bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staphylococcus aureus Epicutaneous Infection Is Suppressed by Lactococcus lactis Strain Plasma via Interleukin 17A Elicitation
Authors: Tsuji Ryohei , Fujii Toshio , Nakamura Yuumi , Yazawa Kamiyu , Kanauchi Osamu 
Published: April 2019

AbstractBackgroundLactococcus lactis strain Plasma (LC-Plasma) was revealed to stimulate plasmacytoid dendritic cells and induce antiviral immunity in vitro and in vivo. In this study, we assessed the effects of LC-Plasma on skin immunity.MethodsTo evaluate the effect of LC-Plasma on skin immunity and Staphylococcus aureus epicutaneous infection, lymphocyte activities in skin-draining lymph nodes (SLNs) and gene expression in skin were analyzed after 2 weeks of oral administration of LC-Plasma. To evaluate the mechanisms of interleukin 17A production, SLN lymphocytes were cultured with or without LC-Plasma, and the interleukin 17A concentrations in supernatants were measured.ResultsOral administration of LC-Plasma activated plasma dendritic cells in SLNs, augmented skin homeostasis, and elicited suppression of Staphylococcus aureus, Staphylococcus epidermidis, and Propionibacterium acnes proliferation. In addition, significant suppression of the S. aureus burden and reduced skin inflammation were observed following oral administration of LC-Plasma. Furthermore, a subsequent in vitro study revealed that LC-Plasma could elicit interleukin 17A production from CD8+ T cells and that its induction mechanism depended on the Toll-like receptor 9 signaling pathway, with type I interferon partially involved.ConclusionsOur results suggest that LC-Plasma oral administration enhances skin homeostasis via plasma dendritic cell activation in SLNs, resulting in suppression of S. aureus epicutaneous infection and skin inflammation.
A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans
Authors: Jaeger Martin , Matzaraki Vasiliki , Aguirre-Gamboa Raúl , Gresnigt Mark S , Chu Xiaojing , Johnson Melissa D , Oosting Marije , Smeekens Sanne P , Withoff Sebo , Jonkers Iris , Perfect John R , van de Veerdonk Frank L , Kullberg Bart-Jan , Joosten Leo A B , Li Yang , Wijmenga Cisca , Netea Mihai G , Kumar Vinod 
Published: April 2019

AbstractBackgroundCandidemia, one of the most common causes of fungal bloodstream infection, leads to mortality rates up to 40% in affected patients. Understanding genetic mechanisms for differential susceptibility to candidemia may aid in designing host-directed therapies.MethodsWe performed the first genome-wide association study on candidemia, and we integrated these data with variants that affect cytokines in different cellular systems stimulated with Candida albicans.ResultsWe observed strong association between candidemia and a variant, rs8028958, that significantly affects the expression levels of PLA2G4B in blood. We found that up to 35% of the susceptibility loci affect in vitro cytokine production in response to Candida. Furthermore, potential causal genes located within these loci are enriched for lipid and arachidonic acid metabolism. Using an independent cohort, we also showed that the numbers of risk alleles at these loci are negatively correlated with reactive oxygen species and interleukin-6 levels in response to Candida. Finally, there was a significant correlation between susceptibility and allelic scores based on 16 independent candidemia-associated single-nucleotide polymorphisms that affect monocyte-derived cytokines, but not with T cell-derived cytokines.ConclusionsOur results prioritize the disturbed lipid homeostasis and oxidative stress as potential mechanisms that affect monocyte-derived cytokines to influence susceptibility to candidemia.
Epidemiology of Hepatitis E in England and Wales: A 10-Year Retrospective Surveillance Study, 2008–2017
Authors: Oeser Clarissa , Vaughan Aisling , Said Bengü , Ijaz Samreen , Tedder Richard , Haywood Becky , Warburton Fiona , Charlett Andre , Elson Richard , Morgan Dilys 
Published: April 2019

