bluuebunny/crossref_metadata_2025 huggingface dataset:
PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Authors: Thejer Bashar M. , Adhikary Partho P. , Teakel Sarah L. , Fang Johnny , Weston Paul A. , Gurusinghe Saliya , Anwer Ayad G. , Gosnell Martin , Jazayeri Jalal A. , Ludescher Marina , Gray Lesley-Ann , Pawlak Michael , Wallace Robyn H. , Pant Sameer D. , Wong Marie , Fischer Tamas , New Elizabeth J. , Fehm Tanja N. , Neubauer Hans , Goldys Ewa M. , Quinn Jane C. , Weston Leslie A. , Cahill Michael A.
Published: April 2020

Background

Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation.

Results

Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture.

Conclusions

A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
CHD9 upregulates RUNX2 and has a potential role in skeletal evolution
Authors: Newton Axel H. , Pask Andrew J.
Published: April 2020

Background

Changes in gene regulation are widely recognized as an important driver of adaptive phenotypic evolution. However, the specific molecular mechanisms that underpin such changes are still poorly understood. Chromatin state plays an essential role in gene regulation, by influencing the accessibility of coding loci to the transcriptional machinery. Changes in the function of chromatin remodellers are therefore strong candidates to drive changes in gene expression associated with phenotypic adaptation. Here, we identify amino acid homoplasies in the chromatin remodeller CHD9, shared between the extinct marsupial thylacine and eutherian wolf which show remarkable skull convergence. CHD9 is involved in osteogenesis, though its role in the process is still poorly understood. We examine whether CHD9 is able to regulate the expression of osteogenic target genes and examine the function of a key substitution in the CHD9 DNA binding domain.

Results

We examined whether CHD9 was able to upregulate its osteogenic target genes, RUNX2, Osteocalcin (OC) and ALP in HEK293T cells. We found that overexpression of CHD9 upregulated RUNX2, the master regulator of osteoblast cell fate, but not the downstream genes OC or ALP, supporting the idea that CHD9 regulates osteogenic progenitors rather than terminal osteoblasts. We also found that the evolutionary substitution in the CHD9 DNA binding domain does not alter protein secondary structure, but was able to drive a small but insignificant increase in RUNX2 activation. Finally, CHD9 was unable to activate an episomal RUNX2 promoter-reporter construct, suggesting that CHD9 requires the full chromatin complement for its function.

Conclusions

We provide new evidence to the role of CHD9 in osteogenic differentiation through its newly observed ability to upregulate the expression of RUNX2. Though we were unable to identify significant functional consequences of the evolutionary substitution in HEK293T cells, our study provides important steps forward in the functional investigation of protein homoplasy and its role in developmental processes. Mutations in coding genes may be a mechanism for driving adaptive changes in gene expression, and their validation is essential towards determining the functional consequences of evolutionary homoplasy.
Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations
Authors: Kimura Risako , Aumpuchin Panyavut , Hamaue Shoya , Shimomura Takumi , Kikuchi Takeshi
Published: April 2020

Background

The details of the folding mechanisms have not yet been fully understood for many proteins, and it is believed that the information on the folding mechanism of a protein is encoded in its amino acid sequence. β-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold symmetric scaffold, despite the proteins’ low sequence identity among superfamilies. In this study, we extract an initial folding unit from the amino acid sequences of irregular β-trefoil proteins by constructing an average distance map (ADM) and utilizing inter-residue average distance statistics to determine the relative contact frequencies for residue pairs in terms of F values. We compare our sequence-based prediction results with the packing between hydrophobic residues in native 3D structures and a Gō-model simulation.

Results

The ADM and F-value analyses predict that the N-terminal and C-terminal regions are compact and that the hydrophobic residues at the central region can be regarded as an interaction center with other residues. These results correspond well to those of the Gō-model simulations. Moreover, our results indicate that the irregular parts in the β-trefoil proteins do not hinder the protein formation. Conserved hydrophobic residues on the β5 strand are always the interaction center of packing between the conserved hydrophobic residues in both regular and irregular β-trefoil proteins.

Conclusions

We revealed that the β5 strand plays an important role in β-trefoil protein structure construction. The sequence-based methods used in this study can extract the protein folding information from only amino acid sequence data, and well corresponded to 3D structure-based Gō-model simulation and available experimental results.
A unified nomenclature for vertebrate olfactory receptors
Authors: Olender Tsviya , Jones Tamsin E. M. , Bruford Elspeth , Lancet Doron
Published: April 2020

Background

Olfactory receptors (ORs) are G protein-coupled receptors with a crucial role in odor detection. A typical mammalian genome harbors ~ 1000 OR genes and pseudogenes; however, different gene duplication/deletion events have occurred in each species, resulting in complex orthology relationships. While the human OR nomenclature is widely accepted and based on phylogenetic classification into 18 families and further into subfamilies, for other mammals different and multiple nomenclature systems are currently in use, thus concealing important evolutionary and functional insights.

