bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial
Authors: Doan Thuy , Hinterwirth Armin , Arzika Ahmed M , Cotter Sun Y , Ray Kathryn J , O’Brien Kieran S , Zhong Lina , Chow Eric D , Zhou Zhaoxia , Cummings Milo E , Fry Dionna , Oldenburg Catherine E , Worden Lee , Porco Travis C , Keenan Jeremy D , Lietman Thomas M 
Published: July 2018

Abstract

Background
Mass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community’s gut microbiome at 6 months after the last distribution.

Methods
In this cluster-randomized controlled trial, children aged 1–60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson’s α diversity.

Results
In the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P &lt; .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson’s index, P = .005).

Conclusions
Two mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.

Clinical Trials Registration
NCT02048007.
The effect of childhood deprivation on weight status and mental health in childhood and adolescence: longitudinal findings from the Millennium Cohort Study
Authors: Noonan Robert J 
Published: July 2018

Abstract

Background
The study aims were to: (i) examine associations between deprivation at age 7 and health outcomes at age 7 and 14, (ii) determine whether a deprivation gradient to health outcomes exists at age 7 and 14, and (iii) assess the extent to which health outcomes at age 7 are associated with health outcomes at age 14.

Methods
Data were from wave four and six of the Millennium Cohort Study. Health outcome measures were weight status, and Strengths and Difficulties Questionnaire measured mental health problems. Deprivation was determined using the 2004 English Indices of Multiple Deprivation. Adjusted logistic and multinomial logistic regressions were conducted.

Results
A total of 6109 children (1890 girls) had complete data. Overweight, obesity and mental health problems were greatest among children in the highest deprivation decile at age 7 and 14 (P < 0.001). Health outcomes at age 7 were significantly associated with health outcomes at age 14 (P < 0.001).

Conclusions
A marked social gradient to weight status and mental health was evident at age 7 and 14, and no evidence of equalization was found. Weight status and mental health in childhood is strongly associated with weight status and mental health in adolescence.
A content analysis of alcohol content in UK television
Authors: Barker Alexander B , Whittamore Kathy , Britton John , Murray Rachael L , Cranwell Jo 
Published: July 2018

Abstract

Background
Exposure to audio-visual alcohol content in media is associated with subsequent alcohol use in young people, but the extent of exposure contained in UK free-to-air prime-time television has not been explored since 2010. We report an analysis of alcohol content in a sample of UK free-to-air prime-time television broadcasts in 2015 and compare this with a similar analysis from 2010.

Methods
Content analysis of all programmes and advertisement/trailer breaks broadcast on the five national UK free-to-air channels in the UK between 6 and 10 pm during three separate weeks in September, October and November 2015.

Results
Alcohol content occurred in over 50% of all programmes broadcast and almost 50% of all advert/trailer periods between programmes. The majority of alcohol content occurred before the 9 pm watershed. Branding occurred in 3% of coded intervals and involved 122 brands, though three brands (Heineken, Corona and Fosters) accounted for almost half of all brand appearances.

Conclusion
Audio-visual alcohol content, including branding, is prevalent in UK television, and is therefore a potential driver of alcohol use in young people. These findings are virtually unchanged from our earlier analysis of programme content from 2010.
Poor sleep is linked to impeded recovery from traumatic brain injury
Authors: Kalmbach David A , Conroy Deirdre A , Falk Hayley , Rao Vani , Roy Durga , Peters Matthew E , Van Meter Timothy E , Korley Frederick K 
Published: July 2018

