bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical utility of fluorodeoxyglucose‐positron emission tomography for investigation of fever in immunocompromised children
Authors: Wang Shiqi Stacie , Mechinaud Francoise , Thursky Karin , Cain Timothy , Lau Eddie , Haeusler Gabrielle M 
Published: December 2017

AimFever in immunocompromised children presents significant challenges. We aimed to determine the clinical impact of fluorodeoxyglucose‐positron emission tomography (FDG‐PET) in combination with computed tomography (CT) in children with malignancy or following haematopoietic stem cell transplantation with prolonged or recurrent fever.MethodsImmunocompromised children who underwent FDG‐PET/CT for investigation of prolonged or recurrent fever were identified from hospital databases. The clinical impact of the FDG‐PET/CT was considered ‘high’ if it contributed to any of the following: diagnosis of a new site infection/inflammation, change to antimicrobials or chemotherapy, or additional investigations or specialist consult contributing to final diagnosis.ResultsFourteen patients underwent an FDG‐PET/CT for prolonged or recurrent fever. Median age was 11 years and 46% had diagnosis of acute lymphoblastic leukaemia. The median absolute neutrophil count on the day of FDG‐PET/CT was 0.47 cells/μL. The clinical impact of FDG‐PET/CT was ‘high’ in 11 (79%) patients, contributing to rationalisation of antimicrobials in three, and cessation of antimicrobials in five. Compared to conventional imaging, FDG PET/CT identified seven additional sites of clinically significant infection/inflammation in seven patients. Of the 10 patients who had a cause of fever identified, FDG‐PET/CT contributed to the final diagnosis in six (60%).ConclusionThis study has identified potential utility for FDG‐PET/CT in immunocompromised children with prolonged or recurrent fever. Further prospective studies are needed to compare FDG‐PET/CT versus conventional imaging, to identify the optimal timing of FDG‐PET/CT and to study the role of subsequent scans to monitor response to therapy.
Functional polymorphisms of innate immunity receptors are not risk factors for the non‐SBP type bacterial infections in cirrhosis
Authors: Dinya Tamas , Tornai Tamas , Vitalis Zsuzsanna , Tornai Istvan , Balogh Boglárka , Tornai David , Antal‐Szalmas Peter , Sumegi Andrea , Andrikovics Hajnalka , Bors Andras , Tordai Attila , Papp Maria 
Published: December 2017

AbstractBackground & AimsPattern recognition receptors (PRRs) have a key role in the innate host defense. Functional polymorphisms of various PRRs have been established to contribute to an increased susceptibility to spontaneous bacterial peritonitis (SBP). Their role in the development of cirrhosis‐associated bacterial infections (BI), beyond SBP or progressive disease course related to pathological bacterial translocation (BT) remains unknown.MethodsThree hundred and forty‐nine patients with cirrhosis were genotyped for common NOD2 (R702W, G908R and L1007PfsinsC), TLR2 (−16934T>A), and TLR4 (D299G) variants. Incidence of BIs, decompensating events and liver‐related death were assessed in a 5‐year follow‐up observational study. Pathological BT was assessed based on the presence of antimicrobial antibodies or lipopolysaccharide‐binding protein (LBP) level.ResultsIn patients with ascites (n = 88) only NOD2 gene variants were associated with an increased cumulative probability of SBP (76.9% ± 19.9%) compared to wild‐type (30.9% ± 6.9%, PLogRank = .047). Individual or combined PRR genetic profiles were associated with the risk of non‐SBP type BI. Advanced disease stage (HR [95% CI]: 2.11 [1.38‐3.25]) and prior history of a BI episode (HR: 2.42 [1.58‐3.72]) were the major clinical risk factors of a subsequent BI. The risk of a non‐SBP type BI in patients with advanced disease and a prior BI was even higher (HR: 4.74 [2.68‐8.39]). The frequency of antimicrobial antibodies and LBP levels did not differ between various PRR genotypes. Correspondingly, PRR genetic profile was not able to predict the long‐term disease course.ConclusionsIn cirrhosis, functional polymorphisms of PRRs did not improve the identification of patients with high risk of BI beyond SBP or progressive diseases course.
The Chelyabinsk meteorite: Thermal history and variable shock effects recorded by the 40Ar‐39Ar system
Authors: Trieloff Mario , Korochantseva Ekaterina V. , Buikin Alexei I. , Hopp Jens , Ivanova Marina A. , Korochantsev Alexander V. 
Published: December 2017

