bluuebunny/crossref_metadata_2025 huggingface dataset:
A Kinetic Model for Glucose Levels and Hemoglobin A1c Provides a Novel Tool for Individualized Diabetes Management
Authors: Xu Yongjin , Dunn Timothy C. , Ajjan Ramzi A.
Published: January 2020

Background:

Regular assessment of glycated hemoglobin (HbA1c) is central to the management of patients with diabetes. Estimated HbA1c (eHbA1c) from continuous glucose monitoring (CGM) has been proposed as a measure that reflects laboratory HbA1c. However, discrepancies between the two markers are common, limiting the clinical use of eHbA1c. Therefore, developing a glycemic maker that better reflects laboratory HbA1c will be highly relevant in diabetes management.

Methods:

Using CGM data from two previous clinical studies in 120 individuals with diabetes, we derived a novel kinetic model that takes into account red blood cell (RBC) turnover, cross-membrane glucose transport, and hemoglobin glycation processes to individualize the relationship between glucose levels and HbA1c.

Results:

Using CGM data and two laboratory HbA1c measurements, kinetic rate constants for RBC glycation and turnover were calculated. These rate constants were used to project future HbA1c, creating a new individualized glycemic marker, termed calculated HbA1c (cHbA1c). In contrast to eHbA1c, the new glycemic marker cHbA1c gave an accurate estimation of laboratory HbA1c across individuals. The model and data demonstrated a non-linear relationship between laboratory HbA1c and steady-state glucose and also showed that glycation status is modulated by age.

Conclusion:

Our kinetic model offers mechanistic insights into the relationship between glucose levels and glycated hemoglobin. Therefore, the new glycemic marker does not only accurately reflect laboratory HbA1c but also provides novel concepts to explain the mechanisms for the mismatch between HbA1c and average glucose in some individuals, which has implications for future clinical management.
Screening and Identification of an Anti-inflammatory and Anti-adipogenic Constituent from Ligularia taquetii Nakai
Authors: Jang Sungchan , Kim Min-Seon , Park Taejin , Sim Ji H. , Kim Seung-Young
Published: January 2020

Ligularia taquetii (H. Lev. & Vaniot) Nakai has traditionally been used to treat inflammation and skin swelling in the Jeju Island, Korea. The objective of this study was to investigate the anti-inflammatory and anti-adipogenic effects of Ligularia taquetii ethanoic extract (LTE), in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and 3T3-L1 adipocytes. Lipopolysaccharide-induced inflammation was reduced by LTE in a concentration-dependent manner, via the nuclear factor-κB signaling pathway. Ligularia taquetii ethanoic extract (100 µg/mL) inhibited the LPS-induced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), by 60% and 100%, respectively. In comparison, 200 and 100 µg/mL LTE suppressed the LPS-stimulated production of prostaglandin-2 (PGE2) and cyclooxygenase-2 by 50% and 80%, respectively. Ligularia taquetii ethanoic extract also inhibited the secretion of interleukin-1β and interleukin-6 at 300 and 100 μg/mL by 15% and 30%, respectively. High-performance liquid chromatography-photodiode array analysis, combined with mass analysis, revealed chlorogenic acid (CGA) as the anti-inflammatory constituent of LTE. Conversely, 25, 50, 100, and 200 μg/mL LTE lowered the lipid accumulation by 6%, 8%, 25%, and 60%, respectively, while simultaneously increasing cell viability by 7%, 14%, 34%, and 78%. The anti-adipogenic effect of LTE at 100 µg/mL was equivalent to that of CGA at 50 µg/mL. However, LTE treatment promoted cell proliferation by about 30% compared to its CGA-treated counterpart. These results suggest the potential of LTE as a new resource in the discovery of anti-inflammatory and anti-obesity drugs.
Baicalin Ameliorates Bone Cancer Pain by Suppressing TRPV1 in Rat Dorsal Root Ganglia
Authors: Li Ping , Bi Ying , Deng Yuchun , Xiong Donglin , Li Anxue
Published: January 2020