Results

Here, we describe the Mutual Maximum Similarity (MMS) algorithm, a systematic classifier for assigning a human-centric nomenclature to any OR gene based on inter-species hierarchical pairwise similarities. MMS was applied to the OR repertoires of seven mammals and zebrafish. Altogether, we assigned symbols to 10,249 ORs. This nomenclature is supported by both phylogenetic and synteny analyses. The availability of a unified nomenclature provides a framework for diverse studies, where textual symbol comparison allows immediate identification of potential ortholog groups as well as species-specific expansions/deletions; for example, Or52e5 and Or52e5b represent a rat-specific duplication of OR52E5. Another example is the complete absence of OR subfamily OR6Z among primate OR symbols. In other mammals, OR6Z members are located in one genomic cluster, suggesting a large deletion in the great ape lineage. An additional 14 mammalian OR subfamilies are missing from the primate genomes. While in chimpanzee 87% of the symbols were identical to human symbols, this number decreased to ~ 50% in dog and cow and to ~ 30% in rodents, reflecting the adaptive changes of the OR gene superfamily across diverse ecological niches. Application of the proposed nomenclature to zebrafish revealed similarity to mammalian ORs that could not be detected from the current zebrafish olfactory receptor gene nomenclature.

Conclusions

We have consolidated a unified standard nomenclature system for the vertebrate OR superfamily. The new nomenclature system will be applied to cow, horse, dog and chimpanzee by the Vertebrate Gene Nomenclature Committee and its implementation is currently under consideration by other relevant species-specific nomenclature committees.
Automation of Spatial Transcriptomics library preparation to enable rapid and robust insights into spatial organization of tissues
Authors: Berglund Emelie , Saarenpää Sami , Jemt Anders , Gruselius Joel , Larsson Ludvig , Bergenstråhle Ludvig , Lundeberg Joakim , Giacomello Stefania
Published: April 2020

Background

Interest in studying the spatial distribution of gene expression in tissues is rapidly increasing. Spatial Transcriptomics is a novel sequencing-based technology that generates high-throughput information on the distribution, heterogeneity and co-expression of cells in tissues. Unfortunately, manual preparation of high-quality sequencing libraries is time-consuming and subject to technical variability due to human error during manual pipetting, which results in sample swapping and the accidental introduction of batch effects. All these factors complicate the production and interpretation of biological datasets.

Results

We have integrated an Agilent Bravo Automated Liquid Handling Platform into the Spatial Transcriptomics workflow. Compared to the previously reported Magnatrix 8000+ automated protocol, this approach increases the number of samples processed per run, reduces sample preparation time by 35%, and minimizes batch effects between samples. The new approach is also shown to be highly accurate and almost completely free from technical variability between prepared samples.

Conclusions

The new automated Spatial Transcriptomics protocol using the Agilent Bravo Automated Liquid Handling Platform rapidly generates high-quality Spatial Transcriptomics libraries. Given the wide use of the Agilent Bravo Automated Liquid Handling Platform in research laboratories and facilities, this will allow many researchers to quickly create robust Spatial Transcriptomics libraries.
Identification and application of piwi-interacting RNAs from seminal plasma exosomes in Cynoglossus semilaevis
Authors: Zhang Bo , Zhao Na , Jia Lei , Che Jinyuan , He Xiaoxu , Liu Kefeng , Bao Baolong
Published: April 2020

Background

Piwi-interacting RNAs (piRNAs) have been linked to epigenetic and post-transcriptional gene silencing of retrotransposons in germ line cells, particularly in spermatogenesis. Exosomes are important mediators of vesicle transport, and the piRNAs in exosomes might play an important role in cell communication and signal pathway regulation. Moreover, exosomic piRNAs are promising biomarkers for disease diagnosis and physiological status indication. We used Cynoglossus semilaevis because of its commercial value and its sexual dimorphism, particularly the sex reversed “pseudomales” who have a female karyotype, produce sperm, and copulate with normal females to produce viable offspring.

Results

To determine whether piRNAs from fish germ line cells have similar features, seminal plasma exosomes from half-smooth tongue sole, C. semilaevis, were identified, and their small RNAs were sequenced and analysed. We identified six signature piRNAs as biomarkers in exosomes of seminal plasma from males and pseudomale C. semilaevis. Bioinformatic analysis showed that all six signatures were sex-related, and four were DNA methylation-related and transposition-related piRNAs. Their expression profiles were verified using real-time quantitative PCR. The expression of the signature piRNAs was markedly higher in males than in pseudomales. The signature piRNAs could be exploited as male-specific biomarkers in this fish.

Conclusions

These signatures provide an effective tool to explore the regulatory mechanism of sex development in C. semilaevis and may provide guidance for future research on the function of piRNAs in the generative mechanism of sex reversed “pseudomales” in C. semilaevis.
Transcriptomic diversity in seedling roots of European flint maize in response to cold
Authors: Frey Felix P. , Pitz Marion , Schön Chris-Carolin , Hochholdinger Frank
Published: April 2020

Background

Low temperatures decrease the capacity for biomass production and lead to growth retardation up to irreversible cellular damage in modern maize cultivars. European flint landraces are an untapped genetic resource for genes and alleles conferring cold tolerance which they acquired during their adaptation to the agroecological conditions in Europe.

