bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbially influenced formation of Neoarchean ooids
Authors: Flannery David T. , Allwood Abigail C. , Hodyss Robert , Summons Roger Everett , Tuite Michael , Walter Malcolm R. , Williford Kenneth H. 
Published: November 2018

AbstractOoids are accretionary grains commonly reported from turbulent, shallow‐water environments. They have long been associated with microbially dominated ecosystems and often occur in close proximity to, or embedded within, stromatolites, yet have historically been thought to form solely through physicochemical processes. Numerous studies have revealed both constructive and destructive roles for microbes colonizing the surfaces of modern calcitic and aragonitic ooids, but there has been little evidence for the operation of these processes during the Archean and Proterozoic, when both ooids and microbially dominated ecosystems were more widespread. Recently described carbonate ooids from the 2.9 Ga Pongola Supergroup, South Africa, include well‐preserved examples composed of diagenetic dolomite interpreted to have formed from a high‐Mg‐calcite precursor. Spatial distributions of organic matter and elements associated with metabolic activity (N, S, and P) were interpreted as evidence for a biologically induced origin. Here, we describe exceptionally well‐preserved ooids composed of calcite, collected from Earth's oldest known carbonate lake system, the ~2.72 Ga Meentheena Member (Tumbiana Formation), Fortescue Group, Western Australia. We used optical microscopy, Raman spectroscopy, XRD, SEM‐EDS, LA‐ICP‐MS, EA‐IRMS, and a novel micro‐XRF instrument to investigate an oolite shoal deposited between stromatolites that preserve abundant evidence for microbial activity. We report an extremely fine, radial‐concentric, calcitic microfabric that is similar to the primary and early diagenetic fabrics of calcitic ooids reported from modern temperate lakes. Early diagenetic silica has trapped isotopically light and thermally mature organic matter. The close association of organic matter with mineral phases and microfabrics related to primary and early diagenetic processes suggest incorporation of organic matter occurred during accretion, likely due to the presence of microbial biofilms. We conclude that the oldest known calcitic ooids were likely formed through processes similar to those that mediate the accretion of ooids in similar environments today, including formation within a microbial biosphere.
Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis
Authors: Lundqvist Sara , Modvig Signe , Fischer Emilie A. , Frederiksen Jette L. , Degn Matilda 
Published: November 2018

SummaryMouse models of multiple sclerosis (MS) have shown the importance of interleukin‐10 (IL‐10) ‐producing regulatory B (Breg) cells in dampening disease activity and inhibiting disease initiation and progression. In MS and other autoimmune diseases decreased frequency and functionality of Breg cells correlate with disease activity and the percentage of IL‐10‐producing Breg cells decreases during relapse and normalizes in remission. Optic neuritis (ON) is a common first clinical manifestation of MS and IL‐10‐producing Breg cells may be crucial in the transition from ON to MS, we therefore investigate the frequency and function of Breg cells in ON as a clinical model of early demyelinating disease. B cells were purified from 27 patients with ON sampled close to symptom onset (median 23 days, range 7–41 days) and 13 healthy controls. The B cells were stimulated and cultured for 48 hr with CD40 ligand and CpG before measurement of intracellular IL‐10 and the surface markers CD19, CD1d, CD5, CD24, CD38 and CD27 by flow cytometry. The frequency of B‐cell subsets was analysed in peripheral blood and cerebral spinal fluid (CSF) of patients. Sixty‐five per cent of the IL‐10‐producing Breg cells co‐expressed CD24 and CD38, and only 14% were CD24high CD27+, suggesting that the naive B cells are the primary source of IL‐10 in the B‐cell culture, followed by memory cells in both healthy controls and patients. The frequency of naive CD19+ CD24+ CD38+ Breg cells was higher in patients with ON compared with controls. The ability of Breg cells to produce IL‐10 was at normal levels in both ON patients with high risk and those with low risk of progression to MS. We found no correlation between Breg cell function and the presence of brain white matter lesions by magnetic resonance imaging or CSF oligoclonal bands indicative of ON patients carrying a higher risk of conversion to MS. The frequencies of IL‐10‐producing B cells did not correlate with the conversion to MS at 2‐year follow up. Interleukin‐10 was primarily produced by naive and memory B cells. The frequency of IL‐10‐secreting B cells did not correlate with risk factors of MS. Breg cell function at clinical onset of ON is not a determining factor for conversion to MS.
Trauma exposure and post‐traumatic stress disorder in people with intellectual disabilities: A Delphi expert rating
Authors: Rittmannsberger Doris , Kocman Andreas , Weber Germain , Lueger‐Schuster Brigitte 
Published: November 2018