AbstractStudy ObjectivesWhile disruptions in sleep are common after mild traumatic brain injury (TBI), the longitudinal relationships between sleep problems and global functioning after injury are poorly understood. Here, we prospectively investigate risk for functional impairment during the first 6 months of TBI recovery based on sleep onset insomnia symptoms and short sleep.MethodsPatients presenting to the Emergency Department (ED) at Johns Hopkins Hospital within 24 hours of head injury and evaluated for TBI were eligible for our study. Demographic and injury-related information were collected in the ED. Patients then completed in-person surveys and phone interviews to provide follow-up data on global functioning, sleep, and depressive symptoms at 1, 3, and 6 months post-injury. A total of 238 patients provided sufficient data for analysis, and hypotheses were tested using mixed effects modeling.ResultsSleep quality and global functioning improved over the 6 months of TBI recovery, but patients were at increased risk for functional impairment when sleeping poorly (odds ratio [OR] = 7.69, p < .001). Sleep onset insomnia symptoms and short sleep both independently corresponded to poor global functioning. Functional impairment was highest among those with both insomnia and short sleep (43%–79%) compared to good sleepers (15%–25%) and those with short sleep (29%–33%) or insomnia alone (33%–64%). A bidirectional relationship between sleep quality and functioning was observed.ConclusionsFunctionally impaired patients diagnosed predominantly with mild TBI exhibit high rates of insomnia and short sleep, which may impede TBI recovery. Monitoring sleep after head injury may identify patients with poor prognoses and allow for early intervention to improve functional outcomes.
Billing Practices Among US Tobacco Use Treatment Providers
Authors: Bloom Erika Litvin , Burke Michael V. , Kotsen Chris , Goldstein Adam O. , Ripley-Moffitt Carol , Steinberg Michael B. , Dailey Mary , Hunt Laura E. , Bars Matthew P. 
Published: July 2018

Objectives:
The US Affordable Care Act (ACA) now requires almost all health insurance plans to cover tobacco use treatment (TUT), but TUT remains underutilized.

Methods:
We conducted an anonymous online survey of US TUT providers in 2016 regarding their billing practices.

Results:
Participants (n = 131) provided services primarily in medical and behavioral health settings and were from a variety of professions. Most provided intensive individual (>15 minutes per session) and/or group counseling. Although most reported that their organization accepted at least 1 form of insurance, only 34% reported that TUT services were billed, with about equal proportions endorsing billing under their own independent tax ID and “incident to” billing under a supervisor. Half of billers (52%) reported using at least 1 Current Procedural Terminology code. The most common codes were 99406 and 99407, but 18 unique codes were specified. Themes of qualitative responses (n = 101) included concern about how to initiate and sustain adequate reimbursement, and experiences with billing not being “worth” the time or effort.

Conclusions:
Overall, results demonstrate a need for providers, administrators, and billing managers to work collaboratively. Even with the ACA mandate, and consistent with prior reports, reimbursement rates may be inadequate for intensive counseling. Areas for advocacy include recognizing that TUT requires similar intensity, expertise, and reimbursement as other substance use disorders and chronic medical conditions; giving Tobacco Treatment Specialists the ability to bill independently; and improving coordination between intensive therapies validated in research and “real-world” logistics.
Demands for perimenopausal health care in women aged 40 to 60 years—a hospital-based cross-sectional study in Shanghai, China
Authors: Huang Cheng , Zheng Yanwei , Zhu Liping , Li Yang , Du Li , Tao Minfang , Xu Biao 
Published: July 2018

Abstract

Objectives:
The aim of the study was to describe the major complaints of menopausal symptoms among middle-aged women who initiated healthcare seeking for menopausal symptoms and to understand the factors influencing women's decisions to seek perimenopausal health care in Shanghai, China.

Methods:
A cross-sectional study was performed in five hospitals in Shanghai. Women aged 40 to 60 years at their first visit to the perimenopausal outpatient departments/clinics were investigated in person over a 3-month period. Information on sociodemographics, menopausal symptoms, and experiences in seeking perimenopausal health care was collected using a structured questionnaire. Menopausal symptoms were assessed with the modified Kupperman Menopausal Index (mKMI).

Results:
A total of 316 women were enrolled in the study, with an average age of 50.5 years (SD: 5.1 y). The prevalence of menopausal syndrome (mKMI >6 points) was 80%, with 7% of the cases being severe. The top five reported symptoms were hot flushes/sweating (62%), fatigue (54%), sleep disturbance (51%), mood swings (40%), and joint/muscle pain (40%). The median interval between symptom occurrence and seeking perimenopausal health care was 5.0 months (IQR: 2.0-23.3 mo). Cox regression analysis revealed that older age, no health insurance, employment, multiple symptoms, sleep disturbance, urinary incontinence, and visits to nonspecialized departments were significantly associated with a longer delay in seeking perimenopausal health services (P < 0.05).

