bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Mood or Anxiety Disorders in Children of Parents with Multiple Sclerosis
Authors: Razaz Neda , Tremlett Helen , Boyce Thomas , Guhn Martin , Marrie Ruth Ann , Joseph KS 
Published: March 2016

AbstractBackgroundAlthough parental multiple sclerosis (MS) may put children at increased risk for mental health disorders such as anxiety and depression, the incidence and determinants of such disorders have not been examined.MethodWe carried out a retrospective cohort study in British Columbia, Canada, among children of parents with MS and age‐matched children of unaffected parents. Cox regression was used to estimate the association between parental MS and mood or anxiety disorders in children.ResultsThe study included 1028 children of MS parents, 4010 children of unaffected parents, and 25 464 child‐years of follow‐up (median follow‐up of 4 years). Mental health morbidity was more common among MS parents vs. unaffected parents (50.4% vs. 33.1%) and among MS‐affected mothers vs. unaffected mothers (54.6% vs. 38.0%, P < 0.001). The incidence of child mood or anxiety disorders was 8.3 and 6.3 per 1000 child‐years among children of parents with and without MS respectively. Sex of the MS‐affected parent modified the relationship between parental MS and mood or anxiety disorders in children (P = 0.04). Compared with children of unaffected mothers, children of mothers affected by MS had higher rates of mood or anxiety disorders (HR 1.7, 95% CI 1.1, 2.4), whereas children of MS‐affected fathers did not (HR 0.5, 95% CI 0.2, 1.7). Adjustment for mental health morbidity in mothers diminished the association between maternal MS and child mood or anxiety disorders.ConclusionMaternal MS is associated with a higher rate of mood or anxiety disorders in children and this association appeared to be mediated by maternal mental health morbidity.
Cardiovascular and antacid treatment and mortality in oxygen‐dependent pulmonary fibrosis: A population‐based longitudinal study
Authors: Ekström Magnus , Bornefalk‐Hermansson Anna 
Published: March 2016

AbstractBackground and objectiveSevere idiopathic pulmonary fibrosis is associated with an increased risk of cardiovascular disease and gastro‐oesophageal reflux, which may influence prognosis. We evaluated associations between cardiovascular and antacid medications, and mortality, in oxygen‐dependent pulmonary fibrosis (PF) of unknown cause.MethodsProspective population‐based study of adults starting long‐term oxygen therapy (LTOT) for PF in Sweden 2005–2009. PF of unknown cause was defined by excluding patients with known or probable secondary PF. Time‐dependent associations between medications and all‐cause mortality were analysed using extended Cox regression, adjusting for potential confounders including age, sex, vital capacity, blood gases, body mass index, performance status, comorbidity and concurrent medications.ResultsOf 462 included patients, 329 (71%) died under observation. No patient was lost to follow‐up. Angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were associated with reduced adjusted mortality (HR 0.63; 0.47–0.85) and antiplatelet drugs with increased mortality (HR 1.49; 1.11–2.00), largely driven by higher mortality in women. There were no associations with mortality for antacid treatments, β‐blockers, diuretics or statins.ConclusionIn oxygen‐dependent PF, treatment with ACEI/ARB was associated with improved survival, antiplatelet drugs with decreased survival, whereas there was no association between antacid, β‐blocker, diuretic or statin treatment and survival.
ACOUSTICAL STANDARDS NEWS
Authors: Blaeser Susan B. , Struck Christopher J. 
Published: March 2016

American National Standards (ANSI Standards) developed by Accredited Standards Committees S1, S2, S3, S3/SC 1, and S12 in the areas of acoustics, mechanical vibration and shock, bioacoustics, animal bioacoustics, and noise, respectively, are published by the Acoustical Society of America (ASA). In addition to these standards, ASA publishes a catalog of Acoustical American National Standards. To receive a copy of the latest Standards catalog, please contact Susan B. Blaeser.
Comments are welcomed on all material in Acoustical Standards News.
This Acoustical Standards News section in JASA, as well as the National Catalog of Acoustical Standards and other information on the Standards Program of the Acoustical Society of America, are available via the ASA home page: http://acousticalsociety.org.
Survey of variation in human transcription factors reveals prevalent DNA binding changes
Authors: Barrera Luis A. , Vedenko Anastasia , Kurland Jesse V. , Rogers Julia M. , Gisselbrecht Stephen S. , Rossin Elizabeth J. , Woodard Jaie , Mariani Luca , Kock Kian Hong , Inukai Sachi , Siggers Trevor , Shokri Leila , Gordân Raluca , Sahni Nidhi , Cotsapas Chris , Hao Tong , Yi Song , Kellis Manolis , Daly Mark J. , Vidal Marc , Hill David E. , Bulyk Martha L. 
Published: March 2016

