bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoupling Marriage and Parenting
Authors: Shrage Laurie 
Published: August 2016

AbstractThis article argues for separating the institutions of marriage and parenting, conceptually and legally. Marriage is neither necessary nor adequate for fostering cooperative and stable co‐parenting. Because promoting marriage fails to protect all children, the state should develop a more suitable formal mechanism whereby co‐parents can commit to cooperate in good faith in order to best serve the interests of their children. Like civil marriage, many of the terms of these contracts are aspirational and not enforceable, though they can guide arrangements for custody and financial support. Co‐parenting agreements need not be limited to two parents, nor need they be limited to legal parents, but can include de facto parents, such as stepparents, foster parents, and other support parents. One important aim of these agreements is to recognise and support the valuable work that married or unmarried co‐parents perform, and to protect the parental rights of caregivers in different kinds of situations.
The ecological niche and distribution of Neanderthals during the Last Interglacial
Authors: Benito Blas M. , Svenning Jens‐Christian , Kellberg‐Nielsen Trine , Riede Felix , Gil‐Romera Graciela , Mailund Thomas , Kjaergaard Peter C. , Sandel Brody S. 
Published: August 2016

AbstractAimIn this paper, we investigate the role of climate and topography in shaping the distribution of Neanderthals (Homo neanderthalensis) at different spatial scales. To this end, we compiled the most comprehensive data set on the distribution of this species during the Last Interglacial optimum (MIS 5e) available to date. This was used to calibrate a palaeo‐species distribution model, and analyse variable importance at continental and local scales.LocationEurope and Irano‐Turanian region (20° N to 70° N, 10° W to 70° E).MethodsWe used archaeological records and palaeoclimatic and topographic predictors to calibrate a model based on an ensemble of generalized linear models fitted with different combinations of predictors and weighted background data. Area under the curve scores computed by leave‐one‐out were used to assess variable importance at the continental scale, while local regression combined with recursive partition trees was used to assess variable importance at the local scale.ResultsAnnual rainfall and winter temperatures were the most important predictors at the continental scale, while topography and summer rainfall defined habitat suitability at the local scale. The highest habitat suitability scores were observed along the Mediterranean coastlines. Mountain ranges and continental plains showed low habitat suitability values.Main conclusionsThe model results confirmed that abiotic drivers played an important role in shaping Neanderthals distribution during the Last Interglacial. The high suitability of the Mediterranean coastlines and the low suitability values of most sites at the northern and eastern distribution limits (Germany, Hungary, Ukraine) challenge the notion of Neanderthals as a species with preference for colder environments.
Immediate implant placement and provisionalization in the aesthetic zone using a flapless or a flap‐involving approach: a randomized controlled trial
Authors: Stoupel Janet , Lee Chun‐Teh , Glick Jaclyn , Sanz‐Miralles Elena , Chiuzan Cody , Papapanou Panos N. 
Published: August 2016

AbstractAimWe conducted a randomized controlled trial to compare the effect of flapless (FLS) or flap‐involving (F) immediate placement and provisionalization of single‐tooth implants in the aesthetic zone.Materials and MethodsThirty‐nine patients were randomized following extraction of a non‐restorable tooth to a FLS or F group. All implants were immediately placed and provisionalized. We monitored prospectively changes in the peri‐implant mucosal margin, the interproximal bone and buccal horizontal ridge at 3, 6 and 12 months.ResultsAt 3 months post‐surgery, the mean ± SD [median (interquartile range)] mesiobuccal peri‐implant gingival margin recession from the pre‐surgical soft tissue position amounted to 0.11 ± 0.32 mm [0 (0, 0.5)] in the FLS treatment arm versus 0.43 ± 37 mm [0.5 (0, 0.5)] in the F treatment arm (p = 0.02); corresponding values at the distobuccal surface were 0.11 ± 32 mm [0 (0, 0)] in the FLS arm versus 0.48 ± 0.44 mm [0.5 (0, 1)] in the F arm (p = 0.01). No other significant differences in soft or hard tissue remodelling between the treatment arms were observed at 3, 6 or 12 months.ConclusionsFlapless and a flap‐involving immediate implant placement and provisionalization in the aesthetic zone resulted in comparable remodelling of the peri‐implant mucosa, interproximal bone and buccal ridge at 6 and 12 months.
Efficacy and safety of adalimumab in Chinese patients with moderate‐to‐severe plaque psoriasis: results from a phase 3, randomized, placebo‐controlled, double‐blind study
Authors: Cai L. , Gu J. , Zheng J. , Zheng M. , Wang G. , Xi L.‐Y. , Hao F. , Liu X.‐M. , Sun Q.‐N. , Wang Y. , Lai W. , Fang H. , Tu Y.‐T. , Sun Q. , Chen J. , Gao X.‐H. , Gu Y. , Teixeira H.D. , Zhang J.‐Z. , Okun M.M. 
Published: August 2016