Conclusions:
The prevalence of menopausal syndrome was relatively high among 40- to 60-year-old women who initiated healthcare seeking in Shanghai. Months of delay occurred before they sought perimenopausal health services. The delay was related to age, the nature and number of symptoms, working status, and health insurance. Improvement of the menopausal health knowledge in Chinese middle-aged women may lead to more timely healthcare seeking. Professional and accessible perimenopausal health services are in high demand in Shanghai.
The day/night difference in the circadian clock’s response to acute lipopolysaccharide and the rhythmic Stat3 expression in the rat suprachiasmatic nucleus
Authors: Moravcová Simona , Pačesová Dominika , Melkes Barbora , Kyclerová Hana , Spišská Veronika , Novotný Jiří , Bendová Zdeňka 
Published: July 2018

AbstractThe circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-inducedStat3mRNA expression in the SCN and show also the circadian rhythm inStat3expression in the SCN, with high levels during the day. Moreover, we examined the effects of LPS (1mg/kg), applied either during the day or the night, on the rhythm in locomotor activity of male Wistar rats. We observed that recovery of normal locomotor activity patterns took longer when the animals were injected during the night. The clock genesPer1, Per2andNr1d1, and phosphorylation of kinases ERK1/2 and GSK3β are sensitive to external cues and function as the molecular entry for external signals into the circadian clockwork. We also studied the immediate changes in these clock genes expressions and the phosphorylation of ERK1/2 and GSK3β in the suprachiasmatic nucleus in response to daytime or night-time inflammatory stimulation. We revealed mild and transient changes with respect to the controls. Our data stress the role of STAT3 in the circadian clock response to the LPS and provide further evidence of the interaction between the circadian clock and immune system.
The monothiol glutaredoxin Grx4 interacts with the Cryptococcus iron regulator Cirl and regulates iron homeostasis and virulence in the Cryptococcus neoformans
Authors: Attarian Rodgoun , Hu Guanggan , Caza Melissa , Sanchez-Leon Eddy , Croll Daniel , Do Eunsoo , Bach Horacio , Missall Tricia , Lodge Jennifer , Jung Won Hee , Kronstad James W. 
Published: July 2018

AbstractThe acquisition of iron and the maintenance of iron homeostasis are important aspects of the virulence in the pathogenic fungus Cryptococcus neoformans. In this study, we identified the monothiol glutaredoxin Grx4 as a binding partner of Cir1, a master regulator of iron-responsive genes and virulence factor elaboration in C. neoformans. Monothiol glutaredoxins are important regulators of iron homeostasis because of their conserved roles in [2Fe-2S] cluster sensing and trafficking. We confirmed that Grx4 binds Cir1 and demonstrated that iron repletion promotes the relocalization of Grx4 from the nucleus to the cytoplasm. Nuclear retention is partially dependent on Cir1 and also influenced by treatment with the proteasome inhibitor bortezomib. Cir1 remains in the nucleus in both iron replete and iron limiting conditions. We also found that a grx4Δ mutant displayed iron-related phenotypes similar to those of a cir1Δ mutant, including poor growth upon iron deprivation. Importantly, a grx4Δ mutant was avirulent in mice, a phenotype consistent with observed defects in the key virulence determinants, capsule and melanin, and poor growth at 37°C. A comparative transcriptome analysis of a grx4Δ mutant and the WT strain in low iron and iron-replete conditions confirmed a central role for Grx4 in iron homeostasis. Dysregulation of iron-related metabolism was consistent with grx4Δ mutant phenotypes related to oxidative stress, mitochondrial function, and DNA repair. Overall, the phenotypes of the grx4Δ mutant and the RNA-Seq analysis support the hypothesis that Grx4 functions as a sensor of iron levels, in part through an interaction with Cir1, to extensively regulate iron homeostasis and contribute to virulence.
Type I-E CRISPR-Cas system as an immune system in a eukaryote
Authors: Rath Devashish , Amlinger Lina , Bindal Gargi , Lundgren Magnus 
Published: July 2018