Variation and transcription factor bindingLittle is known about the phenotypic and functional effects of genetic variants that result in amino acid changes within functional proteins. Barreraet al.investigated whether amino acid variants changed the DNA binding specificity or affinity of transcription factors. Predictive analyses identified changes in the proteins, and protein-binding microarrays verified changes that affected transcription factor function, including those associated with disease. Thus, within-human protein sequence variation can affect transcriptional regulatory networks, which, depending on the genetic variant, may confer robustness and buffer against amino acid changes and could explain phenotypic variation among individuals.Science, this issue p.1450
Validation of a Multiplex Real-Time PCR Assay for Detection of Mycobacterium spp., Mycobacterium tuberculosis Complex, and Mycobacterium avium Complex Directly from Clinical Samples by Use of the BD Max Open System
Authors: Rocchetti Talita T. , Silbert Suzane , Gostnell Alicia , Kubasek Carly , Widen Raymond 
Published: March 2016

ABSTRACT

A multiplex real-time PCR was validated on the BD Max open system to detect different
Mycobacterium tuberculosis
complex,
Mycobacterium avium
complex, and
Mycobacterium
spp. directly from clinical samples. The PCR results were compared to those with traditional cultures. The multiplex PCR assay was found to be a specific and sensitive method for the rapid detection of mycobacteria directly from clinical specimens.
Swiftly Decreasing Cerebrospinal Fluid Cathelicidin Concentration Predicts Improved Outcome in Childhood Bacterial Meningitis
Authors: Savonius Okko , Helve Otto , Roine Irmeli , Andersson Sture , Fernández Josefina , Peltola Heikki , Pelkonen Tuula 
Published: March 2016

ABSTRACT
We investigated cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis on admission and during antimicrobial treatment. CSF cathelicidin concentrations on admission correlated with CSF white cell counts and protein levels but not with bacterial etiology. A greater decrease in the concentration in response to treatment was associated with a better outcome. Since the CSF cathelicidin concentration reflects the degree of central nervous system (CNS) inflammation, it may be used as a novel biomarker in childhood bacterial meningitis. An early decrease during treatment likely signals more rapid mitigation of the disease process and thus a better outcome.
Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy
Authors: Cheng Xing , Wang Weijia , Xu Qi , Harper James , Carroll Danielle , Galinski Mark S. , Suzich JoAnn , Jin Hong 
Published: March 2016

ABSTRACT
Clinical development of a mesogenic strain of Newcastle disease virus (NDV) as an oncolytic agent for cancer therapy has been hampered by its select agent status due to its pathogenicity in avian species. Using reverse genetics, we have generated a lead candidate oncolytic NDV based on the mesogenic NDV-73T strain that is no longer classified as a select agent for clinical development. This recombinant NDV has a modification at the fusion protein (F) cleavage site to reduce the efficiency of F protein cleavage and an insertion of a 198-nucleotide sequence into the HN-L intergenic region, resulting in reduced viral gene expression and replication in avian cells but not in mammalian cells. In mammalian cells, except for viral polymerase (L) gene expression, viral gene expression is not negatively impacted or increased by the HN-L intergenic insertion. Furthermore, the virus can be engineered to express a foreign gene while still retaining the ability to grow to high titers in cell culture. The recombinant NDV selectively replicates in and kills tumor cells and is able to drive potent tumor growth inhibition following intratumoral or intravenous administration in a mouse tumor model. The candidate is well positioned for clinical development as an oncolytic virus.