Abstract
Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as “G3 abcdhij”) is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.
Incidence of healthcare-associated Clostridioides difficile infections and association with ward-level antibiotic consumption in a German university hospital: an ecological study
Authors: Kipnis Marina , Schwab Frank , Kramer Tobias S , Stegemann Miriam S , Isner Caroline , Pilarski Georg , Märtin Nayana , Bui Minh Trang , Boldt Anne-C , Behnke Michael , Denkel Luisa A , Wiese-Posselt Miriam , Zweigner Janine , Gastmeier Petra , Rohde Anna M 
Published: April 2019

Abstract

Objectives
Clostridioides difficile infection (CDI) is one of the most important healthcare-associated infections. We aimed to describe the incidence density of healthcare-associated CDI (HA-CDI) in Germany’s largest hospital and to identify associations with ward-level antimicrobial consumption.

Methods
We used surveillance data on CDI and antimicrobial consumption from 2014 to 2017 and analysed a potential association by means of multivariable regression analysis.

Results
We included 77 wards with 404998 admitted patients and 1850862 patient-days. Six hundred and seventy-one HA-CDI cases were identified, resulting in a pooled mean incidence density of 0.36/1000 patient-days (IQR = 0.34–0.39). HA-CDI incidence density on ICU and haematological–oncological wards was about three times higher than on surgical wards [incidence rate ratio (IRR) = 3.00 (95% CI = 1.96–4.60) and IRR = 2.78 (95% CI = 1.88–4.11), respectively]. Ward-level consumption of third-generation cephalosporins was the sole antimicrobial risk factor for HA-CDI. With each DDD/100 patient-days administered, a ward’s HA-CDI incidence density increased by 2% [IRR = 1.02 (95% CI = 1.01–1.04)]. Other risk factors were contemporaneous community-associated CDI cases [IRR = 1.32 (95% CI = 1.07–1.63)] and CDI cases in the previous month [IRR = 1.27 (95% CI = 1.07–1.51)]. Furthermore, we found a significant decrease in HA-CDI in 2017 compared with 2014 [IRR = 0.68 (95% CI = 0.54–0.86)].

Conclusions
We confirmed that ward-level antimicrobial use influences HA-CDI and specifically identified third-generation cephalosporin consumption as a risk factor.
Effects of dietary soy isoflavones and soy protein source on response of weanling pigs to porcine reproductive and respiratory syndrome viral infection
Authors: Smith Brooke Nicole , Morris Antrison , Oelschlager Maci Lynn , Connor Jordan , Dilger Ryan Neil 
Published: April 2019

AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) is the most prevalent disease of swine globally. Infection of weanling pigs with PRRSV leads to a complex immune response resulting in significant disease and decreased growth performance. Previous experimental evidence suggests that increasing concentrations of soybean meal in the diet of young pigs confer benefits in terms of growth performance and immune parameters. The objective of this experiment was to identify potential modes of action for this benefit, specifically the ability for soy-derived isoflavones (ISF) to confer immunological benefits to young pigs infected with PRRSV. Four dietary treatments differing in soy protein source (soy protein concentrate vs. enzyme-treated soybean meal) and ISF supplementation (none vs. 1,500 mg total ISF/kg) were fed; the control diet (CON) contained soy protein concentrate and no supplemental ISF. Weanling pigs (60 barrows, 21 d of age, 5.71 ± 0.44 kg) from a naturally Mycoplasma hyopneumoniae (Mh)–infected source herd were individually housed in disease containment chambers and provided ad libitum access to experimental diets for 7 d before receiving either a sham inoculation or a 9.28 × 103 50% tissue culture infective dose of PRRSV at 28 d of age (0 d postinoculation). A total of 5 experimental treatments included an uninfected group receiving the CON diet, plus four infected groups each receiving a different dietary treatment. Growth performance and rectal temperatures were recorded throughout the study, and blood was collected for quantification of serum PRRSV load, presence of anti-PRRSV antibodies, differential complete blood counts, cytokine concentrations, and T-cell immunophenotyping. Data were analyzed as a 2-way or 3-way ANOVA for all treatments including PRRSV-infected pigs, in addition to a single degree of freedom contrast to compare uninfected and infected pigs receiving the CON diet. PRRSV-infection reduced growth rate and efficiency compared with noninfected controls with minimal influences by ISF. Supplemental ISF reduced PRRSV-induced band neutrophilia and improved cytotoxic-to-helper T-cell ratios. These results suggest that ISF contribute to activation of adaptive immune system pathways and could benefit recovery from and clearance of PRRSV infections.
Revenue-Capped Efficient Auctions
Authors: Muto Nozomu , Shirata Yasuhiro , Yamashita Takuro 
Published: April 2019