Results

Based on a phenotyping experiment of 276 doubled haploid lines derived from the European flint landrace “Petkuser Ferdinand Rot” diverging for cold tolerance, we selected 21 of these lines for an RNA-seq experiment. The different genotypes showed highly variable transcriptomic responses to cold. We identified 148, 3254 and 563 genes differentially expressed with respect to cold treatment, cold tolerance and growth rate at cold, respectively. Gene ontology (GO) term enrichment demonstrated that the detoxification of reactive oxygen species is associated with cold tolerance, whereas amino acids might play a crucial role as antioxidant precursors and signaling molecules.

Conclusion

Doubled haploids representing a European maize flint landrace display genotype-specific transcriptome patterns associated with cold response, cold tolerance and seedling growth rate at cold. Identification of cold regulated genes in European flint germplasm, could be a starting point for introgressing such alleles in modern breeding material for maize improvement.
Identification and analysis of the FAD gene family in walnuts (Juglans regia L.) based on transcriptome data
Authors: Liu Kai , Zhao Shugang , Wang Shuang , Wang Hongxia , Zhang Zhihua
Published: April 2020

Background

Walnut kernels contain a large amount of unsaturated fatty acids, such as linoleic acid and linolenic acid, which are essential fatty acids for humans and have important effects on growth and health. The main function of fatty acid desaturase (FAD), which is widely distributed in organisms, is to remove hydrogen from carbon chains in the biosynthesis of unsaturated fatty acids to generate C=C bonds.

Results

By performing a series of bioinformatics analysis, 24 members of the JrFAD gene family were identified from the genome database of walnut, and then compared with the homologous genes from Arabidopsis. Phylogenetic analysis showed that JrFADs were classified into four subfamilies: the SAD desaturase subfamily, Δ7/Δ9 desaturase subfamily, Δ12/ω-3 desaturase subfamily and “front-end” desaturase subfamily. Meanwhile, the expression of fatty acid synthesis genes in walnut kernels at different developmental stages was analysed by transcriptome sequencing, with expression of JrFAD3-1, which encodes an enzyme involved in linolenic acid synthesis, being particularly prominent. The relative expression level of JrFAD3-1 changed dramatically with the kernel development stages and exhibited a Bell-Shaped Curve. A significant positive correlation was observed between the expression of JrFAD3-1 during 70–100 DAF (Days after flowering) and the content of alpha-linolenic acid during 100–130 DAF, with a correlation coefficient of 0.991. Additionally, JrFAD3-1 was proved closely related to homologous genes in Betula pendula and Corylus heterophylla, indicating that the conserved structure of FADs is consistent with classical plant taxonomy.

Conclusion

Twenty-four members JrFADs in walnut were identified and classified into four subfamilies. JrFAD3-1 may play significant roles in the biosynthesis of polyunsaturated fatty acids in walnut.
Kobuviruses carried by Rattus norvegicus in Guangdong, China
Authors: You Fang-Fei , Zhang Min-Yi , He Huan , He Wen-Qiao , Li Yong-Zhi , Chen Qing
Published: April 2020

Background

Murine kobuviruses (MuKV) are newly recognized picornaviruses first detected in murine rodents in the USA in 2011. Little information on MuKV epidemiology in murine rodents is available. Therefore, we conducted a survey of the prevalence and genomic characteristics of rat kobuvirus in Guangdong, China.

Results

Fecal samples from 223 rats (Rattus norvegicus) were collected from Guangdong and kobuviruses were detected in 12.6% (28) of samples. Phylogenetic analysis based on partial 3D and complete VP1 sequence regions showed that rat kobuvirus obtained in this study were genetically closely related to those of rat/mouse kobuvirus reported in other geographical areas. Two near full-length rat kobuvirus genomes (MM33, GZ85) were acquired and phylogenetic analysis of these revealed that they shared very high nucleotide/amino acids identity with one another (95.4%/99.4%) and a sewage-derived sequence (86.9%/93.5% and 87.5%/93.7%, respectively). Comparison with original Aichivirus A strains, such human kobuvirus, revealed amino acid identity values of approximately 80%.

Conclusion

Our findings indicate that rat kobuvirus have distinctive genetic characteristics from other Aichivirus A viruses. Additionally, rat kobuvirus may spread via sewage.
Silver diamine fluoride (SDF) used in childhood caries management has potent antifungal activity against oral Candida species
Authors: Fakhruddin Kausar Sadia , Egusa Hiroshi , Ngo Hien Chi , Panduwawala Chamila , Pesee Siripen , Venkatachalam Thenmozhi , Samaranayake Lakshman Perera
Published: April 2020

Background

The microbiome of Severe-Early Childhood Caries (S-ECC), is characterized by an ecosystem comprising bacterial and fungal species, with a predominance of Candida species. Hence, an anti-cariogen effective against both bacteria and fungi would be valuable in the management of S-ECC.

