bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic signatures coupled with lineage shift characterise endemic evolution of Dengue virus serotype 2 during 2015 outbreak in Delhi, India
Authors: Choudhary Manish Chandra , Gupta Ekta , Sharma Shvetank , Hasnain Nadeem , Agarwala Pragya 
Published: May 2017

AbstractObjectiveIn 2015, New Delhi witnessed a massive outbreak of Dengue virus (DENV) resulting in high morbidity and mortality. We report the molecular characterisation of the dominant circulatingDENVstrain to understand its evolution and dispersal.Materials and methodsDENVinfections were diagnosed by detection of IgM/NS1 antigen, and serotyping was performed by C‐PrMPCR. Envelope gene was amplified, and variation(s) in envelope gene were analysed. Phylogenetic tree construction, time‐based phylogeny and origin ofDENVwere analysed. Site‐specific selection pressure of envelope gene variants was analysed.ResultsConfirmedDENVinfection was observed in 11.34% (32 of 282) cases, whilePCRpositivity for C‐PrM region was observed in 54.16% (13 of 24) ofNS1 antigen‐positive cases. All samples belonged to serotype 2 and cosmopolitan genotype. Phylogenetic analysis using envelope gene revealed segregation of cosmopolitan genotype strains into specific lineages. The Indian strains clustered separately forming a distinct monophyletic lineage (lineageIII) with a signature amino acid substitution viz., I162V and R288K. Selection pressure analysis revealed that 215D, 288R and 304K were positively selected sites. The rate of nucleotide substitution was 6.93 × 10−4substitutions site‐1 year‐1 with time to most common ancestor was around 10 years withJX475906 (Hyderabad strain) andJN030345 (Singapore strain) as its most probable ancestor.ConclusionWe observed evolution of a distinct lineage ofDENV‐2 strains on the Indian subcontinent with possible changes in endemic circulating dengue strains that might give rise to more pathogenic strains.
Index case finding facilitates identification and linkage to care of children and young persons living with HIV/AIDS in Malawi
Authors: Ahmed Saeed , Sabelli Rachael A. , Simon Katie , Rosenberg Nora E. , Kavuta Elijah , Harawa Mwelura , Dick Spencer , Linzie Frank , Kazembe Peter N. , Kim Maria H. 
Published: May 2017

AbstractObjectivesEvaluation of a novel index case finding and linkage‐to‐care programme to identify and link HIV‐infected children (1–15 years) and young persons (>15–24 years) to care.MethodsHIV‐infected patients enrolled in HIV services were screened and those who reported untested household members (index cases) were offered home‐ or facility‐based HIV testing and counselling (HTC) of their household by a community health worker (CHW). HIV‐infected household members identified were enrolled in a follow‐up programme offering home and facility‐based follow‐up by CHWs.ResultsOf the 1567 patients enrolled in HIV services, 1030 (65.7%) were screened and 461 (44.8%) identified as index cases; 93.5% consented to HIV testing of their households and of those, 279 (64.7%) reported an untested child or young person. CHWs tested 711 children and young persons, newly diagnosed 28 HIV‐infected persons (yield 4.0%; 95% CI: 2.7–5.6), and identified an additional two HIV‐infected persons not enrolled in care. Of the 30 HIV‐infected persons identified, 23 (76.6%) were linked to HIV services; 18 of the 20 eligible for ART (90.0%) were initiated. Median time (IQR) from identification to enrolment into HIV services was 4 days (1–8) and from identification to ART start was 6 days (1–8).ConclusionsAlmost half of HIV‐infected patients enrolled in treatment services had untested household members, many of whom were children and young persons. Index case finding, coupled with home‐based testing and tracked follow‐up, is acceptable, feasible and facilitates the identification and timely linkage to care of HIV‐infected children and young persons.
Capsule Production and Glucose Metabolism Dictate Fitness during
Serratia marcescens
Bacteremia
Authors: Anderson Mark T. , Mitchell Lindsay A. , Zhao Lili , Mobley Harry L. T. 
Published: May 2017