Bone cancer pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates, which could produce tolerance or addiction. Baicalin is a flavonoid compound extracted from Huang Qin, possesses antioxidant properties, and has an analgesic effect on nitroglycerin-induced migraine in rats and neuropathic pain in spinal nerve ligation rats. However, the effect of baicalin on bone cancer pain is still unclear. Therefore, the aim of this study is to examine the analgesic effect of baicalin in a rat model of bone cancer pain. Bone cancer pain animal model was created by tumor cell implantation (TCI). Animal behaviors were measured using a set of mechanical or electronic von Frey apparatus and hot plate. mRNA expression and inflammation cytokine levels were examined by Quantitative polymerase chain reaction (qPCR) and enzyme linked immunosorbent assay (ELISA) methods. Baicalin suppressed the upregulation of transient receptor potential vanilloid 1 (TRPV1), but not transient receptor potential A1 in dorsal root ganglion (DRG) of TCI rats. In addition, the phosphorylation of extracellular regulated protein kinases (ERK) was also suppressed by baicalin injection in DRG of TCI rats. Our results revealed that baicalin might play a promising analgesic role by preventing the upregulation of TRPV1 in DRG of TCI rats. Baicalin administration prevented the progress of bone cancer pain and reduced mechanical allodynia and thermal hyperalgesia. Our study clearly established a novel role of baicalin as an analgesic agent for bone cancer pain. And the analgesic role of baicalin in bone cancer pain might involve a TRPV1.
Cryptotanshinone Induces Apoptosis and Inhibits Migration and Invasion in Human Hepatocellular Carcinoma Cells In Vitro
Authors: Zhang Qianyu , Wang Liqun , Gan Cailing , Yu Yan , Li Yali , Deng Yuanle , Liu Hongyao , You Jia , Yin Wenya
Published: January 2020

Cryptotanshinone (CPT), an active quinoid diterpene isolated from Salvia miltiorrhiza Bunge, was previously reported to have potential anticancer effects. However, the mechanisms of CPT on hepatocellular carcinoma (HCC) cells are not well understood. In this study, we investigated the anticancer effects of CPT on HCC cells. Thiazolyl blue tetrazolium bromide assay showed dose-dependent and time-dependent cytotoxicity of CPT on human HCC cells, especially in HCCLM3 and Huh-7 cells. Hoechst 33258 stain, flow cytometry assay, and Western blot assay all indicated that CPT could distinctly induce the apoptosis of human HCC cells and break intracellular homeostasis by triggering the imbalance of mitochondrial transmembrane potential ( Δψm) and reactive oxygen species. In addition, CPT could significantly inhibit HCCLM3 and Huh-7 cells’ migration and invasion via the signal transducers and activators of transcription 3/matrix metalloproteinases mediated signaling pathway. Our findings demonstrated that the antitumor effects of CPT on human HCC cells were by suppressing cell proliferation, inducing cell apoptosis and impairing cell migration and invasion.
Chemical Constituents From the Aerial Part of Tiliacora triandra (Colebr.) Diels and Their α-Glucosidase and α-Amylase Inhibitory Activity
Authors: Makinde Emmanuel Ayobami , Ovatlarnporn Chitchamai , Sontimuang Chonlatid , Herbette Gaëtan , Olatunji Opeyemi Joshua
Published: January 2020

Two new fatty acid derivatives identified as 5,7-dihydroxy-6-oxoheptadecanoic acid (1) and ethyl-5,7-dihydroxy-6-oxooctadecanoate (2) together with four known compounds, ethyl linolenate (3), ethyl linoleate (4), ethyl pheophorbide A (5), and pheophorbide A (6), were isolated from the aerial parts of Tiliacora triandra. All the compounds were isolated from T. triandra for the first time. The structures of the compounds were elucidated using high-resolution electrospray ionization mass spectrometry, 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy, and comparison with literature data. All the isolated compounds were evaluated for their in vitro inhibitory activity against α-glucosidase and α-amylase. Compounds 1-6 exhibited α-glucosidase inhibitory activity with half-maximal inhibitory concentration values (IC50) values in the range of 11.58-424.06 μM, while only compound 1 displayed inhibitory activity against α-amylase at an IC50 value of 26.27 μM.
‘The shadow of her wings’: Respectability politics and the self-narration of geography
Authors: Roy Ananya
Published: January 2020

In engagement with Natalie Oswin’s essay, ‘An Other Geography’, I argue that despite the Southern turn in urban studies, the epistemologies and methodologies of inquiry remain more or less untouched by forms of knowledge designated as the ‘other’ of dominant Theory. Indeed, these other traditions of thought, be it postcolonial critique or Black geographies, are often assimilated and integrated into the self-narration of disciplines, including geography, a process I describe as citationary alibi. Following Oswin, I am interested in not only how such assimilation can be rejected and ruptured, but also how solidarity can be built across different modes of difference. This requires, I argue, a radical break with respectability politics and its citationary practice. It also requires ontologies of subversion in the global universities of the North Atlantic.
Let’s talk about sex: A review of expectations, body image and sexual function in exstrophy
Authors: Tregunna Rebecca L , Wood Dan
Published: January 2020

Background:

The bladder exstrophy epispadias complex (BEEC) is a rare disorder characterised by a number of genito-urinary abnormalities. The condition and subsequent treatment may result in lasting effects on continence, renal function and fertility. There are equally important psychosocial and psychosexual effects as part of overall long-term quality of life. The literature consists largely of small studies with variable methodology; this study aims to consolidate these data.

