bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteochondral Autograft Plugs versus Paste Graft: Ex Vivo Morselization Increases Chondral Matrix Production
Authors: Grande Daniel , Goldstein Todd , Turek Thomas J. , Hennessy Susan , Walgenbach Ann W. , Do Le Hanh Dung , Greene David , Stone Kevin R.
Published: May 2020

Objective

Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs.

Design

This institutional review board–approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology.

Results

Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively ( P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant ( P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae.

Conclusions

Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.
A little less autonomy? The future of working time flexibility and its limits
Authors: Glowacka Marta
Published: May 2020

The European Court of Justice has recently issued rulings on the interpretation of the European Working Time Directive 2003/88, which appear to restrict flexible working time arrangements (especially Matzak C-518/15, Syndicat C-254/18 and CCOO C-55/18). Only a few months prior to the latter ruling of the CJEU, the Austrian legislator amended the Working Time Act in order to make it more flexible. The article argues that the measures taken by the Austrian legislator to enable more flexibility and autonomy can still be regarded as compatible with Union law. In general, the article tackles the question of possible further legislative developments in order to strike a balance between autonomy and the need for security of both parties to the employment relationship. Among other suggestions, the article introduces the concept of molecularisation of working time and examines whether work intensity should be introduced as a qualitative dimension to the concept of working time, thus deviating from the current European Working Time Directive. Finally, the article suggests security measures – often referring to Austria as a best practice example – in order to safeguard workers in view of working time flexibility.
Incorporating hematopoietic stem-cell transplantation after second-line carfilzomib-lenalidomide-dexamethasone (KRd)
Authors: Byun Ja Min , Yoon Sung-Soo , Koh Youngil , Min Chang-Ki , Lee Jae Hoon , Jo Jaemin , Park Hyunkyung , Lee Jiyun , Kang Ka-Won , Lee Yoojin ,   and the Korean Multiple Myeloma Working Party (KMMWP)
Published: May 2020

Background:

Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents.

Methods:

A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes.

Results:

The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression ( n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd ( n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) ( p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039).

Conclusions:

In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.
The challenges of working with “real” teams: Introduction to the second installment
Authors: Shuffler Marissa L. , Cronin Matthew A.
Published: May 2020

We introduce the next two papers in our running special section on the challenges studying modern teams—those that may not have identifiable boundaries, stable membership, or members who belong only to that single team. Our perspective is that many of the assumptions about teams themselves are no longer correct, so rather than further exploiting our traditional approaches, the field should explore new or different ways to analyze the team experience. Thus, in these special sections, we present theoretical arguments made based on disciplined imagination and actual experience for why such new approaches are credible. This installment presents two papers that should enrich researchers’ sophistication in their ontological assumptions about teams. They are excellent complements to each other, as both are about questions of meaning and both have clear methodological implications for research design, but one zooms in to the nature of teams and the other zooms out to the nature of knowledge itself.
A 5-year experience characterizing the demographic and clinical profile and directly observed treatment short-course treatment outcome in National Tuberculosis Center of Duhok province, Iraqi Kurdistan
Authors: Merza Muayad Aghali
Published: May 2020

Background:

The objectives were to describe the demographic and clinical profile and treatment outcomes in the National Tuberculosis Program Center of Duhok governorate.

Methods:

This was a descriptive retrospective study of all forms of drug-susceptible tuberculosis cases in the National Tuberculosis Program Center of Duhok. The Electronic Nominal Recording Reporting System data of tuberculosis cases were reviewed during 2014–2018. Information on the demographic, clinical, and laboratory characteristics of the patients were analyzed. Tuberculosis trends and treatment outcomes were determined.

Results:

A total of 1063 tuberculosis patients visited the National Tuberculosis Program Center, of whom 905 were from Duhok. The estimated tuberculosis notification rate per 100,000 people in Duhok governorate was 14.06, 16.16, 10.43, 11.05, and 10.34 for the years 2014, 2015, 2016, 2017, and 2018, respectively. The most affected age group was 15–24 years. The male cases were predominant. Most patients (97.3%) were native Iraqi. There were 718 (67.5%) pulmonary tuberculosis cases and 345 (32.5%) extra-pulmonary tuberculosis cases; tuberculosis lymphadenitis was the most common presentation. The majority of extra-pulmonary tuberculosis patients were females aged 15–24 years (p = 0.019), and patients aged ⩾65 years were associated with pulmonary tuberculosis and extra-pulmonary tuberculosis in males (p ⩽ 0.001). The highest tuberculosis incidence occurred in winter (288 patients). The patient treatment outcomes were as follows: 90.7% successful treatment, 1.6% lost to follow-up, 6.7% death, 0.3 transferred out, and 0.8 treatment failure.

