bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Epidemiology of Dairy Cattle-Associated Escherichia coli Carrying
bla
CTX-M
Genes in Washington State
Authors: Afema Josephine A. , Ahmed Sara , Besser Thomas E. , Jones Lisa P. , Sischo William M. , Davis Margaret A. 
Published: January 2018

ABSTRACT

An increase in the prevalence of commensal
Escherichia coli
carrying
bla
CTX-M
genes among dairy cattle was observed between 2008 and 2012 in Washington State. To study the molecular epidemiology of this change, we selected 126
bla
CTX-M
-positive and 126
bla
CTX-M
-negative isolates for determinations of the multilocus sequence types (MLSTs) and antibiotic resistance phenotypes from
E. coli
obtained during a previous study. For 99 isolates, we also determined the
bla
CTX-M
alleles using PCR and sequencing and identified the replicon types of
bla
CTX-M
-carrying plasmids. The
bla
CTX-M
-negative
E. coli
isolates comprised 76 sequence types (STs) compared with 32 STs in
bla
CTX-M
-positive
E. coli
isolates. The
bla
CTX-M
-positive
E. coli
isolates formed three MLST clonal complexes, accounting for 83% of these isolates; 52% of
bla
CTX-M
-negative
E. coli
isolates clustered into 10 clonal complexes, and the remainder were singletons. Overall,
bla
CTX-M
-negative
E. coli
isolates had more diverse genotypes that were distinct to farms, whereas
bla
CTX-M
-positive
E. coli
isolates had a clonal population structure and were widely disseminated on farms in both regions included in the study. Plasmid replicon types included IncI1 which predominated, followed by IncFIB and IncFIA/FIB.
bla
CTX-M-15
was the predominant CTX-M gene allele, followed by
bla
CTX-M-27
and
bla
CTX-M-14
. There was no significant association between plasmid replicon types and bacterial STs, and neither clonal complexes nor major plasmid groups were associated with two discrete dairy-farming regions of Washington State.

IMPORTANCE
Infections caused by extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
occur globally and present treatment challenges because of their resistance to multiple antimicrobial drugs. Cattle are potential reservoirs of ESBL-producing
Enterobacteriaceae
, and so understanding the causes of successful dissemination of
bla
CTX-M
genes in commensal bacteria will inform future approaches for the prevention of antibiotic-resistant pathogen emergence.
Mutations in Escherichia coli Polyphosphate Kinase That Lead to Dramatically Increased
In Vivo
Polyphosphate Levels
Authors: Rudat Amanda K. , Pokhrel Arya , Green Todd J. , Gray Michael J. 
Published: January 2018

ABSTRACT

Bacteria synthesize inorganic polyphosphate (polyP) in response to a wide variety of stresses, and production of polyP is essential for stress response and survival in many important pathogens and bacteria used in biotechnological processes. However, surprisingly little is known about the molecular mechanisms that control polyP synthesis. We have therefore developed a novel genetic screen that specifically links growth of
Escherichia coli
to polyP synthesis, allowing us to isolate mutations leading to enhanced polyP production. Using this system, we have identified mutations in the polyP-synthesizing enzyme polyP kinase (PPK) that lead to dramatic increases in
in vivo
polyP synthesis but do not substantially affect the rate of polyP synthesis by PPK
in vitro
. These mutations are distant from the PPK active site and found in interfaces between monomers of the PPK tetramer. We have also shown that high levels of polyP lead to intracellular magnesium starvation. Our results provide new insights into the control of bacterial polyP accumulation and suggest a simple, novel strategy for engineering bacteria with increased polyP contents.

IMPORTANCE
PolyP is an ancient, universally conserved biomolecule and is important for stress response, energy metabolism, and virulence in a remarkably broad range of microorganisms. PolyP accumulation by bacteria is also important in biotechnology applications. For example, it is critical to enhanced biological phosphate removal (EBPR) from wastewater. Understanding how bacteria control polyP synthesis is therefore of broad importance in both the fields of bacterial pathogenesis and biological engineering. Using
Escherichia coli
as a model organism, we have identified the first known mutations in polyP kinase that lead to increases in cellular polyP content.
Monitoring of Cytomegalovirus (CMV)-Specific Cell-Mediated Immunity in Heart Transplant Recipients: Clinical Utility of the QuantiFERON-CMV Assay for Management of Posttransplant CMV Infection
Authors: Chiereghin Angela , Potena Luciano , Borgese Laura , Gibertoni Dino , Squarzoni Diego , Turello Gabriele , Petrisli Evangelia , Piccirilli Giulia , Gabrielli Liliana , Grigioni Francesco , Lazzarotto Tiziana 
Published: January 2018

