bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of nanomaterial-induced hepatotoxicity using a 3D human primary multi-cellular microtissue exposed repeatedly over 21 days - the suitability of the in vitro system as an in vivo surrogate
Authors: Kermanizadeh Ali , Berthing Trine , Guzniczak Ewa , Wheeldon Melanie , Whyte Graeme , Vogel Ulla , Moritz Wolfgang , Stone Vicki 
Published: November 2019

Abstract
Background
With ever-increasing exposure to engineered nanomaterials (NMs), there is an urgent need to evaluate the probability of consequential adverse effects. The potential for NM translocation to distal organs is a realistic prospect, with the liver being one of the most important target organs. Traditional in vitro or ex vivo hepatic toxicology models are often limiting (i.e. short life-span, reduced metabolic activity, lacking important cell populations, etc.). In this study, we scrutinize a 3D human liver microtissue (MT) model (composed of primary hepatocytes and non-parenchymal cells). This unique experiment benefits from long-term (3 weeks) repeated very low exposure concentrations, as well as incorporation of recovery periods (up to 2 weeks), in an attempt to account for the liver’s recovery capacity in vivo. As a means of assessing the toxicological potential of NMs, cell cytotoxicity (cell membrane integrity and aspartate aminotransferase (AST) activity), pro/anti-inflammatory response and hepatic function were investigated.

Results
The data showed that 2 weeks of cell culture might be close to limits before subtle ageing effects start to overshadow low sub-lethal NM-induced cellular responses in this test system (adenylate kinase (AK) cytotoxicity assay). We showed that in vitro AST measurement are not suitable in a nanotoxicological context. Moreover, the cytokine analysis (IL6, IL8, IL10 and TNF-α) proved useful in highlighting recovery periods as being sufficient for allowing a reduction in the pro-inflammatory response. Next, low soluble NM-treated MT showed a concentration-dependent penetration of materials deep into the tissue.

Conclusion
In this study the advantages and pitfalls of the multi-cellular primary liver MT are discussed. Furthermore, we explore a number of important considerations for allowing more meaningful in vitro vs. in vivo comparisons in the field of hepatic nanotoxicology.
Potential risk factors and triggers for back pain in children and young adults. A scoping review, part I: incident and episodic back pain
Authors: Beynon Amber M , Hebert Jeffrey J , Lebouef-Yde Charlotte , Walker Bruce F 
Published: November 2019

Abstract
Background
The one-month prevalence of back pain in children and adolescents has been reported at 33, 28 and 48% at ages 9, 13 and 15 respectively. There are many suspected risk factors and triggers of back pain in young people.

Objective
The purpose of this scoping review was to identify potential risk factors and potential triggers for back pain in young people. The purpose of part I was to identify potential risk factors for incident and episodic back pain in young people. Part II included all eligible studies with unclear or mixed types of back pain.

Methods
Due to the vast number of studies on “risk factors” for back pain, a two-part scoping review of the literature was chosen as the best way to summarise the evidence. We adhered to the PRISMA-ScR guideline for scoping reviews. General potential risk factors and triggers for back pain in children and young adults (≤ 24 years) were included, incorporating physical, environmental, and/or physiological factors. A search was conducted using PubMed and Cochrane databases from inception to September 2018, limited to the English language. Within part I, and because of their importance, only the results of the studies that investigated risk factors of incident back pain and back pain episodes are presented.

Results
The search identified 7356 articles, of which 91 articles were eligible for this scoping review. The majority of the eligible articles had an unclear definition of back pain (results presented in scoping review part II). There were 7 inception cohort studies included and 1 cohort study that met the criteria for part I. The most consistent risk factors for incident and episodic back pain are female sex and older age.

Conclusion
Due to inconsistent ways of reporting on the type of back pain, no definitive risk factor for back pain has been identified. In general, females often report more symptoms, also for other diseases, and older age is not a useful risk factor as it merely indicates that the onset may not be in childhood. Clearly, the time has come to study the causes of back pain from different angles.
Population-level analysis reveals the widespread occurrence and phenotypic consequence of DNA methylation variation not tagged by genetic variation in maize
Authors: Xu Jing , Chen Guo , Hermanson Peter J. , Xu Qiang , Sun Changshuo , Chen Wenqing , Kan Qiuxin , Li Minqi , Crisp Peter A. , Yan Jianbing , Li Lin , Springer Nathan M. , Li Qing 
Published: November 2019