Conclusion:

There was a high frequency of extra-pulmonary tuberculosis, which may reflect overestimation in its diagnosis. Therefore, meticulous evaluations should be provided. The treatment outcome was satisfactory in the center. Hence, we should maintain the favorable work to attain tuberculosis control objectives. Performing GeneXpert for all tuberculosis cases and introducing culture and drug susceptibility testing should be an urgent plan to strengthen the diagnosis of susceptible and drug-resistant tuberculosis cases.
Digital Resilience Tactics of Syrian Refugees in the Netherlands: Social Media for Social Support, Health, and Identity
Authors: Udwan Ghadeer , Leurs Koen , Alencar Amanda
Published: May 2020

The process of adjusting to a new country may carry important stressors for refugees. In the light of neoliberal policies, refugees are expected to become resilient in a local arrival infrastructure and perform a specific subjectivity based on gratefulness, adaptability, and digital sensitivity to successfully integrate. Drawing on a qualitative, in-depth case study with Syrians living in the Netherlands, this article explores the impact of the retreat of the welfare state and unfolding digital transitions on resilience tactics of marginalized people like refugees. While recognizing the systemic violence and historic trauma many refugees have experienced, we focus on how refugees are expected to and develop ways to become resilient. Three digital resilience tactics are discussed: digital social support, digital health, and digital identities. Social support was mainly sought from family, friends, organizations, and social media platforms, whereas refugees’ engagement in meaningful digital practices aimed at fostering health promotion and identity management. Our fieldwork resurfaces paradoxes of digital resilience as described by careful emotional digital labor refugees engage in when communicating with families, the role of socio-cultural factors in shaping refugees’ ICT (information and communication technology) adoption and use for health support, and negotiation of different and conflicting identity axes online. Finally, our study provides some insights into the implementation of more effective online and offline practices in the context of social and health support by host countries.
The Association of MRI Findings and Long-Term Disability in Patients With Chronic Low Back Pain
Authors: Udby Peter Muhareb , Ohrt-Nissen Søren , Bendix Tom , Brorson Stig , Carreon Leah Y. , Andersen Mikkel Østerheden
Published: May 2020

Study Design:

Longitudinal cohort study with 13-year follow-up.

Objective:

To assess whether long-term disability is associated with baseline degenerative magnetic resonance imaging (MRI) findings in patients with low back pain (LBP).

Methods:

In 2004-2005, patients aged 18 to 60 years with chronic LBP were enrolled in a randomized controlled trial and lumbar MRI was performed. Patients completed the Roland-Morris Disability Questionnaire (RMDQ) and the LBP Rating Scale, at baseline and 13 years after the MRI. Multivariate regression analysis was performed with 13-year RMDQ as the dependent variable and baseline disc degeneration (DD, Pfirrmann grade), Modic changes (MC), facet joint degeneration (FJD, Fujiwara grade) smoking status, body mass index, and self-reported weekly physical activity at leisure as independent variables.

Results:

Of 204 patients with baseline MRI, 170 (83%) were available for follow-up. Of these, 88 had Pfirrmann grade >III (52%), 67 had MC (39%) and 139 had Fujiwara grade >2 (82%) on at least 1 lumbar level. Only MC (β = −0.15, P = .031) and weekly physical activity at leisure (β = −0.51, P < .001) were significantly, negatively, associated with 13-year RMDQ-score ( R2 = 0.31).

Conclusion:

DD and FJD were not associated with long-term disability. Baseline MC and weekly physical activity at leisure were statistically significantly associated with less long-term disability.
Enacting and resisting biosecurity citizenship: More-than-human geographies of enrolment in a disease eradication scheme in Scotland
Authors: Shortall Orla , Brown Katrina
Published: May 2020