ABSTRACT

The clinical utility of the QuantiFERON-CMV (QFN-CMV) assay in heart transplant recipients was assessed. Forty-four cytomegalovirus (CMV)-seropositive patients were enrolled: 17 received antiviral prophylaxis, and 27 were managed preemptively. CMV-DNAemia monitoring was performed by the use of a quantitative real-time PCR assay. The QFN-CMV assay was retrospectively performed on blood samples collected at five posttransplant time points. A higher proportion of patients with an indeterminate QFN-CMV result after the suspension of prophylaxis than of patients who showed a global T-cell responsiveness developed CMV infection (
P
= 0.036). Patients who reconstituted a CMV-specific response following the first CMV-DNAemia-positive result (42.9%) showed a median CMV-DNAemia peak 1 log of magnitude lower than that seen with patients with indeterminate results, and all controlled viral replication spontaneously. The 25% of patients with an indeterminate result developed CMV disease. In the preemptive strategy group, no differences in the development of subsequent infection, magnitude of viral load, and viral control were observed on the basis of QFN-CMV measurements performed before and after the first CMV-DNAemia-positive result. Considering both CMV prevention strategies, viral relapse was associated with the failure to reconstitute CMV-specific cell-mediated immunity (CMI) after the resolution of the first episode of CMV infection (
P
= 0.032). QFN-CMV measurements can be a useful tool for identifying patients (i) at higher risk of developing infection after discontinuing antiviral prophylaxis, (ii) with late CMV infection who would benefit from appropriate antiviral interventions, and (iii) at higher risk of viral relapses. QFN-CMV measurements taken within 1 month posttransplantation (early period) are not revealing.
Tuberculosis: Just the FAQs
Authors: Guinn Kristine M. , Rubin Eric J. 
Published: January 2018

ABSTRACT
Tuberculosis is responsible for more deaths worldwide than any other infectious disease. For anyone looking to learn more about this persistent public health threat, this conversational “frequently asked questions” style review addresses a breadth of questions. It offers a brief, somewhat opinionated, review of what is and is not known, particularly in light of how findings in the lab do or do not help inform the understanding of human tuberculosis.
Case of nasogastric tube dysfunction
Authors: Rainer Florian , Prenner Guenther , Binder Lukas Peter , Fickert Peter , Plank Johannes 
Published: January 2018

Clinical presentationAn elderly female patient was admitted to intensive care for prolonged vasopressor therapy and mechanical ventilation after cardiac arrest and acute percutaneous coronary intervention. Antiplatelet, thyroid hormone replacement and statin therapies were administered through a 14-French nasogastric tube (Nestlé Health Science) and enteral feeding was initiated. Correct position of the nasogastric tube was confirmed radiologically. On the seventh day in the intensive care, our patient was seen to regurgitate soft crumbs into her mouth. The blocked nasogastric tube was removed, but attempts to reinsert another tube failed.Upper GI endoscopy revealed an obstruction of the oesophagus with a milky-yellowish caseous substance 20 cm from the incisors (figure 1). The proximal part of the mass showed a central hole and ring-shaped layers resembling the cut face of a tree trunk.Figure 1Obstruction of the oesophagus with a milky-yellowish caseous substance.QuestionsWhat caused the obstruction?How should we manage such a problem?
Arterial stiffness association with chronic inflammatory disorders in the UK Biobank study
Authors: Dregan Alex 
Published: January 2018