Here we evaluate the antifungal effect of silver diamine fluoride (SDF) against 35-clinical yeast isolates (Ten-each of C. albicans, C. krusei, C. tropicalis and five C. glabrata strains) from dentinal caries-lesions from S-ECC.

Results

Disc-diffusion and time-kill assays as well as MIC50 and MIC90 evaluations against therapeutic concentrations confirmed the broad-spectrum anti-candidal potency of SDF. Ultrastructural images revealed morphologic aberrations of yeast-cell walls on exposure to SDF. All C. krusei and C. glabrata isolates were significantly more sensitive to SDF, relative to the standard antifungal fluconazole. Further, SDF appears to effectively abrogate filamentation of C. albicans even at very low concentrations.

Conclusions

Our data, for the first time, elucidate the antifungal potency of SDF, in addition to its known antibacterial activity, in the management of S-ECC.
Identification of a virulence tal gene in the cotton pathogen, Xanthomonas citri pv. malvacearum strain Xss-V2–18
Authors: Haq Fazal , Xie Shiwang , Huang Kunxuan , Shah Syed Mashab Ali , Ma Wenxiu , Cai Lulu , Xu Xiameng , Xu Zhengyin , Wang Sai , Zou Lifang , Zhu Bo , Chen Gongyou
Published: April 2020

Background

Bacterial blight of cotton (BBC), which is caused by the bacterium Xanthomonas citri pv. malvacearum (Xcm), is a destructive disease in cotton. Transcription activator-like effectors (TALEs), encoded by tal-genes, play critical roles in the pathogenesis of xanthomonads. Characterized strains of cotton pathogenic Xcm harbor 8–12 different tal genes and only one of them is functionally decoded. Further identification of novel tal genes in Xcm strains with virulence contributions are prerequisite to decipher the Xcm-cotton interactions.

Results

In this study, we identified six tal genes in Xss-V2–18, a highly-virulent strain of Xcm from China, and assessed their role in BBC. RFLP-based Southern hybridization assays indicated that Xss-V2–18 harbors the six tal genes on a plasmid. The plasmid-encoded tal genes were isolated by cloning BamHI fragments and screening clones by colony hybridization. The tal genes were sequenced by inserting a Tn5 transposon in the DNA encoding the central repeat region (CRR) of each tal gene. Xcm TALome evolutionary relationship based on TALEs CRR revealed relatedness of Xss-V2–18 to MSCT1 and MS14003 from the United States. However, Tal2 of Xss-V2–18 differs at two repeat variable diresidues (RVDs) from Tal6 and Tal26 in MSCT1 and MS14003, respectively, inferred functional dissimilarity. The suicide vector pKMS1 was then used to construct tal deletion mutants in Xcm Xss-V2–18. The mutants were evaluated for pathogenicity in cotton based on symptomology and growth in planta. Four mutants showed attenuated virulence and all contained mutations in tal2. One tal2 mutant designated M2 was further investigated in complementation assays. When tal2 was introduced into Xcm M2 and expressed in trans, the mutant was complemented for both symptoms and growth in planta, thus indicating that tal2 functions as a virulence factor in Xcm Xss-V2–18.

Conclusions

Overall, the results demonstrated that Tal2 is a major pathogenicity factor in Xcm strain Xss-V2–18 that contributes significantly in BBC. This study provides a foundation for future efforts aimed at identifying susceptibility genes in cotton that are targeted by Tal2.
LncRNA regulates tomato fruit cracking by coordinating gene expression via a hormone-redox-cell wall network
Authors: Xue Lingzi , Sun Mintao , Wu Zhen , Yu Lu , Yu Qinghui , Tang Yaping , Jiang Fangling
Published: April 2020

Background

Fruit cracking occurs easily under unsuitable environmental conditions and is one of the main types of damage that occurs in fruit production. It is widely accepted that plants have developed defence mechanisms and regulatory networks that respond to abiotic stress, which involves perceiving, integrating and responding to stress signals by modulating the expression of related genes. Fruit cracking is also a physiological disease caused by abiotic stress. It has been reported that a single or several genes may regulate fruit cracking. However, almost none of these reports have involved cracking regulatory networks.