Abstract
We study an auction that maximizes the expected social surplus under an upper-bound constraint on the seller’s expected revenue, which we call a revenue cap. Such a constrained-efficient auction may arise, for example, when (i) the auction designer is “pro-buyer”, that is, he maximizes the weighted sum of the buyers’ and seller’s auction payoffs, where the weight for the buyers is greater than that for the seller; (ii) the auction designer maximizes the (unweighted) total surplus in a multiunit auction in which the number of units the seller owns is private information; or (iii) multiple sellers compete to attract buyers before the auction. We characterize the mechanisms for constrained-efficient auctions and identify their important properties. First, the seller sets no reserve price and sells the good for sure. Second, with a nontrivial revenue cap, “bunching” is necessary. Finally, with a sufficiently severe revenue cap, the constrained-efficient auction has a bid cap, so that bunching occurs at least “at the top,” that is, “no distortion at the top” fails.
Identifying the Perpetrators of Chemical Attacks in Syria
Authors: Sossai Mirko 
Published: April 2019

Abstract
In June 2018, the Conference of States Parties of the 1993 Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction (Chemical Weapons Convention) decided to create an Investigation and Identification Team. This is a new mechanism within the Organisation for the Prohibition of Chemical Weapons (OPCW) Technical Secretariat ‘to identify the perpetrators of the use of chemical weapons in the Syrian Arab Republic’. This article analyses the background and main features of this decision and draws some preliminary conclusions on the role of the Investigation and Identification Team and its potential impact for the investigation and prosecution of crimes linked to the use of chemical weapons in Syria. Thus, after describing the events surrounding various fact-finding missions in Syria under the auspices of the OPCW and the United Nations, it considers the legal basis to interpret the Chemical Weapons Convention as enabling the OPCW to put in place arrangements to identify the perpetrators of the use of chemical weapons in Syria and elsewhere.
A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells
Authors: Shah Kushani , King Gwendalyn D , Jiang Hao 
Published: April 2019

AbstractIt remains unknown whether H3K4 methylation, an epigenetic modification associated with gene activation, regulates fate determination of the postnatal neural stem and progenitor cells (NSPCs). By inactivating the Dpy30 subunit of the major H3K4 methyltransferase complexes in specific regions of mouse brain, we demonstrate a crucial role of efficient H3K4 methylation in maintaining both the self-renewal and differentiation capacity of postnatal NSPCs. Dpy30 deficiency disrupts development of hippocampus and especially the dentate gyrus and subventricular zone, the major regions for postnatal NSC activities. Dpy30 is indispensable for sustaining the self-renewal and proliferation of NSPCs in a cell-intrinsic manner and also enables the differentiation of mouse and human neural progenitor cells to neuronal and glial lineages. Dpy30 directly regulates H3K4 methylation and the induction of several genes critical in neurogenesis. These findings link a prominent epigenetic mechanism of gene expression to the fundamental properties of NSPCs and may have implications in neurodevelopmental disorders.
Do Forced-Choice (FC) Questions Trigger Deeper Cognition than Check-All-That-Apply (CATA) Questions?
Authors: Neuert Cornelia E 
Published: April 2019