AbstractBackgroundThis phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF‐α inhibitor, adalimumab, for Chinese patients with moderate‐to‐severe plaque psoriasis.MethodsIn the 12‐week, double‐blind, placebo‐controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every‐other‐week (following a single 80 mg dose), or placebo every‐other‐week. In the subsequent 12‐week, open‐label, Period B, all patients received adalimumab 40 mg every‐other‐week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug.ResultsFor the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All‐adalimumab Population), treatment‐emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All‐adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure).ConclusionIn these Chinese patients with moderate‐to‐severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.
Bibliometric analysis on global Behçet disease publications during 1980–2014: is there a Silk Road in the literature?
Authors: Şenel E. , Demir E. , Alkan R.M. 
Published: August 2016

AbstractBackgroundBehçet disease (BD) is a chronic and multisystemic vasculitis characterized with recurrent oral and genital ulcers, uveitis, arthritis and skin manifestations. The highest prevalence of the disease has been reported in regions historically involved in the Silk Road routes.ObjectiveWe aimed to analyse Behçet literature and evaluate whether there is a concordance between ancient Silk Road regions and the distribution of publication productivity.MethodsThe bibliometric analysis of the publications published during 1980–2014 using Thomson Reuters Web of Science database was performed. We generated infographics of productivity and also analysed the correlations among economical productivities, technological advancement levels and humanity index and productivity performances of 78 countries in Behçet literature.ResultsTurkey ranked first in Behçet literature with 1837 articles followed by Japan and the USA. Turkey, Tunisia and Israel occupied the first three places in productivity. Significant correlations were noted between 2014 gross economic and technological indices and publication numbers of the countries. We found that European countries had high productivity, although they had low prevalence of BD. We detected no concordance between the productivity density of the countries and the ancient Silk Road routes.ConclusionMost publications were reported from developed countries although undeveloped or developing countries had higher prevalence of BD. Physicians in undeveloped and developing countries should be supported and encouraged to perform novel studies on BD.
The culture of pretence: a hidden barrier to recognising, disclosing and ending domestic violence
Authors: Francis Lyn , Loxton Deborah , James Colin 
Published: August 2016

Aims and objectivesTo explore in detail how women perceived their experience of domestic violence and leaving or ending the abuse. This research also examined how service providers identified their professional role in assisting women to end such relationships.BackgroundDomestic violence against women continues to occur internationally. Reliable statistics are difficult to capture because of inconsistent definitions, contradictory methods of acquiring data and unreported incidents.DesignA qualitative study, undertaken in two phases, was conducted in Australia.MethodsTwelve women who had experienced domestic violence and ended those relationships participated in one semistructured interview (Phase 1). Twenty‐five professionals from health, social sciences and law, whose work included assisting women experiencing domestic violence, participated in three focus groups (Phase 2). Thematic analysis guided by a narrative inquiry approach forms the framework for information collection and interpretation of data in this project.FindingsThe barriers that impede women from disclosing abuse and taking action to end domestic violence are complex and varied between participants. Women did not always acknowledge or realise their relationship was precarious and often denied or minimised the abuse to cope with the domestic violence. Professionals identified that women did not always identify or acknowledge abuse inherent in their relationship although this delayed the provision of appropriate services.ConclusionWhether women disclose abuse or deny violence in their relationship, acceptance by service providers and the offer of support is crucial to assisting women in violent relationships.Relevance to clinical practiceIt is hoped that the findings may assist health practitioners, including nurses, to provide nonjudgemental support to women experiencing domestic violence whether women acknowledge the abusive relationship or not.
Signatures of selection and host‐adapted gene expression of the Phytophthora infestans RNA silencing suppressor PSR2
Authors: de Vries Sophie , von Dahlen Janina K. , Uhlmann Constanze , Schnake Anika , Kloesges Thorsten , Rose Laura E. 
Published: August 2016