Results

Here, RNA expression in 0 h, 8 h and 30 h saturated irrigation-treated fruits from two contrasting tomato genotypes, ‘LA1698’ (cracking-resistant, CR) and ‘LA2683’ (cracking-susceptible, CS), was analysed by mRNA and lncRNA sequencing. The GO pathways of the differentially expressed mRNAs were mainly enriched in the ‘hormone metabolic process’, ‘cell wall organization’, ‘oxidoreductase activity’ and ‘catalytic activity’ categories. According to the gene expression analysis, significantly differentially expressed genes included Solyc02g080530.3 (Peroxide, POD), Solyc01g008710.3 (Mannan endo-1,4-beta-mannosidase, MAN), Solyc08g077910.3 (Expanded, EXP), Solyc09g075330.3 (Pectinesterase, PE), Solyc07g055990.3 (Xyloglucan endotransglucosylase-hydrolase 7, XTH7), Solyc12g011030.2 (Xyloglucan endotransglucosylase-hydrolase 9, XTH9), Solyc10g080210.2 (Polygalacturonase-2, PG2), Solyc08g081010.2 (Gamma-glutamylcysteine synthetase, gamma-GCS), Solyc09g008720.2 (Ethylene receptor, ER), Solyc11g042560.2 (Ethylene-responsive transcription factor 4, ERF4) etc. In addition, the lncRNAs (XLOC_16662 and XLOC_033910, etc) regulated the expression of their neighbouring genes, and genes related to tomato cracking were selected to construct a lncRNA-mRNA network influencing tomato cracking.

Conclusions

This study provides insight into the responsive network for water-induced cracking in tomato fruit. Specifically, lncRNAs regulate the hormone-redox-cell wall network, including plant hormone (auxin, ethylene) and ROS (H2O2) signal transduction and many cell wall-related mRNAs (EXP, PG, XTH), as well as some lncRNAs (XLOC_16662 and XLOC_033910, etc.).
Identification and validation of mutation points associated with waxy phenotype in cassava
Authors: do Carmo Cátia Dias , Sousa Massaine Bandeira e , dos Santos Silva Priscila Patrícia , Oliveira Gilmara Alvarenga Fachardo , Ceballos Hernán , de Oliveira Eder Jorge
Published: April 2020

Background

The granule-bound starch synthase I (GBSSI) enzyme is responsible for the synthesis of amylose, and therefore, its absence results in individuals with a waxy starch phenotype in various amylaceous crops. The validation of mutation points previously associated with the waxy starch phenotype in cassava, as well as the identification of alternative mutant alleles in the GBSSI gene, can allow the development of molecular-assisted selection to introgress the waxy starch mutation into cassava breeding populations.

Results

A waxy cassava allele has been identified previously, associated with several SNPs. A particular SNP (intron 11) was used to develop SNAP markers for screening heterozygote types in cassava germplasm. Although the molecular segregation corresponds to the expected segregation at 3:1 ratio (dominant gene for the presence of amylose), the homozygotes containing the SNP associated with the waxy mutation did not show waxy phenotypes. To identify more markers, we sequenced the GBSS gene from 89 genotypes, including some that were segregated from a cross with a line carrying the known waxy allele. As a result, 17 mutations in the GBSSI gene were identified, in which only the deletion in exon 6 (MeWxEx6-del-C) was correlated with the waxy phenotype. The evaluation of mutation points by discriminant analysis of principal component analysis (DAPC) also did not completely discriminate the waxy individuals. Therefore, we developed Kompetitive Allele Specific PCR (KASP) markers that allowed discrimination between WX and wx alleles. The results demonstrated the non-existence of heterozygous individuals of the MeWxEx6-del-C deletion in the analyzed germplasm. Therefore, the deletion MeWxEx6-del-C should not be used for assisted selection in genetic backgrounds different from the original source of waxy starch. Also, the alternative SNPs identified in this study were not associated with the waxy phenotype when compared to a panel of accessions with high genetic diversity.

Conclusion

Although the GBSSI gene can exhibit several mutations in cassava, only the deletion in exon 6 (MeWxEx6-del-C) was correlated with the waxy phenotype in the original AM206–5 source.
High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience
Authors: Zhuang Yu-Gang , Chen Yuan-Zhuo , Zhou Shu-Qin , Peng Hu , Chen Yan-Qing , Li Dong-Jie
Published: April 2020

Background

Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines (interleukin-17 [IL-8], IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post–cardiac arrest period.

Methods

This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated “survivors”. The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays.

Results

Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC.

Conclusion

These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients.

Trial registration

Clinicaltrial.govNCT02297776, 2014-11-21.
The interaction between serum uric acid and triglycerides level on blood pressure in middle-aged and elderly individuals in China: result from a large national cohort study
Authors: Zhang Lin , Li Jin-long , Guo Lei-lei , Li Hong , Li Dan , Xu Guang
Published: April 2020

Background

The purpose of the research was to explore the extent of interaction between triglycerides (TG) and serum uric acid (SUA) level with blood pressure (BP) in middle-aged and elderly individuals in China.

Methods

Data were selected from the China Health and Retirement Longitudinal Study (CHARLS), a cross-sectional study. 3345(46.99%) men with average ages of 60.24 ± 9.24 years and 3774 (53.01%) women with average ages of 59.91 ± 9.95 years were included in the study. Differences between gender, or between categories of blood pressure levels were evaluated by t-test or chi-square test. The adjusted associations between various characteristics and BP status were first compared using linear regression models, as appropriate. Then, A general linear model adjusted for confounding factors (socio-demographic characteristics [age, educational levels, marital status, place of residence], health behaviors [cigarette smoking, alcohol drinking, eating habits, social and leisure activities, accidental injury, physical activities], medical history [history of cardiovascular diseases, hepatitis history, antidiabetic drugs, history of antilipidemic medication, anti-hypertensive therapy], metabolic measures [C-reactive protein (CRP), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), body mass index (BMI)]) was used to examine the synergistic effect of SUA and TG level on BP in middle-aged and elderly individuals in China.

