bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipocyte Model of Mycobacterium tuberculosis Infection Reveals Differential Availability of Iron to Bacilli in the Lipid-Rich Caseous Environment
Authors: Nandy Ananya , Mondal Anupam Kumar , Pandey Rajesh , Arumugam Prabhakar , Dawa Stanzin , Jaisinghani Neetika , Rao Vivek , Dash Debasis , Gandotra Sheetal 
Published: April 2018

ABSTRACT

Mycobacterium tuberculosis
, a successful human pathogen, utilizes multiple carbon sources from the host but adapts to a fatty-acid-rich environment
in vivo
. We sought to delineate the physiologic response of
M. tuberculosis
to a lipid-rich environment by using differentiated adipocytes as a model system. Global transcriptome profiling based on RNA sequencing was performed for bacilli from infected adipocytes and preadipocytes. Genes involved in
de novo
fatty acid synthesis were downregulated, while those predicted to be involved in triglyceride biosynthesis were upregulated, in bacilli isolated from adipocytes, indicating reliance on host-derived fatty acids. Transcription factor network analysis indicated suppression of IdeR-regulated genes, suggesting decreased iron uptake by
M. tuberculosis
in the adipocyte model. This suppression of iron uptake coincided with higher ferritin and iron levels in adipocytes than in preadipocytes. In accord with the role of iron in mediating oxidative stress, we observed upregulation of genes involved in mitigating oxidative stress in
M. tuberculosis
isolated from adipocytes. We provide evidence that oleic acid, a major host-derived fatty acid, helps reduce the bacterial cytoplasm, thereby providing a safe haven for an
M. tuberculosis
mutant that is sensitive to iron-mediated oxidative stress. Via an independent mechanism, host ferritin is also able to rescue the growth of this mutant. Our work highlights the inherent synergy between macronutrients and micronutrients of the host environment that converge to provide resilience to the pathogen. This complex synergy afforded by the adipocyte model of infection will aid in the identification of genes required by
M. tuberculosis
in a caseous host environment.
Comparative Analysis of
UL16
Mutants Derived from Multiple Strains of Herpes Simplex Virus 2 (HSV-2) and HSV-1 Reveals Species-Specific Requirements for the UL16 Protein
Authors: Gao Jie , Yan Xiaohu , Banfield Bruce W. 
Published: April 2018

ABSTRACT

Orthologs of the herpes simplex virus (HSV)
UL16
gene are conserved throughout the
Herpesviridae
. Because of this conservation, one might expect that the proteins perform similar functions for all herpesviruses. Previous studies on a
UL16
-null mutant derived from HSV-2 strain 186 revealed a roughly 100-fold replication defect and a critical role for UL16 in the nuclear egress of capsids. These findings were in stark contrast to what has been observed with
UL16
mutants of HSV-1 and pseudorabies virus, where roughly 10-fold replication deficiencies that were accompanied by defects in the secondary envelopment of cytoplasmic capsids were reported. One possible explanation for this discrepancy is that HSV-2 strain 186 is not representative of the HSV-2 species. To address this possibility, multiple
UL16
-null mutants were constructed in multiple HSV-2 and HSV-1 strains by CRISPR/Cas9 mutagenesis, and their phenotypes were characterized side by side. This analysis showed that all the HSV-2
UL16
mutants had 50- to 100-fold replication deficiencies that were accompanied by defects in the nuclear egress of capsids, as well as defects in the secondary envelopment of cytoplasmic capsids. By contrast, most HSV-1
UL16
mutants had 10-fold replication deficiencies that were accompanied by defects in secondary envelopment of cytoplasmic capsids. These findings indicated that UL16 has HSV species-specific functions. Interestingly, HSV-1 UL16 could promote the nuclear egress of HSV-2
UL16
-null strains, suggesting that, unlike HSV-1, HSV-2 lacks an activity that can promote nuclear egress in the absence of UL16.

IMPORTANCE
HSV-2 and HSV-1 are important human pathogens that cause distinct diseases in their hosts. A complete understanding of the morphogenesis of these viruses is expected to reveal vulnerabilities that can be exploited in the treatment of HSV disease. UL16 is a virion structural component that is conserved throughout the
Herpesviridae
and functions in virus morphogenesis; however, previous studies have suggested different roles for UL16 in the morphogenesis of HSV-2 and HSV-1. This study sought to resolve this apparent discrepancy by analyzing multiple UL16 mutant viruses derived from multiple strains of HSV-2 and HSV-1. The data indicate that UL16 has HSV species-specific functions, as HSV-2 has a requirement for UL16 in the escape of capsids from the nucleus whereas both HSV-2 and HSV-1 require UL16 for final envelopment of capsids at cytoplasmic membranes.
Microbiota and Metatranscriptome Changes Accompanying the Onset of Gingivitis
Authors: Nowicki Emily M. , Shroff Raghav , Singleton Jacqueline A. , Renaud Diane E. , Wallace Debra , Drury Julie , Zirnheld Jolene , Colleti Brock , Ellington Andrew D. , Lamont Richard J. , Scott David A. , Whiteley Marvin 
Published: April 2018