AbstractBackgroundDNA methylation can provide a source of heritable information that is sometimes entirely uncoupled from genetic variation. However, the extent of this uncoupling and the roles of DNA methylation in shaping diversity of both gene expression and phenotypes are hotly debated. Here, we investigate the genetic basis and biological functions of DNA methylation at a population scale in maize.ResultsWe perform targeted DNA methylation profiling for a diverse panel of 263 maize inbred genotypes. All genotypes show similar levels of DNA methylation globally, highlighting the importance of DNA methylation in maize development. Nevertheless, we identify more than 16,000 differentially methylated regions (DMRs) that are distributed across the 10 maize chromosomes. Genome-wide association analysis with high-density genetic markers reveals that over 60% of the DMRs are not tagged by SNPs, suggesting the presence of unique information in DMRs. Strong associations between DMRs and the expression of many genes are identified in both the leaf and kernel tissues, pointing to the biological significance of methylation variation. Association analysis with 986 metabolic traits suggests that DNA methylation is associated with phenotypic variation of 156 traits. There are some traits that only show significant associations with DMRs and not with SNPs.ConclusionsThese results suggest that DNA methylation can provide unique information to explain phenotypic variation in maize.
Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data
Authors: Liu Fenglin , Zhang Yuanyuan , Zhang Lei , Li Ziyi , Fang Qiao , Gao Ranran , Zhang Zemin 
Published: November 2019

AbstractBackgroundSystematic interrogation of single-nucleotide variants (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single-cell level. While SNV detection from abundant single-cell RNA sequencing (scRNA-seq) data is applicable and cost-effective in identifying expressed variants, inferring sub-clones, and deciphering genotype-phenotype linkages, there is a lack of computational methods specifically developed for SNV calling in scRNA-seq. Although variant callers for bulk RNA-seq have been sporadically used in scRNA-seq, the performances of different tools have not been assessed.ResultsHere, we perform a systematic comparison of seven tools including SAMtools, the GATK pipeline, CTAT, FreeBayes, MuTect2, Strelka2, and VarScan2, using both simulation and scRNA-seq datasets, and identify multiple elements influencing their performance. While the specificities are generally high, with sensitivities exceeding 90% for most tools when calling homozygous SNVs in high-confident coding regions with sufficient read depths, such sensitivities dramatically decrease when calling SNVs with low read depths, low variant allele frequencies, or in specific genomic contexts. SAMtools shows the highest sensitivity in most cases especially with low supporting reads, despite the relatively low specificity in introns or high-identity regions. Strelka2 shows consistently good performance when sufficient supporting reads are provided, while FreeBayes shows good performance in the cases of high variant allele frequencies.ConclusionsWe recommend SAMtools, Strelka2, FreeBayes, or CTAT, depending on the specific conditions of usage. Our study provides the first benchmarking to evaluate the performances of different SNV detection tools for scRNA-seq data.
Effectiveness of music therapy for alleviating pain during haemodialysis access cannulation for patients undergoing haemodialysis: a multi-facility, single-blind, randomised controlled trial
Authors: Kishida Masatsugu , Yamada Yosuke , Inayama Emi , Kitamura Mineaki , Nishino Tomoya , Ota Keiko , Shintani Ayumi , Ikenoue Tatsuyoshi 
Published: November 2019

AbstractBackgroundRepeated pain during haemodialysis access cannulations is a serious problem for haemodialysis patients even when prescribed oral or topical analgesics. Although some studies have observed the efficacy of music therapy for improving pain and anxiety, its effectiveness during haemodialysis access cannulations during dialysis is uncertain. The purpose of this study is to investigate the effects of music therapy for pain when cannulating haemodialysis access for haemodialysis patients.MethodsA prospective, multi-facility, single-blind, crossover, randomised controlled trial will be implemented. The intervention includes listening to Mozart, along with a white noise control condition. One hundred twenty haemodialysis patients will be enrolled across five facilities. Patients will be randomly allocated to either an Early-sequence group or a Later-sequence group. The Early-sequence group will receive cannulation while listening to Mozart’s Sonata for two pianos in D major (K.448) during the second week (Music period) and white noise during the fourth week (White noise period). The Later-sequence group will receive cannulation along with white noise first, followed by Mozart. All patients will also undergo cannulation during a no-sound period (wearing only headphones) during the first and third week (No-sound period). The music or no-music protocol will begin 8 min prior to the cannulating procedure, and participants will finish listening after starting haemodialysis during each period. The primary outcomes that will be assessed include the Visual Analogue Scale (VAS) score for pain during cannulation, and secondary outcomes are blood pressure, heart rate, VAS anxiety score, State-Trait Anxiety Inventory score, and salivary amylase activity. The operators who are in charge of haemodialysis access cannulation will be blind to the listening condition and VAS report.DiscussionThe proposed study has several methodological benefits. First, using white noise is a suitable control condition for addressing the role of sound in pain management. Additionally, using a crossover design with repeated measurements can help control individual differences between participants, which should better distinguish between- and within-participant variability. Overall, music therapy is a safe and inexpensive intervention that does not have the problematic side effects typically associated with pharmacological treatment. If effective, music therapy can be easily implemented for reducing pain and anxiety during cannulation.Trial registrationThis trial was prospectively registered to UMIN Clinical Trials Registry on 1 July 2018 (UMIN000032850).
Deep person re-identification in UAV images
Authors: Grigorev Aleksei , Tian Zhihong , Rho Seungmin , Xiong Jianxin , Liu Shaohui , Jiang Feng 
Published: November 2019