ABSTRACT

Serratia marcescens
is an opportunistic pathogen that causes a range of human infections, including bacteremia, keratitis, wound infections, and urinary tract infections. Compared to other members of the
Enterobacteriaceae
family, the genetic factors that facilitate
Serratia
proliferation within the mammalian host are less well defined. An
in vivo
screen of transposon insertion mutants identified 212
S. marcescens
fitness genes that contribute to bacterial survival in a murine model of bloodstream infection. Among those identified, 11 genes were located within an 18-gene cluster encoding predicted extracellular polysaccharide biosynthesis proteins. A mutation in the
wzx
gene contained within this locus conferred a loss of fitness in competition infections with the wild-type strain and a reduction in extracellular uronic acids correlating with capsule loss. A second gene,
pgm
, encoding a phosphoglucomutase exhibited similar capsule-deficient phenotypes, linking central glucose metabolism with capsule production and fitness of
Serratia
during mammalian infection. Further evidence of the importance of central metabolism was obtained with a
pfkA
glycolytic mutant that demonstrated reduced replication in human serum and during murine infection. An MgtB magnesium transporter homolog was also among the fitness factors identified, and an
S. marcescens mgtB
mutant exhibited decreased growth in defined medium containing low concentrations of magnesium and was outcompeted ~10-fold by wild-type bacteria in mice. Together, these newly identified genes provide a more complete understanding of the specific requirements for
S. marcescens
survival in the mammalian host and provide a framework for further investigation of the means by which
S. marcescens
causes opportunistic infections.

IMPORTANCE
Serratia marcescens
is a remarkably prolific organism that replicates in diverse environments, including as an opportunistic pathogen in human bacteremia. The genetic requirements for
S. marcescens
survival in the mammalian bloodstream were defined in this work by transposon insertion sequencing. In total, 212 genes that contribute to bacterial fitness were identified. When sorted via biological function, two of the major fitness categories identified herein were genes encoding capsule polysaccharide biogenesis functions and genes involved in glucose utilization. Further investigation determined that certain glucose metabolism fitness genes are also important for the generation of extracellular polysaccharides. Together, these results identify critical biological processes that allow
S. marcescens
to colonize the mammalian bloodstream.
Evaluating the quality improvement impact of the Global Tracheostomy Collaborative in four diverse NHS hospitals
Authors: McGrath Brendan A , Lynch James , Bonvento Barbarella , Wallace Sarah , Poole Val , Farrell Ann , Diaz Cristina , Khwaja Sadie , Roberson David W 
Published: May 2017

Tracheostomies are predominantly used in Head & Neck Surgery and the critically ill. The needs of these complex patients frequently cross traditional speciality working boundaries and locations and any resulting airway problems can rapidly lead to significant harm. The Global Tracheostomy Collaborative (GTC) was formed in 2012 with the aim of bringing together international expertise in tracheostomy care in order to bring about rapid adoption of best practices and to improve the quality and safety of care to this vulnerable group.The primary aim of this project was to improve the safety and quality of care delivered to adult patients with new or existing tracheostomies. We implemented changes guided by the GTC using multiple PDSA cycles over a 12-month period. Interventions were across three themes: educational, patient-centred (earlier vocalisation and enteral intake) and organisational. We hypothesised that systematic healthcare improvements would reduce the severity of harm resulting from tracheostomy-related safety incidents and improve surrogate markers of the quality of patient-centred care. Furthermore, we hypothesised that raising the quality and safety of healthcare services would lead to more efficient care, measured by earlier tracheostomy decannulation times and reduced hospital lengths of stay.This Quality Improvement project implemented the GTC into four diverse NHS Trusts in Greater Manchester. Key drivers implemented included multidisciplinary tracheostomy steering groups, ward rounds and bedside teams, standardisation of tracheostomy protocols, staff education and meaningful involvement of patient and family. Surrogates for the quality and safety of care were captured for all patients using a bespoke database.Implementing the GTC into four NHS Trusts rapidly and positively impacted on patient safety metrics and surrogates for the quality of care delivered. It is likely that the comprehensive resources of the GTC will be of benefit to other NHS hospitals and indeed other healthcare systems around the world.
Self-intersection of foliation cycles on complex manifolds
Authors: Kaufmann Lucas 
Published: May 2017

Let [Formula: see text] be a compact Kähler manifold and let [Formula: see text] be a foliation cycle directed by a transversely Lipschitz lamination on [Formula: see text]. We prove that the self-intersection of the cohomology class of [Formula: see text] vanishes as long as [Formula: see text] does not contain currents of integration along compact manifolds. As a consequence, we prove that transversely Lipschitz laminations of low codimension in certain manifolds, e.g. projective spaces, do not carry any foliation cycles except those given by integration along compact leaves.
Luminescent properties and first-principles calculations of (Cr,Ca):YAG crystals
Authors: Wan Yan , Li Meiyu , Xie Erjuan , Xu Shoulei , Huang Yuyang , Deng Wen 
Published: May 2017