Abstract
Existing research shows that response options are endorsed at a higher rate when presented in forced-choice format (FC, yes-no grids) than in check-all-that-apply format (CATA). Information Processing Theory explains this contrast with differential effects on the level of cognitive reflection. The study tests this hypothesis with eye movement data collected in a randomized laboratory experiment in which 131 respondents participated in a web survey with four treatment questions. In one condition (CATA) the questions were presented in check-all format, in the other (FC) in forced-choice structure. I find higher levels of affirmative responses and longer completion times in FC compared to CATA in three of the questions. With all four questions, respondents invested more cognitive effort—measured by fixation counts and times—in FC than in CATA when considering the question in total. I find no differences when considering only the list of response options, however. This indicates that the longer fixation times did not result from a more careful evaluation of the response options. Other possible causes and practical implications are discussed.
In vivo analysis of influenza A mRNA secondary structures identifies critical regulatory motifs
Authors: Simon Lisa Marie , Morandi Edoardo , Luganini Anna , Gribaudo Giorgio , Martinez-Sobrido Luis , Turner Douglas H , Oliviero Salvatore , Incarnato Danny 
Published: April 2019

AbstractThe influenza A virus (IAV) is a continuous health threat to humans as well as animals due to its recurring epidemics and pandemics. The IAV genome is segmented and the eight negative-sense viral RNAs (vRNAs) are transcribed into positive sense complementary RNAs (cRNAs) and viral messenger RNAs (mRNAs) inside infected host cells. A role for the secondary structure of IAV mRNAs has been hypothesized and debated for many years, but knowledge on the structure mRNAs adopt in vivo is currently missing. Here we solve, for the first time, the in vivo secondary structure of IAV mRNAs in living infected cells. We demonstrate that, compared to the in vitro refolded structure, in vivo IAV mRNAs are less structured but exhibit specific locally stable elements. Moreover, we show that the targeted disruption of these high-confidence structured domains results in an extraordinary attenuation of IAV replicative capacity. Collectively, our data provide the first comprehensive map of the in vivo structural landscape of IAV mRNAs, hence providing the means for the development of new RNA-targeted antivirals.
DIPG-03. TARGETING PI3K USING THE BLOOD BRAIN BARRIER PENETRABLE INHIBITOR, GDC-0084, FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Duchatel Ryan , Jackson Evangeline , Patabendige Adjanie , Cain Jason , Tsoli Maria , Monje Michelle , Alvaro Frank , Ziegler David , Dun Matthew 
Published: April 2019

Abstract
BACKGROUND: Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating, incurable childhood brain cancer. 80% of patients harbour a genetic lesion to Histone-H3 with a substitution of lysine 27 for a methionine (K27M) (H3F3A/H3.3 and HIST1H3B/H3.1) which results in the loss of methylation, interfering with chromatin function, activating oncogenic transcription. Unfortunately, H3 mutations are not directly targetable. RTK-RAS-PI3Kpathway alterations occur in more than half of these patients (69%), and may represent a more promising therapeutic target. However, PI3K inhibitors have been notoriously ineffective due to their inability to cross the blood-brain-barrier (BBB). Targeting downstream components of the PI3K-AKT-mTOR signalling axis is a promising paradigm for PI3K mutant patients. This project aims to overcome the limitations of targeting downstream effectors of the PI3K pathway by utilising a novel PIK3CA specific, BBB permeable inhibitor, GDC-0084, currently in clinical trials for Glioblastoma (GBM) and DIPG. METHODS: Utilising DIPG patient derived (PDX) cells harboringH3K27M mutations (n=6), and +/- PI3Kmutations, we examined the in-vitroefficacy of GDC-0084 on cell proliferation compared to Rapamycin. Phosphoproteomic profiling is currently underway investigating the role GDC-0084 has on inhibition of downstream oncogenic signalling pathways. Assessment of efficacy in a PDX in-vivo model is currently in progress. RESULTS: GDC-0084 significantly reduced the growth of all DIPG cell lines regardless of whether they harboredPI3K mutations (p=&lt;0.001), and were significantly more cytotoxic than the mTORC1 inhibitor Rapamycin (p=&lt;0.01). DIPG cell lines were also more sensitive to PI3K inhibition by GDC-0084 compared to GBM cell lines (n=4, p=&lt;0.001) highlighting the therapeutic potential of GDC-0084 for the treatment of DIPG. Combining GDC-0084 and Vandetanib in DIPG revealed synergistic effects. CONCLUSIONS: While there are currently no therapeutics effective against the transcriptional programs elicited by H3 mutations, these studies re-ignite the potential for PI3K inhibition as a therapeutic target for DIPG.
The Relationship Between Migraine or Severe Headache and Chronic Health Conditions: A Cross-Sectional Study from the National Health Interview Survey 2013–2015
Authors: Minen Mia T , Weissman Judith , Tietjen Gretchen E 
Published: April 2019

