bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of effectiveness among frequent treatments of recurrent spontaneous abortion: A Bayesian network meta‐analysis
Authors: Lv Sha , Yu Jing , Xu Xiaoxiao 
Published: April 2018

ObjectiveA comprehensive network meta‐analysis was designed to clarify contradictions and offer valuable clinical guidance in the treatment of recurrent spontaneous abortion (RSA).MethodThe included clinical trials were selected from the relevant medical journal databases and screened. Treatments were ranked by the surface under the cumulative ranking curve. Heat plots were constructed to analyze the inconsistency between direct data and network results, and adjusted funnel plots were constructed to assess publication bias.ResultsForty‐nine randomized controlled trials involving a total of 8496 RSA patients were selected. With placebo as control, corticosteroid plus low dose aspirin (LDA) plus unfractionated heparin (UFH), granulocyte colony‐stimulating factor (G‐CSF) alone, and LDA plus low molecular weight heparin (LMWH) all demonstrated effectiveness in increasing successful live birth rates and reducing the incidences of miscarriage. However, no treatment was demonstrably superior to placebo in terms of pregnancy success. For all 3 endpoints (live birth, abortion and success pregnancy), the adjusted funnel plots were symmetric to zero and indicated no publication bias. In terms of live birth and abortion rates, no treatment outperformed placebo in patients with antiphospholipid syndrome.ConclusionIn consideration of live birth and abortion rates, corticosteroid plus LDA plus UFH appeared to be the optimum treatment strategy; G‐CSF was second, followed by LDA with LMWH, LDA plus LMWH plus intravenous immunoglobulin, corticosteroid with LDA and others. Subgroup analysis demonstrated no benefit of antithrombotic therapy in patients with antiphospholipid syndrome.
Magnesium sulfate differentially modulates fetal membrane inflammation in a time‐dependent manner
Authors: Cross Sarah N. , Nelson Rachel A. , Potter Julie A. , Norwitz Errol R. , Abrahams Vikki M. 
Published: April 2018

ProblemChorioamnionitis and infection‐associated inflammation are major causes of preterm birth. Magnesium sulfate (MgSO4) is widely used in obstetrics as a tocolytic; however, its mechanism of action is unclear. This study sought to investigate how MgSO4 modulates infection‐associated inflammation in fetal membranes (FMs), and whether the response was time dependent.Method of StudyHuman FM explants were treated with or without bacterial lipopolysaccharide (LPS); with or without MgSO4 added either: 1 hour before LPS; at the same time as LPS; 1 hour post‐LPS; or 2 hours post‐LPS. Explants were also treated with or without viral dsRNA and LPS, alone or in combination; and MgSO4 added 1 hour post‐LPS After 24 hours, supernatants were measured for cytokines/chemokines; and tissue lysates measured for caspase‐1 activity.ResultsLipopolysaccharide‐induced FM inflammation by upregulating the secretion of a number of inflammatory cytokines/chemokines. Magnesium sulfate administered 1‐hour post‐LPS inhibited FM secretion of IL‐1β, IL‐6, G‐CSF, RANTES, and TNFα. Magnesium sulfate administered 2 hours post‐LPS augmented FM secretion of these factors as well as IL‐8, IFNγ, VEGF, GROα and IP‐10. Magnesium sulfate delivered 1‐ hour post‐LPS inhibited LPS‐induced caspase‐1 activity, and inhibited the augmented IL‐1β response triggered by combination viral dsRNA and LPS.ConclusionMagnesium sulfate differentially modulates LPS‐induced FM inflammation in a time‐dependent manner, in part through its modulation of caspase‐1 activity. Thus, the timing of MgSO4 administration may be critical in optimizing its anti‐inflammatory effects in the clinical setting. MgSO4 might also be useful at preventing FM inflammation triggered by a polymicrobial viral‐bacterial infection.
National Parliaments’ Use of the Political Dialogue: Institutional Lobbyists, Traditionalists or Communicators?
Authors: Rasmussen Mette Buskjær , Dionigi Maja Kluger 
Published: April 2018