This paper explores farmers’ responses to a cattle disease eradication scheme in Scotland by examining geographies of biopower and biosecurity citizenship. Biosecurity citizenship is a project to enact disease control for the good of a particular community. The paper uses the concept of biosecurity citizenship to explore how successful the scheme was at enrolling farmers as ‘Scottish’ biosecurity citizens with a sense of responsibility to the national territory. It explores the kinds of relationships the scheme created between farmers and animals and the kinds of animal ‘citizens’ created. The scheme was found to be partially successful in fostering a sense of biosecurity citizenship among farmers. Points of tension were the replacement of farmers’ own ways of assessing the value of their animals with an epidemiological lens that framed value in terms of the presence or absence of the bovine viral diarrhoea pathogen. These animals were constituted by the scheme as anonymous non-human citizens who became known through their administrative record of geographical relationship to Scottish national territory. The logic of the scheme differentiating Scotland as a distinct epidemiological space was variously accepted and resisted by farmers based on distance from the English border, and how ‘Scottish’ associated economic supply chains were. The paper thus highlights a new type of interaction between biosecurity and trade, showing how epidemiological initiatives can entangle with ‘quality’ supply chains that differentiate produce based on cultural links with a national territory. This in turn underlines the importance of understanding the dynamics of biosecurity citizenship in creating particular geographies of human–animal relationships and supply chains.
A mathematical form of probabilistic vulnerability model for loss and casualty ratios
Authors: Grant Damian N
Published: May 2020

A parametric mathematical form of vulnerability function is developed that gives a full probabilistic description of losses as a function of earthquake ground shaking intensity. The model is intended to be used with any loss measure that can take values between 0% and 100%, inclusive, including normalized financial losses (damage ratios), human casualty rates, or debris cover. It is a mixed discrete-continuous probability distribution, in that it assigns a discrete probability mass to experiencing exactly 0% or 100% loss, and a continuous probability density to values in between. The model can be used with empirical or analytical loss data. Two possible regression approaches are presented and Monte Carlo analysis is used to demonstrate that the regressions give unbiased estimates of the model parameters. Finally, the model is applied to a data set of debris cover percentages estimated from detailed finite element analysis of Dutch unreinforced masonry buildings.
IKAROS and CK2 regulate expression of BCL-XL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia
Authors: Song Chunhua , Ge Zheng , Ding Yali , Tan Bi-Hua , Desai Dhimant , Gowda Krishne , Amin Shantu , Gowda Raghavendra , Robertson Gavin P. , Yue Feng , Huang Suming , Spiegelman Vladimir , Payne Jonathon L. , Reeves Mark E. , Gurel Zafer , Iyer Soumya , Dhanyamraju Pavan Kumar , Xiang Meixian , Kawasawa Yuka Imamura , Cury Nathalia M. , Yunes José Andrés , McGrath Mary , Schramm Joe , Su Ruijun , Yang Yiping , Zhao Zhijun , Lyu Xiaoguang , Muschen Markus , Payne Kimberly J. , Gowda Chandrika , Dovat Sinisa
Published: May 2020

High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the IKAROS (encoded by the IKZF1 gene) tumor suppressor. Here, we report that IKAROS regulates expression of the BCL2L1 gene (encodes the BCL-XL protein) in human B-ALL. Gain-of-function and loss-of-function experiments demonstrate that IKAROS binds to the BCL2L1 promoter, recruits histone deacetylase HDAC1, and represses BCL2L1 expression via chromatin remodeling. In leukemia, IKAROS’ function is impaired by oncogenic casein kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces IKAROS binding and recruitment of HDAC1 to the BCL2L1 promoter. This results in a loss of IKAROS-mediated repression of BCL2L1 and increased expression of BCL-XL. Increased expression of BCL-XL and/or CK2, as well as reduced IKAROS expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, increases binding of IKAROS to the BCL2L1 promoter and enhances IKAROS-mediated repression of BCL2L1 in B-ALL. Treatment with CX-4945 increases sensitivity to doxorubicin in B-ALL, and reverses resistance to doxorubicin in multidrug-resistant B-ALL. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia. These data lay the groundwork for clinical testing of a rationally designed, targeted therapy that combines the CK2 inhibitor, CX-4945, with doxorubicin for the treatment of hematopoietic malignancies.
MDH1-mediated malate-aspartate NADH shuttle maintains the activity levels of fetal liver hematopoietic stem cells
Authors: Gu Hao , Chen Chiqi , Hao Xiaoxin , Su Ni , Huang Dan , Zou Yejun , Lin Shu-Hai , Chen Xianjun , Zheng Denghao , Liu Ligen , Yu Zhuo , Xie Li , Zhang Yaping , He Xiaoxiao , Lai Xiaoyun , Zhang Xiaocui , Chen Guo-Qiang , Zhao Yuzheng , Yang Yi , Loscalzo Joseph , Zheng Junke
Published: May 2020

