biology, germ cells, such as oocytes or sperm, are exposed to severe changes in pH, resulting in dramatic changes in their characteristics. To date, the effect of the pH has not been investigated regarding the reprogramming of somatic cells and the maintenance and differentiation of pluripotent stem cells.

Methods

In order to investigate the effects of the pH on cell culture, the methods to produce induced pluripotent stem cells (iPSCs) and to differentiate embryonic stem cells (ESCs) into mesendoderm and neuroectoderm were performed at each medium pH from 6.6 to 7.8. Using the cells of the Oct4‐GFP (green fluorescent protein) carrying mouse, the effects of pH changes were examined on the timing and colony formation at cell reprogramming and on the cell morphology and direction of the differentiation of the ESCs.

Results

The colony formation rate and timing of the reprogramming of the somatic cells varied depending on the pH of the culture medium. In addition, mesendodermal differentiation of the mouse ESCs was enhanced at the high pH level of 7.8.

Conclusion

These results suggest that the pH in the culture medium is one of the key factors in the induction of the reprogramming of somatic cells and in the differentiation of pluripotent stem cells.
Polycystic ovary syndrome: early diagnosis and intervention are necessary for fertility preservation in young women with endometrial cancer under 35 years of age
Authors: Okamura Yoshinori , Saito Fumitaka , Takaishi Kiyomi , Motohara Takeshi , Honda Ritsuo , Ohba Takashi , Katabuchi Hidetaka
Published: January 2017

Aim

Polycystic ovary syndrome (PCOS) is a significant risk factor for premenopausal endometrial cancer (EC) and/or atypical endometrial hyperplasia (AEH). The aim was to elucidate the clinical background and detailed menstrual history of EC and/or AEH in young women with PCOS.

Methods

From January 2001 to December 2013, women under 35 years of age who had been diagnosed with EC and/or AEH and who had been treated at Kumamoto University Hospital, Japan, were recruited. The patients’ clinical characteristics, clinical stages of EC and/or AEH, medication and operation methods, endocrine profiles, and menstrual history were assessed retrospectively.

Results

Of all the cases of EC and/or AEH, 25 (4.6%) were under 35 years of age. The mean age was 29.0 years and all the patients were nulligravida. The clinical stages of EC and/or AEH that were identified included: AEH (five cases), stage IA (18 cases), IB (one case), and IIIA (one case). Fourteen (56%) cases met the criteria for PCOS. Both the Body Mass Index and Homeostatic Model Assessment–insulin resistance were significantly higher in the patients with PCOS than in the patients without PCOS. Medroxyprogesterone acetate therapy was not effective for the patients with PCOS and they underwent a hysterectomy more often than the patients without PCOS. All the patients with PCOS exhibited irregular menstruation or amenorrhea, the mean duration of which was 13.1 years before PCOS and EC and/or AEH were diagnosed.

Conclusion

Although both the patients with and without PCOS had irregular menstruation, the patients with PCOS were less likely to have fertility‐sparing surgery than the patients without PCOS because they had more advanced disease or failed to respond to medroxyprogesterone acetate therapy.
Range of Movement for Impingement and Dislocation Avoidance in Total Hip Replacement Predicted by Finite Element Model
Authors: Ezquerra Laura , Quilez María Paz , Pérez María Ángeles , Albareda Jorge , Seral Belén
Published: January 2017

Dislocation is a serious complication in total hip replacement (THR). An inadequate range of movement (ROM) can lead to impingement of the prosthesis neck on the acetabular cup; furthermore, the initiation of subluxation and dislocation may occur. The objective of this study was to generate a parametric three-dimensional finite element (FE) model capable of predicting the dislocation stability for various positions of the prosthetic head, neck, and cup under various activities. Three femoral head sizes (28, 32, and 36 mm) were simulated. Nine acetabular placement positions (abduction angles of 25°, 40° and 60° combined with anteversion angles of 0°, 15° and 25°) were analyzed. The ROM and maximum resisting moment (RM) until dislocation were evaluated based on the stress distribution in the acetabulum component. The analysis allowed for the definition of a “safe zone” of movement for impingement and dislocation avoidance in THR: an abduction angle of 40°–60° and anteversion angle of 15°–25°. It is especially critical that the anteversion angle does not fall to 10°–15°. The sequence of the RM is a valid parameter for describing dislocation stability in FE studies.
Peripheral inflammatory markers indicate microstructural damage within periventricular white matter hyperintensities in Alzheimer's disease: A preliminary report
Authors: Swardfager Walter , Yu Di , Ramirez Joel , Cogo‐Moreira Hugo , Szilagyi Gregory , Holmes Melissa F. , Scott Christopher J.M. , Scola Gustavo , Chan Pak C. , Chen Jialun , Chan Parco , Sahlas Demetrios J. , Herrmann Nathan , Lanctôt Krista L. , Andreazza Ana C. , Pettersen Jacqueline A. , Black Sandra E.
Published: January 2017

Introduction

White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear.