AbstractIn this article, we examine the reasons behind national parliamentary engagement in the political dialogue with the Commission. We do so through a qualitative content analysis of over 200 national parliamentary opinions submitted to the Commission in recent years and interviews with national parliamentary representatives and Commission officials. We demonstrate that national parliaments’ engagement with the Commission is not simply a story about venue shopping in which parliaments seek to compensate for their domestic weaknesses. Their activity is driven by a rich repertoire of institutional actions, where parliaments simultaneously act as institutional lobbyists, traditionalists and communicators. They follow three main strategies, including attempts to control their government, influencing EU legislation directly, and engaging in parliamentary branding. Direct parliamentary lobbying of the Commission does not, however, render parliaments’ traditional role of controlling their government redundant as it improves domestic scrutiny methods.
Systemic inflammation and immune cell phenotypes are associated with neuro‐psychiatric symptoms in patients with chronic inflammatory liver diseases
Authors: Aregay Amare , Dirks Meike , Schlaphoff Verena , Owusu Sekyere Solomon , Haag Kim , Falk Christine Susanne , Hengst Julia , Bremer Birgit , Schuppner Ramona , Manns Michael P. , Pflugrad Henning , Cornberg Markus , Wedemeyer Heiner , Weissenborn Karin 
Published: April 2018

AbstractBackground & AimsChronic inflammatory liver diseases are frequently associated with neuropsychiatric and cognitive dysfunctions. We hypothesized that symptomatic patients may show altered levels of soluble inflammatory mediators (SIMs) as well as changes in immune cell phenotypes.MethodsA comprehensive immune‐phenotyping including investigation of 50 SIMs as well as ex‐vivo phenotypes of NK‐cells, CD3+, CD4+, CD8+ and regulatory T cells in 40 patients with viral and autoimmune chronic liver diseases was performed. The patients’ cognitive functions were assessed using an extensive battery of neuropsychological testing.Results and ConclusionOverall, our data indicate that while SIMs are significantly up‐regulated, NK‐ and T‐cells are less‐activated in patients with neuropsychiatric symptoms accompanying chronic inflammatory liver diseases compared to patients without these symptoms. Moreover, HCV patients showed a unique pattern of immune alterations as compared to patients with HBV, autoimmune hepatitis and primary biliary cirrhosis. These findings hint towards potential mechanisms explaining these symptoms in patients with chronic liver diseases.
Placental expression of asialoglycoprotein receptor associated with Hepatitis B virus transmission from mother to child
Authors: Vyas Ashish Kumar , Ramakrishna Usha , Sen Bijoya , Islam Mojahidul , Ramakrishna Gayatri , Patra Sharda , Rastogi Archana , Sarin Shiv Kumar , Trehanpati Nirupma 
Published: April 2018

AbstractBackgroundAsialoglycoprotein receptor expression on hepatocytes has been associated with endocytosis, binding and uptake of hepatitis B virus. The role of asialoglycoprotein receptor in hepatitis B virus vertical transmission and its expression on placenta has not yet been studied.Patients and MethodsThirty‐four HBsAg+ve and 13 healthy pregnant mothers along with their newborns were enrolled. The former were categorized into transmitting and non‐transmitting mothers based on their newborns being hepatitis B surface antigen and hepatitis B virus DNA positive. Expression of asialoglycoprotein receptor and hepatitis B surface antigen in placenta and isoform of asialoglycoprotein receptor on dendritic cell in peripheral and cord blood dendritic cells were analysed using flowcytometry, immune histochemistry, immune florescence and qRT‐PCR.ResultsTwelve HBsAg+ve mothers transmitted hepatitis B virus to their newborns whereas the rest (n = 22) did not. Hepatitis B virus‐transmitting mothers showed increased expression of asialoglycoprotein receptor in trophoblasts of placenta. Immunofluorescence microscopy revealed colocalization of hepatitis B surface antigen and asialoglycoprotein receptor in placenta as well as in DCs of transmitting mothers. There was no significant difference in the expression of asialoglycoprotein receptor on peripheral blood mononuclear cells or chord blood mononuclear cells between the 2 groups. However, hepatitis B virus‐transmitting mothers and their HBsAg+ve newborns showed increased mRNA levels of isoform of asialoglycoprotein receptor on dendritic cell in peripheral blood mononuclear cells. Hepatitis B virus‐transmitting mothers and their HBsAg+ve newborns showed an increased expression of isoform of asialoglycoprotein receptor on dendritic cell on circulating dendritic cells compared to hepatitis B virus non‐transmitting mothers and their negative newborns.ConclusionsThis study revealed that increased expression of asialoglycoprotein receptor in placenta and colocalization with hepatitis B surface antigen strongly indicates its role in intrauterine transmission of hepatitis B virus. Asialoglycoprotein receptor‐blocking strategy can be used for therapeutic intervention of vertical transmission.
Stop the war on DXA!
Authors: Lewiecki E. Michael , Binkley Neil , Bilezikian John P. 
Published: April 2018

