bluuebunny/crossref_metadata_2025_split huggingface dataset:
Videourodynamic factors predictive of successful onabotulinumtoxinA urethral sphincter injection for neurogenic or non‐neurogenic detrusor underactivity
Authors: Jiang Yuan‐Hong , Jhang Jia‐Fong , Chen Sheng‐Fu , Kuo Hann‐Chorng 
Published: October 2017

ObjectiveThe aim of the present study was to analyze treatment outcomes and identify videourodynamic factors predictive of successful urethral onabotulinumtoxinA treatment of neurogenic and non‐neurogenic detrusor underactivity (DU).MethodsPatients with DU refractory to medical treatment were treated with injections totaling 100 U onabotulinumtoxinA into the urethral sphincter. Treatment outcomes were assessed 1 month after treatment using the Global Response Assessment. The videourodynamic parameters evaluated included bladder neck status during voiding, bladder sensation, detrusor pressure, maximum flow rate, and post‐void residual volume. Treatment outcome was analyzed by patient and baseline videourodynamic characteristics.ResultsIn all, 60 patients (27 with non‐neurogenic and 33 with neurogenic DU) were included in the study and received urethral sphincter injections of 100 U onabotulinumtoxinA in total. Good outcomes were reported in 36 (60%) patients (20 [74.1%] with non‐neurogenic and 16 [48.5%] with neurogenic DU). Treatment outcome was significantly better in patients with non‐neurogenic than neurogenic DU (P = .039). However, good treatment outcome was not related to age, gender, or any videourodynamic variables, except for an open bladder neck during voiding vs non‐opening bladder neck (94.3% vs. 12.0%; P < .0001). The duration of the therapeutic effect was similar between patients with non‐neurogenic and neurogenic DU (mean [± SD] 7.37 ± 3.69 vs. 7.69 ± 3.18 months, respectively; P = .788). In all, 12 patients reported de novo urinary incontinence after urethral onabotulinumtoxinA injection, 4 of whom developed stress urinary incontinence and 8 who had exacerbated urgency urinary incontinence.ConclusionUrethral sphincter injection of onabotulinumtoxinA is effective in 60% of patients with DU. Careful videourodynamic interpretation of bladder neck opening enables urologists to select appropriate candidates for onabotulinumtoxinA treatment.
Pregnant Metaphors and Surrogate Meanings: Bringing the Ethnography of Pregnancy and Surrogacy into Conversation in Israel and Beyond
Authors: Ivry Tsipy , Teman Elly 
Published: October 2017

AbstractThis article explores the way that surrogacy and normal pregnancy share cultural assumptions about pregnancy. Through a juxtaposition of our ethnographic studies of two groups of Jewish–Israeli women—women who have undergone “normal,” low‐risk pregnancies and women who have given birth as gestational surrogates—we argue that surrogacy and pregnancy emerge as potent metaphors for one another. Both pregnant women and surrogates divided their bodies into two separate realms: fetus and maternal pregnant body. Both trivialized the effect of gestational influence on fetal health, making the fetus seem detached from gestational capacities of the mother. We argue for closer scrutiny of the way local cultural priorities and experiences of pregnancy shape surrogacy and for bringing the scholarship on pregnancy and on surrogacy into deeper conversation.
Phosphorylation coexists with O‐GlcNAcylation in a plant virus protein and influences viral infection
Authors: Martínez‐Turiño Sandra , Pérez José De Jesús , Hervás Marta , Navajas Rosana , Ciordia Sergio , Udeshi Namrata D. , Shabanowitz Jeffrey , Hunt Donald F. , García Juan Antonio 
Published: October 2017

SummaryPhosphorylation and O‐GlcNAcylation are two widespread post‐translational modifications (PTMs), often affecting the same eukaryotic target protein. Plum pox virus (PPV) is a member of the genus Potyvirus which infects a wide range of plant species. O‐GlcNAcylation of the capsid protein (CP) of PPV has been studied extensively, and some evidence of CP phosphorylation has also been reported. Here, we use proteomics analyses to demonstrate that PPV CP is phosphorylated in vivo at the N‐terminus and the beginning of the core region. In contrast with the ‘yin–yang’ mechanism that applies to some mammalian proteins, PPV CP phosphorylation affects residues different from those that are O‐GlcNAcylated (serines Ser‐25, Ser‐81, Ser‐101 and Ser‐118). Our findings show that PPV CP can be concurrently phosphorylated and O‐GlcNAcylated at nearby residues. However, an analysis using a differential proteomics strategy based on iTRAQ (isobaric tags for relative and absolute quantitation) showed a significant enhancement of phosphorylation at Ser‐25 in virions recovered from O‐GlcNAcylation‐deficient plants, suggesting that crosstalk between O‐GlcNAcylation and phosphorylation in PPV CP takes place. Although the preclusion of phosphorylation at the four identified phosphotarget sites only had a limited impact on viral infection, the mimicking of phosphorylation prevents PPV infection in Prunus persica and weakens infection in Nicotiana benthamiana and other herbaceous hosts, prompting the emergence of potentially compensatory second mutations. We postulate that the joint action of phosphorylation and O‐GlcNAcylation in the N‐proximal segment of CP allows a fine‐tuning of protein stability, providing the amount of CP required in each step of viral infection.
Percutaneous transapical approach and transcatheter closure for ventricular tachycardia ablation
Authors: Vurgun Veysel Kutay , Altin Ali Timucin , Kilickap Mustafa , Candemir Basar , Akyurek Omer 
Published: October 2017