Methods

Inflammatory markers were assayed in 54 elderly participants (n = 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid‐attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging.

Results

Mean FA within periventricular WMH was associated with an inflammatory factor consisting of interleukin (IL)‐1β, tumor necrosis factor, IL‐10, IL‐21, and IL‐23 in patients with AD (ρ = −0.703, P = .002) but not in healthy elderly (ρ = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425, P = .008) but not in patients with AD (ρ = 0.174, P = .520).

Discussion

Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.
Sleep‐wake cycle disturbances in elderly acute general medical inpatients: Longitudinal relationship to delirium and dementia
Authors: FitzGerald James M. , O'Regan Niamh , Adamis Dimitrios , Timmons Suzanne , Dunne Colum P. , Trzepacz Paula T. , Meagher David J.
Published: January 2017

Introduction

Sleep disturbances in elderly medical inpatients are common, but their relationship to delirium and dementia has not been studied.

Methods

Sleep and delirium status were assessed daily for a week in 145 consecutive newly admitted elderly acute general hospital patients using the Delirium Rating Scale‐Revised‐98 (DRS‐R98), Diagnostic and Statistical Manual 5, and Richards‐Campbell Sleep Quality Scale measures. The longitudinal relationship between DRS‐R98 and Richards‐Campbell Sleep Quality Scale sleep scores and delirium, also with dementia as a covariate, was evaluated using generalized estimating equation logistic regression.

Results

The cohort was divided into delirium only, dementia only, comorbid delirium‐dementia, and no‐delirium/no‐dementia subgroups. Mean age of total group was 80 ± 6.3, 48% were female, and 31 (21%) had dementia, 29 had delirium at admission (20%), and 27 (18.5%) experienced incident delirium. Mild sleep disturbance (DRS‐R98 sleep item score ≥1) occurred for at least 1 day in all groups, whereas moderate sleep disturbance (score ≥2) occurred in significantly more of the prevalent delirium‐only (81%; n = 17) cases than incident delirium‐only (46%; n = 13) cases (P < .001). There were more cases with DRS‐R98 sleep item scores ≥2 (P < .001) in the delirium‐only group compared with the other subgroups. Severity of sleep‐wake cycle disturbance over time was significantly associated with Diagnostic and Statistical Manual 5 delirium status but not with age, sex, or dementia (P < .001).

Conclusions

Observer‐rated more severe sleep‐wake cycle disturbances are highly associated with delirium irrespective of dementia status, consistent with being a core feature of delirium. Monitoring for altered sleep‐wake cycle patterns may be a simple way to improve delirium detection.
Reduced relative volume in motor and attention regions in developmental coordination disorder: A voxel‐based morphometry study
Authors: Reynolds Jess E. , Licari Melissa K. , Reid Siobhan L. , Elliott Catherine , Winsor Anne M. , Bynevelt Michael , Billington Jac
Published: January 2017

Background and objectives

Developmental coordination disorder (DCD) is a prevalent childhood movement disorder, impacting the ability to perform movement skills at an age appropriate level. Although differences in grey matter (GM) volumes have been found in related developmental disorders, no such evidence has been linked with DCD to date. This cross‐sectional study assessed structural brain differences in children with and without DCD.

Methods

High‐resolution structural images were acquired from 44 children aged 7.8–12 years, including 22 children with DCD (≤16th percentile on MABC‐2; no ADHD/ASD), and 22 typically developing controls (≥20th percentile on MABC‐2). Structural voxel‐based morphology analysis was performed to determine group differences in focal GM volumes.

Results

Children with DCD were found to have significant, large, right lateralised reductions in grey matter volume in the medial and middle frontal, and superior frontal gyri compared to controls. The addition of motor proficiency as a covariate explained the between‐group GM volume differences, suggesting that GM volumes in motor regions are reflective of the level of motor proficiency. A positive correlation between motor proficiency and relative GM volume was also identified in the left posterior cingulate and precuneus.

Conclusions

GM volume reductions in premotor frontal regions may underlie the motor difficulties characteristic of DCD. It is possible that intervention approaches targeting motor planning, attention, and executive functioning processes associated with the regions of reduced GM volume may result in functional improvements in children with DCD.
Paediatric First-Time Patella Dislocators: An Approach to Conservative Management
Authors: Yet Lam Kai , Collin Looi , Arjandas Mahadev
Published: January 2017

Background

First-time lateral patella dislocations are generally treated nonoperatively. However, the ideal form of conservative management and immobilization remains unknown. We compare the clinical outcomes after different immobilization methods.

Methods

Paediatric-age patients that met our inclusion criteria, and presenting with a first episode of lateral patella dislocation to our hospital from 2006 to 2013, were enrolled. Different immobilization methods included brace, backslab, or cylinder cast. A retrospective review was performed to compare bracing against other immobilization methods, using a primary outcome measure of redislocation rate, and secondary outcome measures like progression to surgery, range-of-motion, pain, and weight-bearing status.