AbstractDual‐energy X‐ray absorptiometry (DXA) is a versatile technology that is widely used in clinical practice in the management of osteoporosis and other skeletal diseases. It is a safe and inexpensive procedure that measures bone mineral density (BMD) to diagnose osteoporosis, assess fracture risk, and monitor osteoporosis treatment. However, DXA has been subjected to recurring claims that it is overutilized, too expensive, and not helpful in patient management. In recent years, there has been a decline in the number of office‐based DXA facilities, a reduction in BMD tests performed, and fewer women being diagnosed and treated for osteoporosis, despite aging of the population with more people at risk for fractures. Here, we identify some of the challenges to DXA, which in the aggregate amount to a disturbing war on DXA and, as a result, a threat to good patient care. We suggest potential strategies to restore DXA to its proper role in osteoporosis management.
ESRD‐induced dyslipidemia—Should management of lipid disorders differ in dialysis patients?
Authors: Moradi Hamid , Streja Elani , Vaziri Nosratola D. 
Published: April 2018

AbstractCardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Although numerous modifiable risk factors in the pathogenesis of CVD and its associated mortality have been identified, dyslipidemia remains to be a key focus for therapy. In this regard, significant progress has been made in reducing cardiovascular mortality via the use of lipid‐lowering agents such as HMG CoA reductase inhibitors (statins). Yet, despite the disproportionate risk of CVD and mortality in patients with advanced chronic and end stage renal disease (ESRD), treatment of dyslipidemia in this patient population has not been associated with a notable improvement in outcomes. Furthermore, observational studies have not consistently found an association between dyslipidemia and poor outcomes in patients with ESRD. However, it is imperative that examination of dyslipidemia and its association with outcomes take place in the context of the many factors that are unique to kidney disease and may contribute to the abnormalities in lipid metabolism in patients with ESRD. Understanding these intricacies and distinct features will be vital not only to the interpretation of the available clinical data in regards to outcomes, but also to the individualization of lipid therapy in ESRD. In this review, we will examine the nature and underlying mechanisms responsible for dyslipidemia, the association of serum lipids and lipoprotein concentrations with outcomes and the results of major trials targeting cholesterol (mainly statins) in patients with ESRD.
Free-Chlorine Disinfection as a Selection Pressure on Norovirus
Authors: Rachmadi Andri Taruna , Kitajima Masaaki , Watanabe Kozo , Yaegashi Sakiko , Serrana Joeselle , Nakamura Arata , Nakagomi Toyoko , Nakagomi Osamu , Katayama Kazuhiko , Okabe Satoshi , Sano Daisuke 
Published: April 2018

ABSTRACT
Human noroviruses are excreted in feces from infected individuals and included in wastewater. It is critical to remove/inactivate them in wastewater treatment processes, particularly in the disinfection step, before release to aquatic environments. However, the high mutation rates of human noroviruses raise concerns about the emergence of strains that are less susceptible to disinfectants and can survive even after wastewater treatment. This study aimed to demonstrate the strain-dependent susceptibility of norovirus to free chlorine. A population originated from the murine norovirus strain S7-PP3, a surrogate for human noroviruses in environmental testing, was exposed to free chlorine and then propagated in a host cell. This cycle of free chlorine exposure followed by propagation in cells was repeated 10 times, and populations with lower susceptibility to free chlorine were obtained from two independent trials of chlorine exposure cycles. Open reading frame 2 (ORF2) and ORF3 of the murine norovirus genome were analyzed by next-generation sequencing, and a unique nonsynonymous mutation (corresponding to a change from phenylalanine to serine) at nucleotide (nt) 7280 in ORF3, which encodes the minor capsid protein VP2, was found in chlorine-exposed populations from both trials. It was confirmed that all of the clones from the chlorine-treated population had lower susceptibility to free chlorine than those from the control population. These results indicate that exposure to free chlorine and dilution exert different driving forces to form murine norovirus (MNV) quasispecies, and that there is a selective force to form MNV quasispecies under free chlorine exposure.