AbstractDefense against viruses and other mobile genetic elements (MGEs) is important in many organisms. The CRISPR-Cas systems found in bacteria and archaea constitute adaptive immune systems that acquire the ability to recognize MGEs by introducing nucleic acid samples, spacers, in the CRISPR locus. The CRISPR is transcribed and processed, and the produced CRISPR RNAs guide Cas proteins to degrade matching nucleic acid sequences. No CRISPR-Cas system is found to occur naturally in eukaryotic cells but here we demonstrate interference by type I-E CRISPR-Cas system from Escherichia coli introduced in Saccharomyces cerevisiae. The designed CRISPR arrays are properly expressed and processed in S. cerevisiae. Targeted plasmids display reduced transformation efficiency, indicative of DNA cleavage. Unlike e.g. Cas9-based systems, which can be used to inactivate MGEs in eukaryotes by introducing specific mutations, type I-E systems processively degrade the target. The type I-E system thus allows for defense without knowledge of MGE gene function. The reconstituted CRISPR-Cas system in S. cerevisiae can also function as a basic research platform for testing the role of various factors in the interference process.
The reovirus μ1 protein contributes to the environmental stability of virions
Authors: Snyder Anthony J. , Wang Joseph Che-Yen , Danthi Pranav 
Published: July 2018

AbstractThe mammalian orthoreovirus (reovirus) outer capsid is composed of 200 μ1-σ3 heterohexamers and a maximum of 12 σ1 trimers. During cell entry, σ3 is degraded by luminal or intracellular proteases to generate a metastable intermediate, called infectious subviral particle (ISVP). Prior to disassembly, σ3 stabilizes the virion by capping μ1. Reovirus fails to establish a productive infection when σ3 degradation is prevented, suggesting proteolytic priming is required for entry. Once uncovered, ISVPs are converted to ISVP*s, which is accompanied by a μ1 rearrangement. Nonetheless, whether σ3 degradation can be bypassed for virions to adopt an altered conformation is undetermined. In this report, we utilized the T1L/T3D M2 reassortant, which encodes a mismatched outer capsid, to further investigate the determinants of reovirus stability. When μ1-σ3 were derived from different strains, virions resembled wild type in structure and protease sensitivity. Using heat as a surrogate for environmental assault, T1L/T3D M2 ISVPs were more susceptible to inactivation than wild type ISVPs. In contrast, virions of each strain were equally stable. Surprisingly, virion associated μ1 rearranged into an ISVP*-like conformation concurrent with loss of infectivity. Despite the presence σ3, a hyperstable variant of μ1 also contributed to heat resistance. The dual layered architecture of reovirus allowed for differential sensitivity to inactivating agents; the inner capsid (core) displayed exceptional resistance to heating. Together, these findings reveal a previously undefined contribution from μ1 in maintaining virion stability.
Schizophrenia risk and reproductive success: A Mendelian randomization study
Authors: Lawn Rebecca B , Sallis Hannah M , Taylor Amy E , Wootton Robyn E , Smith George Davey , Davies Neil M , Hemani Gibran , Fraser Abigail , Penton-Voak Ian S , Munafò Marcus R 
Published: July 2018