The connections between energy metabolism and stemness of hematopoietic stem cells (HSCs) at different developmental stages remain largely unknown. We generated a transgenic mouse line for the genetically encoded NADH/NAD+ sensor (SoNar) and demonstrate that there are 3 distinct fetal liver hematopoietic cell populations according to the ratios of SoNar fluorescence. SoNar-low cells had an enhanced level of mitochondrial respiration but a glycolytic level similar to that of SoNar-high cells. Interestingly, 10% of SoNar-low cells were enriched for 65% of total immunophenotypic fetal liver HSCs (FL-HSCs) and contained approximately fivefold more functional HSCs than their SoNar-high counterparts. SoNar was able to monitor sensitively the dynamic changes of energy metabolism in HSCs both in vitro and in vivo. Mechanistically, STAT3 transactivated MDH1 to sustain the malate-aspartate NADH shuttle activity and HSC self-renewal and differentiation. We reveal an unexpected metabolic program of FL-HSCs and provide a powerful genetic tool for metabolic studies of HSCs or other types of stem cells.
Developmental trajectory of prehematopoietic stem cell formation from endothelium
Authors: Zhu Qin , Gao Peng , Tober Joanna , Bennett Laura , Chen Changya , Uzun Yasin , Li Yan , Howell Elizabeth D. , Mumau Melanie , Yu Wenbao , He Bing , Speck Nancy A. , Tan Kai
Published: May 2020

Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the major arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters (IAC) before colonizing the fetal liver. To examine the cell and molecular transitions between endothelial (E), HE, and IAC cells, and the heterogeneity of HSPCs within IACs, we profiled ∼40 000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of 9.5 days post coitus (dpc) to 11.5 dpc mouse embryos by single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing. We identified a continuous developmental trajectory from E to HE to IAC cells, with identifiable intermediate stages. The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. A developmental bottleneck separates pre-HE from HE, with RUNX1 dosage regulating the efficiency of the pre-HE to HE transition. A distal candidate Runx1 enhancer exhibits high chromatin accessibility specifically in pre-HE cells at the bottleneck, but loses accessibility thereafter. Distinct developmental trajectories within IAC cells result in 2 populations of CD45+ HSPCs; an initial wave of lymphomyeloid-biased progenitors, followed by precursors of hematopoietic stem cells (pre-HSCs). This multiomics single-cell atlas significantly expands our understanding of pre-HSC ontogeny.
How should scientists spread interest in, understanding of, and desire to practice, science more widely among the public?
Authors: Leigh Egbert Giles
Published: May 2020

This is a review of Bruce MacFadden’s Broader Impacts of Science on Society. Here, MacFadden suggests how scientists should, and how the National Science Foundation tries to, spread interest in and understanding of science more widely, especially to underserved minorities, and make science-related professions more accessible to and attractive for these minorities.
Moderate inundation stimulates plant community assembly in the drawdown zone of China’s Three Gorges Reservoir
Authors: Chen Zhongli , Yuan Xingzhong , Roß-Nickoll Martina , Hollert Henner , Schäffer Andreas
Published: May 2020

Background

While a dam is constructed to adjust and store water resources, it has negative impacts on biodiversity of the corresponding ecosystems. In particular, the dam regulation induces water-level fluctuations (WLFs), resulting in remarkable effects on the riparian vegetation succession of the drawdown zone ecosystem. These riparian plant responses play important roles in the biodiversity conservation. However, in-depth investigative adequate studies are still lacking. The objective of this study was to assess the community assembly under the anti-seasonal WLFs of China’s Three Gorges Reservoir (TGR). To analyze the WLFs’ impacts on plant community, the drawdown zone of the TGR was divided into four sub-zones (zone I, II, III, and IV) according to the inundation periods. The community biomass, height, total coverage, and species diversity in each sub-zone were surveyed. To detect the response of individual plant to the WLFs, dominant plants of Echinochloa crusgalli, Setaria viridis, Bidens pilosa, and Xanthium sibiricum were selected as targeted species to compare the plant’s morphological and physiological traits between non-flooded area and the moderately inundated area.

Results

The peaks of community biomass (1859.62 ± 663.77 g), total coverage (103.93 ± 11.81%), and diversity indexes were found in zone II that experienced 90 days of inundation. Community height and total coverage were both significantly negatively correlated to the inundated gradients. Generalized linear models and quadratic regression analyses revealed that community biomass, height, and total coverage were strongly related to the inundated gradients, implying that the inundation is the major factor contributing to the variation of the riparian vegetation patterns. The values of morphological traits (plant height and biomass) in the zone II were higher than those in the non-flooded zone, and were significantly positively correlated with physiological traits.