ABSTRACT
Over half of adults experience gingivitis, a mild yet treatable form of periodontal disease caused by the overgrowth of oral microbes. Left untreated, gingivitis can progress to a more severe and irreversible disease, most commonly chronic periodontitis. While periodontal diseases are associated with a shift in the oral microbiota composition, it remains unclear how this shift impacts microbiota function early in disease progression. Here, we analyzed the transition from health to gingivitis through both 16S v4-v5 rRNA amplicon and metatranscriptome sequencing of subgingival plaque samples from individuals undergoing an experimental gingivitis treatment. Beta-diversity analysis of 16S rRNA reveals that samples cluster based on disease severity and patient but not by oral hygiene status. Significant shifts in the abundance of several genera occurred during disease transition, suggesting a dysbiosis due to development of gingivitis. Comparing taxonomic abundance with transcriptomic activity revealed concordance of bacterial diversity composition between the two quantification assays in samples originating from both healthy and diseased teeth. Metatranscriptome sequencing analysis indicates that during the early stages of transition to gingivitis, a number of virulence-related transcripts were significantly differentially expressed in individual and across pooled patient samples. Upregulated genes include those involved in proteolytic and nucleolytic processes, while expression levels of those involved in surface structure assembly and other general virulence functions leading to colonization or adaptation within the host are more dynamic. These findings help characterize the transition from health to periodontal disease and identify genes associated with early disease.

IMPORTANCE
Although more than 50% of adults have some form of periodontal disease, there remains a significant gap in our understanding of its underlying cause. We initiated this study in order to better characterize the progression from oral health to disease. We first analyzed changes in the abundances of specific microorganisms in dental plaque collected from teeth during health and gingivitis, the mildest form of periodontal disease. We found that the clinical score of disease and patient from whom the sample originated but not tooth brushing are significantly correlated with microbial community composition. While a number of virulence-related gene transcripts are differentially expressed in gingivitis samples relative to health, not all are increased, suggesting that the overall activity of the microbiota is dynamic during disease transition. Better understanding of which microbes are present and their function during early periodontal disease can potentially lead to more targeted prophylactic approaches to prevent disease progression.
Viral Diversity of House Mice in New York City
Authors: Williams Simon H. , Che Xiaoyu , Garcia Joel A. , Klena John D. , Lee Bohyun , Muller Dorothy , Ulrich Werner , Corrigan Robert M. , Nichol Stuart , Jain Komal , Lipkin W. Ian 
Published: April 2018

ABSTRACT

The microbiome of wild
Mus musculus
(house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Unbiased high-throughput sequencing of feces revealed 36 viruses from 18 families and 21 genera, including at least 6 novel viruses and 3 novel genera. A representative screen of 15 viruses by PCR confirmed the presence of 13 of these viruses in liver. We identified an uneven distribution of diversity, with several viruses being associated with specific locations. Higher mouse weight was associated with an increase in the number of viruses detected per mouse, after adjusting for site, sex, and length. We found neither genetic footprints to known human viral pathogens nor antibodies to lymphocytic choriomeningitis virus.

IMPORTANCE
Mice carry a wide range of infectious agents with zoonotic potential. Their proximity to humans in the built environment is therefore a concern for public health. Laboratory mice are also the most common experimental model for investigating the pathobiology of infectious diseases. In this survey of mice trapped in multiple locations within New York City over a period of 1 year, we found a diverse collection of viruses that includes some previously not associated with house mice and others that appear to be novel. Although we found no known human pathogens, our findings provide insights into viral ecology and may yield models that have utility for clinical microbiology.
Role of kinesiophobia on pain, disability and quality of life in people suffering from chronic musculoskeletal pain: a systematic review
Authors: Luque-Suarez Alejandro , Martinez-Calderon Javier , Falla Deborah 
Published: April 2018