Results

Age-adjusted partial Pearson’s correlation coefficient showed that SUA and TG level positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both men and women. Multiple linear regression analysis showed the TG level was significantly and positively associated with SBP and DBP in both men (SBP: β =0.068, P = 0.001; DBP: β =0.064, P = 0.002) and women (SBP: β =0.061, P = 0.002; DBP: β =0.084, P = 0.000), but SUA were significantly and positively associated with SBP in both men (SBP: β =0.047, P = 0.013) and women (SBP: β =0.040, P = 0.028), regardless of other confounding factors. After adjusting for related potential confounders, evidence of interaction between SUA and TG level on SBP (men: β = − 1.090, P = 0.726; women: β = − 0.692, P = 0.861) and DBP (men: β = − 1.026, P = 0.572; women: β = − 0.794, P = 0.842) was not observed.

Conclusion

The interaction effect of SUA and TG level on BP was not observed in our study. Moreover, high SUA level was significantly associated with SBP, while high TG level was strongly related to both DBP and SBP.
Clustering of continuous and binary outcomes at the general practice level in individually randomised studies in primary care - a review of 10 years of primary care trials
Authors: Stuart Beth , Becque Taeko , Moore Michael , Little Paul
Published: April 2020

Background

In randomised controlled trials, the assumption of independence of individual observations is fundamental to the design, analysis and interpretation of studies. However, in individually randomised trials in primary care, this assumption may be violated because patients are naturally clustered within primary care practices. Ignoring clustering may lead to a loss of power or, in some cases, type I error.

Methods

Clustering can be quantified by intra-cluster correlation (ICC), a measure of the similarity between individuals within a cluster with respect to a particular outcome. We reviewed 17 trials undertaken by the Department of Primary Care at the University of Southampton over the last ten years. We calculated the ICC for the primary and secondary outcomes in each trial at the practice level and determined whether ignoring practice-level clustering still gave valid inferences. Where multiple studies collected the same outcome measure, the median ICC was calculated for that outcome.

Results

The median intra-cluster correlation (ICC) for all outcomes was 0.016, with interquartile range 0.00–0.03.

The median ICC for symptom severity was 0.02 (interquartile range (IQR) 0.01 to 0.07) and for reconsultation with new or worsening symptoms was 0.01 (IQR 0.00, 0.07). For HADS anxiety the ICC was 0.04 (IQR 0.02, 0.05) and for HADS depression was 0.02 (IQR 0.00, 0.05). The median ICC for EQ. 5D-3 L was 0.01 (IQR 0.01, 0.04).

Conclusions

There is evidence of clustering in individually randomised trials primary care. The non-zero ICC suggests that, depending on study design, clustering may not be ignorable. It is important that this is fully considered at the study design phase.
Examining Interprofessional teams structures and processes in the implementation of a primary care intervention (Health TAPESTRY) for older adults using normalization process theory
Authors: Valaitis Ruta , Cleghorn Laura , Dolovich Lisa , Agarwal Gina , Gaber Jessica , Mangin Derelie , Oliver Doug , Parascandalo Fiona , Ploeg Jenny , Risdon Cathy
Published: April 2020

Background

Many countries are engaged in primary care reforms to support older adults who are living longer in the community. Health Teams Advancing Patient Experience: Strengthening Quality [Health TAPESTRY] is a primary care intervention aimed at supporting older adults that involves trained volunteers, interprofessional teams, technology, and system navigation. This paper examines implementation of Health TAPESTRY in relation to interprofessional teamwork including volunteers.

Methods

This study applied Normalization Process Theory (NPT) and used a descriptive qualitative approach [1] embedded in a mixed-methods, pragmatic randomized controlled trial. It was situated in two primary care practice sites in a large urban setting in Ontario, Canada. Focus groups and interviews were conducted with primary care providers, clinical managers, administrative assistants, volunteers, and a volunteer coordinator. Data was collected at 4 months (June–July 2015) and 12 months (February–March 2016) after intervention start-up. Patients were interviewed at the end of the six-month intervention. Field notes were taken at weekly huddle meetings.

Results

Overall, 84 participants were included in 17 focus groups and 13 interviews; 24 field notes were collected. Themes were organized under four NPT constructs of implementation: 1) Coherence- (making sense/understanding of the program’s purpose/value) generating comprehensive assessments of older adults; strengthening health promotion, disease prevention, and self-management; enhancing patient-focused care; strengthening interprofessional care delivery; improving coordination of health and community services. 2) Cognitive Participation- (enrolment/buy-in) tackling new ways of working; attaining role clarity. 3) Collective Action- (enactment/operationalizing) changing team processes; reconfiguring resources. 4) Reflective Monitoring- (appraisal) improving teamwork and collaboration; reconfiguring roles and processes.

Conclusions

This study contributes key strategies for effective implementation of interventions involving interprofessional primary care teams. Findings indicate that regular communication among all team members, the development of procedures and/or protocols to support team processes, and ongoing review and feedback are critical to implementation of innovations involving primary care teams.

Trial registration

ClinicalTrials.gov, no. NCT02283723 November 5, 2014. Prospectively registered.
Primary isolated asymptomatic gastric tuberculosis of the cardia mimicking gastric stromal tumor: a rare case report and literature review
Authors: Lv Mingnan , Tang Kejiang , Meng Yajie , Tian Chuan , Wang Min
Published: April 2020

Background

Primary isolated gastric TB of the cardia presenting as a submucosal tumor is extremely rare.

Case presentation

A 60-year-old female was admitted to our department; endoscopy revealed a smooth protruding lesion in the gastric cardia. The patient was diagnosed with a gastric cardia stromal tumor and the lesion was seen in muscularis propria by endoscopic ultrasonography (EUS). Endoscopic submucosal dissection (ESD) revealed that the lesion was filled with a milky, white liquid and white granulation tissue. Acid-fast specimen staining was negative. Hematoxylin and eosin staining showed patches of caseating necrosis and granulomatous inflammation. Gene sequencing subsequent to polymerase chain reaction (PCR) analysis of the ESD specimen identified Mycobacterium tuberculosis (M. TB) DNA fragments. The patient was put on ATT for 6 months.

Conclusion

Primary isolated gastric TB of the cardia should be suspected in patients without clinical symptoms whose manifestations are similar to those associated with submucosal tumors. TB-PCR may be helpful for further diagnosis.
Baseline levels of dynamic CD4+ T cell adhesion to MAdCAM-1 correlate with clinical response to vedolizumab treatment in ulcerative colitis: a cohort study
Authors: Allner Clarissa , Melde Michaela , Becker Emily , Fuchs Friederike , Mühl Laura , Klenske Entcho , Müller Lisa , Morgenstern Nadine , Fietkau Konstantin , Hirschmann Simon , Atreya Raja , Atreya Imke , Neurath Markus F. , Zundler Sebastian
Published: April 2020

Background

While the number of therapeutic options for treating inflammatory bowel diseases (IBD) is increasing, evidence for rational treatment decisions is scarce in many cases. In particular, appropriate biomarkers to predict the response to the anti-α4β7 integrin antibody vedolizumab are currently lacking.

Methods

We performed a cohort study with 21 patients suffering from ulcerative colitis (UC), in which first-time treatment with vedolizumab was initiated. CD4+ T cells were isolated from the peripheral blood and dynamic adhesion to recombinant mucosal vascular addressin cell adhesion molecule (MAdCAM-)1 in vitro as well as the effect of vedolizumab on such adhesion in vitro was determined. The expression of α4β1 integrin on peripheral blood CD4+ T cells was quantified by flow cytometry. Electronic patient records were reviewed to determine clinical response to vedolizumab.

Results

Dynamic adhesion of peripheral blood CD4+ T cells to MAdCAM-1 and the reduction of adhesion following vedolizumab treatment in vitro were higher and the change in α4β1 expression on CD4+ T cells was different in vedolizumab responders and non-responders. Responders could be identified with high specificity and positive-predictive value.

Conclusions

Determining dynamic adhesion of CD4+ T cells to MAdCAM-1 and the in vitro response to vedolizumab before treatment initiation or dynamic integrin regulation in the early course of treatment seem to be promising tools to predict the clinical response to vedolizumab therapy. Larger prospective studies are warranted.
Lower level of complement component C3 and C3a in the plasma means poor outcome in the patients with hepatitis B virus related acute-on-chronic liver failure
Authors: Li Qian , Lu Qing , Zhu Meng-Qi , Huang Chong , Yu Kang-Kang , Huang Yu-Xian , Zhao Xu , Luo Xing-Guang , Zheng Jian-Ming
Published: April 2020

Background

The purpose of this study is to investigate whether or not the complement system is systemically activated and to specify the clinical and prognostic implications of its components during hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF).

Methods

Blood samples were taken from twenty-seven patients diagnosed with HBV-ACLF, twenty-five patients diagnosed with chronic hepatitis B but without liver failure (CHB), and nine healthy volunteers (the control group). Plasma complement components were measured with Enzyme-linked immunosorbent assay. Correlative analysis were assessed between the levels of complement components and the liver failure related index.