Conclusions

Community structure, diversity, and functional traits analysis indicated that the drawdown zone referencing to the 90-day inundation was suitable for the plant community establishment. Results on plant functional traits suggest the adaption of riparian plants to the TGR hydrological regime. However, further investigative studies with more plant species are necessary to elucidate their adaptation mechanisms.
TAMA: improved metagenomic sequence classification through meta-analysis
Authors: Sim Mikang , Lee Jongin , Lee Daehwan , Kwon Daehong , Kim Jaebum
Published: May 2020

Background

Microorganisms are important occupants of many different environments. Identifying the composition of microbes and estimating their abundance promote understanding of interactions of microbes in environmental samples. To understand their environments more deeply, the composition of microorganisms in environmental samples has been studied using metagenomes, which are the collections of genomes of the microorganisms. Although many tools have been developed for taxonomy analysis based on different algorithms, variability of analysis outputs of existing tools from the same input metagenome datasets is the main obstacle for many researchers in this field.

Results

Here, we present a novel meta-analysis tool for metagenome taxonomy analysis, called TAMA, by intelligently integrating outputs from three different taxonomy analysis tools. Using an integrated reference database, TAMA performs taxonomy assignment for input metagenome reads based on a meta-score by integrating scores of taxonomy assignment from different taxonomy classification tools. TAMA outperformed existing tools when evaluated using various benchmark datasets. It was also successfully applied to obtain relative species abundance profiles and difference in composition of microorganisms in two types of cheese metagenome and human gut metagenome.

Conclusion

TAMA can be easily installed and used for metagenome read classification and the prediction of relative species abundance from multiple numbers and types of metagenome read samples. TAMA can be used to more accurately uncover the composition of microorganisms in metagenome samples collected from various environments, especially when the use of a single taxonomy analysis tool is unreliable. TAMA is an open source tool, and can be downloaded at https://github.com/jkimlab/TAMA.
ICGEC: a comparative method for measuring epigenetic conservation of genes via the integrated signal from multiple histone modifications between cell types
Authors: Tang Jing , Wu Zefeng , Tian Yuhan , Yang Ruolin
Published: May 2020

Background

Histone post-translational modifications play crucial roles in epigenetic regulation of gene expression and are known to be associated with the phenotypic differences of different cell types. Therefore, it is of fundamental importance to dissect the genes and pathways involved in such a phenotypic variation at the level of epigenetics. However, the existing comparative approaches are largely based on the differences, especially the absolute difference in the levels of individual histone modifications of genes under contrasting conditions. Thus, a method for measuring the overall change in the epigenetic circumstance of each gene underpinned by multiple types of histone modifications between cell types is lacking.

Results

To address this challenge, we developed ICGEC, a new method for estimating the degree of epigenetic conservation of genes between two cell lines. Different from existing comparative methods, ICGEC provides a reliable score for measuring the relative change in the epigenetic context of corresponding gene between two conditions and simultaneously produces a score for each histone mark. The application of ICGEC to the human embryonic stem cell line H1 and four H1-derived cell lines with available epigenomic data for the same 16 types of histone modifications indicated high robustness and reliability of ICGEC. Furthermore, the analysis of the epigenetically dynamic and conserved genes which were defined based on the ICGEC output results demonstrated that ICGEC can deepen our understanding of the biological processes of cell differentiation to overcome the limitations of traditional expression analysis. Specifically, the ICGEC-derived differentiation-direction-specific genes were shown to have putative functions that are well-matched with cell identity. Additionally, H3K79me1 and H3K27ac were found to be the main histone marks accounting for whether an epigenetically dynamic gene was differentially expressed between two cell lines.

Conclusions

The use of ICGEC creates a convenient and robust way to measure the overall epigenetic conservation of individual genes and marks between two conditions. Thus, it provides a basis for exploring the epigenotype-phenotype relationship. ICGEC can be deemed a state-of-the-art method tailored for comparative epigenomic analysis of changes in cell dynamics.
Transcriptomic analysis of poco1, a mitochondrial pentatricopeptide repeat protein mutant in Arabidopsis thaliana
Authors: Emami Hossein , Kumar Abhishek , Kempken Frank
Published: May 2020

Background

Flowering is a crucial stage during plant development. Plants may respond to unfavorable conditions by accelerating reproductive processes like flowering. In a recent study, we showed that PRECOCIOUS1 (POCO1) is a mitochondrial pentatricopeptide repeat (PPR) protein involved in flowering time and abscisic acid (ABA) signaling inArabidopsis thaliana. Here, we use RNA-seq data to investigate global gene expression alteration in thepoco1mutant.

