bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Method to Correct for Habitat Filtering in Microbial Correlation Networks
Authors: Brisson Vanessa , Schmidt Jennifer , Northen Trent R. , Vogel John P. , Gaudin Amélie 
Published: November 2018

AbstractAmplicon sequencing of 16S, ITS, and 18S regions of microbial genomes is a commonly used first step toward understanding microbial communities of interest for human health, agriculture, and the environment. Correlation network analysis is an emerging tool for investigating the interactions within these microbial communities. However, when data from different habitats (e.g sampling sites, host genotype, etc.) are combined into one analysis, habitat filtering (co-occurrence of microbes due to habitat sampled rather than biological interactions) can induce apparent correlations, resulting in a network dominated by habitat effects and masking correlations of biological interest. We developed an algorithm to correct for habitat filtering effects in microbial correlation network analysis in order to reveal the true underlying microbial correlations. This algorithm was tested on simulated data that was constructed to exhibit habitat filtering. Our algorithm significantly improved correlation detection accuracy for these data compared to Spearman and Pearson correlations. We then used our algorithm to analyze a real data set of 16S-V4 amplicon sequences that was expected to exhibit habitat filtering. Our algorithm was found to effectively reduce habitat effects, enabling the construction of consensus correlation networks from data sets combining multiple related sample habitats.
Chemically-induced Neurite-like Outgrowth Reveals Multicellular Network Function in Patient-derived Glioblastoma Cells
Authors: da Silva Barbara , Polson Euan S. , Droop Alastair , Mathew Ryan K. , Stead Lucy F. , Williams Jennifer , Short Susan C. , Scarcia Margherita , Mavria Georgia , Wurdak Heiko 
Published: November 2018

SummaryTumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of Glioblastoma Multiforme (GBM), the most aggressive type of brain cancer in adults. We show that small molecule inhibition of RHO-associated serine/threonine kinase (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formedde novo-induced cellular network (iNet) ‘webs’, which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range calcium signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet websex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.
Ribosomal protein imbalance launches a C/EBP-based program to preserve tissue integrity
Authors: Baillon Ludovic 
Published: November 2018

SummaryGenes encoding ribosomal proteins are expressed at rate limiting levels, rendering their biological function highly sensitive to the copy-number variation that results from genomic instability. Cells with a reduced number of ribosomal protein genes (RPGs) are eliminated, when intermingled with wild type cells, via a process known as cell competition. The mechanisms underlying this phenomenon are poorly understood. Here we report the function of a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1, that is critically required for the elimination of cells with a hemizygous RPG genotype. In such cells,Xrp1is transcriptionally upregulated by an autoregulatory loop and is able to trigger cell elimination. Since genomic instability is likely to cause the loss of a haploinsufficient RPG, we propose a molecular model of how RPGs, together with a C/EBP-dependent transcriptional program, could preserve the genomic integrity of tissues.
Growth responses to soil water potential indirectly shape local species distributions of tropical forest seedlings
Authors: Kupers Stefan J. , Engelbrecht Bettina M. J. , Hernández Andrés , Wright S. Joseph , Wirth Christian , Rüger Nadja 
Published: November 2018

Abstract

Local tree species distributions in tropical forests correlate strongly with soil water availability. However, it is unclear how species distributions are shaped by demographic responses to soil water availability. Specifically, it remains unknown how growth affects species distributions along water availability gradients relative to mortality.

We quantified spatial variation in dry season soil water potential (SWP) in the moist tropical forest on Barro Colorado Island, Panama, and used a hierarchical Bayesian approach to evaluate relationships between demographic responses of naturally regenerating seedlings to SWP (RGRs and first‐year mortality) and species distributions along the SWP gradient for 62 species. We also tested whether species that were more abundant at the wet or dry end of the gradient performed better (a) at their “home end” of the gradient (“best at home” hypothesis) and (b) “at home” compared to co‐occurring species (“home advantage” hypothesis).