AbstractThe person re-identification is one of the most significant problems in computer vision and surveillance systems. The recent success of deep convolutional neural networks in image classification has inspired researchers to investigate the application of deep learning to the person re-identification. However, the huge amount of research on this problem considers classical settings, where pedestrians are captured by static surveillance cameras, although there is a growing demand for analyzing images and videos taken by drones. In this paper, we aim at filling this gap and provide insights on the person re-identification from drones. To our knowledge, it is the first attempt to tackle this problem under such constraints. We present the person re-identification dataset, namedDRoneHIT(DRHIT01), which is collected by using a drone. It contains 101 unique pedestrians, which are annotated with their identities. Each pedestrian has about 500 images. We propose to use a combination of triplet and large-margin Gaussian mixture (L-GM) loss to tackle the drone-based person re-identification problem. The proposed network equipped with multi-branch design, channel group learning, and combination of loss functions is evaluated on the DRHIT01 dataset. Besides, transfer learning from the most popular person re-identification datasets is evaluated. Experiment results demonstrate the importance of transfer learning and show that the proposed model outperforms the classic deep learning approach.
A hybrid approach to inferring the Internet of Things for complex activity recognition
Authors: Li Qingjuan , Ning Huansheng , Zhu Tao , Cui Shan , Chen Liming 
Published: November 2019

AbstractWith the rapid development and large-scale uptake of the Internet of Things, smart home is evolving from a vision towards a realistically viable solution for assisted living. Activity recognition is one of the fundamental tasks in order to provide accurate and timely assistance and service. As daily living scenarios are full of similar activities, missing data, and noise, inferring complex activities using knowledge-driven reasoning algorithms suffers from several drawbacks, e.g., real-time raw sensor data segmentation, poor generalization, higher computational complexity, and scalability. To address these problems, this paper proposes a hybrid approach to complex daily activity recognition by merging the first-order logic and probability graphic modeling. Specifically, we develop a novel “Markov logic network” combining data-driven multi-feature and simplified rule-based modeling and inference, thus enabling and supporting the applicability and robustness of daily activity recognition. To evaluate the approach and associated methods, we design a testing scenario with a number of similar activity groups, missing data, or disturbance test datasets in a multi-modeling sensor scene. Initial results show our approach outperforms the traditional approach with a better accuracy in the situations of similar activities with missing data and noise disturbance. Experiments are also conducted to compare the Gibbs sampling and MC-SAT sampling algorithms for Markov logic network, and the results show that the Gibbs is better in our experimental settings.
Many continuous variables should be analyzed using the relative scale: a case study of β2-agonists for preventing exercise-induced bronchoconstriction
Authors: Hemilä Harri , Friedrich Jan O. 
Published: November 2019

AbstractBackgroundThe relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1).MethodsFrom the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects.ResultsFourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1decline by 28 pp., and on the relative scale, they decreased the FEV1decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect.ConclusionsCompared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.
User-centred participatory design of visual cues for isolation precautions
Authors: Clack Lauren , Stühlinger Manuel , Meier Marie-Theres , Wolfensberger Aline , Sax Hugo 
Published: November 2019

Abstract
Background
Isolation precautions are intended to prevent transmission of infectious agents, yet healthcare provider (HCP) adherence remains suboptimal. This may be due to ambiguity regarding the required precautions or to cognitive overload of HCPs. In response to the challenge of changing HCP behaviour, increasing attention should be paid to the role of engineering controls and facility design that incorporate human factors elements. In the current study, we aimed to develop an isolation precaution signage system that provides visual cues, serves as a cognitive aid at the point of care, and removes ambiguity regarding which precautions are necessary (e.g. masks, gowns, gloves, single rooms) when caring for isolated patients.