Results

RNA-seq analysis was performed during different developmental stages for wild-type andpoco1plants. The most profound differences in gene expression were found when wild-type andpoco1plants of the same developmental stage were compared. Coverage analysis confirmed the T-DNA insertion inPOCO1, which was concomitant with truncated transcripts. Many biological processes were found to be enriched. Several flowering-related genes such asFLOWERING LOCUS T(FT), which may be involved in the early-flowering phenotype ofpoco1, were differentially regulated. Numerous ABA-associated genes, including the core components of ABA signaling such as ABA receptors, protein phosphatases, protein kinases, and ABA-responsive element (ABRE) binding proteins (AREBs)/ABRE-binding factors (ABFs) as well as important genes for stomatal function, were mostly down-regulated inpoco1. Drought and oxidative stress-related genes, including ABA-induced stress genes, were differentially regulated. RNA-seq analysis also uncovered differentially regulated genes encoding various classes of transcription factors and genes involved in cellular signaling. Furthermore, the expression of stress-associated nuclear genes encoding mitochondrial proteins (NGEMPs) was found to be altered inpoco1. Redox-related genes were affected, suggesting that the redox state inpoco1might be altered.

Conclusion

The identification of various enriched biological processes indicates that complex regulatory mechanisms underliepoco1development. Differentially regulated genes associated with flowering may contribute to the early-flowering phenotype ofpoco1. Our data suggest the involvement of POCO1 in the early ABA signaling process. The down-regulation of many ABA-related genes suggests an association ofpoco1mutation with the ABA signaling deficiency. This condition further affects the expression of many stress-related, especially drought-associated genes inpoco1, consistent with the drought sensitivity ofpoco1.poco1mutation also affects the expression of genes associated with the cellular regulation, redox, and mitochondrial perturbation.
One-step generation of composite soybean plants with transgenic roots by Agrobacterium rhizogenes-mediated transformation
Authors: Fan Ying-lun , Zhang Xing-hui , Zhong Li-jing , Wang Xiu-yuan , Jin Liang-shen , Lyu Shan-hua
Published: May 2020

Background

Agrobacterium rhizogenes-mediated (ARM) transformation is a highly efficient technique for generating composite plants composed of transgenic roots and wild-type shoot, providing a powerful tool for studying root biology. The ARM transformation has been established in many plant species, including soybean. However, traditional transformation of soybean, transformation efficiency is low. Additionally, the hairy roots were induced in a medium, and then the generated composite plants were transplanted into another medium for growth. This two-step operation is not only time-consuming, but aggravates contamination risk in the study of plant-microbe interactions.

Results

Here, we report a one-step ARM transformation method with higher transformation efficiency for generating composite soybean plants. Both the induction of hairy roots and continuous growth of the composite plants were conducted in a single growth medium. The primary root of a 7-day-old seedling was decapitated with a slanted cut, the residual hypocotyl (maintained 0.7-1 cm apical portion) was inoculated withA.rhizogenesharboring the gene construct of interest. Subsequently, the infected seedling was planted into a pot with wet sterile vermiculite. Almost 100% of the infected seedlings could produce transgenic positive roots 16 days post-inoculation in 7 tested genotypes. Importantly, the transgenic hairy roots in each composite plant are about three times more than those of the traditional ARM transformation, indicating that the one-step method is simpler in operation and higher efficiency in transformation. The reliability of the one-step method was verified by CRISPR/Cas9 system to knockout the soybeanRfg1, which restricts nodulation in Williams 82 (Nod-) bySinorhizobium frediiUSDA193. Furthermore, we applied this method to analyze the function ofArabidopsis YAOpromoter in soybean. The activity ofYAOpromoter was detected in whole roots and stronger in the root tips. We also extended the protocol to tomato.

Conclusions

We established a one-step ARM transformation method, which is more convenient in operation and higher efficiency (almost 100%) in transformation for generating composite soybean plants. This method has been validated in promoter functional analysis and rhizobia-legume interactions. We anticipate a broad application of this method to analyze root-related events in tomato and other plant species besides soybean.
Adaptive strategy of allohexaploid wheat to long-term salinity stress
Authors: Bhanbhro Nadeem , Xiao Binbin , Han Lei , Lu Huiying , Wang Huan , Yang Chunwu
Published: May 2020

Background

Most studies of crop salinity tolerance are conducted under short-term stress condition within one growth stage. Understanding of the mechanisms of crop response to long-term salinity stress (LSS) is valuable for achieving the improvement of crop salinity tolerance. In the current study, we exposed allohexaploid wheat seeds to LSS conditions from germination stage to young seedling stage for 30 days. To elucidate the adaptive strategy of allohexaploid wheat to LSS, we analyzed chloroplast ultrastructure, leaf anatomy, transcriptomic profiling and concentrations of plant hormones and organic compatible solutes, comparing stressed and control plants.