Four and five species responded significantly to SWP in terms of growth or mortality respectively. Growth (but not mortality) responses were positively related to species distributions along the SWP gradient; species with a more positive (negative) growth response to SWP were more abundant at higher (lower) SWP, that is, at wetter (drier) sites. In addition, wet distributed species grew faster on the wet end of the SWP gradient than on the dry end (“best at home”) and grew faster on the wet end than dry distributed species (“home advantage”). Mortality rates declined with seedling size for all species. Thus, seedling growth responses to SWP indirectly shaped local species distributions by influencing seedling size and thereby mortality risk.

Synthesis. By demonstrating how growth responses to spatial variation in soil water availability affect species distributions, we identified a demographic process underlying niche differentiation on hydrological gradients in tropical forests. Recognizing the role of these growth responses in shaping species distributions should improve the understanding of tropical forest composition and diversity along rainfall gradients and with climate change.
Greening Displacements, Displacing Green: Environmental Subjectivity, Slum Clearance, and the Embodied Political Ecologies of Dispossession in Mumbai
Authors: Doshi Sapana 
Published: November 2018

AbstractIn Indian cities, informal ‘slum’ settlements have long been targeted for removal as an environmental improvement strategy, despite their relatively low impact. Slum clearance has escalated with the combination of speculative development and environmental change, creating uneven precarity throughout Mumbai's neighborhoods. State agents play a direct role in slum evictions, but they do not act unilaterally. Diverse lower‐income and middle‐class residents seeking better living conditions have sometimes converged in their embrace of slum clearances and resettlements that advance elite development interests. In other moments, the dispossessing effects of market‐based and elite‐biased slum rehabilitation have fomented contestation. This article analyzes how differently situated groups emerge as ‘environmental subjects’ that embrace or contest improvement projects. It suggests three dimensions of subject formation: governing logics and discourses of urban environmental improvement, the territorial politics of informality, and differentiated embodied experiences of precarity and dispossession. Environmental subject formation is explored through two interventions that entail slum clearance—mangrove and green space conservation and an urban transport infrastructure project. Findings suggest that the connection between displacement and improvement cannot be explained through theories of environmental gentrification but require attention to the simultaneously inclusive and dispossessing regimes of postcolonial development.
Malpresentation in low‐ and middle‐income countries: Associations with perinatal and maternal outcomes in the Global Network
Authors: Duffy Cassandra R. , Moore Janet L. , Saleem Sarah , Tshefu Antoinette , Bose Carl L. , Chomba Elwyn , Carlo Waldemar A. , Garces Ana L. , Krebs Nancy F. , Hambidge K. Michael , Goudar Shivaprasad S. , Derman Richard J. , Patel Archana , Hibberd Patricia L. , Esamai Fabian , Liechty Edward A. , Wallace Dennis D. , McClure Elizabeth M. , Goldenberg Robert L. ,   the NICHD Global Network for Women's and Children's Health Research
Published: November 2018

AbstractIntroductionUncertainty exists regarding the impact of malpresentation on pregnancy outcomes and the optimal mode of delivery in low‐ and middle‐income countries. We sought to compare outcomes between cephalic and non‐cephalic pregnancies.Material and methodsUsing the NICHD Global Network's prospective, population‐based registry of pregnancy outcomes from 2010 to 2016, we studied outcomes in 436 112 singleton pregnancies. Robust Poisson regressions were used to estimate the risk of adverse outcomes associated with malpresentation. We examined rates of cesarean delivery for malpresentation and compared outcomes between cesarean and vaginal delivery by region.ResultsAcross all regions, stillbirth and neonatal mortality rates were higher among deliveries with malpresentation. In adjusted analysis, malpresentation was significantly associated with stillbirth (adjusted relative risk [aRR] 4.0, 95% confidence interval [CI] 3.7‐4.5) and neonatal mortality (aRR 2.3, 95% CI 2.1‐2.6). Women with deliveries complicated by malpresentation had higher rates of morbidity and mortality. Rates of cesarean delivery for malpresentation ranged from 27% to 87% among regions. Compared with cesarean delivery, vaginal delivery for malpresentation was associated with increased maternal risk, especially postpartum hemorrhage (aRR 5.0, 95% CI; 3.6‐7.1).ConclusionsIn a cohort of deliveries in low‐ and middle‐income countries, malpresentation was associated with increased perinatal and maternal risk. Further research is needed to determine the best management of these pregnancies.
Associations of cytokine concentrations in aqueous humour with retinal vascular abnormalities and exudation in Coats’ disease
Authors: Zhang Juan , Jiang Chen , Ruan Lu , Huang Xin 
Published: November 2018