IMPORTANCE
This study showed that free chlorine disinfection exerted a selection pressure for murine norovirus (MNV). The strain-dependent viral susceptibility to the disinfectant elucidated in this study highlights the importance of employing less susceptible strains as representative viruses in disinfection tests, because the disinfection rate values obtained from more susceptible strains would be less useful in predicting the virus inactivation efficiency of circulating strains under practical disinfection conditions.
Guanine Limitation Results in CodY-Dependent and -Independent Alteration of Staphylococcus aureus Physiology and Gene Expression
Authors: King Alyssa N. , Borkar Samiksha A. , Samuels David J. , Batz Zachary , Bulock Logan L. , Sadykov Marat R. , Bayles Kenneth W. , Brinsmade Shaun R. 
Published: April 2018

ABSTRACT

In
Staphylococcus aureus
, the global transcriptional regulator CodY modulates the expression of hundreds of genes in response to the availability of GTP and the branched-chain amino acids isoleucine, leucine, and valine (ILV). CodY DNA-binding activity is high when GTP and ILV are abundant. When GTP and ILV are limited, CodY's affinity for DNA drops, altering expression of CodY-regulated targets. In this work, we investigated the impact of guanine nucleotides (GNs) on
S. aureus
physiology and CodY activity by constructing a
guaA
null mutant (Δ
guaA
strain).
De novo
biosynthesis of guanine monophosphate is abolished due to the
guaA
mutation; thus, the mutant cells require exogenous guanosine for growth. We also found that CodY activity was reduced when we knocked out
guaA
, activating the Agr two-component system and increasing secreted protease activity. Notably, in a rich, complex medium, we detected an increase in alternative sigma factor B activity in the Δ
guaA
mutant, which results in a 5-fold increase in production of the antioxidant pigment staphyloxanthin. Under biologically relevant flow conditions, Δ
guaA
cells failed to form robust biofilms when limited for guanine or guanosine. Transcriptome sequencing (RNA-Seq) analysis of the
S. aureus
transcriptome during growth in guanosine-limited chemostats revealed substantial CodY-dependent and -independent alterations of gene expression profiles. Importantly, these changes increase production of proteases and δ-toxin, suggesting that
S. aureus
exhibits a more invasive lifestyle when limited for guanosine. Further, gene products upregulated under GN limitation, including those necessary for lipoic acid biosynthesis and sugar transport, may prove to be useful drug targets for treating Gram-positive infections.

IMPORTANCE
Staphylococcus aureus
infections impose a serious economic burden on health care facilities and patients because of the emergence of strains resistant to last-line antibiotics. Understanding the physiological processes governing fitness and virulence of
S. aureus
in response to environmental cues is critical for developing efficient diagnostics and treatments.
De novo
purine biosynthesis is essential for both fitness and virulence in
S. aureus
since inhibiting production cripples
S. aureus
's ability to cause infection. Here, we corroborate these findings and show that blocking guanine nucleotide synthesis severely affects
S. aureus
fitness by altering metabolic and virulence gene expression. Characterizing pathways and gene products upregulated in response to guanine limitation can aid in the development of novel adjuvant strategies to combat
S. aureus
infections.
Evaluation of the illumigene Mycoplasma Direct DNA Amplification Assay
Authors: Kanwar Neena , Pence Morgan A. , Mayne Donna , Michael Jeffrey , Selvarangan Rangaraj 
Published: April 2018