Results

A total of 142 patients (with 147 affected knees) with minimum 1 -year follow-up were included in the study. Bracing was found to be superior to other immobilization methods in preventing repeat dislocations, and need for subsequent surgery. At 6 weeks, patients treated with the backslab had the highest incidence of pain. There were no differences with regards to range-of-motion or weight-bearing status.

Conclusion

We recommend the use of a brace, with a progressive rehabilitation protocol in the management of first-time lateral patella dislocators. This study is also unique, in that it specifically addresses nonoperative management of first time patella dislocators in a paediatric-age population group.
Thirty years of endoscopic sinus surgery: What have we learned?
Authors: Tajudeen Bobby A. , Kennedy David W.
Published: January 2017

Prior to adaptation of endoscopic approaches for sinonasal pathology, patients regularly endured significant morbidity from open approaches to the sinonasal cavity that were often fraught with failure. With improvements in transnasal endoscopy, functional endoscopic sinus surgery subsequently emerged from the work of Messerklinger and other pioneers in the field. The popularity of endoscopic sinus surgery quickly escalated and expanded to pathology other than inflammation. Here, we discuss the evolution of endoscopic sinus surgery as it relates to improvements in understanding disease pathogenesis, improvements in instrumentation and expansion of indications.
Myeloid‐derived suppressor cells can be efficiently generated from human hematopoietic progenitors and peripheral blood monocytes
Authors: Casacuberta‐Serra Sílvia , Parés Marta , Golbano Arantxa , Coves Elisabet , Espejo Carmen , Barquinero Jordi
Published: January 2017

Myeloid‐derived suppressor cells (MDSCs) have an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex vivo‐generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34+ hematopoietic progenitors from apheresis products and CD14+ cells isolated from buffy coats were cultured in the presence of different combinations of cytokines. The resulting myeloid cell populations were then characterized phenotypically and functionally. Progenitor cells cultured in the presence of SCF+TPO+FLT3‐L+GM‐CSF+IL‐6 gave rise to both monocytic (M)‐ and granulocytic (G)‐MDSCs but production of the latter was partially inhibited by IL‐3. M‐MDSCs but not G‐MDSCs were obtained by culturing peripheral blood monocytes with GM‐CSF+IL‐6 or GM‐CSF+TGF‐β1 for 6 days. CD14 expression was downregulated in the cultured cells. PD‐L1 expression at baseline was lower in hematopoietic progenitor cell‐derived than in monocyte‐derived MDSCs, but was markedly increased in response to stimulation with LPS+IFN‐γ. The functionality of the two MDSC subtypes was confirmed in studies of the suppression of allogeneic and mitogen‐induced proliferation and by cytokine profiling. Here we describe both the culture conditions that allow the generation of MDSCs and the phenotypical and functional characterization of these cell populations.
Quantitative bioimaging of Ca, Fe, Cu and Zn in breast cancer tissues by LA-ICP-MS
Authors: González de Vega Raquel , Fernández-Sánchez María Luisa , Pisonero Jorge , Eiró Noemí , Vizoso Francisco J. , Sanz-Medel Alfredo
Published: January 2017

LA-ICP-MS has been used for the first time to study the simultaneous elemental quantitative distribution of Ca, Fe, Cu and Zn in breast cancer samples.
Synthesis of a nano-sized hybrid C3N4/TiO2 sample for enhanced and steady solar energy absorption and utilization
Authors: Yan Junqing , Li Ping , Bian Hui , Wu Huan , Liu Shengzhong (Frank)
Published: January 2017

A sub-15 nm C3N4/TiO2 heterojunction is reported for the steady and constant photocatalytic hydrogen evolution under weak and strong incident light conditions.
Effects of miR-338 on morphine tolerance by targeting CXCR4 in a rat model of bone cancer pain
Authors: Mei Hong-Xia , Zhou Min-Hong , Zhang Xing-Wang , Huang Xi-Xi , Wang Yong-Le , Wang Pei-Fang , Zhan Gong-Hao
Published: January 2017

The present study aimed to investigate the effects of miR-338 on morphine tolerance through the targeting of CXC chemokine receptor-4 (CXCR4) in a rat model of bone cancer pain (BCP). Sprague–Dawley (SD) rats were obtained and divided into model saline (n=10), model morphine (n=50), normal saline (n=10) and normal morphine (healthy rats, n=10) groups. After BCP rat model establishment, the remaining SD rats (n=40) in the model saline group were assigned into pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA, blank and PBS groups. Luciferase reporter gene assay was used for luciferase activity. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect the miR-338 and CXCR4 mRNA and protein expression. The model saline group showed increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group, and the model morphine group had increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group. The mRNA and protein expressions of miR-338 in the pLV-THM-miR-338 group increased remarkably while those of the pLV-THM-anti-miR-338 group decreased significantly compared with the CXCR4 shRNA, blank and PBS groups. The pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA and CXCR4 mRNA groups all had lower mRNA and protein expressions of CXCR4 than those in the blank and PBS groups. miR-338 exerts significant influence in the inhibition of morphine tolerance by suppressing CXCR4 in BCP.
Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells
Authors: Cui Xiaobo , Song Laixiao , Bai Yunfei , Wang Yaping , Wang Boqian , Wang Wei
Published: January 2017

Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival.
Plasma miR-21 expression: an indicator for the severity of Type 2 diabetes with diabetic retinopathy
Authors: Jiang Qi , Lyu Xue-Man , Yuan Yi , Wang Ling
Published: January 2017

To investigate the roles of plasma miR-21 in the pathogenic process of Type 2 diabetes (T2D) with diabetic retinopathy (DR). T2D patients included patients without DR (NDR) group, patients with non-proliferative/background DR (BDR) group and patients with proliferative DR (PDR) group. Healthy individuals served as control group. Fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), triacylglycerol (TG), total cholesterol (TC), urine creatinine (Cr), fasting blood glucose (FBG), blood urea nitrogen (BUN), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS) and plasma miR-21 expression were measured. Quantitative real-time PCR (qRT-PCR) was applied to detect miR-21 expression. Pearson analysis was used to conduct correlation analysis and receiver operating characteristic (ROC) curve was used to analyse the diagnostic value of miR-21 in T2D with DR. Compared with the control group, FBG and HbA1c increased in the NDR group; compared with the control and NDR groups, disease course, HbA1c, FPG levels and homoeostasis model assessment of insulin resistance (HOMA-IR) were increased in the BDR and PDR groups; and compared with the BDR group, disease course, HbA1c and FPG levels were higher in the PDR group. miR-21 expression was higher in the BDR group than the control group, and higher in the PDR group than the BDR group. miR-21 expression was positively related with disease course, HbA1C, FPG and HOMA-IR, and had diagnostic value for T2D with DR and PDR. The plasma miR-21 expression was increased in the development of T2D with DR and can be used as an indicator for the severity of T2D with DR.
Paired assessment of liver telomere lengths in hepatocellular cancer is a reliable predictor of disease persistence
Authors: Feng Wendu , Yu Decai , Li Binghua , Luo Ou-yang , Xu Tiancheng , Cao Yajuan , Ding Yitao
Published: January 2017

In the present study, we used a small series of highly defined patients, where we had matched timed peripheral blood samples (PBS), as well as paired liver biopsies obtained during collection of blood samples from patients with diagnosed hepatocellular carcinoma (HCC) and compared the correlation between the changes of telomere lengths in these defined samples. Patients included had either HCC alone or in conjunction with either pre-existing hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. PCR-based assay incorporating primers to the telomeric hexamer repeats to polymerize and detect telomeric DNA was used. The average telomere length for each independent assessment was measured by seeing the differences in the intensity of the sample’s telomere signal (T) to the signal from a single-copy gene (S-, β-globin) to estimate the standard ratio. Our results provide the first convincing evidence that PBS may be utilized to assay telomere shortening as a predictor for disease persistence in HCC resulting after HBV or HCV infection, but not in non-infectious cause-stimulated HCC. These findings provide incipient opportunity to develop telomere length assessment as a biomarker tool for prediction of HCC in patients with HBV or HCV infection, as well as to gauge responses to chemotherapy and other treatment modalities.
Surgical Repair of Moderate Ischemic Mitral Regurgitation—A Systematic Review and Meta-analysis
Authors: Aggarwal Saurabh , Reddy Yogesh , Alla Venkata , Baskaran Janani , Kanmanthareddy Arun , Suri Rakesh , Anantha Narayanan Mahesh
Published: January 2017

Introduction Moderate mitral regurgitation (MR) of ischemic etiology has been associated with worse outcomes after coronary artery bypass grafting (CABG). Studies comparing concomitant mitral valve replacement/repair (MVR/Re) with CABG and standalone CABG have reported conflicting results. We performed a systematic review and meta-analysis of the published literature.

Patients and Methods We searched using PubMed, Cochrane, EMBASE, CINAHL, and Google scholar databases from January 1960 to June 2016 for clinical trials comparing CABG to CABG + MVR/Re for moderate MR. Pooled risk ratio or mean difference (MD) with 95% confidence intervals (CI) for individual outcomes were calculated using random effects model and heterogeneity was assessed using Cochrane's Q-statistic.