Results

Transcriptomic profiling and biochemical analysis showed that energy partitioning between general metabolism maintenance and stress response may be crucial for survival of allohexaploid wheat under LSS. Under LSS, wheat appeared to shift energy from general maintenance to stress response through stimulating the abscisic acid (ABA) pathway and suppressing gibberellin and jasmonic acid pathways in the leaf. We further distinguished the expression status of the A, B, and D homeologs of any gene triad, and also surveyed the effects of LSS on homeolog expression bias for salinity-tolerant triads. We found that LSS had similar effects on expression of the three homeologs for most salinity-tolerant triads. However, in some of these triads, LSS induced different effects on the expression of the three homeologs.

Conclusions

The shift of the energy from general maintenance to stress response may be important for wheat LSS tolerance. LSS influences homeolog expression bias of salinity-tolerant triads.
Elevated glycosylated hemoglobin levels and their interactive effects on hypertension risk in nondiabetic Chinese population: a cross-sectional survey
Authors: Song Jian , Wei Nana , Zhao Yingying , Jiang Yuhong , Wu Xuesen , Gao Huaiquan
Published: May 2020

Background

Abnormal glucose metabolism has been suggested to be involved in the development of hypertension. This study investigated the effect of the association and potential interaction of glycosylated hemoglobin (HbA1c) and other factors on the risk of hypertension among Chinese nondiabetic adults.

Methods

As a cross-sectional survey, the current work deployed a questionnaire survey, anthropometric tests, and biochemical measures for each of the eligible participants. The HbA1c levels were quantified and grouped by quartiles. Correlations between HbA1c and hypertension, isolated systolic hypertension (ISH), and isolated diastolic hypertension (IDH) risk were investigated by logistic analyses. For evaluating the interactive effects, the parameters of relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were calculated, respectively.

Results

In the current study, 1462 nondiabetic subjects were enrolled. In total, the prevalence rates of hypertension, ISH and IDH were 22.4, 9.6 and 4.5%, respectively. When HbA1c levels were grouped by quartile, it was revealed that the prevalence rates of hypertension and ISH were substantially elevated across groups (Pfor trend < 0.001). In the multivariable logistic regression analyses, in comparison with the first quartile of HbA1c, the normalized OR for hypertension risk was 1.90 (95% CI: 1.28–2.80) for the highest quartile. Also, the risk of ISH was significantly increased with HbA1c level in the highest quartile relative to in the bottom quartile (OR: 2.23,95% CI:1.47–3.71). However, no significant relationship between the HbA1c level and IDH risk was observed (OR: 1.78, 95% CI: 0.82–3.84). Eventually, it was demonstrated from the interactive effect analysis that HbA1c significantly interacted with abdominal obesity (RERI: 1.48, 95% CI: 0.38–2.58; AP: 0.37, 95% CI: 0.14–0.60 and SI: 1.96, 95% CI: 1.06–3.62) and family history of hypertension (AP: 0.37, 95% CI: 0.05–0.70) in influencing the risk of hypertension in nondiabetic participants.

Conclusion

Higher HbA1c levels significantly enhanced the risk of hypertension and ISH, but not IDH among Chinese nondiabetic adults. Moreover, the risk of hypertension was also aggravated by the upregulated HbA1c in a synergistic manner alongside abdominal obesity and family history of hypertension.
Transthoracic echocardiography-monitored CO2-insufflation esophageal endoscopy for diagnosis of Atrioesophageal fistula and prevention of iatrogenic air embolism: a case report
Authors: Rong Bing , Zhang Xiquan , Tian Hui , Zhang Hongyu , Zhong Ning , Zhong Jingquan
Published: May 2020

Background

Atrioesophageal fistula (AEF) is the most fatal complication associated with catheter ablation for atrial fibrillation and cannot be easily detected when thoracic contrast-enhanced computed tomography (CT) is normal.

Case presentation

In this report, we described a diagnostic tool for detecting AEF with doubtful chest CT in which we introduced CO2-insufflation esophageal endoscopy with transthoracic echocardiography monitoring. Using this modified esophageal endoscopy, AEF was established due to the presence of both esophageal lesions and bubbles into the left atrium. That way, our patient accepted to be operated in time with good clinical prognosis.