Methods:

This study reviews the available literature sourced from the Medline database using the keywords listed below.

Results:

Patients appear to be high achievers with good overall health-related quality of life. Most form close personal friendships although express anxiety related to revelation of their condition. Data suggest the majority of patients are able to engage in and be satisfied with sexual intercourse. Fertility may be adversely affected, but this can usually be overcome with assisted reproductive techniques and specialist input during pregnancy and delivery.

Conclusions:

Psychosocial and psychosexual outcomes in patients with BEEC may be excellent. Therefore careful transition and psychological support combined with long-term follow-up is important to allow these patients to maximise their quality of life.

Level of evidence:

Not applicable.
Significant Burden and Psychological Distress Among Caregivers of Children With Nephrotic Syndrome: A Cross-Sectional Study
Authors: Esezobor Christopher I. , Solarin Adaobi U. , Olagunju Andrew T.
Published: January 2020

Background:

Childhood nephrotic syndrome (NS) follows a chronic course in most children. However, little is known about the psychosocial burden of NS on the caregivers despite evidence that caregiver burden or impairment in their well-being may alter the outcome of chronic childhood illnesses.

Objectives:

To determine the frequency and predictors of significant caregiver burden and psychological distress among caregivers of children with NS.

Design:

A cross-sectional study.

Setting:

Two pediatric nephrology clinics in Lagos, Nigeria.

Patients:

We included primary caregivers of children with idiopathic NS for at least 6 months.

Measurements:

The primary outcomes were psychological distress and significant caregiver burden among caregivers.

Methods:

We interviewed caregivers using the 12-item General Health Questionnaire (GHQ-12) and the 6-item Zarit Burden Interview (ZBI-6). The GHQ-12 scores ≥ 3 and ZBI-6 scores ≥ 6 indicated psychological distress and significant caregiver burden, respectively.

Results:

The caregivers were mostly mothers (77.9%) and married (92.4%), whereas the children (n = 172) were mainly male (65.1%). Most of the children (n = 152; 88.4%) had steroid-sensitive NS including 24 (14%) children with frequent relapses or steroid dependence and 20 (11.6%) with steroid-resistant NS. Of the 172 caregivers, 53 (30.8%) and 30 (17.4%) reported psychological distress and significant burden, respectively. Caregivers of children in relapse had adjusted an odds ratio (aOR) with 95% confidence interval (CI) of 2.45 (1.05-5.67) and 3.30 (1.22-8.92) of psychological distress and significant caregiver burden, respectively. Furthermore, caregivers of male children and those who needed help paying for health care had an aOR of 4.61 (1.34-15.68) and 3.06 (1.06-8.87) of significant caregiver burden, respectively.

Limitations:

The study was limited by its cross-sectional design and the use of generic rather than disease-specific instruments.

Conclusion:

One in every 6 caregivers of children with idiopathic NS reported significant caregiver burden, and it was associated with psychological distress. Our findings underscore the need for psychosocial support for caregivers of children with NS, especially those with identifiable vulnerability.
Application and effectiveness of eHealth strategies for metabolic and bariatric surgery patients: A systematic review
Authors: Messiah Sarah E , Sacher Paul M , Yudkin Joshua , Ofori Ashley , Qureshi Faisal G , Schneider Benjamin , Hoelscher Deanna M , de la Cruz-Muñoz Nestor , Barlow Sarah E
Published: January 2020

Objective

To date the application of eHealth strategies among adults and adolescents undergoing metabolic and bariatric surgery (MBS) has not been systematically reviewed. This study comprehensively examines eHealth intervention studies among MBS patients within the RE-AIM framework to assess reach, effectiveness, adoption, implementation and maintenance of these efforts.

Methods

A search was conducted using PubMed, EMBASE, CINAHL, PsycNET and SCOPUS of original research relating to eHealth strategies for MBS patients published in peer-reviewed journals and revealed 38 published articles between 2011 and 2019.

Results

Studies varied widely in terms of design (qualitative to randomized controlled trials) and eHealth delivery method (telemedicine to blog post content) with a balance of pre- or post-MBS use. No studies included adolescents and very few reported (1) a conceptual framework to support study design/outcomes; and (2) race/ethnicity composition.