IMPORTANCE
Avian paramyxovirus type 1, NDV, has been an attractive oncolytic agent for cancer virotherapy. However, this virus can cause epidemic disease in poultry, and concerns about the potential environmental and economic impact of an NDV outbreak have precluded its clinical development. Here we describe generation and characterization of a highly potent oncolytic NDV variant that is unlikely to cause Newcastle disease in its avian host, representing an essential step toward moving NDV forward as an oncolytic agent. Several attenuation mechanisms have been genetically engineered into the recombinant NDV that reduce chicken pathogenicity to a level that is acceptable worldwide without impacting viral production in cell culture. The selective tumor replication of this recombinant NDV, both
in vitro
and
in vivo
, along with efficient tumor cell killing makes it an attractive oncolytic virus candidate that may provide clinical benefit to patients.
Influence of Respiratory Syncytial Virus F Glycoprotein Conformation on Induction of Protective Immune Responses
Authors: Palomo Concepción , Mas Vicente , Thom Michelle , Vázquez Mónica , Cano Olga , Terrón María C. , Luque Daniel , Taylor Geraldine , Melero José A. 
Published: March 2016

ABSTRACTHuman respiratory syncytial virus (hRSV) vaccine development has received new impetus from structure-based studies of its main protective antigen, the fusion (F) glycoprotein. Three soluble forms of F have been described: monomeric, trimeric prefusion, and trimeric postfusion. Most human neutralizing antibodies recognize epitopes found exclusively in prefusion F. Although prefusion F induces higher levels of neutralizing antibodies than does postfusion F, postfusion F can also induce protection against virus challenge in animals. However, the immunogenicity and protective efficacy of the three forms of F have not hitherto been directly compared. Hence, BALB/c mice were immunized with a single dose of the three proteins adjuvanted with CpG and challenged 4 weeks later with virus. Serum antibodies, lung virus titers, weight loss, and pulmonary pathology were evaluated after challenge. Whereas small amounts of postfusion F were sufficient to protect mice, larger amounts of monomeric and prefusion F proteins were required for protection. However, postfusion and monomeric F proteins were associated with more pathology after challenge than was prefusion F. Antibodies induced by all doses of prefusion F, in contrast to other F protein forms, reacted predominantly with the prefusion F conformation. At high doses, prefusion F also induced the highest titers of neutralizing antibodies, and all mice were protected, yet at low doses of the immunogen, these antibodies neutralized virus poorly, and mice were not protected. These findings should be considered when developing new hRSV vaccine candidates.IMPORTANCEProtection against hRSV infection is afforded mainly by neutralizing antibodies, which recognize mostly epitopes found exclusively in the viral fusion (F) glycoprotein trimer, folded in its prefusion conformation, i.e., before activation for membrane fusion. Although prefusion F is able to induce high levels of neutralizing antibodies, highly stable postfusion F (found after membrane fusion) is also able to induce neutralizing antibodies and protect against infection. In addition, a monomeric form of hRSV F that shares epitopes with prefusion F was recently reported. Since each of the indicated forms of hRSV F may have advantages and disadvantages for the development of safe and efficacious subunit vaccines, a direct comparison of the immunogenic properties and protective efficacies of the different forms of hRSV F was made in a mouse model. The results obtained show important differences between the noted immunogens that should be borne in mind when considering the development of hRSV vaccines.
Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression
Authors: MacParland Sonya A. , Ma Xue-Zhong , Chen Limin , Khattar Ramzi , Cherepanov Vera , Selzner Markus , Feld Jordan J. , Selzner Nazia , McGilvray Ian D. 
Published: March 2016

ABSTRACTInflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states.IMPORTANCEInflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states.
Kaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS (KicGAS), Encoded by ORF52, Is an Abundant Tegument Protein and Is Required for Production of Infectious Progeny Viruses
Authors: Li Wenwei , Avey Denis , Fu Bishi , Wu Jian-jun , Ma Siming , Liu Xia , Zhu Fanxiu 
Published: March 2016

ABSTRACT
Although Kaposi's sarcoma-associated herpesvirus (KSHV) ORF52 (also known as KSHV inhibitor of cGAS [KicGAS]) has been detected in purified virions, the roles of this protein during KSHV replication have not been characterized. Using specific monoclonal antibodies, we revealed that ORF52 displays true late gene expression kinetics and confirmed its cytoplasmic localization in both transfected and KSHV-infected cells. We demonstrated that ORF52 comigrates with other known virion proteins following sucrose gradient centrifugation. We also determined that ORF52 resides inside the viral envelope and remains partially associated with capsid when extracellular virions are treated with various detergents and/or salts. There results indicate that ORF52 is a tegument protein abundantly present in extracellular virions. To characterize the roles of ORF52 in the KSHV life cycle, we engineered a recombinant KSHV ORF52-null mutant virus and found that loss of ORF52 results in reduced virion production and a further defect in infectivity. Upon analysis of the virion composition of ORF52-null viral particles, we observed a decrease in the incorporation of ORF45, as well as other tegument proteins, suggesting that ORF52 is important for the packaging of other virion proteins. In summary, our results indicate that, in addition to its immune evasion function, KSHV ORF52 is required for the optimal production of infectious virions, likely due to its roles in virion assembly as a tegument protein.