AbstractPurposeTo investigate the associations of cytokine concentrations in aqueous humour with the severity of retinal vascular abnormalities, exudation and fibrosis in patients with Coats’ disease.MethodsAqueous humour samples were collected in 23 paediatric patients (23 eyes) with Coats’ disease and six age‐matched control patients (six eyes) with congenital cataract in this cross‐sectional, case–control study. Through Cytometric Bead Array technology, six angiogenic, inflammatory and fibrotic cytokines were measured for their concentrations in aqueous humour. Ophthalmologic characteristics including retinal vessel abnormalities, exudation and fibrosis of Coats’ disease were also clinically evaluated for analysis.ResultsThe aqueous levels of vascular endothelial growth factor (VEGF) (p = 0.006) and monocyte chemoattractant protein‐1 (MCP‐1) (p < 0.001) were significantly higher in the Coats’ disease group than in the control group. The concentrations of angiogenin were peaked in eyes with first‐grade vessels tortuosity (p < 0.001), and also positively correlated with the severity of retinal capillary abnormalities (r = 0.910, p < 0.001). The concentrations of MCP‐1 (r = 0.966, p < 0.001) and VEGF (r = 0. 765, p = 0.002) were significantly correlated with the extent of retinal exudation. The aqueous humour transforming growth factor‐β (TGFβ) concentrations were higher in eyes with retinal fibrosis than in non‐fibrotic eyes with Coats’ disease (p = 0.004).ConclusionIn Coats’ disease, angiogenin may act as a potential biomarker for retinal vascular abnormalities. The concentrations of VEGF and MCP‐1 may positively correlate with the severity of retinal exudation.
Energy efficient physiologic coupling of gait and respiration is altered in chronic obstructive pulmonary disease
Authors: Yentes Jennifer M. , Denton William , Samson Kaeli , Schmid Kendra K. , Wiens Casey , Rennard Stephen I. 
Published: November 2018

AbstractAimsCoupling between walking and breathing in humans is well established. In healthy systems, the ability to couple and uncouple leads to energy economization. It is unknown if physiologic efficiency is susceptible to alteration, particularly in individuals with airflow obstruction. The aim of this research was to determine if coupling was compromised in a disease characterized by abnormal airflow and dyspnoea, and if this was associated with reduced energy efficiency.MethodsAs a model of airflow obstruction, 17 chronic obstructive pulmonary disease (COPD) patients and 23 control subjects were included and walked on a treadmill for 6 minutes at three speeds (preferred speed and ±20% preferred speed) while energy expenditure, breathing, and walking were recorded. Rating of perceived exertion was recorded at the end of each walking trial. The most commonly used frequency ratio (ie, strides:breath) and cross recurrence quantification analysis were used to quantify coupling. Linear regression models were used to determine associations.ResultsLess complex frequency ratios, simpler ratios, (ie, 1:1 and 3:2) accompanied with stronger coupling were moderately associated with increased energy expenditure in COPD subjects. This was found for all three speeds.ConclusionThe novel finding was that increased energy expenditure was associated with stronger and less complex coupling. Increased effort is needed when utilizing a frequency ratio of 1:1 or 3:2. The more stable the coupling, the more effort it takes to walk. In contrast to the complex energy efficient coupling of controls, those with airflow obstruction manifested simpler and stronger coupling associated with reduced energy efficiency.
Successful and safe long‐term treatment of cerebral aspergillosis with high‐dose voriconazole guided by therapeutic drug monitoring
Authors: Cojutti Pier Giorgio , Merelli Maria , Allegri Lorenzo , Damante Giuseppe , Bassetti Matteo , Pea Federico 
Published: November 2018

We report the case of a patient who had cerebral aspergillosis after otorhinolaryngologic surgery and who was successfully and safely treated with high‐dose voriconazole (200 mg q6h) for more than 1 year thanks to a TDM‐guided approach coupled with pharmacological review and with genotyping of CYP2C19 polymorphisms. The findings support the idea that personalized medicine based on TDM coupled with the need of avoiding drug–drug interactions may be helpful for maximizing the net benefit (probability of efficacy vs. probability of adverse events) of voriconazole in the management of long‐term treatment of cerebral aspergillosis.
Pharmacokinetic–pharmacodynamic modelling of platelet response to ticagrelor in stable coronary artery disease and prior myocardial infarction patients
Authors: Åstrand Magnus , Amilon Carl , Röshammar Daniel , Himmelmann Anders , Angiolillo Dominick J. , Storey Robert F. , Gurbel Paul A. , Bonaca Marc P. , Hamrén Bengt 
Published: November 2018

AimsTo characterize ticagrelor exposure‐response relationship for platelet inhibition in patients with stable coronary artery disease (CAD) and a history of myocardial infarction (MI), using nonlinear mixed effects modelling and simulation.MethodsPlatelet function data were integrated with plasma concentration data of ticagrelor and its active metabolite AR‐C1249010XX in a population pharmacokinetic (PK) and pharmacodynamic (PD) model, based on two clinical studies. In the ONSET/OFFSET study, PK and platelet function were assessed in 123 CAD patients receiving placebo, ticagrelor (180 mg followed by 90 mg twice daily) or clopidogrel (600 mg followed by 75 mg once daily). In the PEGASUS‐TIMI 54 platelet function substudy, PK and platelet function were assessed during maintenance dosing in 180 prior MI patients receiving placebo, ticagrelor 60 mg or ticagrelor 90 mg twice daily.ResultsPlatelet inhibition by ticagrelor was described by a sigmoidal Emax model. On average, half maximal inhibition was reached at ticagrelor concentrations of 116 (RSE: 5.3%) nmol l–1. Simulations showed that near maximal platelet inhibition is achieved with both ticagrelor 60 and 90 mg twice daily. At simulated lower doses, platelet inhibition is overall reduced, more variable between patients, and show greater peak‐to‐trough variability. Ticagrelor antiplatelet response was similar between the studied patient populations.ConclusionsIn patients with stable CAD or a history of MI, near maximal platelet inhibition is achieved with both ticagrelor 60 and 90 mg twice daily. At modelled doses <60 mg, the response is reduced overall, more variable between patients, and patients will display greater peak‐to‐trough variability.
Influence of midwifery presence in United States centers on labor care and outcomes of low‐risk parous women: A Consortium on Safe Labor study
Authors: Carlson Nicole S. , Neal Jeremy L. , Tilden Ellen L. , Smith Denise C. , Breman Rachel B. , Lowe Nancy K. , Dietrich Mary S. , Phillippi Julia C. 
Published: November 2018

AbstractBackgroundSixty percent of United States births are to multiparous women. Hospital‐level policies and culture may influence intrapartum care and birth outcomes for this large population, yet have been poorly explored using a large, diverse sample. We sought to use national United States data to analyze the association between midwifery presence in maternity care teams and the birth processes and outcomes of low‐risk parous women.MethodsWe conducted a retrospective cohort study using Consortium on Safe Labor data from low‐risk parous women in either interprofessional care (n = 12 125) or noninterprofessional care centers (n = 8996). Unadjusted, adjusted (age, race, health insurance type), propensity‐adjusted, and propensity‐matched logistic regression models were used to assess processes and outcomes.ResultsThere was concordance in outcome differences across regression models. With propensity score matching, women at interprofessional centers, compared with women at noninterprofessional centers, were 85% less likely to have labor induced (risk ratio [RR] 0.15; 95% CI 0.14‐0.17). The risk for primary cesarean birth among low‐risk parous women was 36% lower at interprofessional centers (RR 0.64; 95% CI 00.52‐0.79), whereas the likelihood of vaginal birth after cesarean for this population was 31% higher (RR 1.31; 95% CI 1.10‐1.56). There were no significant differences in neonatal outcomes.ConclusionsParous women have significantly higher rates of vaginal birth, including vaginal birth after cesarean, and lower likelihood of labor induction when cared for in centers with midwives. Our findings are consistent with smaller analyses of midwifery practice and support integrated, team‐based models of perinatal care to improve maternal outcomes.
Th1‐type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II‐dependent hypertension and vascular dysfunction
Authors: Czesnikiewicz‐Guzik Marta , Nosalski Ryszard , Mikolajczyk Tomasz P , Vidler Francesca , Dohnal Tomasz , Dembowska Elzbieta , Graham Delyth , Harrison David G , Guzik Tomasz J 
Published: November 2018

Background and PurposeEmerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation and vascular dysfunction.Experimental ApproachTh1 immune responses were elicited through immunizations using P. gingivalis lysate antigens (10 μg) conjugated with aluminium oxide (50 μg) and IL‐12 (1 μg). The hypertension and vascular endothelial dysfunction evoked by subpressor doses of angiotensin II (0.25 mg·kg−1·day−1) were studied, and vascular inflammation was quantified by flow cytometry and real‐time PCR.Key ResultsSystemic T‐cell activation, a characteristic of hypertension, was exacerbated by P. gingivalis antigen stimulation. This translated into increased aortic vascular inflammation with enhanced leukocyte, in particular, T‐cell and macrophage infiltration. The expression of the Th1 cytokines, IFN‐γ and TNF‐α, and the transcription factor, TBX21, was increased in aortas of P. gingivalis/IL‐12/aluminium oxide‐immunized mice, while IL‐4 and TGF‐β were unchanged. These immune changes in mice with induced T‐helper‐type 1 immune responses were associated with an enhanced elevation of BP and endothelial dysfunction compared with control mice in response to 2 week infusion of a subpressor dose of angiotensin II.Conclusions and ImplicationsThese results support the concept that Th1 immune responses induced by bacterial antigens such as P. gingivalis can increase sensitivity to subpressor pro‐hypertensive insults such as low‐dose angiotensin II, thus providing a mechanistic link between chronic infection, such as periodontitis, and hypertension.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Mitochondrial protective effect of neferine through the modulation of nuclear factor erythroid 2‐related factor 2 signalling in ischaemic stroke
Authors: Wu Chuanhong , Chen Jianxin , Yang Ruocong , Duan Feipeng , Li Shaojing , Chen Xiuping 
Published: November 2018

Background and PurposeIschaemic stroke is a leading cause of death and long‐term disability. Promising neuroprotective compounds are urgently needed to overcome clinical therapeutic limitations. Neuroprotective agents are limited to single‐target agents, which further limit their clinical effectiveness. Due to the brain's particular energy requirements, the energy micro‐environment, centred in mitochondria, is a new research hotspot in the complex pathology of ischaemic stroke. Here, we studied the effects of neferine (Nef), a bis‐benzylisoquinoline alkaloid extracted from the seed embryo of Nelumbo nucifera Gaertn, on ischaemic stroke and its underlying mitochondrial protective mechanisms.Experimental ApproachRats with permanent middle cerebral artery occlusion (pMCAO)‐induced focal cerebral ischaemia and tert‐butyl hydroperoxide (t‐BHP)‐injured PC12 cells were used to investigate the neuroprotective effects of Nef, particularly with regard to energy micro‐environment regulation by mitochondria and its mechanism in vivo and in vitro.Key ResultsNef protected t‐BHP‐injured PC12 cells in vitro and ameliorated neurological score, infarct volume, regional cerebral blood flow, cerebral microstructure and oxidant‐related enzyme deficits in pMCAO rats in vivo. Nef also prevented mitochondrial dysfunction both in vivo and in vitro. The underlying mechanism of the mitochondrial protective effect of Nef might be attributed to the increased translocation of Nrf2 to the nucleus. Furthermore, the translocation of Nrf2 to nucleus was also decreased by sequestosome 1 (p62) knockdown.Conclusions and ImplicationsOur results demonstrated that Nef might have therapeutic potential for ischaemic stroke and may exert its protective role through mitochondrial protection. This protection might be attributed to the modulation of Nrf2 signalling.