Results A total of 11 studies were included. Mean follow-up was 35.3 months. All-cause mortality (Mantel–Haenszel [MH] risk ratio [RR]: 0.96, 95% CI: 0.75–1.24, p = 0.775), early mortality (MH RR: 0.65, 95% CI: 0.39–1.07, p = 0.092), and stroke rates (MH RR 0.65, 95% CI: 0.21–2.03, p = 0.464) were similar between CABG and CABG + MVR/Re groups. Adverse event at follow-up was lower with CABG (MH RR: 0.90, 95% CI: 0.61–1.32, p = 0.584). MD of change from baseline in left ventricular (LV) end-systolic dimension (MD: − 2.50, 95% CI: − 5.21 to − 0.21, p = 0.071) and LV ejection fraction (MD: 0.48, 95% CI: − 2.48 to 3.44, p = 0.750) were not significantly different between the groups. Incidence of moderate MR (MH RR: 3.24, 95% CI: 1.79–5.89, p < 0.001) was higher in the CABG only group.

Conclusion Addition of MVR/Re to CABG in patients with moderate ischemic MR did not result in improvement in early or overall mortality, stroke risk, or intermediate markers of LV function when compared with CABG alone.
Dynamical theory of shear bands in structural glasses
Authors: Wisitsorasak Apiwat , Wolynes Peter G.
Published: January 2017

Significance

When glasses are under imposed stresses or strains, they are subject to plastic deformation. Unlike their crystal counterparts, shear within the glasses localizes in thin bands, known as shear bands. Forming the shear bands can lead to structural failure of the whole sample and prevent using glasses as structural materials. In this work, we show how shear bands arise dynamically by the coupling of activated dynamics of configurationally rearranging regions with elastic strain transport. This result also explains the non-Newtonian flow of glasses.
Large anomalous features in the microstructure of chromium carbide weld overlays
Authors: Barnes Nairn , Borle Steven , Mendez Patricio F.
Published: January 2017

This paper discusses the existence of large ( [Formula: see text] ) anomalous features observed in the microstructure of chromium carbide weld overlays. Microhardness testing (Vickers), Auger electron spectroscopy, electron backscatter diffraction, and energy dispersive x-ray spectroscopy were employed to identify the origin, composition, and phase of the large anomalous features. Analysis of the results revealed the large anomalous features are unmelted powder granules with a different composition of the orthorhombic M7C3 phase of the primary carbides.
Back to the roots of regulated necrosis
Authors: Todorov Vladimir , Linkermann Andreas
Published: January 2017

In recent years, our knowledge of how cells die by regulated pathways of necrosis has increased tremendously. In this issue, Distéfano et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201605110) provide yet another milestone in our understanding of regulated necrosis as they identify a ferroptosis-like cell death in Arabidopsis thaliana.
miRmine: a database of human miRNA expression profiles
Authors: Panwar Bharat , Omenn Gilbert S , Guan Yuanfang
Published: January 2017

Motivation

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in post-transcriptional regulation of gene expression. In this high-throughput sequencing era, a tremendous amount of RNA-seq data is accumulating, and full utilization of publicly available miRNA data is an important challenge. These data are useful to determine expression values for each miRNA, but quantification pipelines are in a primitive stage and still evolving; there are many factors that affect expression values significantly.

Results

We used 304 high-quality microRNA sequencing (miRNA-seq) datasets from NCBI-SRA and calculated expression profiles for different tissues and cell-lines. In each miRNA-seq dataset, we found an average of more than 500 miRNAs with higher than 5x coverage, and we explored the top five highly expressed miRNAs in each tissue and cell-line. This user-friendly miRmine database has options to retrieve expression profiles of single or multiple miRNAs for a specific tissue or cell-line, either normal or with disease information. Results can be displayed in multiple interactive, graphical and downloadable formats.

Availability and Implementation

http://guanlab.ccmb.med.umich.edu/mirmine

Supplementary information

Supplementary data are available at Bioinformatics online.
aRNApipe: a balanced, efficient and distributed pipeline for processing RNA-seq data in high-performance computing environments
Authors: Alonso Arnald , Lasseigne Brittany N , Williams Kelly , Nielsen Josh , Ramaker Ryne C , Hardigan Andrew A , Johnston Bobbi , Roberts Brian S , Cooper Sara J , Marsal Sara , Myers Richard M
Published: January 2017

The wide range of RNA-seq applications and their high-computational needs require the development of pipelines orchestrating the entire workflow and optimizing usage of available computational resources. We present aRNApipe, a project-oriented pipeline for processing of RNA-seq data in high-performance cluster environments. aRNApipe is highly modular and can be easily migrated to any high-performance computing (HPC) environment. The current applications included in aRNApipe combine the essential RNA-seq primary analyses, including quality control metrics, transcript alignment, count generation, transcript fusion identification, alternative splicing and sequence variant calling. aRNApipe is project-oriented and dynamic so users can easily update analyses to include or exclude samples or enable additional processing modules. Workflow parameters are easily set using a single configuration file that provides centralized tracking of all analytical processes. Finally, aRNApipe incorporates interactive web reports for sample tracking and a tool for managing the genome assemblies available to perform an analysis.