AbstractBackgroundThere is a lack of research on trauma in people with intellectual disabilities. This study assessed expert consensus on the traumatic potential of a broader range of adverse life events, and differences in symptom manifestation and behavioural symptom equivalents of post‐traumatic stress disorder (PTSD) symptoms.MethodThe present authors conducted a three‐step Delphi survey using a mixed‐methods design. Twenty‐nine expert raters participated in the survey, and 16 persisted to the final round. Consensus was calculated using the interquartile range.ResultsTraumatic potential was attributed to adverse life events, particularly revolving around sexuality and autonomy. DSM‐5 symptoms of PTSD were rated as partially adequate, with behavioural symptom expression being the main difference to the general population.ConclusionThe range of traumatic events should be broadened for people with intellectual disabilities. A specific subset of events need to be defined in future research. Detection of PTSD depends upon determining specific symptom correlates of challenging behaviour.
Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
Authors: Lu Yingfeng , Li Rui , Zhu Junyi , Wu Yanqing , Li Duohui , Dong Lupeng , Li Yiyang , Wen Xin , Yu Fangzheng , Zhang Hongyu , Ni Xiao , Du Shenghu , Li Xiaokun , Xiao Jian , Wang Jian 
Published: November 2018

AbstractSeeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention. Fibroblast growth factor 21 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation. Furthermore, local FGF21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid‐2‐related factor 2 (Nrf‐2) transcription and extracellular regulated protein kinases (ERK) phosphorylation. We detected FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3‐MA partially abolishes anti‐oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 in remyelination and nerve regeneration after PNI was probably related to inhibit the excessive activation of ERK/Nrf‐2 signalling‐regulated oxidative stress and autophagy‐induced cell death. Overall, our work suggests that FGF21 administration may provide a new therapy for PNI.
TRPV4 regulates matrix stiffness and TGFβ1‐induced epithelial‐mesenchymal transition
Authors: Sharma Shweta , Goswami Rishov , Zhang David X. , Rahaman Shaik O. 
Published: November 2018

AbstractSubstrate stiffness (or rigidity) of the extracellular matrix has important functions in numerous pathophysiological processes including fibrosis. Emerging data support a role for both a mechanical signal, for example, matrix stiffness, and a biochemical signal, for example, transforming growth factor β1 (TGFβ1), in epithelial‐mesenchymal transition (EMT), a process critically involved in fibrosis. Here, we report evidence showing that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive channel, is the likely mediator of EMT in response to both TGFβ1 and matrix stiffness. Specifically, we found that: (a) genetic ablation or pharmacological inhibition of TRPV4 blocked matrix stiffness and TGFβ1‐induced EMT in normal mouse primary epidermal keratinocytes (NMEKs) as determined by changes in morphology, adhesion, migration and alterations of expression of EMT markers including E‐cadherin, N‐cadherin (NCAD) and α‐smooth muscle actin (α‐SMA), and (b) TRPV4 deficiency prevented matrix stiffness‐induced EMT in NMEKs over a pathophysiological range. Intriguingly, TRPV4 deletion in mice suppressed expression of mesenchymal markers, NCAD and α‐SMA, in a bleomycin‐induced murine skin fibrosis model. Mechanistically, we found that: (a) TRPV4 was essential for the nuclear translocation of YAP/TAZ (yes‐associated protein/transcriptional coactivator with PDZ‐binding motif) in response to matrix stiffness and TGFβ1, (b) TRPV4 deletion inhibited both matrix stiffness‐ and TGFβ1‐induced expression of YAP/TAZ proteins and (c) TRPV4 deletion abrogated both matrix stiffness‐ and TGFβ1‐induced activation of AKT, but not Smad2/3, suggesting a mechanism by which TRPV4 activity regulates EMT in NMEKs. Altogether, these data identify a novel role for TRPV4 in regulating EMT.
Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families
Authors: Reis Sabrina T. , Leite Katia R. M. , Marchini Giovanni S. , Guimarães Ronaldo M. , Viana Nayara I. , Pimenta Ruan C. A. , Torricelli Fabio C. , Danilovic Alexandre , Vicentini Fábio Carvalho , Nahas William Carlos , Srougi Miguel , Mazzucchi Eduardo 
Published: November 2018