Conclusions

Although some studies report that eHealth strategies/interventions are effective in producing post-MBS weight loss and other positive health outcomes, most are pilot studies or have study design limitations. There is an opportunity for development of (1) tailored eHealth interventions to support pre- and post-MBS sustained behavior change and improved outcomes; and (2) rigorous studies that employ robust conceptual frameworks so dissemination and implementation efforts can be mapped to construct-driven outcomes.
Green Entrepreneurial Orientation and Green Innovation: The Mediating Effect of Supply Chain Learning
Authors: Guo Ying , Wang LiFang , Chen Yanyu
Published: January 2020

As a combination of innovation and environmental development concepts, green innovation is of great significance to sustainable development. This article takes supply chain learning as an intermediary to examine the direct and indirect effects of green entrepreneurial orientation (GEO) on green innovation. This study builds a theoretical model among GEO, green incremental innovation, and green radical innovation, and uses empirical data from 416 enterprises in China for testing. The results show that corporate GEO has a positive impact on green incremental innovation and radical innovation. Supply chain learning has a significant positive effect on green incremental and radical innovation. In addition, corporate supply chain learning plays a mediating role in the relationship between GEO and green radical innovation, as well as plays a mediating role in the relationship between GEO and green incremental innovation. This study has an important contribution to enrich the theory of entrepreneurial orientation, green innovation, and supply chain learning, and is of great significance for managers to understand how to use GEO in the process of green innovation development.
Application of the Measure of Peer Justice Climate to a Multiethnic Sample
Authors: Marcano Blaine , Castaño-Collado Gloria
Published: January 2020

The measure created by H. Li offers a useful tool for investigating justice perceptions among team members or peer justice climate; however, more research is required to confirm its structure in lieu of competing models. This study provides evidence for the three-dimensional structure of peer justice climate within a multiethnic context and explores its relation to outcome variable performance. Participants were 304 undergraduate students from universities in the multiethnic, Republic of Trinidad and Tobago. Competing structures of peer justice climate were compared using exploratory and confirmatory factor analyses. Results indicated that peer justice climate is best conceptualized as having three dimensions (distributive, procedural, interactional) with an overarching justice factor connecting them. Suggestions are made for improving the measure. Procedural peer justice climate was found to have a significant positive relation with team performance.
Influence of Trust on Customer Engagement: Empirical Evidence From the Insurance Industry in Ghana
Authors: Agyei James , Sun Shaorong , Abrokwah Eugene , Penney Emmanuel Kofi , Ofori-Boafo Richmond
Published: January 2020

This study examined the influence of trust dimensions on customer engagement, and the resultant impact of customer engagement on customer loyalty in the context of life insurance. Furthermore, it investigated the mediating role of customer engagement in the relationships between trust dimensions and customer loyalty. A total of 452 valid responses from life insurance customers in Ghana were examined using structural equation modeling (SEM). The results revealed that trust in service provider, trust in the regulator, economy-based trust, and information-based trust significantly influence customer engagement, with trust in service provider and trust in the regulator driving a higher level of customer engagement. The results also uncovered that customer engagement significantly enriches customer loyalty and mediated the relationships between the trust dimensions and customer loyalty. The findings highlight the importance of building convincing customer trust to advance customer engagement and customer loyalty.
Measles (Rubeola) 2019
Authors: Emanuele Patricia
Published: January 2020

Outbreaks of measles increased in the United States in 2019. Occupational health nurses need to be aware of this highly infectious disease, disseminate accurate information, and emphasize the benefits of immunization to workers.
Helping Others and Feeling Engaged in the Context of Workplace Flexibility: The Importance of Communication Control
Authors: ter Hoeven Claartje L. , van Zoonen Ward
Published: January 2020

Workplace flexibility can lead to fewer physical encounters, impacting the extent to which employees can help others. This is important because giving help to coworkers facilitates engagement. This study draws on two-wave panel data from 329 employees to examine the relationship between workplace flexibility and engagement through helping behavior. Furthermore, the role of communication control—that is, an employee’s ability to regulate the use of work-related communication technologies—is examined, as it may buffer the negative associations between workplace flexibility and helping behavior. The results demonstrate that spatial flexibility is detrimental to engagement because it reduces helping behavior. Importantly, this negative impact may be alleviated by high levels of communication control (as opposed to low levels). Furthermore, the study provides insights into the independent effects of spatial and temporal flexibility on helping behavior and supports the notion that doing good may lead to feeling good, as helping behavior is positively associated with engagement.
Genome-guided analysis allows the identification of novel physiological traits in Trichococcus species
Authors: Strepis Nikolaos , Naranjo Henry D. , Meier-Kolthoff Jan , Göker Markus , Shapiro Nicole , Kyrpides Nikos , Klenk Hans-Peter , Schaap Peter J. , Stams Alfons J. M. , Sousa Diana Z.
Published: January 2020

Background

The genus Trichococcus currently contains nine species: T. flocculiformis, T. pasteurii, T. palustris, T. collinsii, T. patagoniensis, T. ilyis, T. paludicola, T. alkaliphilus, and T. shcherbakoviae. In general, Trichococcus species can degrade a wide range of carbohydrates. However, only T. pasteurii and a non-characterized strain of Trichococcus, strain ES5, have the capacity of converting glycerol to mainly 1,3-propanediol. Comparative genomic analysis of Trichococcus species provides the opportunity to further explore the physiological potential and uncover novel properties of this genus.