The single crystals of YAG, Cr:YAG and (Cr,Ca):YAG were grown in an optical floating zone furnace. The experimental results show that the optical bandgap of the YAG, (Cr,Ca):YAG and Cr:YAG crystals is about 6.52, 6.31 and 5.50 eV, respectively. The optical bandgap of the (Cr,Ca):YAG crystal is smaller than YAG and larger than Cr:YAG. First-principles calculation results showed that the additions of Cr into YAG will give rise to the change of the electronic states. In a Cr:YAG crystal, the Cr[Formula: see text] impurity introduces a band of 3[Formula: see text] occupied state near the Fermi level, which significantly narrowed the bandgap of Cr:YAG. In a (Cr,Ca):YAG crystal, as the Ca[Formula: see text] ions substitute for the Y[Formula: see text] ions, some of the Cr[Formula: see text] ions will change into Cr[Formula: see text] ions due to the charge balance, which increased the bandgap of the (Cr,Ca):YAG crystal in comparison with that of the Cr:YAG crystal. The calculation is in agreement with the experimental results.
Radionuclides in groundwater, rocks and stream sediments in Austria – results from a recent survey
Authors: Schubert Gerhard , Berka Rudolf , Katzlberger Christian , Motschka Klaus , Denner Monika , Grath Johannes , Philippitsch Rudolf 
Published: May 2017

Abstract

In 2014, the Geological Survey of Austria (GBA) published – in cooperation with further national institutions – an overview map on radionuclides in groundwater, rocks and stream sediments at a scale of 1:500 000 with explanatory notes. In the frame of this activity, the uranium,
228
Ra,
226
Ra,
222
Rn,
210
Pb and
210
Po analyses in groundwater studies made by the Austrian Agency for Health and Food Safety (AGES) and Environment Agency of Austria (Umweltbundesamt), as well as the uranium and thorium analyses of stream sediments of the GBA and whole-rock analyses from different sources, were evaluated statistically. Furthermore, the GBA's comprehensive airborne radiometric data were exploited. The aim of this study was to work out typical spectra of the radionuclide content in the groundwater and aquifers of different geological settings.

It appeared that the concentration of
222
Rn in groundwater depends significantly on the uranium content of the aquifer. In contrast to this, the other radionuclides in groundwater did not show a clear correlation with uranium and thorium in the subsurface geology. Concerning
228
Ra,
226
Ra,
210
Pb and
210
Po, the lack of relationship to the subsurface composition seems to be a result of the low concentrations in groundwater. With respect to uranium in groundwater, there is a mixed situation: on the one hand, high uranium concentrations in groundwater can be observed in the Alps in regions with uranium bearing orthogneisses. On the other hand, in sediment basins of NE Austria where the underlying geology contains little uranium. Whether this is caused by special geological features combined with the given low precipitation or by the extensive agriculture (uranium from phosphate fertilizer) is under examination.

Concerning the threshold values of the radionuclides in groundwater (radiation), no exceedance could be observed. In spite of this, the concentration of the heavy metal uranium sometimes exceeded the threshold value of 15 µg l
−1
: this is especially true for the regions mentioned above.

In addition, an attempt was made to compare the Austrian values with data from neighbouring countries. It became clear that only a few published datasets exist that are comparable. Radon analyses of soil gas in the Czech Republic and Bavaria show the same geological patterns as the Austrian radon analyses of the groundwater. In addition, to enable the reader to compare the Austrian data with datasets from other countries, additional tables are included here for all types of data. They show the statistic distributions of different geological classes in a coordinated way.
Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair
Authors: Krüger Leandi , Gonzalez Liara M. , Pridgen Tiffany A. , McCall Shannon J. , von Furstenberg Richard J. , Harnden Ivan , Carnighan Gwendolyn E. , Cox Abigail M. , Blikslager Anthony T. , Garman Katherine S. 
Published: June 2017

Esophageal injury is a risk factor for diseases such as Barrett’s esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair. NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given the anatomical and physiological similarities between pigs and humans.
The Damaging Effect of Passenger Mutations on Cancer Progression
Authors: McFarland Christopher D. , Yaglom Julia A. , Wojtkowiak Jonathan W. , Scott Jacob G. , Morse David L. , Sherman Michael Y. , Mirny Leonid A. 
Published: May 2017