Objective(1) To explore the level of association between kinesiophobia and pain, disability and quality of life in people with chronic musculoskeletal pain (CMP) detected via cross-sectional analysis and (2) to analyse the prognostic value of kinesiophobia on pain, disability and quality of life in this population detected via longitudinal analyses.DesignA systematic review of the literature including an appraisal of the risk of bias using the adapted Newcastle Ottawa Scale. A synthesis of the evidence was carried out.Data sourcesAn electronic search of PubMed, AMED, CINAHL, PsycINFO, PubPsych and grey literature was undertaken from inception to July 2017.Eligibility criteria for selecting studiesObservational studies exploring the role of kinesiophobia (measured with the Tampa Scale for Kinesiophobia) on pain, disability and quality of life in people with CMP.ResultsSixty-three articles (mostly cross-sectional) (total sample=10 726) were included. We found strong evidence for an association between a greater degree of kinesiophobia and greater levels of pain intensity and disability and moderate evidence between a greater degree of kinesiophobia and higher levels of pain severity and low quality of life. A greater degree of kinesiophobia predicts the progression of disability overtime, with moderate evidence. A greater degree of kinesiophobia also predicts greater levels of pain severity and low levels of quality of life at 6 months, but with limited evidence. Kinesiophobia does not predict changes in pain intensity.Summary/conclusionsThe results of this review encourage clinicians to consider kinesiophobia in their preliminary assessment. More longitudinal studies are needed, as most of the included studies were cross-sectional in nature.Trial registration numberCRD42016042641.
Associations of smoking and alcohol consumption with healthy ageing: a systematic review and meta-analysis of longitudinal studies
Authors: Daskalopoulou Christina , Stubbs Brendon , Kralj Carolina , Koukounari Artemis , Prince Martin , Prina A. Matthew 
Published: April 2018

ObjectivesThe number of older people is growing across the world; however, quantitative synthesis of studies examining the impact of lifestyle factors on the ageing process is rare. We conducted a systematic review and meta-analysis of longitudinal studies to synthesise the associations of smoking and alcohol consumption with healthy ageing (HA).MethodsMajor electronic databases were searched from inception to March 2017 (prospectively registered systematic reviews registration number CRD42016038130). Studies were assessed for methodological quality. Random-effect meta-analysis was performed to calculate pooled ORs and 95% CI.ResultsIn total, we identified 28 studies (n=184 543); 27 studies reported results on smoking, 22 on alcohol consumption. 23 studies reported a significant positive association of never or former smoking with HA and 4 non-significant. 12 studies reported a significant positive association of alcohol consumption with HA, 9 no association and 1 negative. Meta-analysis revealed increased pooled OR of HA for never smokers compared with current smokers (2.36, 95% CI 2.03 to 2.75), never smokers compared with former smokers (1.32, 95% CI 1.23 to 1.41), former or never smokers compared with current smokers (1.72, 95% CI 1.20 to 2.47), never smokers compared with past or current smokers (1.29, 95% CI 1.16 to 1.43); drinkers compared with non-drinkers (1.28, 95% CI 1.08 to 1.52), light drinkers compared with non-drinkers (1.12, 95% CI 1.03 to 1.22), moderate drinkers compared with non-drinkers (1.35, 95% CI 0.93 to 1.97) and high drinkers compared with non-drinkers (1.25, 95% CI 1.09 to 1.44). There was considerable heterogeneity in the definition and measurement of HA and alcohol consumption.ConclusionsThere is consistent evidence from longitudinal studies that smoking is negatively associated with HA. The associations of alcohol consumption with HA are equivocal. Future research should focus on the implementation of a single metric of HA, on the use of consistent drinking assessment among studies and on a full-range of confounding adjustment. Our research also highlighted the limited research on ageing in low-and-middle-income countries.
Prognostic value of ki67 in BCG-treated non-muscle invasive bladder cancer: a meta-analysis and systematic review
Authors: He Yuhui , Wang Ning , Zhou Xiaofeng , Wang Jianfeng , Ding Zhenshan , Chen Xing , Deng Yisen 
Published: April 2018

ObjectivesThe aim of this study was to explore the prognostic value of ki67 as a marker in patients with non-muscle invasive bladder cancer (NMIBC) treated with BCG.MethodsStudies were systematically retrieved from the relevant databases (Web of Science, PubMed, Cochrane Library and Embase), and the expiry date was May 2017. The research steps referred to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.ResultsA total of 11 studies that complied with the inclusion criteria were included. The expression of ki67 was not statistically significantly associated with recurrence-free survival (RFS) (HR 1.331; 95% CI 0.980 to 1.809). No significant heterogeneity was found among all included studies (I2=36.7%, p=0.148). The expression of ki67 was statistically significantly associated with progression-free survival (PFS) (HR 2.567; 95% CI 1.562 to 4.219), and the overexpression of ki67 was the risk factor for PFS. Significant heterogeneity was noted among all the included studies (I2=55.6%, p=0.021). The studies that might cause heterogeneity were excluded using the Galbraith plot, and then the meta-analysis was performed again. The results showed that the expression of ki67 was still associated with PFS (HR 2.922; 95% CI 2.002 to 4.266).ConclusionsThe overexpression of ki67 was the risk factor for PFS, and the relationship between the expression of ki67 and RFS was not statistically significant in patients with NMIBC treated with BCG intravesical immunotherapy. Well-designed, prospective, with a large sample size are still needed to validate the findings.
Preventing emergency department (ED) visits and hospitalisations of older adults with cognitive impairment compared with the general senior population: what do we know about avoidable incidents? Results from a scoping review
Authors: Gagnon-Roy Mireille , Hami Benyahia , Généreux Mélissa , Veillette Nathalie , Sirois Marie-Josée , Egan Mary , Provencher Véronique 
Published: April 2018