Methods
We employed a user-centred, participatory design approach in which HCPs were actively involved in generating an isolation precaution signage system based on human factors design principles. HCPs were purposefully sampled for each design phase to include a representative sample of potential system users. We conducted front-end analysis through interviews and observations to identify challenges related to the existing signage and to establish design requirements for new signage. This was followed by the creation of user personas, design thinking workshops, and prototyping, which then underwent iterative cycles of evaluation. Graphical symbols were developed and tested for comprehensibility.

Results
Front-end analysis revealed several barriers to use of the current signage system such as unclear target audience, low signal-to-noise ratio, and ambiguity regarding the applicable precautions. A comprehensive list of design requirements was generated. The project ultimately resulted in a collection of validated, comprehensible symbols and signs for contact, droplet, and airborne isolation, as well as the identification of several systems-level solutions for work re-organisation to improve compliance with isolation precautions.

Conclusions
The introduction of visual cues in the form of signage offers a promising opportunity to make guidelines available directly at the frontline. Anecdotal evidence based on observations and interviews with HCP have shown that the current solution is superior to previous isolation signage. User-centred participatory design was a useful approach that holds potential for further improving design in healthcare settings.
Maternal betaine suppresses adrenal expression of cholesterol trafficking genes and decreases plasma corticosterone concentration in offspring pullets
Authors: Abobaker Halima , Hu Yun , Omer Nagmeldin A. , Hou Zhen , Idriss Abdulrahman A. , Zhao Ruqian 
Published: November 2019

Abstract
Background
Laying hens supplemented with betaine demonstrate activated adrenal steroidogenesis and deposit higher corticosterone (CORT) in the egg yolk. Here we further investigate the effect of maternal betaine on the plasma CORT concentration and adrenal expression of steroidogenic genes in offspring pullets.

Results
Maternal betaine significantly reduced (P < 0.05) plasma CORT concentration and the adrenal expression of vimentin that is involved in trafficking cholesterol to the mitochondria for utilization in offspring pullets. Concurrently, voltage-dependent anion channel 1 and steroidogenic acute regulatory protein, the two mitochondrial proteins involved in cholesterol influx, were both down-regulated at mRNA and protein levels. However, enzymes responsible for steroid syntheses, such as cytochrome P450 family 11 subfamily A member 1 and cytochrome P450 family 21 subfamily A member 2, were significantly (P < 0.05) up-regulated at mRNA or protein levels in the adrenal gland of pullets derived from betaine-supplemented hens. Furthermore, expression of transcription factors, such as steroidogenic factor-1, sterol regulatory element-binding protein 1 and cAMP response element-binding protein, was significantly (P < 0.05) enhanced, together with their downstream target genes, such as 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, LDL receptor and sterol regulatory element-binding protein cleavage-activating protein. The promoter regions of most steroidogenic genes were significantly (P < 0.05) hypomethylated, although methyl transfer enzymes, such as AHCYL, GNMT1 and BHMT were up-regulated.

Conclusions
These results indicate that the reduced plasma CORT in betaine-supplemented offspring pullets is linked to suppressed cholesterol trafficking into the mitochondria, despite the activation of cholesterol and corticosteroid synthetic genes associated with promoter hypomethylation.
Gut microbiome and CAR-T therapy
Authors: Abid Muhammad Bilal , Shah Nirav N. , Maatman Theresa C. , Hari Parameswaran N. 
Published: November 2019

AbstractConsiderable progress has been made in cancer therapeutics recently with targeted strategies that are efficacious and less toxic. Immunotherapy and chimeric antigen receptor (CAR) T-cells are increasingly being evaluated in a variety of tumors in the relapsed/refractory as well as frontline disease settings, predominantly in hematologic malignancies (HM). Despite impressive outcomes in select patients, there remains significant heterogeneity in clinical response to CAR T-cells. The gut microbiome has emerged as one of the key host factors that could potentially be modulated to enhance responses to immunotherapy. Several recent human studies receiving immunotherapy showed a significantly superior response and survival in patients with the more diverse gut microbiome. Currently, it is unknown if gut microbiota modulates anti-tumor responses to CAR T-cells. Based on molecular and immunological understanding, we hypothesize that strategically manipulating gut microbiota may enhance responses to CAR T-cells. In this review, we further discuss resistance mechanisms to CAR T-cells in HM, potential approaches to overcome resistance by harnessing gut microbiota and other related novel strategies.