Results

In this study, a genotype-phenotype comparative analysis of Trichococcus strains was performed. The genome of Trichococcus strain ES5 was sequenced and included in the comparison with the other nine type strains. Genes encoding functions related to e.g. the utilization of different carbon sources (glycerol, arabinan and alginate), antibiotic resistance, tolerance to low temperature and osmoregulation could be identified in all the sequences analysed. T. pasteurii and Trichococcus strain ES5 contain a operon with genes encoding necessary enzymes for 1,3-PDO production from glycerol. All the analysed genomes comprise genes encoding for cold shock domains, but only five of the Trichococcus species can grow at 0 °C. Protein domains associated to osmoregulation mechanisms are encoded in the genomes of all Trichococcus species, except in T. palustris, which had a lower resistance to salinity than the other nine studied Trichococcus strains.

Conclusions

Genome analysis and comparison of ten Trichococcus strains allowed the identification of physiological traits related to substrate utilization and environmental stress resistance (e.g. to cold and salinity). Some substrates were used by single species, e.g. alginate by T. collinsii and arabinan by T. alkaliphilus. Strain ES5 may represent a subspecies of Trichococcus flocculiformis and contrary to the type strain (DSM 2094T), is able to grow on glycerol with the production of 1,3-propanediol.
Natural and pathogenic protein sequence variation affecting prion-like domains within and across human proteomes
Authors: Cascarina Sean M. , Ross Eric D.
Published: January 2020

Background

Impaired proteostatic regulation of proteins with prion-like domains (PrLDs) is associated with a variety of human diseases including neurodegenerative disorders, myopathies, and certain forms of cancer. For many of these disorders, current models suggest a prion-like molecular mechanism of disease, whereby proteins aggregate and spread to neighboring cells in an infectious manner. The development of prion prediction algorithms has facilitated the large-scale identification of PrLDs among “reference” proteomes for various organisms. However, the degree to which intraspecies protein sequence diversity influences predicted prion propensity has not been systematically examined.

Results

Here, we explore protein sequence variation introduced at genetic, post-transcriptional, and post-translational levels, and its influence on predicted aggregation propensity for human PrLDs. We find that sequence variation is relatively common among PrLDs and in some cases can result in relatively large differences in predicted prion propensity. Sequence variation introduced at the post-transcriptional level (via alternative splicing) also commonly affects predicted aggregation propensity, often by direct inclusion or exclusion of a PrLD. Finally, analysis of a database of sequence variants associated with human disease reveals a number of mutations within PrLDs that are predicted to increase prion propensity.

Conclusions

Our analyses expand the list of candidate human PrLDs, quantitatively estimate the effects of sequence variation on the aggregation propensity of PrLDs, and suggest the involvement of prion-like mechanisms in additional human diseases.
Evolutionary relationships among bifidobacteria and their hosts and environments
Authors: Rodriguez Cynthia I. , Martiny Jennifer B. H.
Published: January 2020

Background

The assembly of animal microbiomes is influenced by multiple environmental factors and host genetics, although the relative importance of these factors remains unclear. Bifidobacteria (genus Bifidobacterium, phylum Actinobacteria) are common first colonizers of gut microbiomes in humans and inhabit other mammals, social insects, food, and sewages. In humans, the presence of bifidobacteria in the gut has been correlated with health-promoting benefits. Here, we compared the genome sequences of a subset of the over 400 Bifidobacterium strains publicly available to investigate the adaptation of bifidobacteria diversity. We tested 1) whether bifidobacteria show a phylogenetic signal with their isolation sources (hosts and environments) and 2) whether key traits encoded by the bifidobacteria genomes depend on the host or environment from which they were isolated. We analyzed Bifidobacterium genomes available in the PATRIC and NCBI repositories and identified the hosts and/or environment from which they were isolated. A multilocus phylogenetic analysis was conducted to compare the genetic relatedness the strains harbored by different hosts and environments. Furthermore, we examined differences in genomic traits and genes related to amino acid biosynthesis and degradation of carbohydrates.