AbstractWe studied three lithologies (light and dark chondritic and impact melt rock) differing in shock stage from the LL5 chondrite Chelyabinsk. Using the 40Ar‐39Ar dating technique, we identified low‐ and high‐temperature reservoirs within all samples, ascribed to K‐bearing oligoclase feldspar and shock‐induced jadeite–feldspar glass assemblages in melt veins, respectively. Trapped argon components had variable 40Ar/36Ar ratios even within low‐ and high‐temperature reservoirs of individual samples. Correcting for trapped argon revealed a lithology‐specific response of the K‐Ar system to shock metamorphism, thereby defining two distinct impact events affecting the Chelyabinsk parent asteroid (1) an intense impact event ~1.7 ± 0.1 Ga ago formed the light–dark‐structured and impact‐veined Chelyabinsk breccia. Such a one‐stage breccia formation is consistent with petrological observations and was recorded by the strongly shocked lithologies (dark and impact melt) where a significant fraction of oligoclase feldspar was transformed into jadeite and feldspathic glass; and (2) a young reset event ~30 Ma ago particularly affected the light lithology due to its low argon retentivity, while the more retentive shock‐induced phases were more resistant against thermal reset. Trapped argon with 40Ar/36Ar ratios up to 1900 was likely incorporated during impact‐induced events on the parent body, and mixed with terrestrial atmospheric argon contamination. Had it not been identified via isochrons based on high‐resolution argon extraction, several geochronologically meaningless ages would have been deduced.
Association between urologic malignancies and end‐stage renal disease: A meta‐analysis
Authors: Kompotiatis Panagiotis , Thongprayoon Charat , Manohar Sandhya , Cheungpasitporn Wisit , Gonzalez Suarez Maria L , Craici Iasmina M , Mao Michael A , Herrmann Sandra M 
Published: December 2017

ABSTRACTAimPrevious studies have suggested a higher incidence of urologic malignancies in end‐stage renal disease (ESRD) patients. However, incidence trends of urologic malignancies in ESRD patients remain unclear. The aims of the present study were: (i) to investigate the pooled incidence/incidence trends; and (ii) to assess the risk of urologic malignancies in ESRD patients.MethodsA literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through April 2017. Studies that reported incidence or odds ratios of urologic malignancies among ESRD patients were included. Pooled odds ratios (OR) and 95%CI were calculated using a random‐effect model. The protocol for this meta‐analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067687).ResultsNineteen observational studies with 1 931 073 ESRD patients were enrolled. The pooled estimated incidence of kidney cancer and urothelial cancers (carcinomas of the bladder, ureters, and renal pelvis) in ESRD patients were 0.3% (95%CI: 0.2–0.5%) and 0.5% (95%CI: 0.3–0.8%), respectively. Meta‐regression showed significant positive correlation between incidence of urologic malignancies in ESRD patients and year of study (slopes = +0.05 and +0.07, P < 0.001 for kidney cancer and urothelial cancers, respectively). Compared to non‐ESRD status, ESRD was significantly associated with both kidney cancer (pooled OR 6.04; 95% CI 4.70–7.77) and urothelial cancers (pooled OR 4.37; 95% CI 2.40–7.96).ConclusionOur study demonstrates a significant association between ESRD and urologic malignancies. The overall estimated incidence rates of kidney cancer and urothelial cancers are 0.4% and 0.5%, respectively. There is a significant positive correlation between the incidence of urologic malignancies and year of study.
Inflammatory cytokine and C‐reactive protein concentrations in dogs with systemic inflammatory response syndrome
Authors: Gommeren Kris , Desmas Isabelle , Garcia Alexandra , Bauer Natalie , Moritz Andreas , Roth Joachim , Peeters Dominique 
Published: December 2017