ObjectiveThe present study tested the hypothesis that arterial stiffness will be elevated across overall and specific inflammatory disorders compared with an inflammation-free comparison group.MethodsAdults (n=171 125) aged 40–70 years from the UK Biobank who were cardiovascular disease (CVD) free and who had their arterial stiffness assessed at the time of study recruitment between 2006 and 2010 were included. The main exposure was represented by a global measure of chronic inflammatory disorders. Two inflammatory biomarker measures (eg, leucocytes count, granulocytes count) were included as markers of inflammation severity. The arterial stiffness index assessed by a non-invasive technique represented the study primary outcome measure.ResultsA total of 5976 (3%) participants diagnosed with inflammatory disorders and 165 149 participants without an inflammatory disorder had data on arterial stiffness. Adjusted linear regression analyses revealed a 14% increment in mean arterial stiffness for chronic inflammatory disorders (beta coefficient (β) 1.14, 95% CI 1.05 to 1.24, P=0.002) compared with no chronic inflammatory disorder. Arterial stiffness tended to increase (P value=0.031) with tertiles of leucocytes and granulocytes count. For instance, mean arterial stiffness values increased from 1.11 (95% CI 0.96 to 1.29) in the first tertile to 1.17 (95% CI 1.02 to 1.34) in the second tertile, and 1.21 (95% CI 1.05 to 1.39) in the third tertile of leucocytes count. There was evidence for similar associations with some of the most common individual inflammatory disorders, including psoriasis and rheumatoid arthritis.ConclusionArterial stiffness was associated with multiple chronic inflammatory disorders. An increasing trend in mean arterial stiffness was also documented with increasing tertiles of different inflammatory biomarkers. Future studies are needed to investigate the discriminant value of arterial stiffness to predict major CVD events within various inflammatory disorders.
Low Self-rated Health Is Related to Blood Hypercoagulability in Patients Admitted with Acute Myocardial Infarction
Authors: von Känel Roland , Meister-Langraf Rebecca , Schmid Jean-Paul , Barth Jürgen , Znoj Hansjörg , Schnyder Ulrich , Princip Mary 
Published: January 2018

AbstractSelf-rated health (SRH) is independently associated with all-cause mortality and adverse cardiovascular outcomes in individuals with and without cardiovascular disease. We examined whether SRH relates to haemostatic factors of a hypercoagulable state with prognostic impact in patients admitted with acute myocardial infarction (MI). We assessed 190 patients (median age: 59 years; all Caucasian; 83% men) within 48 hours of an acute coronary intervention in terms of demographic factors, medical and psychiatric comorbidity, health behaviours, cardiac-related variables and psychosocial characteristics. Patients rated their health state before MI retrospectively with the EuroQol Visual Analogue Scale ranging from 0 (‘worst imaginable health state’) to 100 (‘best imaginable health state’). Circulating levels of fibrinogen, fibrin D-dimer and von Willebrand factor (VWF) antigen were measured the morning after hospital referral. The median score of SRH was 75 (range: 20–100). SRH was inversely associated with fibrinogen (r =  − 0.25, p = 0.001) and D-dimer (r =  − 0.17, p = 0.021) levels in the bivariate analysis. Stronger relationships emerged for fibrinogen (r =  − 0.33, p < 0.001), D-dimer (r =  − 0.25, p = 0.001) and also VWF (r =  − 0.19, p = 0.015) levels in fully adjusted linear regression models. As for SRH, the Global Registry of Acute Coronary Events (GRACE) risk score was the only covariate showing an independent association with all haemostatic factors (fibrinogen: r = 0.31, D-dimer: r = 0.29, VWF: r = 0.30; all p-values < 0.001). Lower SRH was associated with greater coagulability in patients with acute MI, independent of covariates and comparable with the GRACE risk score. The findings provide a novel psychobiological mechanism that may potentially link SRH with cardiovascular outcome in patients with an acute coronary syndrome.
Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study
Authors: Burnley-Hall Nicholas , Abdul Fairoz , Androshchuk Vitaliy , Morris Keith , Ossei-Gerning Nick , Anderson Richard , Rees D. , James Philip 
Published: January 2018