ObjectivesOlder cognitively impaired adults present a higher risk of hospitalisation and mortality following a visit to the emergency department (ED). Better understanding of avoidable incidents is needed to prevent them and the associated ED presentations in community-dwelling adults. This study aimed to synthetise the actual knowledge concerning these incidents leading this population to ED presentation, as well as possible preventive measures to reduce them.DesignA scoping review was performed according to the Arksey and O’Malley framework.MethodsScientific and grey literature published between 1996 and 2017 were examined in databases (Medline, Cumulative Index of Nursing and Allied Health, Ageline, Scopus, ProQuest Dissertations/theses, Evidence-based medecine (EBM) Reviews, Healthstar), online library catalogues, governmental websites and published statistics. Sources discussing avoidable incidents leading to ED presentations were included and then extended to those discussing hospitalisation and mortality due to a lack of sources. Data (type, frequency, severity and circumstances of incidents, preventive measures) was extracted using a thematic chart, then analysed with content analysis.Results67 sources were included in this scoping review. Five types of avoidable incidents (falls, burns, transport accidents, harm due to self-negligence and due to wandering) emerged, and all but transport accidents were more frequent in cognitively impaired seniors. Differences regarding circumstances were only reported for burns, as scalding was the most prevalent mechanism of injury for this population compared with flames for the general senior population. Multifactorial interventions and implications of other professionals (eg, pharmacist, firefighters) were reported as potential interventions to reduce avoidable incidents. However, few preventive measures were specifically tested in this population.ConclusionsPrimary research that screens for cognitive impairment and involves actors (eg, paramedics) to improve our understanding of avoidable incidents leading to ED visits is greatly needed. This knowledge is essential to develop preventive measures tailored to the needs of older cognitively impaired adults.
Competencies necessary for becoming a leader in the field of community medicine: a Japanese qualitative interview study
Authors: Kainuma Mosaburo , Kikukawa Makoto , Nagata Masaharu , Yoshida Motofumi 
Published: April 2018

ObjectivesTo clarify competencies for inclusion in our curriculum that focuses on developing leaders in community medicine.DesignQualitative interview study.SettingAll six regions of Japan, including urban and rural areas.ParticipantsNineteen doctors (male: 18, female: 1) who play an important leadership role in their communities participated in semistructured interviews (mean age 48.3 years, range 34–59; mean years of clinical experience 23.1 years, range 9–31).MethodSemistructured interviews were held and transcripts were independently analysed and coded by the first two authors. The third and fourth authors discussed and agreed or disagreed with the results to give a consensus agreement. Doctors were recruited by maximum variation sampling until thematic saturation was achieved.ResultsSix themes emerged: (1)‘Medical ability’: includes psychological issues and difficult cases in addition to basic medical problems. High medical ability gives confidence to other medical professionals. (2)‘Long term perspective’: the ability to develop a long-term, comprehensive vision and to continuously work to achieve the vision. Cultivation of future generations of doctors is included. (3) ‘Team building’:the ability to drive forward programmes that include residents and local government workers, to elucidate a vision, to communicate and to accept other medical professionals. (4)‘Ability to negotiate’: the ability to negotiate with others to ensure that programmes and visions progress smoothly (5) ‘Management ability’: the ability to run a clinic, medical unit or medical association. (6) ‘Enjoying oneself’: doctors need to feel an attraction to community medicine, that it be fun and challenging for them.ConclusionsWe found six competencies that are needed by leaders in the field of community medicine. The results of this study will contribute to designing a curriculum that develops such leaders.
The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol
Authors: Levieux Karine , Patural Hugues , Harrewijn Inge , Briand Huchet Elisabeth , de Visme Sophie , Gallot Géraldine , Chalumeau Martin , Gras Le Guen Christèle , Hanf Matthieu 
Published: April 2018

IntroductionEven after ‘back-to-sleep’ campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area.Methods and analysisThis observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths.Ethics and disseminationThe French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l’Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences.