bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Overweight and Obesity and Genital Anomalies in Male Offspring: A Population‐Based Swedish Cohort Study
Authors: Arendt Linn Håkonsen , Ramlau‐Hansen Cecilia Høst , Lindhard Morten Søndergaard , Henriksen Tine Brink , Olsen Jørn , Yu Yongfu , Cnattingius Sven 
Published: June 2017

AbstractBackgroundOverweight and obese pregnant women face higher risk of several critical birth outcomes, including an overall increased risk of congenital abnormalities. Only few studies have focused on associations between maternal overweight and the genital anomalies in boys, cryptorchidism and hypospadias, and results are inconclusive.MethodsWe performed a population‐based cohort study and assessed the associations between maternal body mass index (BMI) in early pregnancy and occurrence of cryptorchidism and hypospadias. All live‐born singleton boys born in Sweden from 1992 to 2012 were included. From the Swedish Patient Register, information on cryptorchidism and hypospadias was available. Data were analysed using Cox proportional hazards regression adjusted for potential confounders. Mediation analyses were performed to estimate how much of the association between BMI and genital anomalies were mediated through obesity‐related diseases.ResultsOf the 1 055 705 live‐born singleton boys born from 1992 to 2012, 6807 (6.4 per 1000) were diagnosed with hypospadias and 16 469 (15.6 per 1000) were diagnosed with cryptorchidism, of which 9768 (9.3 per 1000) underwent corrective surgery for cryptorchidism. We observed dose‐response associations between maternal BMI and hypospadias and cryptorchidism. Boys of mothers with BMI ≥40.0 kg/m2 had the highest adjusted hazard ratios for hypospadias (HR 1.35, 95% confidence interval [CI] 1.04, 1.76) and cryptorchidism (HR 1.25, 95% CI 1.00, 1.58). A substantial proportion of the associations between BMI and the genital anomalies were mediated through preeclampsia.ConclusionThis large register‐based study adds to the current literature and indicates that the occurrence of hypospadias and cryptorchidism increase with maternal overweight and obesity severity.
Is aid for trade effective? A panel quantile regression approach
Authors: Martínez‐Zarzoso Inmaculada , Nowak‐Lehmann D. Felicitas , Rehwald Kai 
Published: June 2017

AbstractThis paper investigates whether Aid for Trade (AfT) leads to greater exports in recipient countries. Using panel quantile regression and two strategies to address endogeneity (AfT lagged by two periods and dynamic OLS), our results suggest that total AfT disbursements promote the export of goods and services mainly for the lower quantiles (0.1, 0.25, 0.50) of the conditional distribution of exports. Hence, countries that export less in volume are those benefitting most from AfT. This effect is mainly driven by the impact on exports of goods rather than on that of services. We also investigate which types of AfT are effective when endogeneity is controlled for. The main results show that whereas aid to improve trade policy and regulation is associated with higher exports for all quantiles, aid used to build infrastructure is found to affect exports at only the lowest tails of the distribution (0.10–0.35) and aid to build productive capacity is generally more effective for the lower quantiles of the export distribution (0.10–0.50). In contrast, aid disbursed for general budget support (an untargeted type of aid) is not associated with greater export levels. This finding holds irrespective of the quantile.
Wrench Uncertainty Quantification and Reconfiguration Analysis in
Loosely Interconnected Cooperative Systems
Authors: Sovizi Javad , Rai Rahul , Krovi Venkat 
Published: June 2017

Abstract
Loosely interconnected cooperative systems such as cable robots are particularly susceptible to uncertainty. Such uncertainty is exacerbated by addition of the base mobility to realize reconfigurability within the system. However, it also sets the ground for predictive base reconfiguration in order to reduce the uncertainty level in system response. To this end, in this paper, we systematically quantify the output wrench uncertainty based on which a base reconfiguration scheme is proposed to reduce the uncertainty level for a given task (uncertainty manipulation). Variations in the tension and orientation of the cables are considered as the primary sources of the uncertainty responsible for nondeterministic wrench output on the platform. For nonoptimal designs/configurations, this may require complex control structures or lead to system instability. The force vector corresponding to each agent (e.g., pulley and cable) is modeled as random vector whose magnitude and orientation are modeled as random variables with Gaussian and von Mises distributions, respectively. In a probabilistic framework, we develop the closed-form expressions of the means and variances of the output force and moment given the current state (tension and orientation of the cables) of the system. This is intended to enable the designer to efficiently characterize an optimal configuration (location) of the bases in order to reduce the overall wrench fluctuations for a specific task. Numerical simulations as well as real experiments with multiple iRobots are performed to demonstrate the effectiveness of the proposed approach.
In Vitro
Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections
Authors: McCurdy S. , Lawrence L. , Quintas M. , Woosley L. , Flamm R. , Tseng C. , Cammarata S. 
Published: June 2017

ABSTRACT

Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad-spectrum
in vitro
activity, including activity against Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The
in vitro
activity of delafloxacin and the percent microbiological response in subjects infected with fluoroquinolone-susceptible and nonsusceptible
Staphylococcus aureus
isolates were determined from two global phase 3 studies of delafloxacin versus vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infections (ABSSSI). Patients from 23 countries, predominately the United States but also Europe, South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 1,042 patients from which 685
S. aureus
isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, North Liberty, IA). The comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Nonsusceptibility to these antibiotics was determined using CLSI breakpoints.
S. aureus
isolates were 33.7% levofloxacin nonsusceptible (LVX-NS). The delafloxacin MIC
90
values against levofloxacin-nonsusceptible
S. aureus
, methicillin-resistant
S. aureus
(MRSA), and methicillin-susceptible
S. aureus
isolates were all 0.25 μg/ml. Delafloxacin demonstrated high rates of microbiological response against LVX-NS isolates as well as isolates with documented mutations in the quinolone resistance-determining region (QRDR).
S. aureus
was eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin-nonsusceptible
S. aureus
isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). Microbiological response rates of 98.6% were observed with delafloxacin-treated subjects with
S. aureus
isolates with the S84L mutation in
gyrA
and the S80Y mutation in
parC
, the most commonly observed mutations in global phase 3 studies. The data suggest that delafloxacin could be a good option for the treatment of infections caused by
S. aureus
isolates causing ABSSSI, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin nonsusceptibility are observed. (The phase 3 studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT01984684 and NCT01811732.)
β-Lactam Antibiotics with a High Affinity for PBP2 Act Synergistically with the FtsZ-Targeting Agent TXA707 against Methicillin-Resistant Staphylococcus aureus
Authors: Ferrer-González Edgar , Kaul Malvika , Parhi Ajit K. , LaVoie Edmond J. , Pilch Daniel S. 
Published: June 2017

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. We present here results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin-binding proteins (PBPs) of
S. aureus
using a fluorescence anisotropy competition assay. A comparison of the resulting PBP binding affinities with our corresponding synergy results reveals that β-lactams with a high affinity for PBP2 afford the greatest degree of synergy with TXA707 against MRSA. In addition, we present fluorescence and electron microscopy studies that suggest a potential mechanism underlying the synergy between TXA707 and the β-lactam antibiotics. In this connection, our microscopy results show a disruption of septum formation in TXA707-treated MRSA cells, with a concomitant mislocalization of the PBPs from midcell to nonproductive peripheral sites. Viewed as a whole, our results indicate that PBP2-targeting β-lactam antibiotics are optimal synergistic partners with FtsZ-targeting agents for use in combination therapy of MRSA infections.
Pseudomonas Quinolone Signal Induces Oxidative Stress and Inhibits Heme Oxygenase-1 Expression in Lung Epithelial Cells
Authors: Abdalla Maher Y. , Hoke Traci , Seravalli Javier , Switzer Barbara L. , Bavitz Melissa , Fliege Jill D. , Murphy Peter J. , Britigan Bradley E. 
Published: June 2017

ABSTRACTPseudomonasaeruginosacauses lung infections in patients with cystic fibrosis (CF). ThePseudomonasquinolone signal (PQS) compound is a secretedP. aeruginosavirulence factor that contributes to the pathogenicity ofP. aeruginosa. We were able to detect PQS in sputum samples from CF patients infected withP. aeruginosabut not in samples from uninfected patients. We then tested the hypothesis that PQS induces oxidative stress in host cells by determining the ability of PQS to induce the production of reactive oxygen species (ROS) in lung epithelial cells (A549 and primary normal human bronchial epithelial [NHBE]) cells and macrophages (J774A.1 and THP-1). ROS production induced by PQS was detected with fluorescent probes (dichlorodihydrofluorescein diacetate, dihydroethidium, and MitoSOX Red) in conjunction with confocal microscopy and flow cytometry. PQS induced ROS production in lung epithelial (A549 and NHBE) cells and macrophages (J774A.1 and THP-1 cells). NHBE cells were sensitive to PQS concentrations as low as 500 ng/ml. PQS significantly induced early apoptosis (P< 0.05,n= 6) in lung epithelial cells, as measured by annexin/propidium iodide detection by flow cytometry. However, no change in apoptosis upon PQS treatment was seen in J774A.1 cells. Heme oxygenase-1 (HO-1) protein is an antioxidant enzyme usually induced by oxidative stress. Interestingly, incubation with PQS significantly reduced HO-1 and NrF2 expression in A549 and NHBE cells but increased HO-1 expression in J774A.1 cells (P< 0.05,n= 3), as determined by immunoblotting and densitometry. These PQS effects on host cells could play an important role in the pathogenicity ofP. aeruginosainfections.
Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2
Authors: Holden James A. , O'Brien-Simpson Neil M. , Lenzo Jason C. , Orth Rebecca K. H. , Mansell Ashley , Reynolds Eric C. 
Published: June 2017

ABSTRACT

Porphyromonas gulae
is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by
P. gulae
and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to
P. gulae
resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2
−/−
, and TLR4
−/−
macrophages. The addition of
P. gulae
to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide.
P. gulae-
induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent.
P. gulae
induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for
P. gulae
activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by
P. gulae
are mainly dependent on TLR2. In conclusion,
P. gulae
induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals.
Effectiveness of conservative interventions including exercise, manual therapy and medical management in adults with shoulder impingement: a systematic review and meta-analysis of RCTs
Authors: Steuri Ruedi , Sattelmayer Martin , Elsig Simone , Kolly Chloé , Tal Amir , Taeymans Jan , Hilfiker Roger 
Published: June 2017

ObjectiveTo investigate the effectiveness of conservative interventions for pain, function and range of motion in adults with shoulder impingement.DesignSystematic review and meta-analysis of randomised trials.Data sourcesMedline, CENTRAL, CINAHL, Embase and PEDro were searched from inception to January 2017.Study selection criteriaRandomised controlled trials including participants with shoulder impingement and evaluating at least one conservative intervention against sham or other treatments.ResultsFor pain, exercise was superior to non-exercise control interventions (standardised mean difference (SMD) −0.94, 95% CI −1.69 to −0.19). Specific exercises were superior to generic exercises (SMD −0.65, 95% CI −0.99 to −0.32). Corticosteroid injections were superior to no treatment (SMD −0.65, 95% CI −1.04 to −0.26), and ultrasound guided injections were superior to non-guided injections (SMD −0.51, 95% CI −0.89 to −0.13). Nonsteroidal anti-inflammatory drugs (NSAIDS) had a small to moderate SMD of −0.29 (95% CI −0.53 to −0.05) compared with placebo. Manual therapy was superior to placebo (SMD −0.35, 95% CI −0.69 to −0.01). When combined with exercise, manual therapy was superior to exercise alone, but only at the shortest follow-up (SMD −0.32, 95% CI −0.62 to −0.01). Laser was superior to sham laser (SMD −0.88, 95% CI −1.48 to −0.27). Extracorporeal shockwave therapy (ECSWT) was superior to sham (−0.39, 95% CI −0.78 to –0.01) and tape was superior to sham (−0.64, 95% CI −1.16 to −0.12), with small to moderate SMDs.ConclusionAlthough there was only very low quality evidence, exercise should be considered for patients with shoulder impingement symptoms and tape, ECSWT, laser or manual therapy might be added. NSAIDS and corticosteroids are superior to placebo, but it is unclear how these treatments compare to exercise.
‘It’s a hard conversation to have’. Healthcare professionals’ views concerning advance care discussions with young people affected by life-limiting neuromuscular diseases: an interview study
Authors: Hiscock Andy , Barclay Stephen 
Published: June 2017

ObjectiveLife-limiting neuromuscular disease, such as some of the muscular dystrophies, are often diagnosed in early childhood: when death comes, commonly in the second or third decade of life, patients rarely have advance care plans in place or documented end-of-life care preferences. There is very limited literature concerning the discussions about end-of-life plans healthcare professionals have with young people affected by life-limiting neuromuscular diseases. The aim of this study was to investigate the views and experiences of healthcare professionals concerning having discussions about advance care plans and end-of-life care with teenagers and young adult patients affected by life-limiting neuromuscular diseases.MethodsSemistructured interviews with a maximum variety sample of nine professionals involved in the care of young people with life-limiting neuromuscular diseases in one region of the UK.ResultsWhile recognising the inevitable progression of the conditions, there was no consensus among interviewees concerning best approaches to discuss end-of-life care plans. Several environmental and personal barriers were identified that lead to avoidance of the emotionally challenging and difficult conversations.ConclusionsCommunity-based professionals with well-established relationships with patients and families may be best placed to take the lead and coordinate discussions, but individual case-by-case preferences need to be carefully considered.
Vaccination with High-Affinity Epitopes Impairs Antitumor Efficacy by Increasing PD-1 Expression on CD8+ T Cells
Authors: Zahm Christopher D. , Colluru Viswa T. , McNeel Douglas G. 
Published: June 2017

AbstractAntitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination. In this report, we use two murine models to investigate whether the dose, MHC affinity, or TCR affinity of an epitope affected the antitumor response via the PD-1/PD-L1 axis. T cells activated with high-affinity epitopes resulted in prolonged APC:T-cell contact time that led to elevated, persistent PD-1 expression, and expression of other checkpoint molecules, in vitro and in vivo. Immunization with high-affinity epitopes also decreased antitumor efficacy in the absence of PD-1 blockade. Thus, APC:T-cell contact time can be altered by epitope affinity and lead to therapeutically relevant changes in vaccine efficacy mediated by changes in PD-1 expression. These findings have implications for the use of agents targeting PD-1 expression or function whenever high-affinity CD8 T cells are elicited or supplied by means of vaccination or adoptive transfer. Cancer Immunol Res; 5(8); 630–41. ©2017 AACR.
The Role of Forcings in the Twentieth-Century North Atlantic Multidecadal Variability: The 1940–75 North Atlantic Cooling Case Study
Authors: Bellucci A. , Mariotti A. , Gualdi S. 
Published: June 2017

Abstract
Results from a study inspecting the origins of multidecadal variability in the North Atlantic sea surface temperature (NASST) are presented. The authors target in particular the 1940–75 “warm-to-cold” transition, an event that is generally framed in the context of the longer-term Atlantic multidecadal variability (AMV) cycle, in turn associated with the Atlantic meridional overturning circulation (AMOC) internal variability. Here the authors examine the ability of uninitialized, historical integrations from the phase 5 of the Coupled Model Intercomparison Project (CMIP5) archive to retrospectively reproduce this specific episode of twentieth-century climatic history, under a hierarchy of forcing conditions. For this purpose, both standard and so-called historical Misc CMIP5 simulations of the historical climate (combining selected natural and anthropogenic forcings) are exploited. Based on this multimodel analysis, evidence is found for a significant influence of anthropogenic agents on multidecadal sea surface temperature (SST) fluctuations across the Atlantic sector, suggesting that anthropogenic aerosols and greenhouse gases might have played a key role in the 1940–75 North Atlantic cooling. However, the diagnosed forced response in CMIP5 models appears to be affected by a large uncertainty, with only a limited subset of models displaying significant skill in reproducing the mid-twentieth-century NASST cooling. Such uncertainty originates from the existence of well-defined behavioral clusters within the analyzed CMIP5 ensembles, with the bulk of the models splitting into two main clusters. Such a strong polarization calls for some caution when using a multimodel ensemble mean in climate model analyses, as averaging across fairly distinct model populations may result, through mutual cancellation, in a rather artificial description of the actual multimodel ensemble behavior.
A potentially important role for both anthropogenic aerosols and greenhouse gases with regard to the observed North Atlantic multidecadal variability has clear implications for decadal predictability and predictions. The uncertainty associated with alternative aerosol and greenhouse gas emission scenarios should be duly accounted for in designing a common protocol for coordinated decadal forecast experiments.
Distributions of Tropical Precipitation Cluster Power and Their Changes under Global Warming. Part I: Observational Baseline and Comparison to a High-Resolution Atmospheric Model
Authors: Quinn Kevin M. , Neelin J. David 
Published: June 2017

Abstract
The total amount of precipitation integrated across a precipitation feature (contiguous precipitating grid cells exceeding a minimum rain rate) is a useful measure of the aggregate size of the disturbance, expressed as the rate of water mass lost or latent heat released (i.e., the power of the disturbance). The probability distribution of cluster power is examined over the tropics using Tropical Rainfall Measuring Mission (TRMM) 3B42 satellite-retrieved rain rates and global climate model output. Observed distributions are scale-free from the smallest clusters up to a cutoff scale at high cluster power, after which the probability drops rapidly. After establishing an observational baseline, precipitation from the High Resolution Atmospheric Model (HiRAM) at two horizontal grid spacings (roughly 0.5° and 0.25°) is compared. When low rain rates are excluded by choosing a minimum rain-rate threshold in defining clusters, the model accurately reproduces observed cluster power statistics at both resolutions. Middle and end-of-century cluster power distributions are investigated in HiRAM in simulations with prescribed sea surface temperatures and greenhouse gas concentrations from a “business as usual” global warming scenario. The probability of high cluster power events increases strongly by end of century, exceeding a factor of 10 for the highest power events for which statistics can be computed. Clausius–Clapeyron scaling accounts for only a fraction of the increased probability of high cluster power events.