Abstract

Objective
To estimate the prevalence of having at least one or two or more chronic health conditions among US adults with self-reported migraine or severe headaches.

Design
Cross-sectional study.

Methods
Using data collected from the 2013–2015 National Health Interview Survey, we examined adults with and without migraine or severe headache and associations with chronic obstructive pulmonary disease, cancer, heart disease, stroke, diabetes, and hypertension. We calculated point estimates, variances, and 95% confidence intervals and conducted bivariate and multivariable logistic regression modeling to examine the relationships between migraine or severe headache and each of the chronic health conditions, as well as multinomial modeling, to examine the relationship between migraine or severe headache and having one or more chronic health conditions.

Results
A total of 104,926 people were in the study. Adults aged 18 to 44 years (18.2%), women (20.1%), and those with some college education (17.6%) had the greatest proportion with migraine or severe headache (P &lt; 0.0001). Using multinomial modeling with the number of chronic health conditions as the dependent variable, adults reporting migraine had an increased odds of reporting a single chronic health condition (adjusted odds ratio [aOR] = 1.7, 95% confidence interval [CI] = 1.6–1.8) and more than double the odds of reporting two or more chronic health conditions (aOR = 2.5, 95% CI = 2.3–2.8) compared with adults who did not have migraine or severe headache.

Conclusions
Our study confirms observed relationships between migraine or severe headache and chronic health conditions and supports the need for further research to uncover the shared biological pathways.
The Source and the Course of the Articular Branches to the T4-T8 Zygapophysial Joints
Authors: Joshi Anand , Amrhein Timothy J , Holmes Megan A , Talsma Joel , Shonyo Megan , Taylor Andrea B 
Published: April 2019

AbstractObjectiveTo define the source and the course of the articular branches to the midthoracic zygapophysial (“z”) joints.DesignCadaveric dissection.SettingThe Gross Anatomy Laboratory of the Duke University School of Medicine.SubjectsTen human cadaveric thoraces.MethodsGross and stereoscopic dissection of dorsal rami T4-T8 was performed bilaterally on 10 adult embalmed cadavers. The medial and lateral branches were traced to their origins from the dorsal rami, and the course of the articular nerves was documented through digital photography. Radio-opaque wire (20 gauge) was applied to the nerves. Fluoroscopic images were obtained to delineate their radiographic course with respect to osseous landmarks.ResultsForty-eight inferior articular branches were identified. Three (6.3%) originated from the medial branch and 44 (91.7%) from the dorsal ramus. One was indeterminate. Fifty-one superior articular branches were identified. Eight (15.7%) originated from the medial branch and 43 (84.3%) from the dorsal ramus. In 12% of cases (6/50), there was side-to-side asymmetry in the origins of the articular branches. Nerves were commonly suspended in the intertransverse space. The articular branches contacted an osseous structure in only 39% of cases. As previously reported, a “descending branch” was not identified in any specimen.ConclusionsArticular branches to the T4-T8 z-joints have substantial inter- and intraspecimen variability of origin. They typically arise from the dorsal ramus rather than the medial branch and frequently do not contact any osseous structure to allow percutaneous needle placement.