Abstract
Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution; most are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established. To assess this, we introduced increasing passenger loads into human cell lines and immunocompromised mouse models. We found that passengers dramatically reduced proliferative fitness (∼3% per Mb), slowed tumor growth, and reduced metastatic progression. We developed new genomic measures of damaging passenger load that can accurately predict the fitness costs of passengers in cell lines and in human breast cancers. We conclude that genomic instability and an elevated load of DNA alterations in cancer is a double-edged sword: it accelerates the accumulation of adaptive drivers, but incurs a harmful passenger load that can outweigh driver benefit. The effects of passenger alterations on cancer fitness were unrelated to enhanced immunity, as our tests were performed either in cell culture or in immunocompromised animals. Our findings refute traditional paradigms of passengers as neutral events, suggesting that passenger load reduces the fitness of cancer cells and slows or prevents progression of both primary and metastatic disease. The antitumor effects of chemotherapies can in part be due to the induction of genomic instability and increased passenger load. Cancer Res; 77(18); 4763–72. ©2017 AACR.
Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697)
Authors: Butterfield Lisa H. , Zhao Fengmin , Lee Sandra , Tarhini Ahmad A. , Margolin Kim A. , White Richard L. , Atkins Michael B. , Cohen Gary I. , Whiteside Theresa L. , Kirkwood John M. , Lawson David H. 
Published: May 2017

Abstract
Purpose: E4697 was a multicenter intergroup randomized placebo-controlled phase III trial of adjuvant GM-CSF and/or a multiepitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma.
Experimental Design: A total of 815 patients were enrolled from December 1999 to October 2006 into this six-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in montanide was designed to promote melanoma-specific CD8+ T-cell responses.
Results: Although the overall RFS and OS were not significantly improved with the vaccine or GM-CSF when compared with placebo, immunomodulatory effects were observed in peripheral blood and served as important correlates to this therapeutic study. Peripheral blood was examined to evaluate the impact of GM-CSF and/or the peptide vaccine on peripheral blood immunity and to investigate potential predictive or prognostic biomarkers. A total of 11.3% of unvaccinated patients and 27.1% of vaccinated patients developed peptide-specific CD8+ T-cell responses. HLA-A2+ patients who had any peptide-specific CD8+ T-cell response at day +43 tended to have poorer OS in univariate analysis. Patients receiving GM-CSF had significant reduction in percentages of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) at day +43. In a subset of patients who received GM-CSF, circulating myeloid-derived suppressor cells (MDSC), and anti-GM-CSF–neutralizing antibodies (Nabs) were also modulated. The majority of patients developed anti-GM-CSF Nabs, which correlated with improved RFS and OS.
Conclusions: The assessment of cellular and humoral responses identified counterintuitive immune system changes correlating with clinical outcome. Clin Cancer Res; 23(17); 5034–43. ©2017 AACR.
Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK
Authors: Moriwaki Kazumasa , Asahi Michio 
Published: May 2017

Abstract
O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.
Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. Mol Cancer Res; 15(9); 1287–98. ©2017 AACR.
Apixaban pharmacodynamic activity in umbilical cord, paediatric, and adult plasma
Authors: Yetman Robert , Barrett Yu , Wang Zhaoqing , Adamczyk Robert , Wang Jessie , Ramacciotti Eduardo , Frost Charles 
Published: May 2017

SummaryThe objective was to characterise apixaban pharmacodynamic (PD) activity in umbilical cord (UC), paediatric, and adult plasma. Plasma was obtained from blood samples from six UC donors, 70 paediatric (neonates [birth–≤1 month], infants [>1–≤6 months], toddlers [>6 months–≤2 years], young children [>2–≤6 years], children [>6–≤12 years], adolescents [>12–≤18 years]), and six adult (19–45 years) subjects. Plasma spiked with apixaban 0 (baseline), 30, or 110 ng/ml was analysed for anti-factor Xa activity, factor X levels, prothrombin time (PT), and modified PT (mPT). Apixaban had similar concentration-related effects on anti-factor Xa activity across groups (30 ng/ml: 0.223–0.295 IU/ml; 110 ng/ml: 1.212–1.474 IU/ml). Endogenous baseline factor X levels were 43%–68% lower in plasma from UC and subjects ≤6 months versus adults. Factor Xa inhibition (percentage change from baseline in apparent factor X levels) was similar for both apixaban concentrations across groups, except UC, neonate, and infant groups, which showed greater inhibition vs adults for apixaban 110 ng/ml. Baseline PT and mPT were similar across groups. Apixaban had no effect on PT at the concentrations tested. Apixaban 110 ng/ml prolonged mPT similarly across groups (44.4–53.2 s to 64.5–70.0 s); no prolongation was found with apixaban 30 ng/ml. Apixaban demonstrated consistent concentration-related effects on other PD endpoints in plasma samples from all age groups, except factor Xa inhibition.Supplementary Material to this article is available at www.thrombosis-online.com.