Availability and documentation

https://github.com/HudsonAlpha/aRNAPipe; DOI: 10.5281/zenodo.202950

Supplementary information

Supplementary data are available at Bioinformatics online.
Quantification of fibrous spatial point patterns from single-molecule localization microscopy (SMLM) data
Authors: Peters Ruby , Benthem Muñiz Marta , Griffié Juliette , Williamson David J , Ashdown George W , Lorenz Christian D , Owen Dylan M
Published: January 2017

Motivation

Unlike conventional microscopy which produces pixelated images, SMLM produces data in the form of a list of localization coordinates—a spatial point pattern (SPP). Often, such SPPs are analyzed using cluster analysis algorithms to quantify molecular clustering within, for example, the plasma membrane. While SMLM cluster analysis is now well developed, techniques for analyzing fibrous structures remain poorly explored.

Results

Here, we demonstrate a statistical methodology, based on Ripley’s K-function to quantitatively assess fibrous structures in 2D SMLM datasets. Using simulated data, we present the underlying theory to describe fiber spatial arrangements and show how these descriptions can be quantitatively derived from pointillist datasets. We also demonstrate the techniques on experimental data acquired using the image reconstruction by integrating exchangeable single-molecule localization (IRIS) approach to SMLM, in the context of the fibrous actin meshwork at the T cell immunological synapse, whose structure has been shown to be important for T cell activation.

Availability and Implementation

Freely available on the web at https://github.com/RubyPeters/Angular-Ripleys-K. Implemented in MatLab.

Supplementary information

Supplementary data are available at Bioinformatics online.
Incorporating technology to advance asthma controller adherence
Authors: Anderson William C.
Published: January 2017

Purpose of review

Technological innovations, including text messaging, smart phone applications, and electronic monitoring devices, aimed at improving asthma controller adherence are being rapidly introduced both into clinical care and directly marketed to patients. This review analyzes recent clinical trials implementing these interventions, with a focus on their benefits and shortcomings.

Recent findings

Poor medication adherence continues to exert significant morbidity on patients with asthma. Objective, real-time measures to monitor adherence can overcome the limitations of prior methods, including self-report and prescription refills. Technological advances, especially those incorporating reminder systems, have demonstrated improved controller adherence. The increased adherence in these trials has not translated into consistent clinical improvement, including reducing hospitalizations, emergency department visits, and asthma exacerbations, possibly secondary to study design and poor inhalation technique.

Novel monitoring and reminder technology can augment patient medication adherence and provide clues to management before escalating therapy. Further studies are needed to investigate the overarching clinical impact of this technology, especially as it grows into routine clinical practice.
Management of preschool recurrent wheezing and asthma: a phenotype-based approach
Authors: Beigelman Avraham , Bacharier Leonard B.
Published: January 2017

Purpose of review

The purpose of this review is to summarize the recent evidence on the management of preschool children with wheezing and asthma, and to propose a phenotype-based approach to the management of these children.

Recent findings

Recent studies have begun to identify populations of preschool children that are likely to benefit from inhaled corticosteroids (ICS) therapy and defined ICS regimens: daily ICS in preschool children with persistent asthma, and pre-emptive high-dose intermittent ICS among preschool children with intermittent disease reduce the risk of exacerbation. In addition, among preschool children with mild persistent asthma, the presence of aeroallergen sensitivity and/or blood eosinophil counts of 300/μL or greater are predictors of good response to daily ICS therapy. Other studies identified intermittent azithromycin as a therapy to prevent, and potentially to treat, acute exacerbations.

The uncertainty of the role of oral corticosteroids (OCS) as a therapy for acute exacerbations continues, as a recent meta-analysis showed that OCS did not prevent hospitalizations or urgent visits, and did not reduce the need for additional courses of OCS. Whereas previous epidemiologic studies suggested acetaminophen may increase risk of exacerbations, a clinical trial clearly demonstrated acetaminophen use, compared to ibuprofen use,does not increase exacerbation risk among preschool children with mild-persistent asthma.

Recent studies have shown potential for phenotypic-driven therapies for the management of preschool children with asthma. Targeting airway bacteria has emerged as a promising therapeutic approach, but its effect on antibiotic resistance still needs to be investigated. Finally, more studies are required to evaluate if oral corticosteroids provide any benefits for acute episodic wheeze.
Asthma guidelines: the Global Initiative for Asthma in relation to national guidelines
Authors: Becker Allan B. , Abrams Elissa M.
Published: January 2017

Purpose of review

To compare and contrast national asthma guidelines with the Global Initiative for Asthma (GINA) strategy for asthma management and prevention.

Recent findings

The common goal of GINA and national asthma guidelines is to improve asthma care using the best evidence available from published data. This evidence-based approach has evolved from an initial perspective of expert opinion but with that evolution has not always considered the breadth of asthma phenotypes. GINA and national guidelines differ in a number of ways. GINA reviews available data and updates the core document and recommendations based on the latest data on a yearly basis to offer local, regional and national guidelines materials needed for knowledge mobilization. It remains the purview of those organizations to structure and implement those locally appropriate guidelines.