SummaryPhytophthora infestans is a devastating pathogen in agricultural systems. Recently, an RNA silencing suppressor (PSR2, ‘Phytophthora suppressor of RNA silencing 2’) has been described in P. infestans. PSR2 has been shown to increase the virulence of Phytophthora pathogens on their hosts. This gene is one of the few effectors present in many economically important Phytophthora species. In this study, we investigated: (i) the evolutionary history of PSR2 within and between species of Phytophthora; and (ii) the interaction between sequence variation, gene expression and virulence. In P. infestans, the highest PiPSR2 expression was correlated with decreased symptom expression. The highest gene expression was observed in the biotrophic phase of the pathogen, suggesting that PSR2 is important during early infection. Protein sequence conservation was negatively correlated with host range, suggesting host range as a driver of PSR2 evolution. Within species, we detected elevated amino acid variation, as observed for other effectors; however, the frequency spectrum of the mutations was inconsistent with strong balancing selection. This evolutionary pattern may be related to the conservation of the host target(s) of PSR2 and the absence of known corresponding R genes. In summary, our study indicates that PSR2 is a conserved effector that acts as a master switch to modify plant gene regulation early during infection for the pathogen's benefit. The conservation of PSR2 and its important role in virulence make it a promising target for pathogen management.
Novel approaches to characterize age‐related remodelling of the dermal‐epidermal junction in 2D, 3D and in vivo
Authors: Newton V. L. , Bradley R. S. , Seroul P. , Cherel M. , Griffiths C. E. M. , Rawlings A. V. , Voegeli R. , Watson R. E. B. , Sherratt M. J. 
Published: August 2016

Background/purposeThe dermal‐epidermal junction (DEJ) forms epidermal protrusions down into the dermis (rete ridges) and dermal projections up into the epidermis (dermal papillae). Usually visualized in two‐dimensions (2D), our knowledge of how the DEJ changes with ageing is limited. We aimed to characterize how this structure exists in 3D and changes with age.MethodsPhotoprotected and photoexposed skin were imaged using reflectance confocal microscopy (RCM) in young and aged individuals. Biopsies of the imaged areas were processed for histological sectioning and for imaging using micro‐computed X‐ray tomography (microCT).ResultsImages obtained from RCM and microCT were used to 3D reconstruct the DEJ. DEJ heights obtained from microCT images showed strong correlation with histology‐measured heights. We proposed a novel definition of rete ridges (RRm) and dermal papillae (DPm), which allowed easier automated measurement of reduced DPm and RRm volumes in aged skin from microCT reconstructions. An algorithm to map DPm connectivity showed reduced lengths of DPm branches with age.ConclusionThree‐dimensional images illustrated the complex topography of the DEJ and highlighted the distinct morphology of dermal papillae compared with rete ridges, which is not evident when evaluating 2D sections. Ex vivo imaging was more successful in differentiating DEJ architecture with respect to age.
Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine
Authors: Khatri Amit , Trinh Roger , Zhao Weihan , Podsadecki Thomas , Menon Rajeev 
Published: August 2016

ABSTRACT

The direct-acting antiviral regimen of 25 mg ombitasvir–150 mg paritaprevir–100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (
n
= 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (
C
max
) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean
C
max
and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean
C
max
and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment.
Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor
Authors: Owens Christopher M. , Brasher Bradley B. , Polemeropoulos Alex , Rhodin Michael H. J. , McAllister Nicole , Wong Kelly A. , Jones Christopher T. , Jiang Lijuan , Lin Kai , Or Yat Sun 
Published: August 2016