Results

We found that bifidobacteria diversity appears to have evolved with their hosts as strains isolated from the same host were non-randomly associated with their phylogenetic relatedness. Moreover, bifidobacteria isolated from different sources displayed differences in genomic traits such as genome size and accessory gene composition and on particular traits related to amino acid production and degradation of carbohydrates. In contrast, when analyzing diversity within human-derived bifidobacteria, we observed no phylogenetic signal or differences on specific traits (amino acid biosynthesis genes and CAZymes).

Conclusions

Overall, our study shows that bifidobacteria diversity is strongly adapted to specific hosts and environments and that several genomic traits were associated with their isolation sources. However, this signal is not observed in human-derived strains alone. Looking into the genomic signatures of bifidobacteria strains in different environments can give insights into how this bacterial group adapts to their environment and what types of traits are important for these adaptations.
The transcriptome of Pinus pinaster under Fusarium circinatum challenge
Authors: Hernandez-Escribano Laura , Visser Erik A. , Iturritxa Eugenia , Raposo Rosa , Naidoo Sanushka
Published: January 2020

Background

Fusarium circinatum, the causal agent of pitch canker disease, poses a serious threat to several Pinus species affecting plantations and nurseries. Although Pinus pinaster has shown moderate resistance to F. circinatum, the molecular mechanisms of defense in this host are still unknown. Phytohormones produced by the plant and by the pathogen are known to play a crucial role in determining the outcome of plant-pathogen interactions. Therefore, the aim of this study was to determine the role of phytohormones in F. circinatum virulence, that compromise host resistance.

Results

A high quality P. pinaster de novo transcriptome assembly was generated, represented by 24,375 sequences from which 17,593 were full length genes, and utilized to determine the expression profiles of both organisms during the infection process at 3, 5 and 10 days post-inoculation using a dual RNA-sequencing approach. The moderate resistance shown by Pinus pinaster at the early time points may be explained by the expression profiles pertaining to early recognition of the pathogen, the induction of pathogenesis-related proteins and the activation of complex phytohormone signaling pathways that involves crosstalk between salicylic acid, jasmonic acid, ethylene and possibly auxins. Moreover, the expression of F. circinatum genes related to hormone biosynthesis suggests manipulation of the host phytohormone balance to its own benefit.

Conclusions

We hypothesize three key steps of host manipulation: perturbing ethylene homeostasis by fungal expression of genes related to ethylene biosynthesis, blocking jasmonic acid signaling by coronatine insensitive 1 (COI1) suppression, and preventing salicylic acid biosynthesis from the chorismate pathway by the synthesis of isochorismatase family hydrolase (ICSH) genes. These results warrant further testing in F. circinatum mutants to confirm the mechanism behind perturbing host phytohormone homeostasis.
Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data
Authors: Bhati Meenu , Kadri Naveen Kumar , Crysnanto Danang , Pausch Hubert
Published: January 2020

Background

Autochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution.

Results

We annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive xanthinuria and albinism. The average nucleotide diversity (1.6 ﻿ × 10− 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (FROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (FROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus.

Conclusions

We provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.
Evaluation of resazurin-based assay for rapid detection of polymyxin-resistant gram-negative bacteria
Authors: Jia Huaiyu , Fang Renchi , Lin Jie , Tian Xuebin , Zhao Yajie , Chen Lijiang , Cao Jianming , Zhou Tieli
Published: January 2020

Background

Colistin resistance is considered a serious problem due to a lack of alternative antibiotics. The Rapid ResaPolymyxin Acinetobacter/Pseudomonas NP test is a resazurin reduction-based technique that relies on the visual detection of bacterial growth in the presence of a defined concentration of colistin. The aim of this study was to evaluate the performance of the Rapid ResaPolymyxin Acinetobacter/Pseudomonas NP test in the detection of colistin susceptibility in common clinical Gram-negative bacteria.

Results

A total of 253 clinical isolates from a teaching hospital, including Acinetobacter baumanii (n = 58, 8 colistin-resistant), Pseudomonas aeruginosa (n = 61, 11 colistin-resistant), Klebsiella pneumoniae (n = 70, 20 colistin-resistant) and Escherichia coli (n = 64, 14 colistin-resistant) were tested in this study. The sensitivity and specificity of the Rapid ResaPolymyxin Acinetobacter/Pseudomonas NP test compared to Broth microdilution method was 100 and 99%, respectively.