AbstractThe aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome‐Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0‐fold (P = 0.036). Pre‐B‐cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3‐fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild‐type homozygote genotype had overexpression of PBX1. There is a 3‐fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.
Clinical association of metabolic syndrome, C‐reactive protein and testosterone levels with clinically significant prostate cancer
Authors: Gómez‐Gómez Enrique , Carrasco‐Valiente Julia , Campos‐Hernández Juan Pablo , Blanca‐Pedregosa Ana Maria , Jiménez‐Vacas Juan Manuel , Ruiz‐García Jesus , Valero‐Rosa Jose , Luque Raul Miguel , Requena‐Tapia María José 
Published: November 2018

AbstractRecently, the influence that metabolic syndrome (MetS), hormonal alterations and inflammation might have on prostate cancer (PCa) risk has been a subject of controversial debate. Herein, we aimed to investigate the association between MetS‐components, C‐reactive protein (CRP) and testosterone levels, and the risk of clinically significant PCa (Sig‐PCa) at the time of prostate biopsy. For that, men scheduled for transrectal ultrasound guided biopsy of the prostate were studied. Clinical, laboratory parameters and criteria for MetS characterization just before the biopsy were collected. A total of 524 patients were analysed, being 195 (37.2%) subsequently diagnosed with PCa and 240 (45.8%) meet the diagnostic criteria for MetS. Among patients with PCa, MetS‐diagnosis was present in 94 (48.2%). Remarkably, a higher risk of Sig‐PCa was associated to MetS, greater number of MetS‐components and higher CRP levels (odds‐ratio: 1.83, 1.30 and 2.00, respectively; P < 0.05). Moreover, higher circulating CRP levels were also associated with a more aggressive Gleason score in PCa patients. Altogether, our data reveal a clear association between the presence of MetS, a greater number of MetS‐components or CRP levels >2.5 mg/L with an increased Sig‐PCa diagnosis and/or with aggressive features, suggesting that MetS and/or CRP levels might influence PCa pathophysiology.
Osterix promotes the migration and angiogenesis of breast cancer by upregulation of S100A4 expression
Authors: Qu Shuang , Wu Jiahui , Bao Qianyi , Yao Bing , Duan Rui , Chen Xiang , Li Lingyun , Yuan Hongyan , Jin Yucui , Ma Changyan 
Published: November 2018

AbstractAs a key transcription factor required for bone formation, osterix (OSX) has been reported to be overexpressed in various cancers, however, its roles in breast cancer progression remain poorly understood. In this study, we demonstrated that OSX was highly expressed in metastatic breast cancer cells. Moreover, it could upregulate the expression of S100 calcium binding protein A4 (S100A4) and potentiate breast cancer cell migration and tumor angiogenesis in vitro and in vivo. Importantly, inhibition of S100A4 impaired OSX‐induced cell migration and capillary‐like tube formation. Restored S100A4 expression rescued OSX‐short hairpin RNA‐suppressed cell migration and capillary‐like tube formation. Moreover, the expression levels of OSX and S100A4 correlated significantly in human breast tumors. Our study suggested that OSX acts as an oncogenic driver in cell migration and tumor angiogenesis, and may serve as a potential therapeutic target for human breast cancer treatment.
Endogenous reduction of miR‐185 accelerates cardiac function recovery in mice following myocardial infarction via targeting of cathepsin K
Authors: Li Chuan‐Chang , Qiu Xue‐Ting , Sun Quan , Zhou Ji‐Peng , Yang Hui‐Jun , Wu Wan‐Zhou , He Ling‐Fang , Tang Can‐E , Zhang Guo‐Gang , Bai Yong‐Ping 
Published: November 2018