SummarySchizophrenia is a debilitating and heritable mental disorder associated with lower reproductive success. However, the prevalence of schizophrenia is stable over populations and time, resulting in an evolutionary puzzle: how is schizophrenia maintained in the population given its apparent fitness costs? One possibility is that increased genetic liability for schizophrenia, in the absence of the disorder itself, may confer some reproductive advantage. We assessed the correlation and causal effect of genetic liability for schizophrenia with number of children and age at first birth using data from the Psychiatric Genomics Consortium and UK Biobank. Linkage disequilibrium score regression showed little evidence of genetic correlation between genetic liability for schizophrenia and number of children (rg=0.002,p=0.84) or age at first birth (rg=-0.007,p=0.45). Mendelian randomization indicated no robust evidence of a causal effect of genetic liability for schizophrenia on number of children (mean difference: 0.003 increase in number of children per doubling in the natural log odds ratio of schizophrenia risk, 95% CI: −0.003 to 0.009,p=0.39) or age at first birth (−0.004 years lower age at first birth, 95% CI: −0.043 to 0.034,p=0.82). These results suggest that increased genetic liability for schizophrenia does not confer a reproductive advantage.
Draft genome sequences ofHirudo medicinalisand salivary transcriptome of three closely related medicinal leeches
Authors: Babenko Vladislav V. , Podgorny Oleg V. , Manuvera Valentin A. , Kasianov Artem S. , Manolov Alexander I. , Grafskaia Ekaterina N. , Shirokov Dmitriy A. , Kurdyumov Alexey S. , Vinogradov Dmitriy V. , Nikitina Anastasia S. , Kovalchuk Sergey I. , Anikanov Nickolay A. , Butenko Ivan O. , Pobeguts Olga V. , Matushkina Daria S. , Rakitina Daria V. , Kostryukova Elena S. , Zgoda Victor G. , Baskova Isolda P. , Trukhan Vladimir M. , Gelfand Mikhail S. , Govorun Vadim M. , Schiöth Helgi B. , Lazarev Vassili N. 
Published: July 2018

AbstractSalivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today. We annotated theHirudo medicinalisgenome and performed RNA-seq on salivary cells isolated from three closely related leech species,H. medicinalis, Hirudo orientalis,andHirudo verbana.Differential expression analysis verified by proteomics identified salivary cell-specific genes, many of which encode previously unknown salivary components. However, the genes encoding known anticoagulants were not differentially expressed in the salivary cells. The function-related analysis of the unique salivary cell genes enabled an update of the concept of interactions between salivary proteins and components of haemostasis. Thus, our study provides one of the most comprehensive knowledge of the genetic fundamentals of the blood-sucking lifestyle in leeches.
Single-embryo and single-blastomere immunoblotting reports protein expression heterogeneity in early-stage preimplantation embryos
Authors: Rosàs-Canyelles Elisabet , Modzelewski Andrew J. , He Lin , Herr Amy E. 
Published: July 2018

AbstractUnderstanding how a zygote develops from a single cell into a multicellular organism has benefitted from single-cell tools, including RNA sequencing (RNA-Seq) and immunofluorescence (IF). However, scrutinizing inter- and intra-embryonic phenotypic variation is hindered by two fundamental limitations; the loose correlation between transcription and translation and the cross-reactivity of immunoreagents. To address these challenges, we describe a high-specificity microfluidic immunoblot optimized to quantify protein expression from all stages of mouse preimplantation development. Despite limited availability of isoform-specific immunoreagents, the immunoblot resolves inter-embryonic heterogeneity of embryo-specific isoforms (i.e., DICER-1). We observed significantly higher DICER-1 isoform expression in oocytes when compared to two-cell embryos, and further find that protein expression levels follow the same trend as mRNA for both the full-length and truncated DICER-1 isoforms. At the morula stage, we assayed both whole and disaggregated embryos for loading controls (β-tubulin, GAPDH) and markers that regulate cell fate decisions (CDX-2, SOX-2). In disaggregated morula, we found that cell volume showed positive, linear correlation with expression of β-tubulin and SOX-2. In dissociated two-cell and four-cell blastomeres, we detect significant inter-blastomeric variation in GADD45a expression, corroborating suspected cellular heterogeneity even in the earliest multicellular stage of preimplantation embryos. As RNA-Seq and other transcript-centric approaches continue to further probe preimplantation development, the demand for companion protein-based techniques rises. The reported microfluidic immunoblot serves as an essential tool for understanding mammalian development by providing high-specificity and direct measurements of protein targets at single-embryo and single-blastomere resolution.