ABSTRACT

Mycoplasma pneumoniae
is a common cause of community-acquired pneumonia. The
illumigene
Mycoplasma Direct (iMD) DNA amplification assay is a qualitative
in vitro
test utilizing loop-mediated isothermal amplification (LAMP) technology for the direct detection of
M. pneumoniae
DNA in respiratory specimens. The iMD assay does not require the preextraction of nucleic acids from specimens, which is a prerequisite step for the previously approved
illumigene
Mycoplasma (iM) assay. The aim of this prospective multicenter study was to evaluate the performance characteristics of the newly developed iMD assay, compared with the iM assay. Subjects with symptoms of upper respiratory illnesses suggesting
M. pneumoniae
infection were enrolled at three sites in the United States. Respiratory specimens were obtained using dual throat swabs. One swab was tested with the iMD assay at each enrollment site. Reference testing with the iM assay was performed by the manufacturer. Among 456 specimens tested, the iM reference method detected
M. pneumoniae
in 25 specimens (5.5%), while the iMD assay identified 34 specimens (7.5%) as
M. pneumoniae
positive. There were 10 false-positive results and 1 false-negative result with the iMD assay. The overall positive and negative agreement rates were 96.0% (95% confidence interval [CI], 80.5 to 99.3%) and 97.7% (95% CI, 95.8 to 98.7%), respectively. The overall agreement rate was determined to be 97.6% (95% CI, 95.7 to 98.6%). We conclude that the iMD test results were comparable to the iM assay results. The removal of the DNA extraction step for the iMD assay simplifies testing, saves time, and reduces the costs of detecting
M. pneumoniae
from throat swabs, compared to the iM assay.
A systematic analysis of UK cancer research funding by gender of primary investigator
Authors: Zhou Charlie D , Head Michael G , Marshall Dominic C , Gilbert Barnabas J , El-Harasis Majd A , Raine Rosalind , O’Connor Henrietta , Atun Rifat , Maruthappu Mahiben 
Published: April 2018

ObjectivesTo categorically describe cancer research funding in the UK by gender of primary investigator (PIs).DesignSystematic analysis of all open-access data.MethodsData about public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013 were obtained from several sources. Fold differences were used to compare total investment, award number, mean and median award value between male and female PIs. Mann-Whitney U tests were performed to determine statistically significant associations between PI gender and median grant value.ResultsOf the studies included in our analysis, 2890 (69%) grants with a total value of £1.82 billion (78%) were awarded to male PIs compared with 1296 (31%) grants with a total value of £512 million (22%) awarded to female PIs. Male PIs received 1.3 times the median award value of their female counterparts (P<0.001). These apparent absolute and relative differences largely persisted regardless of subanalyses.ConclusionsWe demonstrate substantial differences in cancer research investment awarded by gender. Female PIs clearly and consistently receive less funding than their male counterparts in terms of total investment, the number of funded awards, mean funding awarded and median funding awarded.
Permanent percutaneous endoscopic gastrotomy tube placement in a Hermann’s tortoise
Authors: Reid Siuna Ann 
Published: April 2018

The patient had been diagnosed with renal insufficiency and hepatic lipidosis. A method had to be found to support the patient, providing fluids, nutrition and drug therapies. Standard oesophagostomy tube placement was not tolerated by the patient1. The tortoise kept removing the tube. An alternative method of delivering nutritional support, fluids and medical treatment was sought. No references were found indicating this is a novel method. The tube was fitted under general anaesthetic, through a 4‐mm‐diameter hole that was created in the second pleural scute above the bridge on the left side of the carapace. The hole in the carapace was filled using dental acrylic (Centri Base, WHW Plastics) and has only had to be replaced once in 18 months after placement.
Seismostratigraphic analysis of Paleozoic sequences of the Midlands Microcraton
Authors: Butler Malcolm 
Published: April 2018

Abstract
A regional review of publicly available seismic reflection lines and wells enables the identification across the Midlands Microcraton (MMC) of four Paleozoic seismostratigraphic megasequences, bounded by the Shelveian, Acadian, Symon and Variscan unconformities. The southern boundary of the MMC is drawn at a line of major change in pre-Permian subcrop, and most of central southern England is considered underlain by Paleozoic rocks of MMC character. The Lower Silurian Shelveian Unconformity cuts down through Ordovician and Cambrian rocks to the Precambrian and largely defines the distribution of these rocks in the region. However, more than 2500 m of Tremadoc shales are preserved SW of Swindon. Above the Shelveian, a characteristic shallow-marine Silurian is overlain by up to 3000 m of Old Red Sandstone facies, preserved in a north–south-orientated syncline. The Acadian Unconformity cuts down through folded Lower Paleozoic rocks, with the Frasnian transgression overlying Precambrian in places. Little Carboniferous was deposited across the MMC until uppermost Westphalian–Stephanian Warwickshire Group sandstones and coals were laid down across the erosion surface of the Symon Unconformity. The northern boundary of thin-skinned Variscan thrusting can be interpreted on seismic data but appears to have had little effect on the regional pre-Permian subcrop.