AbstractAngiogenesis is critical for re‐establishing the blood supply to the surviving myocardium after myocardial infarction (MI) in patients with acute coronary syndrome (ACS). MicroRNAs are recognised as important epigenetic regulators of endothelial function. The aim of this study was to determine the roles of microRNAs in angiogenesis. Eighteen circulating microRNAs including miR‐185‐5p were differently expressed in plasma from patients with ACS by high‐throughput RNA sequencing. The expressional levels of miR‐185‐5p were dramatically reduced in hearts isolated from mice following MI and cultured human umbilical vein endothelial cells (HUVECs) under hypoxia, as determined by fluorescence in situ hybridisation and quantitative RT‐PCR. Evidence from computational prediction and luciferase reporter gene activity indicated that cathepsin K (CatK) mRNA is a target of miR‐185‐5p. In HUVECs, miR‐185‐5p mimics inhibited cell proliferations, migrations and tube formations under hypoxia, while miR‐185‐5p inhibitors performed the opposites. Further, the inhibitory effects of miR‐185‐5p up‐regulation on cellular functions of HUVECs were abolished by CatK gene overexpression, and adenovirus‐mediated CatK gene silencing ablated these enhancive effects in HUVECs under hypoxia. In vivo studies indicated that gain‐function of miR‐185‐5p by agomir infusion down‐regulated CatK gene expression, impaired angiogenesis and delayed the recovery of cardiac functions in mice following MI. These actions of miR‐185‐5p agonists were mirrored by in vivo knockdown of CatK in mice with MI. Endogenous reductions of miR‐185‐5p in endothelial cells induced by hypoxia increase CatK gene expression to promote angiogenesis and to accelerate the recovery of cardiac function in mice following MI.
Engineering of TIMP‐3 as a LAP‐fusion protein for targeting to sites of inflammation
Authors: Alberts Ben M. , Sacre Sandra M. , Bush Peter G. , Mullen Lisa M. 
Published: November 2018

AbstractTissue inhibitor of metalloproteinase (TIMP)‐3 is a natural inhibitor of a range of enzymes that degrade connective tissue and are involved in the pathogenesis of conditions such as arthritis and cancer. We describe here the engineering of TIMP‐3 using a novel drug‐delivery system known as the ‘LAP technology’. This involves creating therapeutic proteins in fusion with the latency‐associated peptide (LAP) from the cytokine TGF‐? to generate proteins that are biologically inactive until cleavage of the LAP to release the therapy. LAP‐TIMP‐3 was successfully expressed in mammalian cells and the presence of the LAP resulted in a 14‐fold increase in the quantity of recombinant TIMP‐3 produced. LAP‐TIMP‐3 was latent until release from the LAP by treatment with matrix metalloproteinase when it could inhibit proteases of the adamalysins and adamalysins with thrombospondin motifs families, but not matrix metalloproteinases, indicating that this version of TIMP‐3 is a more specific inhibitor than the native protein. There was sufficient protease activity in synovial fluid from human joints with osteoarthritis to release TIMP‐3 from the LAP fusion. These results demonstrate the potential for development of TIMP‐3 as a novel therapy for conditions where upregulation of catabolic enzymes are part of the pathology.
Evaluation of medical and surgical treatments for hidradenitis suppurativa using real‐life data from the Scandinavian registry (HISREG)
Authors: Grimstad Ø. , Tzellos T. , Dufour D.N. , Bremnes Ø. , Skoie I.M. , Snekvik I. , Jarnæss E. , Kyrgidis A. , Ingvarsson G. 
Published: November 2018