AbstractObjectiveTo evaluate C‐reactive protein (CRP), interleukin 6 (IL‐6), and tumor necrosis factor alpha (TNF‐α) kinetics in dogs with a systemic inflammatory response syndrome (SIRS) presented to an emergency service. We hypothesized serum CRP concentrations would increase and vary during hospitalization, and would correlate with plasma IL‐6 and TNF‐α concentrations, vary in magnitude according to the underlying disease, and predict survival.DesignProspective, observational, clinical study.SettingUniversity emergency department.AnimalsSixty‐nine dogs with SIRS weighing over 5 kg who could tolerate the blood sampling.InterventionsSerum and plasma were collected (and stored at –80°C) at presentation (T0), after 6 (T6), 12 (T12), 24 (T24), and 72 (T72) hours, and at a follow‐up visit at least 1 month after discharge (T1m). Underlying diseases were categorized as infection (I), neoplasia (N), trauma (T), gastric‐dilation and volvulus (GDV), other gastrointestinal (GI), renal (R), and miscellaneous (M) disease.Measurements and Main ResultsSerum CRP concentration was measured using a canine‐specific immunoturbidimetric assay. Biologically active plasma IL‐6 and TNF‐α concentrations were assessed using bioassays. Forty‐four dogs survived, 8 died, and 17 were euthanized. Nineteen dogs had follow‐up visits. At T0, serum CRP concentration was above the reference interval in 73.1% (49/67), and was within the reference interval (0–141.9 nmol/L) throughout hospitalization in only 6% (4/67). Serum CRP concentrations were significantly higher (P< 0.0001) at T0 (882.9 ± 1082.9 nmol/L) and at all time points during hospitalization (P< 0.0001) compared to T1m, with highest concentrations observed at T24 (906. 7 ± 859.0 nmol/L). At T1m, serum CRP concentrations were within the reference interval (22.9 ± 42.9 nmol/L) in 95% (18/19) of dogs. Logarithmic concentrations of serum CRP and plasma IL‐6 were significantly correlated (P< 0.001,r= 0.479). None of the measured cytokines were associated with disease category or outcome.ConclusionsSerum CRP concentration is increased in dogs with SIRS, and decreases during treatment and hospitalization. Serum CRP, plasma IL‐6, and plasma TNF‐α concentrations cannot predict outcome in dogs with SIRS.
Buruli Ulcer, a Prototype for Ecosystem-Related Infection, Caused by Mycobacterium ulcerans
Authors: Zingue Dezemon , Bouam Amar , Tian Roger B. D. , Drancourt Michel 
Published: December 2017

SUMMARY

Buruli ulcer is a noncontagious disabling cutaneous and subcutaneous mycobacteriosis reported by 33 countries in Africa, Asia, Oceania, and South America. The causative agent,
Mycobacterium ulcerans
, derives from
Mycobacterium marinum
by genomic reduction and acquisition of a plasmid-borne, nonribosomal cytotoxin mycolactone, the major virulence factor.
M. ulcerans
-specific sequences have been readily detected in aquatic environments in food chains involving small mammals. Skin contamination combined with any type of puncture, including insect bites, is the most plausible route of transmission, and skin temperature of <30°C significantly correlates with the topography of lesions. After 30 years of emergence and increasing prevalence between 1970 and 2010, mainly in Africa, factors related to ongoing decreasing prevalence in the same countries remain unexplained. Rapid diagnosis, including laboratory confirmation at the point of care, is mandatory in order to reduce delays in effective treatment. Parenteral and potentially toxic streptomycin-rifampin is to be replaced by oral clarithromycin or fluoroquinolone combined with rifampin. In the absence of proven effective primary prevention, avoiding skin contamination by means of clothing can be implemented in areas of endemicity. Buruli ulcer is a prototype of ecosystem pathology, illustrating the impact of human activities on the environment as a source for emerging tropical infectious diseases.
Draft Genome Sequence of Glycomyces fuscus TRM 49117, Isolated from a Hypersaline Soil Sample
Authors: Wang Yang , Luo Xiaoxia , Zhang Lili 
Published: December 2017