IMPORTANCE
The tegument proteins of herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), play key roles in the viral life cycle. Each of the three subfamilies of herpesviruses (alpha, beta, and gamma) encode unique tegument proteins with specialized functions. We recently found that one such gammaherpesvirus-specific protein, ORF52, has an important role in immune evasion during KSHV primary infection, through inhibition of the host cytosolic DNA sensing pathway. In this report, we further characterize ORF52 as a tegument protein with vital roles during KSHV lytic replication. We found that ORF52 is important for the production of infectious viral particles, likely through its role in virus assembly, a critical process for KSHV replication and pathogenesis. More comprehensive investigation of the functions of tegument proteins and their roles in viral replication may reveal novel targets for therapeutic interventions against KSHV-associated diseases.
Perceptions and impact of plain packaging of tobacco products in low and middle income countries, middle to upper income countries and low-income settings in high-income countries: a systematic review of the literature
Authors: Hughes Nicole , Arora Monika , Grills Nathan 
Published: March 2016

ObjectiveTo review the current literature around the potential impact, effectiveness and perceptions of plain packaging in low income settings.MethodA systematic review of the literature.Data sources9 databases (PubMed, Global Health, Social Policy and Practice, Applied Social Sciences Index and Abstracts (ASSIA), CINAHL, PsycINFO, British Library for Development Studies (BLDS), Global Health Library and Scopus) were searched. The terms used for searching combined terms for smoking and tobacco use with terms for plain packaging.Study selectionStudies investigating the impact of plain packaging on the determinants of tobacco use, such as smoking behaviour, appeal, prominence, effectiveness of health warnings, response to plain packs, attitudes towards quitting or likelihood of smoking in low-income settings, were identified. Studies must have been published in English and be original research of any level of rigour.Data extractionTwo independent reviewers assessed studies for inclusion and extracted data.Data synthesisThe results were synthesised qualitatively, with themes grouped under four key headings: appeal and attractiveness; salience of health warnings and perceptions of harm; enjoyment and perceived taste ratings; and perceptions of the impact on tobacco usage behaviour.ResultsThis review has identified four articles that met the inclusion criteria. Studies identified that tobacco products in plain packaging had less appeal than in branded packaging in low-income settings.ConclusionsThis review indicates that plain packaging appears to be successful in reducing appeal of smoking and packets, and supports the call for plain packaging to be widely implemented in conjunction with other tobacco control policies. However, there are considerable gaps in the amount of research conducted outside high-income countries.
Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma
Authors: Brazier Peter , Schauer Uwe , Hamelmann Eckard , Holmes Steve , Pritchard Clive , Warner John O 
Published: March 2016

IntroductionChronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service (NHS). Temperature-controlled laminar airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on treatment option that is non-invasive and has been shown in clinical studies to improve quality of life for patients with poorly controlled allergic asthma. The objective of this study was to quantify the cost-effectiveness of TLA (Airsonett AB) technology as an add-on to standard asthma management drug therapy in the UK.MethodsThe main performance measure of interest is the incremental cost per quality-adjusted life year (QALY) for patients using TLA in addition to usual care versus usual care alone. The incremental cost of TLA use is based on an observational clinical study monitoring the incidence of exacerbations with treatment valued using NHS cost data. The clinical effectiveness, used to derive the incremental QALY data, is based on a randomised double-blind placebo-controlled clinical trial comprising participants with an equivalent asthma condition.ResultsFor a clinical cohort of asthma patients as a whole, the incremental cost-effectiveness ratio (ICER) is £8998 per QALY gained, that is, within the £20 000/QALY cost-effectiveness benchmark used by the National Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates that ICER values range from £18 883/QALY for the least severe patients through to TLA being dominant, that is, cost saving as well as improving quality of life, for individuals with the most severe and poorly controlled asthma.ConclusionsBased on our results, Airsonett TLA is a cost-effective addition to treatment options for stage 4/5 patients. For high-risk individuals with more severe and less well controlled asthma, the use of TLA therapy to reduce incidence of hospitalisation would be a cost saving to the NHS.