AbstractBackgroundHidradenitis suppurativa (HS) substantially affects health‐related quality‐of‐life outcomes. Most treatment options are supported by low quality of evidence without validated outcomes.ObjectiveThe aim of this study was to evaluate the efficacy of surgical and medical interventions using physician‐ and patient‐reported outcomes registered in HISREG.MethodsData were extracted for all adult patients registered in HISREG between January 2013 and April 2016. Primary endpoints included Dermatology Life Quality Index (DLQI) scores, pain as measured using a numeric rating scale (NRS), Sartorius score and Hurley classification. Minimum clinically important differences (MCIDs) for DLQI and NRS pain were analysed. Secondary endpoints included comparisons among different treatment groups, safety and complications of various treatments.ResultsTwo hundred and fifty‐five patients were included in the study: 31, 188, and 36 patients had Hurley stages I, II and III disease, respectively. Treatment with CO2 lasers was the most common treatment modality. One hundred and forty‐nine patients (58.4%) were treated with surgical intervention, 87 (34.1%) received antibiotics and/or anti‐inflammatory treatments, and 19 (7.5%) were treated with both surgery and medical intervention. No patients received biologic treatment. In patients with surgical treatments, Sartorius scores were significantly improved compared with baseline (P = 0.001), 83 patients (55%) achieved a DLQI MCID, and 75 patients (49.7%) achieved an NRS pain MCID. In patients with medical treatments, Sartorius scores were not significantly improved compared with baseline (P = 0.582); 25 patients (28%) achieved a DLQI MCID and 28 patients (31%) achieved an NRS pain MCID. In patients treated with surgical and medical combination, 9 (48%) achieved DLQI and NRS pain MCIDs and Sartorius scores were significantly improved.ConclusionsCO2 laser treatment is more effective than the non‐biologic medical treatments in this analysis based on physician‐ and patient‐derived outcomes. The study provides limited evidence for the combination of medical and surgical therapies in patients with HS.
Apremilast for moderate hidradenitis suppurativa: no significant change in lesional skin inflammatory biomarkers
Authors: Vossen A.R.J.V. , van der Zee H.H. , Davelaar N. , Mus A.M.C. , van Doorn M.B.A. , Prens E.P. 
Published: November 2018

AbstractBackgroundTreatment with apremilast has recently demonstrated clinically meaningful improvement in moderate hidradenitis suppurativa (HS).ObjectiveTo evaluate the change in expression of inflammatory markers in lesional skin of HS patients receiving apremilast 30 mg twice daily (n = 15) for 16 weeks compared with placebo (n = 5).MethodsAt baseline, 5‐mm punch biopsies were obtained from an index lesion (HSL) and non‐lesional (HSN) skin in the same anatomical area. Subsequent HSL samples were taken as close as possible to the previously biopsied site at week 4 and week 16. After sampling, biopsies were split; one half was processed for in vivo mRNA analysis using real‐time quantitative PCR; the other half was cultured for ex vivo protein analysis using a proximity extension assay (Olink). Linear mixed effects models were calculated to compare the levels of inflammatory markers in HSL skin between apremilast and placebo over time.ResultsAt baseline, 17 proteins with a fold change >2 in HSL vs. HSN skin were identified in 20 patients. The top five were IL‐17A (5), S100A12, CST5, IL‐12/23p40, CD6 (1) with fold changes ranging from 6.6 to 1638, respectively (FDR <0.044). Linear mixed effects models for 75 assays were calculated. Protein levels of S100A12 decreased during treatment in the apremilast group compared with the placebo group (p = 0.014, FDR = 0.186). None of the 14 genes exhibited significant changes in expression over time. However, an evident downward trend in relative mRNA expression of IL‐17A and IL‐17F was demonstrated in patients receiving apremilast.ConclusionWe did not detect statistically significant changes in inflammatory markers in HSL skin of HS patients receiving apremilast compared with placebo, despite clinical improvement in the apremilast group. Nonetheless, S100A12 and IL‐17A were significantly elevated in HSL skin and showed a decrease in response to apremilast. The translational model in clinical trials involving HS clearly needs further improvement.