ABSTRACT

Glycomyces
spp. are rare actinomycetes that are potential antibiotic producers. Here, we report the draft genome sequence of
Glycomyces fuscus
TRM 49117. This is the first genome report of a bacterium belonging to the genus
Glycomyces
. The genome information of
G. fuscus
will contribute to studies on the structure and function of antibiotics.
Whole-Genome Sequences of Three Streptococcus macedonicus Strains Isolated from Italian Cheeses in the Veneto Region
Authors: Treu Laura , de Diego-Díaz Beatriz , Papadimitriou Konstantinos , Tsakalidou Effie , Giacomini Alessio , Corich Viviana 
Published: December 2017

ABSTRACT

We report here the genome sequences of three
Streptococcus macedonicus
strains isolated from different cheeses in the Veneto region of Italy. The presented data aim at increasing the scarce genomic information available for this species, which is frequently encountered in fermented foods and appears to be a promising technological microorganism.
Human Cytomegalovirus Replication Is Inhibited by the Autophagy-Inducing Compounds Trehalose and SMER28 through Distinctively Different Mechanisms
Authors: Clark Alex E. , Sabalza Maite , Gordts Philip L. S. M. , Spector Deborah H. 
Published: December 2017

ABSTRACT
Human cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously reported that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles and that debris, including debris with an appearance consistent with that of abnormal virions, is present in multivesicular bodies. Trehalose treatment increased the levels of Rab7, a protein required for lysosomal biogenesis and fusion, and slightly decreased the levels of Rab11, which is associated with recycling endosomes. We also present evidence that trehalose can promote autophagy without altering cellular glucose uptake. We show that SMER28 inhibits HCMV at the level of early protein production and interferes with viral genome replication in a cell type-dependent fashion. Finally, we show that SMER28 treatment does not cause the vacuolation, acidification, or redistribution of Rab7 associated with trehalose treatment and shows only a modest and cell type-dependent effect on autophagy. We propose a model in which the reciprocal effects on Rab7 and Rab11 induced by trehalose contribute to the redirection of enveloped virions from the plasma membrane to acidified compartments and subsequent degradation, and SMER28 treatment results in decreased expression levels of early and late proteins, reducing the number of virions produced without the widespread vacuolation characteristic of trehalose treatment.

IMPORTANCE
There is a need for less toxic HCMV antiviral drugs, and modulation of autophagy to control viral infection is a new strategy that takes advantage of virus dependence on autophagy inhibition. The present study extends our previous work on trehalose by showing a possible mechanism of action and introduces another autophagy-inducing compound, SMER28, that is effective against HCMV in several cell types. The mechanism by which trehalose induces autophagy is currently unknown, although our data show that trehalose does not inhibit cellular glucose uptake in cells relevant for HCMV replication but instead alters virion degradation by promoting acidic vacuolization. The comparison of our cell types and those used by others highlights the cell type-dependent nature of studying autophagy.
A Single Amino Acid Substitution within the Paramyxovirus Sendai Virus Nucleoprotein Is a Critical Determinant for Production of Interferon-Beta-Inducing Copyback-Type Defective Interfering Genomes
Authors: Yoshida Asuka , Kawabata Ryoko , Honda Tomoyuki , Sakai Kouji , Ami Yasushi , Sakaguchi Takemasa , Irie Takashi 
Published: December 2017

ABSTRACT
One of the first defenses against infecting pathogens is the innate immune system activated by cellular recognition of pathogen-associated molecular patterns (PAMPs). Although virus-derived RNA species, especially copyback (cb)-type defective interfering (DI) genomes, have been shown to serve as real PAMPs, which strongly induce interferon-beta (IFN-β) during mononegavirus infection, the mechanisms underlying DI generation remain unclear. Here, for the first time, we identified a single amino acid substitution causing production of cbDI genomes by successful isolation of two distinct types of viral clones with cbDI-producing and cbDI-nonproducing phenotypes from the stock Sendai virus (SeV) strain Cantell, which has been widely used in a number of studies on antiviral innate immunity as a representative IFN-β-inducing virus. IFN-β induction was totally dependent on the presence of a significant amount of cbDI genome-containing viral particles (DI particles) in the viral stock, but not on deficiency of the IFN-antagonistic viral accessory proteins C and V. Comparison of the isolates indicated that a single amino acid substitution found within the N protein of the cbDI-producing clone was enough to cause the emergence of DI genomes. The mutated N protein of the cbDI-producing clone resulted in a lower density of nucleocapsids than that of the DI-nonproducing clone, probably causing both production of the DI genomes and their formation of a stem-loop structure, which serves as an ideal ligand for RIG-I. These results suggested that the integrity of mononegaviral nucleocapsids might be a critical factor in avoiding the undesirable recognition of infection by host cells.