Conclusions

Our results suggest that Rapid ResaPolymyxin Acinetobacter/Pseudomonas NP test could be used as an accurate detection method for colistin resistance.
Genome wide identification and functional characterization of strawberry pectin methylesterases related to fruit softening
Authors: Xue Cheng , Guan Si-Cong , Chen Jian-Qing , Wen Chen-Jin , Cai Jian-Fa , Chen Xu
Published: January 2020

Background

Pectin methylesterase (PME) is a hydrolytic enzyme that catalyzes the demethylesterification of homogalacturonans and controls pectin reconstruction, being essential in regulation of cell wall modification. During fruit ripening stage, PME-mediated cell wall remodeling is an important process to determine fruit firmness and softening. Strawberry fruit is a soft fruit with a short postharvest life, due to a rapid loss of firm texture. Hence, preharvest improvement of strawberry fruit rigidity is a prerequisite for extension of fruit refreshing time. Although PME has been well characterized in model plants, knowledge regarding the functionality and evolutionary property ofPMEgene family in strawberry remain limited.

Results

A total of 54PMEgenes (FvPMEs) were identified in woodland strawberry (Fragaria vesca‘Hawaii 4’). Phylogeny and gene structure analysis divided theseFvPMEgenes into four groups (Group 1–4). Duplicate events analysis suggested that tandem and dispersed duplications effectively contributed to the expansion of the PME family in strawberry. Through transcriptome analysis, we identifiedFvPME38andFvPME39as the most abundant-expressedPMEs at fruit ripening stages, and they were positively regulated by abscisic acid. Genetic manipulation ofFvPME38andFvPME39by overexpression and RNAi-silencing significantly influences the fruit firmness, pectin content and cell wall structure, indicating a requirement of PME for strawberry fruit softening.

Conclusion

Our study globally analyzed strawberry pectin methylesterases by the approaches of phylogenetics, evolutionary prediction and genetic analysis. We verified the essential role ofFvPME38andFvPME39in regulation of strawberry fruit softening process, which provided a guide for improving strawberry fruit firmness by modifying PME level.
A multicenter randomized placebo controlled trial of rifampin to reduce pedal amputations for osteomyelitis in veterans with diabetes (VA INTREPID)
Authors: Bessesen Mary T. , Doros Gheorghe , Henrie Adam M. , Harrington Kelly M. , Hermos John A. , Bonomo Robert A. , Ferguson Ryan E. , Huang Grant D. , Brown Sheldon T.
Published: January 2020

Background

The prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death.

Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates.

Methods/design

This is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years.

Discussion

VA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected.

Trial registration

Registered January 6, 2017 at ClinicalTrials.gov, NCT03012529.
Impact of a community contraceptive counselling intervention on adolescent fertility rates: a quasi-experimental study
Authors: Diez Elia , Lopez Maria J. , Perez Gloria , Garcia-Subirats Irene , Nebot Laia , Carreras Ramon , Villalbi Joan R.
Published: January 2020

Background

From 2000 to 2008, in urban areas in Spain, adolescent fertility and abortion rates underwent unprecedented increases, consecutive to intensive immigration from developing countries. To address unmet needs for contraception information and services, a community-based, gender-sensitive and culturally adapted brief counselling intervention (SIRIAN program) was launched in some deprived neighbourhoods with a high proportion of immigrants in Barcelona. Once a randomized controlled trial demonstrated its effectiveness in increasing the use of contraceptives, we aim to examine its population impact on adolescent fertility rates.

Methods

Quasi-experimental study with comparison group, using population data from 2005 to 2016. Five neighbourhoods in the lowest tercile of Disposable Household Income were intervened in 2011–13. The comparison group included the three neighbourhoods which were in the same municipal district and in the lowest Disposable Household Income tercile, and displayed the highest adolescent fertility rates. Generalized linear models were fitted to assess absolute adolescent fertility rates and adjusted by immigrant population between pre-intervention (2005–10) and post-intervention periods (2011–16); Difference in Differences and relative pre-post changes analysis were performed.

Results

In 2005–10 the intervention group adolescent fertility rate was 27.90 (per 1000 women 15–19) and 21.84 in the comparison group. In 2011–16 intervention areas experienced great declines (adolescent fertility rate change: − 12.30 (− 12.45 to − 12.21); p < 0.001), while comparison neighbourhoods remained unchanged (adolescent fertility rate change: 1.91 (− 2.25 to 6.07); p = 0.368). A reduction of − 10.97 points (− 13.91 to − 8.03); p < 0.001) is associated to the intervention.