Results

The concentrations of C3 was 6568 μg/ml in the HBV-ACLF group, 8916 μg/ml in the CHB group and 15,653 μg/ml in the control group, respectively (P <  0.05). The concentrations of C3a was 852 ng/ml in the HBV-ACLF group, 1008 ng/ml in the CHB group and 1755 ng/ml in the control group, respectively (P <  0.05). The concentrations of C1q was 50,509 ng/ml in the HBV-ACLF group, 114,640 ng/ml in the CHB group and 177,001 ng/ml in the control group, respectively (P <  0.05). The concentrations of C1q, C3, C3a, C4, C4a and sC5b-9 were significantly higher in the control group than those in the HBV-ACLF group (3.5, 2.4, 2.1, 1.4, 1.3 and 6.0 fold, respectively). However, there was no statistical significance of the differences in the plasma concentrations of mannose binding lectin and factor B between the HBV-ACLF group and control group. The levels of C3 and C3a were inversely correlated with MELDs or CLIF-C OFs (P <  0.05).

Conclusions

Our analysis demonstrated that the activation of the classical pathway mediated by C1q may play an important role in the pathogenesis of HBV-ACLF. Furthermore, the plasma levels of C3 and C3a may be potential novel biomarkers in predicting the outcome of HBV-ACLF.
Hospital falls prevention with patient education: a scoping review
Authors: Heng Hazel , Jazayeri Dana , Shaw Louise , Kiegaldie Debra , Hill Anne-Marie , Morris Meg E.
Published: April 2020

Background

Hospital falls remain a frequent and debilitating problem worldwide. Most hospital falls prevention strategies have targeted clinician education, environmental modifications, assistive devices, hospital systems and medication reviews. The role that patients can play in preventing falls whilst in hospital has received less attention. This critical review scopes patient falls education interventions for hospitals. The quality of the educational designs under-pinning patient falls education programmes was also evaluated. The outcomes of patient-centred falls prevention programs were considered for a range of hospital settings and diagnoses.

Methods

The Arksey and O’Malley (2005) framework for scoping reviews was adapted using Joanna Briggs Institute and PRISMA-ScR guidelines. Eight databases, including grey literature, were searched from January 2008 until February 2020. Two reviewers independently screened the articles and data were extracted and summarised thematically. The quality of falls prevention education programs for patients was also appraised using a modified quality metric tool.

Results

Forty-three articles were included in the final analysis. The interventions included: (i) direct face-to-face patient education about falls risks and mitigation; (ii) educational tools; (iii) patient-focussed consumer materials such as pamphlets, brochures and handouts; and (iv) hospital systems, policies and procedures to assist patients to prevent falls. The included studies assessed falls or education related outcomes before and after patient falls prevention education. Few studies reported incorporating education design principles or educational theories. When reported, most educational programs were of low to moderate quality from an educational design perspective.

Conclusions

There is emerging evidence that hospital falls prevention interventions that incorporate patient education can reduce falls and associated injuries such as bruising, lacerations or fractures. The design, mode of delivery and quality of educational design influence outcomes. Well-designed education programs can improve knowledge and self-perception of risk, empowering patients to reduce their risk of falling whilst in hospital.
The association between frailty and incidence of dementia in Beijing: findings from 10/66 dementia research group population-based cohort study
Authors: Li Minghui , Huang Yueqin , Liu Zhaorui , Shen Rui , Chen Hongguang , Ma Chao , Zhang Tingting , Li Shuran , Prince Martin
Published: April 2020

Background

The relationship between frailty and dementia is unclear and there are very few population-based studies regarding this issue in China. The purpose of this study is to estimate the association between frailty and incident dementia in China, and to explore different effects of frailty established by three definitions of frailty on dementia incidence.

Methods

A five-year prospective cohort study was carried out in 2022 participants aged 65 years and over in urban and rural sites in Beijing, China. The participants were interviewed by trained community primary health care workers from 2004 to 2009. Frailty was defined using modified Fried frailty phenotype, physical frailty definition, and multidimensional frailty definition. Dementia was diagnosed using the 10/66 dementia criterion for calculating cumulative incidence. Both competing risk regression models and Cox proportional hazards models were applied to examine the associations between frailty at baseline and five-year cumulative incidence of dementia.

Results

At the end of follow-up the five-year cumulative incidence rates of dementia with frailty and without frailty defined by the modified Fried frailty were 21.0% and 9.6%, those defined by the physical frailty were 19.9% and 9.0%, and those defined by the multidimensional frailty were 22.8% and 8.9%, respectively. Compared with non-frail participants, frail people had a higher risk of incident dementia using multidimensional frailty definition after adjusting covariates based on competing risk regression model (HR = 1.47, 95% CI 1.01~2.17) and Cox proportional hazards model (HR = 1.56, 95% CI 1.07~2.26). The association between frailty and incident dementia was statistically significant in participants in the upper three quartiles of age (aged 68 years and over) using the multidimensional frailty definition based on the competing risk regression model (HR = 1.61, 95% CI 1.06~2.43) and Cox proportional hazard model (HR = 1.76, 95% CI 1.19~2.61).

Conclusions

Multidimensional frailty may play an inherent role in incident dementia, especially in the people aged over 68, which is significant for distinguishing high risk people and determining secondary prevention strategies for dementia patients.