AbstractExtracellular vesicles (EVs) are implicated in the pathogenesis of cardiovascular disease (CVD). Specifically, platelet-derived EVs are highly pro-coagulant, promoting thrombin generation and fibrin clot formation. Nitrate supplementation exerts beneficial effects in CVD, via an increase in nitric oxide (NO) bioavailability. Clopidogrel is capable of producing NO-donating compounds, such as S-nitrosothiols (RSNO) in the presence of nitrite and low pH. The aim of this study was to assess the effect of nitrate supplementation with versus without clopidogrel therapy on circulating EVs in coronary artery disease (CAD) patients. In this randomized, double-blind, placebo-controlled study, CAD patients with (n = 10) or without (n = 10) clopidogrel therapy received a dietary nitrate supplement (SiS nitrate gel) or identical placebo. NO metabolites and platelet activation were measured using ozone-based chemiluminescence and multiple electrode aggregometry. EV concentration and origin were determined using nanoparticle tracking analysis and time-resolved fluorescence. Following nitrate supplementation, plasma RSNO was elevated (4.7 ± 0.8 vs 0.2 ± 0.5 nM) and thrombin-receptor mediated platelet aggregation was reduced (−19.9 ± 6.0 vs 4.0 ± 6.4 U) only in the clopidogrel group compared with placebo. Circulating EVs were significantly reduced in this group (−1.183e11 ± 3.15e10 vs −9.93e9 ± 1.84e10 EVs/mL), specifically the proportion of CD41+ EVs (−2,120 ± 728 vs 235 ± 436 RFU [relative fluorescence unit]) compared with placebo. In vitro experiments demonstrated clopidogrel–SNO can reduce platelet-EV directly (6.209e10 ± 4.074e9 vs 3.94e11 ±  1.91e10 EVs/mL). In conclusion, nitrate supplementation reduces platelet-derived EVs in CAD patients on clopidogrel therapy, increasing patient responsiveness to clopidogrel. Nitrate supplementation may represent a novel approach to moderating the risk of thrombus formation in CAD patients.
Deletion of IκB‐Kinase β in Smooth Muscle Cells Induces Vascular Calcification Through β‐Catenin–Runt‐Related Transcription Factor 2 Signaling
Authors: Al‐Huseini Isehaq , Ashida Noboru , Kimura Takeshi 
Published: January 2018

Background
Vascular calcification was previously considered as an advanced phase of atherosclerosis; however, recent studies have indicated that such calcification can appear in different situations. Nevertheless, there has been a lack of mechanistic insight to explain the difference. For example, the roles of nuclear factor‐κB, a major regulator of inflammation, in vascular calcification are poorly explored, although its roles in atherosclerosis were well documented. Herein, we investigated the roles of nuclear factor‐κB signaling in vascular calcification.

Methods and Results

We produced mice with deletion of
IKK
β, an essential kinase for nuclear factor‐κB activation, in vascular smooth muscle cells (VSMCs; KO mice) and subjected them to the CaCl
2
‐induced aorta injury model. Unexpectedly,
KO
mice showed more calcification of the aorta than their wild‐type littermates, despite the former's suppressed nuclear factor‐κB activity. Cultured
VSMC
s from the aorta of
KO
mice also showed significant calcification in vitro. In the molecular analysis, we found that Runt‐related transcription factor 2, a transcriptional factor accelerating bone formation, was upregulated in cultured
VSMC
s from
KO
mice, and its regulator β‐catenin was more activated with suppressed ubiquitination in
KO VSMC
s. Furthermore, we examined
VSMC
s from mice in which kinase‐active or kinase‐dead
IKK
β was overexpressed in
VSMC
s. We found that kinase‐independent function of
IKK
β is involved in suppression of calcification via inactivation of β‐catenin, which leads to suppression of Runt‐related transcription factor 2 and osteoblast marker genes.

Conclusions

IKK
β negatively regulates
VSMC
calcification through β‐catenin–Runt‐related transcription factor 2 signaling, which revealed a novel function of
IKK
β on vascular calcification.
Uremic Advanced Glycation End Products and Protein‐Bound Solutes Induce Endothelial Dysfunction Through Suppression of Krüppel‐Like Factor 2
Authors: Saum Keith , Campos Begoña , Celdran‐Bonafonte Diego , Nayak Lalitha , Sangwung Panjamaporn , Thakar Charuhas , Roy‐Chaudhury Prabir , Owens A. Phillip 
Published: January 2018

Background

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end‐stage renal disease. The accumulation of uremic solutes in this patient population is associated with endothelial dysfunction and accelerated cardiovascular disease. In this study, we examined the impact of the uremic milieu on the endothelial transcription factor, Krüppel‐like factor 2 (
KLF
2), a key regulator of endothelial function and activation.