Both GINA and national guidelines have furthered asthma care to narrow the care gap from what is known to how asthma care is delivered, hopefully in a more directed, personalized manner. As well, both GINA and national guidelines have helped to shape the direction of research for the future benefit of children and their families.
Childhood asthma is a risk factor for the development of chronic obstructive pulmonary disease
Authors: McGeachie Michael J.
Published: January 2017

Purpose of review

This review will catalog the many recent longitudinal studies that have investigated the relationship between asthma and lung function, or the persistence and trajectories of lung function deficits.

Recent findings

Recent work has reported on 50-year follow-ups of some prominent population cohorts. A history of asthma confers a 10–30-fold risk of chronic obstructive pulmonary disease. Individuals reaching a reduced maximum growth of forced expiratory volume in 1 s in early adulthood are at risk for early or more severe chronic obstructive pulmonary disease (COPD).

Taken together, there is a wealth of overlapping cohort studies of lung function, asthma and COPD. These show that asthma is associated with reduced lung function, which may start in infancy or prenatally, persists through childhood and adulthood and predisposes for early or more severe COPD.
Comparisons in Muscle Function and Training Rehabilitation Outcomes Between Avoidance-Endurance Model Subgroups
Authors: Fehrmann Elisabeth , Tuechler Kerstin , Kienbacher Thomas , Mair Patrick , Spreitzer Juliane , Fischer Linda , Kollmitzer Josef , Ebenbichler Gerold
Published: January 2017

Objectives:

Evidence suggests that chronic low back pain patients with fear-avoidance (FAR) or endurance behavior are at risk of treatment failure and pain maintenance, with bodily overuse or underuse being assumed as mediating mechanisms for pain chronification. This study sought to examine whether or not the avoidance-endurance model subgroups, FAR, distress-endurers (DER), eustress-endurers (EER), and adaptive responders (AR), differed in physical measures and outcomes after training therapy.

Materials and Methods:

A total of 137 chronic low back pain patients were assessed before, at the end of, and 6 months after a 6-month rehabilitation training. Patients performed maximum back extension strength and trunk range-of-motion measures, flexion-relaxation tests, and completed the following questionnaires: Avoidance-Endurance Questionnaire, Roland-Morris Disability Questionnaire, Pain Disability Index, 36-Item Short-Form Health Survey, International Physical Activity Questionnaire, and visual analog scale. Statistical analysis included cluster analysis, analysis of covariances, and mixed-effects models.

Results:

At baseline, avoidance-endurance model subgroups did not differ in physical measures and activity levels. At the end of training, patients’ back-related health was significantly improved in all subgroups. However, the DER and the FAR were found to be more impaired before and after the intervention compared with EER and AR, as indicated by a higher pain intensity, higher disability levels, lower quality of life, and inferior working capacity.

Discussion:

Although FAR and DER did not differ in physical measures or activity levels from EER and AR, they demonstrated poor lower back-related health at baseline and after intervention. Thus, future research should elucidate as to which additional interventions could optimize their health.
Treatment Adherence in Child and Adolescent Chronic Migraine Patients
Authors: Kroon Van Diest Ashley M. , Ramsey Rachelle R. , Kashikar-Zuck Susmita , Slater Shalonda , Hommel Kevin , Kroner John W. , LeCates Susan , Kabbouche Marielle A. , O’Brien Hope L. , Kacperski Joanne , Allen Janelle R. , Peugh James , Hershey Andrew D. , Powers Scott W.
Published: January 2017

Objectives:

To examine treatment adherence among children and adolescents with chronic migraine who volunteered to be in a clinical trial using 3 measures: treatment session attendance, therapy homework completion, and preventive medication use by daily diary.

Materials and Methods:

Analyses are secondary from a trial of 135 youth aged 10 to 17 years diagnosed with chronic migraine and with a Pediatric Migraine Disability Score over 20. Participants were randomly assigned to cognitive-behavioral therapy plus amitriptyline (CBT+A, N=64) or headache education plus amitriptyline (HE+A, N=71). Therapists recorded session attendance. Completion of homework/practice between sessions was reported to therapists by patients. Patients reported preventive medication adherence using a daily headache diary.

Results:

Mean session attendance adherence out of 10 treatment sessions was 95% for CBT+A and 99% for HE+A. CBT+A participants reported completing a mean of 90% of home practice of CBT skills between the 10 sessions. Participants reported taking amitriptyline daily at a mean level of 90% when missing diaries were excluded and 79% when missing diaries were considered as missed doses of medication.