IMPORTANCE
The type I interferon (IFN) system is a pivotal defense against infecting RNA viruses that is activated by sensing viral RNA species. RIG-I is a major sensor for infection with most mononegaviruses, and copyback (cb)-type defective interfering (DI) genomes have been shown to serve as strong RIG-I ligands in real infections. However, the mechanism underlying production of cbDI genomes remains unclear, although DI genomes emerge as the result of an error during viral replication with high doses of viruses. Sendai virus has been extensively studied and is unique in that its interaction with innate immunity reveals opposing characteristics, such as high-level IFN-β induction and strong inhibition of type I IFN pathways. Our findings provide novel insights into the mechanism of production of mononegaviral cbDI genomes, as well as virus-host interactions during innate immunity.
Detection of CytosolicShigella flexnerivia a C-Terminal Triple-Arginine Motif of GBP1 Inhibits Actin-Based Motility
Authors: Piro Anthony S. , Hernandez Dulcemaria , Luoma Sarah , Feeley Eric M. , Finethy Ryan , Yirga Azeb , Frickel Eva M. , Lesser Cammie F. , Coers Jörn 
Published: December 2017

ABSTRACTDynamin-like guanylate binding proteins (GBPs) are gamma interferon (IFN-γ)-inducible host defense proteins that can associate with cytosol-invading bacterial pathogens. Mouse GBPs promote the lytic destruction of targeted bacteria in the host cell cytosol, but the antimicrobial function of human GBPs and the mechanism by which these proteins associate with cytosolic bacteria are poorly understood. Here, we demonstrate that human GBP1 is unique among the seven human GBP paralogs in its ability to associate with at least two cytosolic Gram-negative bacteria,Burkholderia thailandensisandShigella flexneri. Rough lipopolysaccharide (LPS) mutants ofS. flexnericolocalize with GBP1 less frequently than wild-typeS. flexneridoes, suggesting that host recognition of O antigen promotes GBP1 targeting to Gram-negative bacteria. The targeting of GBP1 to cytosolic bacteria, via a unique triple-arginine motif present in its C terminus, promotes the corecruitment of four additional GBP paralogs (GBP2, GBP3, GBP4, and GBP6). GBP1-decoratedShigellaorganisms replicate but fail to form actin tails, leading to their intracellular aggregation. Consequentially, the wild type but not the triple-arginine GBP1 mutant restrictsS. flexnericell-to-cell spread. Furthermore, human-adaptedS. flexneri, through the action of one its secreted effectors, IpaH9.8, is more resistant to GBP1 targeting than the non-human-adapted bacillusB. thailandensis. These studies reveal that human GBP1 uniquely functions as an intracellular “glue trap,” inhibiting the cytosolic movement of normally actin-propelled Gram-negative bacteria. In response to this powerful human defense program,S. flexnerihas evolved an effective counterdefense to restrict GBP1 recruitment.IMPORTANCESeveral pathogenic bacterial species evolved to invade, reside in, and replicate inside the cytosol of their host cells. One adaptation common to most cytosolic bacterial pathogens is the ability to coopt the host’s actin polymerization machinery in order to generate force for intracellular movement. This actin-based motility enables Gram-negative bacteria, such asShigellaspecies, to propel themselves into neighboring cells, thereby spreading from host cell to host cell without exiting the intracellular environment. Here, we show that the human protein GBP1 acts as a cytosolic “glue trap,” capturing cytosolic Gram-negative bacteria through a unique protein motif and preventing disseminated infections in cell culture models. To escape from this GBP1-mediated host defense,Shigellaemploys a virulence factor that prevents or dislodges the association of GBP1 with cytosolic bacteria. Thus, therapeutic strategies to restore GBP1 binding toShigellamay lead to novel treatment options for shigellosis in the future.