Conclusion

Adolescent fertility rate significantly declined in the intervention group but remained stable in the comparison group. This quasi-experimental study provide evidence that, in a country with universal health coverage, a community counselling intervention that increases access to contraception, knowledge and sexual health care in hard-to-reach segments of the population can contribute to substantially reduce adolescent fertility rates. Reducing adolescent fertility rates could become a feasible goal in cities with similar conditions.
Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis
Authors: Richeldi Luca , Kolb Martin , Jouneau Stéphane , Wuyts Wim A. , Schinzel Birgit , Stowasser Susanne , Quaresma Manuel , Raghu Ganesh
Published: January 2020

Background

The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30–79% predicted. The 24-week INSTAGE trial investigated nintedanib plus sildenafil versus nintedanib alone in patients with IPF and DLco ≤35% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline.

Methods

Analyses were conducted in patients treated with nintedanib alone in the INPULSIS and INSTAGE trials and in patients treated with placebo in the INPULSIS trials. Outcomes included the rate of decline in FVC over 24 weeks, the proportions of patients who had a confirmed or suspected idiopathic acute exacerbation over 24 weeks, deaths over 24 weeks, and adverse events. Analyses were descriptive.

Results

In total, 638 and 136 patients received nintedanib alone in the INPULSIS and INSTAGE trials, respectively, and 423 patients received placebo in the INPULSIS trials. Rates of FVC decline were − 52.3 and − 66.7 mL/24 weeks in patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and − 102.8 mL/24 weeks in patients treated with placebo in INPULSIS. Confirmed or suspected idiopathic acute exacerbations were reported in 0.6 and 3.7% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 2.1% of patients treated with placebo in INPULSIS. Deaths occurred in 2.0, 11.0 and 1.9% of patients in these groups, respectively. Diarrhoea adverse events were reported in 52.5 and 48.5% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 16.1% of patients treated with placebo in INPULSIS.

Conclusions

Based on data from the INSTAGE and INPULSIS trials, nintedanib had a similar effect on FVC decline over 24 weeks, and a similar safety and tolerability profile, in patients with IPF and more versus less severe impairment in gas exchange. These data support the use of nintedanib in patients with IPF who have advanced disease.

Trial registration

INPULSIS (NCT01335464 and NCT01335477); INSTAGE (NCT02802345).
A case of Marfan syndrome with massive haemoptysis from collaterals of the lateral thoracic artery
Authors: Yabuuchi Yuki , Goto Hitomi , Nonaka Mizu , Tachi Hiroaki , Akiyama Tatsuya , Arai Naoki , Ishikawa Hiroaki , Hyodo Kentaro , Nemoto Kenji , Miura Yukiko , Hase Isano , Usui Shingo , Oh-ishi Shuji , Hayashihara Kenji , Saito Takefumi , Chonan Tatsuya
Published: January 2020

Background

Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently.

Case presentation

A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts.

Conclusion

We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.
The value of serum Krebs von den lungen-6 as a diagnostic marker in connective tissue disease associated with interstitial lung disease
Authors: Ma Hua , Lu Junhui , Song Yuanyuan , Wang Huixuan , Yin Songlou
Published: January 2020

Objectives

The purpose of this study was to evaluate the value of serum krebs von den lungen-6 (KL-6) level as a diagnostic indicator for connective tissue disease associated with interstitial lung disease (CTD-ILD).

Methods

One hundred fifty five patients with newly diagnosed CTD in our hospital were enrolled and divided into two groups by their ILD manifestations, the CTD-ILD group and the CTD group. In parallel, 61 patients with pulmonary infection and 60 cases of healthy subjects were also enrolled into the study. The difference of serum KL-6 level among the four groups were compared. In CTD-ILD group, carbon monoxide diffusing capacity (DLCo) and high-resolution computed tomography (HRCT) of lung were also tested. The serum KL-6 level of 32 patients from the CTD-ILD group who received cyclophosphamide (CTX) pulse therapy were sampled and measured, by enzyme linked immunosorbent assay (ELISA), at three time points: before treatment, 3 months after treatment and 6 months after treatment.

Results

The serum KL-6 level in the CTD-ILD group (1004.9 (676.41738.1) IU/ml) is significantly higher than three other groups (χ2 = 72.29, P < 0.001). In the CTD-ILD group the level of serum KL-6 was positively correlated with disease severity on HRCT (r = 0.75, P <  0.001), while was negatively correlated with DLCo (r = − 0.50, P <  0.001). In 32 patients who received CTX pulse therapy, the level of serum KL-6 was gradually decreased in 20 cases whose lesions were absorbed within 6 months (F = 13.67, P <  0.001), whereas it remained unchanged in the rest of 12 patients (Z = -1.328, P = 0.198).

Conclusions

Serum KL-6 level can potentially serve as a diagnostic marker for CTD-ILD and be utilized to evaluate the effectiveness of CTX pulse therapy.