Methods and Results

Using serum from uremic pigs with chronic renal insufficiency, our results show that
KLF
2 expression is suppressed by the uremic milieu and individual uremic solutes in vitro. Specifically,
KLF
2 expression is significantly decreased in human umbilical vein endothelial cells after treatment with uremic porcine serum or carboxymethyllysine‐modified albumin, an advanced glycation end product (
AGE
) known to induce endothelial dysfunction.
AGE
‐mediated suppression of
KLF
2 is dependent on activation of the receptor for
AGE
, as measured by small interfering
RNA
knockdown of the receptor for
AGE
. Furthermore,
KLF
2 suppression promotes endothelial dysfunction, because adenoviral overexpression of
KLF
2 inhibits reactive oxygen species production and leukocyte adhesion in human umbilical vein endothelial cells. In addition, the application of hemodynamic shear stress, prolonged serum dialysis, or treatment with the receptor for
AGE
antagonist azeliragon (
TTP
488) is sufficient to prevent
KLF
2 suppression in vitro. To decipher the mechanism by which uremic
AGE
s suppress
KLF
2 expression, we assessed the role of the receptor for
AGE
in activation of nuclear factor‐κB signaling, a hallmark of endothelial cell activation. Using a constitutively active form of IκBα, we show that translocation of p65 to the nucleus is necessary for
KLF
2 suppression after treatment with uremic
AGE
s.

Conclusions

These data identify
KLF
2 suppression as a consequence of the uremic milieu, which may exacerbate endothelial dysfunction and resultant cardiovascular disease.
Coordinated Upper-Troposphere-to-Stratosphere Balloon Experiment in Biak
Authors: Hasebe F. , Aoki S. , Morimoto S. , Inai Y. , Nakazawa T. , Sugawara S. , Ikeda C. , Honda H. , Yamazaki H. , Halimurrahman  , Komala N. , Putri F. A. , Budiyono A. , Soedjarwo M. , Ishidoya S. , Toyoda S. , Shibata T. , Hayashi M. , Eguchi N. , Nishi N. , Fujiwara M. , Ogino S.-Y. , Shiotani M. , Sugidachi T. 
Published: January 2018

AbstractThe stratospheric response to climate forcing, such as an increase in greenhouse gases, is often unpredictable because of interactions between radiation, dynamics, and chemistry. Climate models are unsuccessful in simulating the realistic distribution of stratospheric water vapor. The long-term trend of the stratospheric age of air (AoA), a measure that characterizes the stratospheric turnover time, remains inconsistent between diagnoses in climate models and estimates from tracer observations. For these reasons, observations designed specifically to distinguish the effects of individual contributing processes are required. Here, we report on the Coordinated Upper-Troposphere-to-Stratosphere Balloon Experiment in Biak (CUBE/Biak), an observation campaign organized in Indonesia. Being inside the “tropical pipe” makes it possible to study the dehydration in the tropical tropopause layer and the gradual ascent in the stratosphere while minimizing the effects of multiple circulation pathways and wave mixing. Cryogenic sampling of minor constituents and major isotopes was conducted simultaneously with radiosonde observations of water vapor, ozone, aerosols, and cloud particles. The water vapor “tape recorder,” gravitational separation, and isotopocules are being studied in conjunction with tracers that are accumulated in the atmosphere as dynamical and chemical measures of elapsed time since stratospheric air entry. The observational estimates concerning the AoA and water vapor tape recorder are compared with those derived from trajectory calculations.
Variations in Snow Crystal Riming and ZDR: A Case Analysis
Authors: Kennedy Patrick , Thurai Merhala , Praz Christophe , Bringi V. N. , Berne Alexis , Notaroš Branislav M. 
Published: January 2018

AbstractA case study in terms of variations in differential reflectivity ZDR observed at X band and snow crystal riming is presented for a light-snow event that occurred near Greeley, Colorado, on 26–27 November 2015. In the early portion of the event, ZDR values at near-surface levels were low (0–0.25 dB). During a second time period approximately 8 h later, ZDR values became distinctly positive (+2–3 dB). Digital photographs of the snow particles were obtained by a Multi-Angle Snowflake Camera (MASC) installed at a range of 13 km from the radar. Image-processing and machine-learning techniques applied to the MASC data showed that the snow particles were more heavily rimed during the low-ZDR time period. The aerodynamic effects of these rime deposits promoted a wider distribution of hydrometeor canting angles. The shift toward more random particle orientations underlies the observed reduction in ZDR during the period when more heavily rimed particles were observed in the MASC data.