Conclusions

This modified esophageal endoscopy is an alternative tool for early detection of AEF when normal or doubtful CT findings present.
Are people in residential care entitled to receive rehabilitation services following hip fracture? Views of the public from a citizens’ jury
Authors: Crotty Maria , Gnanamanickam Emmanuel S. , Cameron Ian , Agar Meera , Ratcliffe Julie , Laver Kate
Published: May 2020

Background

Access to rehabilitation services for people living in residential care facilities is frequently limited. A randomised trial of a hospital outreach hip fracture rehabilitation program in residential care facilities has demonstrated improvements in mobility at four weeks and quality of life at 12 months but was not considered cost-effective by standard health economic metrics. The current study aimed to explore the general public’s views on issues involved in the allocation of rehabilitation resources for residents of care facilities.

Methods

A citizens’ jury comprising 13 purposively sampled members of the general public, representative of the South Australian age, gender and household income profile. The jury considered the questions “Should there be an investment of physical rehabilitation services in residential care for older people following a hip fracture? If so, what is the best way of providing this service (considering funding, models of service delivery and equity)?” Deliberations were in the context of a state-wide health reform program. The jury was conducted over two days with an experienced independent facilitator, addressing questions developed by a steering group of research academics and clinicians.

Results

The mean age of the citizens’ jury members was 43 (range 26 to 61). Eleven members voted for investment in outreach hospital rehabilitation services in residential aged care. All jurors agreed a number of strategies in addition to investment should be implemented, including health care planning and decision making, increased emphasis on hip fracture prevention, training of aged care staff in rehabilitation and routine provision of hospital discharge summaries to families. The jury further advocated for an increased focus on rehabilitation in residential care, potentially through accreditation criteria, increasing health literacy of residents and families, implementation of age friendly environment strategies and improving connections of care facilities with community, hospital and tertiary services.

Conclusions

This citizens’ jury representative of the general public recommends that regardless of dementia and frailty, people who live in residential care and are walking and fracture their hips should have access to hospital outreach rehabilitation and recovery services.
Prevalence and burden of orthopaedic implantable-device infections in Italy: a hospital-based national study
Authors: Pirisi Luca , Pennestrì Federico , Viganò Marco , Banfi Giuseppe
Published: May 2020

Background

Healthcare-associated infections (HAIs) represent a serious burden to individual safety and healthcare sustainability. Identifying which patients, procedures and settings are most at risk would offer a significant contribution to HAI management and prevention. The purpose of this study is to estimate 1) orthopaedic implantable device-related infection (OIDRI) prevalence in Italian hospitals and 2) the gap between the remuneration paid by the Italian healthcare system and the real costs sustained by Italian hospitals to treat these episodes.

Methods

This is a cross-sectional study based on hospital discharge forms registered in 2012 and 2014. To address the first goal of this study, the national database was investigated to identify 1) surgical procedures associated with orthopaedic device implantation and 2) among them, which patient characteristics (age, sex), type of admission, and type of discharge were associated with a primary diagnosis of infection. To address the second goal, 1) each episode of infection was multiplied by the remuneration paid by the Italian healthcare system to the hospitals, based on the diagnosis-related group (DRG) system, and 2) the total days of hospitalization required to treat the same episodes were multiplied by the average daily cost of hospitalization, according to estimates from the Ministry of the Economy and Finance (MEF).

Results

In 2014, 1.55% of the total hospitalizations for orthopaedic device implantation procedures were associated with a main diagnosis of infection, with a negligible increase of 0.04% compared with 2012. Hip and knee replacement revisions, male patients and patients older than 65 years were more exposed to infection. A total of 51.63% of patients were planned admissions to the hospital, 68.75% had an ordinary discharge to home, and 0.9% died.

The remuneration paid by the healthcare system to the hospitals was € 37,519,084 in 2014, with 3 DRGs covering 70.6% of the total. The cost of the actual days of hospitalization to treat these episodes was 17.5 million more than the remuneration received.

Conclusions

The OIDRI prevalence was lower than that described in recent surveys in acute care settings, although the numbers were likely underestimated. The cost of treatment varied significantly depending on the remuneration system adopted.
Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups
Authors: Assmann Gunter , Köhm Michaela , Schuster Volker , Behrens Frank , Mössner Rotraut , Magnolo Nina , Oji Vinzenz , Burkhardt Harald , Hüffmeier Ulrike
Published: May 2020

Background

Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene.

Methods

Clinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1.

Results

Palmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S_PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants.

Conclusions

S_PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO’s and CRMO/CNO’s pathogenesis.