ABSTRACT

EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated
in vitro
and
in vivo
. This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments
in vitro
using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs were similarly identified in GT1b NS5A at amino acid positions 31 and 93. Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239 individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H. RAMs were identified in GT1 patients at baseline or after dosing with EDP-239 that were similar to those detected
in vitro
. Baseline RAMs identified at NS5A position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced treatment response. RAMs at additional positions were also detected and may have contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58 (GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks 24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.)
Activity of Cysteamine against the Cystic Fibrosis Pathogen Burkholderia cepacia Complex
Authors: Fraser-Pitt Douglas , Mercer Derry , Lovie Emma , Robertson Jennifer , O'Neil Deborah 
Published: August 2016

ABSTRACTThere are no wholly successful chemotherapeutic strategies againstBurkholderia cepaciacomplex (BCC) colonization in cystic fibrosis (CF). We assessed the impact of cysteamine (Lynovex) in combination with standard-of-care CF antibioticsin vitroagainst BCC CF isolates by the concentration at which 100% of bacteria were killed (MIC100) and checkerboard assays under CLSI standard conditions. Cysteamine facilitated the aminoglycoside-, fluoroquinolone- and folate pathway inhibitor-mediated killing of BCC organisms that were otherwise resistant or intermediately sensitive to these antibiotic classes. Slow-growing BCC strains are often recalcitrant to treatment and form biofilms. In assessing the impact of cysteamine on biofilms, we demonstrated inhibition of BCC biofilm formation at sub-MIC100s of cysteamine.
Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway in Yersinia pseudotuberculosis
Authors: Avican Ummehan , Beckstette Michael , Heroven Ann Kathrin , Lavander Moa , Dersch Petra , Forsberg Åke 
Published: August 2016

ABSTRACT

The twin-arginine translocation (Tat) system mediates the secretion of folded proteins that are identified via an N-terminal signal peptide in bacteria, plants, and archaea. Tat systems are associated with virulence in many bacterial pathogens, and our previous studies revealed that Tat-deficient
Yersinia pseudotuberculosis
was severely attenuated for virulence. Aiming to identify Tat-dependent pathways and phenotypes of relevance for
in vivo
infection, we analyzed the global transcriptome of parental and Δ
tatC
mutant strains of
Y. pseudotuberculosis
during exponential and stationary growth at 26°C and 37°C. The most significant changes in the transcriptome of the Δ
tatC
mutant were seen at 26°C during stationary-phase growth, and these included the altered expression of genes related to virulence, stress responses, and metabolism. Subsequent phenotypic analysis based on these transcriptome changes revealed several novel Tat-dependent phenotypes, including decreased YadA expression, impaired growth under iron-limited and high-copper conditions, as well as acidic pH and SDS. Several functionally related Tat substrates were also verified to contribute to these phenotypes. Interestingly, the phenotypic defects observed in the Tat-deficient strain were generally more pronounced than those in mutants lacking the Tat substrate predicted to contribute to that specific function. Altogether, this provides new insight into the impact of Tat deficiency on
in vivo
fitness and survival/replication of
Y. pseudotuberculosis
during infection.

IMPORTANCE
In addition to its established role in mediating the secretion of housekeeping enzymes, the Tat system has been recognized as being involved in infection. In some clinically relevant bacteria, such as
Pseudomonas
spp., several key virulence determinants can readily be identified among the Tat substrates. In enteropathogens, such as
Yersinia
spp., there are no obvious virulence determinants among the Tat substrates. Tat mutants show no growth defect
in vitro
but are highly attenuated in
in vivo
. This makes Tat an attractive target for the development of novel antimicrobials. Therefore, it is important to establish the causes of the attenuation. Here, we show that the attenuation is likely due to synergistic effects of different Tat-dependent phenotypes that each contributes to lowered
in vivo
fitness.