Discussion:

Our findings demonstrate that youth with chronic migraine who agree to be a part of a clinical trial do quite well at attending therapy sessions, and report that they are adherent to completing home/practice between sessions and taking medication. These results lend further support to consideration of CBT+A as a first-line treatment for youth with chronic migraine and suggest that measurement of adherence when this treatment is provided in practice will be important.
Pain Beliefs and Quality of Life in Young People With Disabilities and Bothersome Pain
Authors: Miró Jordi , Solé Ester , Gertz Kevin , Jensen Mark P. , Engel Joyce M.
Published: January 2017

Objectives:

Pain beliefs have been hypothesized to play an important role in pediatric pain. However, research examining the associations between pain-related beliefs and measures of function in youths with disabilities is limited.

Methods:

In total, 84 youths (mean age, 14.26 y; SD, 3.27) with physical disabilities who indicated they also had bothersome pain were interviewed and asked to rate their average pain intensity in the past week and to complete measures of pain-related beliefs and health-related quality of life.

Results:

A number of pain beliefs were associated with different physical and psychosocial function domains, although different beliefs appeared to play different roles, depending on the function domain examined. Across all of the health-related quality-of-life domains studied, a belief that pain is influenced by one’s emotions was associated with lower levels of function. No differences were found in pain beliefs related to age. In addition, a small difference in pain beliefs was found for sex; specifically, girls were more likely than boys to endorse the belief that pain is influenced by emotions.

Discussion:

The findings provide new information regarding the role that pain beliefs have in predicting function and have important clinical implications regarding how youth with physical disabilities and pain might be most effectively treated.
A Quality Improvement Collaborative Program for Neonatal Pain Management in Japan
Authors: Ozawa Mio , Yokoo Kyoko , Funaba Yuuki , Fukushima Sayo , Fukuhara Rie , Uchida Mieko , Aiba Satoru , Doi Miki , Nishimura Akira , Hayakawa Masahiro , Nishimura Yutaka , Oohira Mitsuko
Published: January 2017

Background:

Neonatal pain management guidelines have been released; however, there is insufficient systematic institutional support for the adoption of evidence-based pain management in Japan.

Purpose:

To evaluate the impact of a collaborative quality improvement program on the implementation of pain management improvements in Japanese neonatal intensive care units (NICUs).

Methods:

Seven Japanese level III NICUs participated in a neonatal pain management quality improvement program based on an Institute for Healthcare Improvement collaborative model. The NICUs developed evidence-based practice points for pain management and implemented these over a 12-month period. Changes were introduced through a series of Plan-Do-Study-Act cycles, and throughout the process, pain management quality indicators were tracked as performance measures. Jonckheere's trend test and the Cochran-Armitage test for trend were used to examine the changes in quality indicator implementations over time (baseline, 3 months, 6 months, and 12 months).

Findings:

Baseline pain management data from the 7 sites revealed substantial opportunities for improvement of pain management, and testing changes in the NICU setting resulted in measurable improvements in pain management. During the intervention phase, all participating sites introduced new pain assessment tools, and all sites developed electronic medical record forms to capture pain score, interventions, and infant responses to interventions.

Implications for Practice:

The use of collaborative quality improvement techniques played a key role in improving pain management in the NICUs.

Implications for Research:

Collaborative improvement programs provide an attractive strategy for solving evidence-practice gaps in the NICU setting.
The heterogeneity of tumor-infiltrating CD8+ T cells in metastatic melanoma distorts their quantification: how to manage heterogeneity?
Authors: Obeid Joseph M. , Hu Yinin , Erdag Gulsun , Leick Katie M. , Slingluff Craig L.
Published: January 2017

CD8+ T-cell infiltration of metastatic melanoma may be a useful biomarker for prediction of prognosis and response to therapy. The heterogeneous distribution of CD8+ T cells within a single tumor, and across different tumors within a single patient, may complicate quantification of infiltration. However, the impact of heterogeneity has not been quantified sufficiently. To address this, we have assessed intratumoral heterogeneity of CD8+ T-cell counts, as well as intertumoral heterogeneity for synchronous and metachronous metastases. In a tissue microarray containing 189 melanoma metastases from 147 patients, the density of CD8+ T cells per sample was determined by immunohistochemistry. The mean density and coefficient of variation were calculated for each tumor and the rates of discordant values were determined. CD8 counts varied widely among different core samples of the same tumors (average coefficient of variation=0.77, 95% confidence interval: 0.70–0.85), with discordance occurring in 40% of tumors. CD8 densities were similar among pairs of simultaneous tumors; however, significant changes in CD8 densities were observed among 35 pairs of metachronous tumors. CD8+ T-cell density is not well represented by a single 1 mm diameter sample. Differences in CD8+ T-cell counts, observed in clinical trials, from pretreatment to post-treatment specimens may be explained by the spatial and temporal heterogeneity of CD8 distribution, especially if the assessed samples are small (i.e. 1 mm2). A sufficiently large biopsy of one of several synchronous tumors may be representative of CD8+ T-cell infiltration of a patient’s disease.