AbstractIn patients with mechanical aortic and mitral valve prosthesis, left ventricular endocardial ablation via retrograde transaortic or antegrade transmitral approach carry high risk of catheter entrapment and death. In such cases, ablation can be performed via ventricular transseptal or transapical approach. Transapical approach, with the ease of catheter maneuverability and better endocardial contact, may be performed surgically or percutaneously. In this case report, we describe a patient with both aortic and mitral mechanical prosthesis who underwent ventricular tachycardia ablation via percutaneous transapical endocardial approach with the use of closure device.
Ideology in a Desert Landscape*
Authors: Torza Alessandro 
Published: October 2017

AbstractOn one influential view, metaphysical fundamentality can be understood in terms of joint‐carving. Ted Sider has recently argued that (i) some first order quantifier is joint‐carving, and (ii) modal notions are not joint‐carving. After vindicating the theoretical indispensability of quantification against recent criticism, I will defend a logical result due to Arnold Koslow which implies that (i) and (ii) are incompatible. I will therefore consider an alternative understanding of Sider's metaphysics to the effect that (i) some first order quantifier is joint‐carving, and (iii) intensional notions are not joint‐carving. Another result due to Koslow entails that (i) and (iii) are also incompatible. I will argue that this second result is inconclusive. Nevertheless, (iii) is incompatible with another tenet of Sider's metaphysics, namely that (iv) ‘being joint‐carving’ is itself joint‐carving. In order to resolve the inconsistency, I will tentatively argue that condition (iv) should be renounced.
How to Be a Substantivalist Without Getting Shifty About It*
Authors: Perry Zee R. 
Published: October 2017

AbstractAccording to substantivalism, spacetime points and regions are real entities whose existence is not dependent on matter. In this paper, I motivate and defend a version of substantivalism which takes the totality of spacetime as fundamental, and show how this position avoids certain problem cases, in particular the objection from static Leibniz shifts, and better conforms to how we think about space in physics. I argue that, even though the static Leibniz shifts do not show ordinary substantivalism is committed to in‐principle undetectable physical structure (pace Dasgupta (2015a)), they do indicate something problematic about the modal profile of space‐time and its constituents. While the problem is modal, the solution cannot be solely a matter of revising the substantivalist's modal claims. Rather, I argue, the substantivalist must revise her background ontology of space‐time. I show how this can be done by developing substantivalist theory that rejects this picture in favor of an alternative ontology of space‐time in the spirit of priority monism.
Morphodynamic evolution and stratal architecture of translating tidal point bars: Inferences from the northern Venice Lagoon (Italy)
Authors: Ghinassi Massimiliano , D'alpaos Andrea , Gasparotto Andrea , Carniello Luca , Brivio Lara , Finotello Alvise , Roner Marcella , Franceschinis Erica , Realdon Nicola , Howes Nick , Cantelli Alessandro 
Published: October 2017

AbstractThe widespread distribution of tidal creeks and channels that undertake meandering behaviour in modern coasts contrasts with their limited documentation in the fossil record, where point‐bar elements arising from the interaction between a mix of both fluvial and tidal currents are mainly documented. The sedimentary products of tidal channel‐bend evolution are relatively poorly known, and few studies have focused previously on specific facies models for tidal point bars present in modern settings. This study improves understanding of tidal channel meander bends through a multi‐disciplinary approach that combines analyses of historical aerial photographs, measurements of in‐channel flow velocity, high‐resolution facies analyses of sedimentary cores and three‐dimensional architectural modelling. The studied channel bend (12 to 15 m wide and 2 to 3 m deep) drains a salt marsh area located in the north‐eastern sector of the microtidal Venice Lagoon, Italy. Historical photographs show that, during the past 77 years, the bend has translated seaward ca 15 m. Results show that the channel bend formed on a non‐vegetated mud flat that was progressively colonized by vegetation. Seaward translation occurred under aggradational conditions, with an overall migration rate of 0·2 to 0·3 m year−1, and was promoted by the occurrence of cohesive, poorly erodible outer bank deposits. Ebb currents are dominant, and translation of the channel bend promotes erosion and deposition along the landward and seaward side of the bar, respectively. Tidal currents show a clear asymmetry in terms of velocity distribution, and their offset pattern provides a peculiar grain‐size distribution within the bar. During the flood stage, sand sedimentation occurs in the upper part of the bar, where the maximum flow velocity occurs. During the ebb stage, the bar experiences the secondary helical flow that accumulates sand at the toe of the bar. Lateral stacking of flood and ebb deposits has caused the formation of localized coarsening‐upward and fining‐upward sedimentary packages, respectively.
Using climate to relate water discharge and area in modern and ancient catchments
Authors: Eide Christian Haug , Müller Reidar , Helland‐Hansen William 
Published: October 2017

AbstractModels relating sediment supply to catchment properties are important in order to use the geological record to deduce landscape evolution and interplay between tectonics and climate. Water discharge (Qw) is an important factor in the widely used ‘BQART’ model, which relates sediment load to a set of measurable catchment parameters. Although many of the factors in this equation may be independently estimated with some degree of certainty in ancient systems, water discharge (Qw) certainly cannot. An analysis of a world database of modern catchments with 1255 entries shows that the commonly applied equation relating catchment area (A) to water discharge (Qw = 0·075A0·8) does not predict water discharge from catchment area well in many cases (R2 = 0·5 and an error spanning about three orders of magnitude). This is because the method does not incorporate the effect of arid and wet climate on river water discharge. The inclusion of climate data into such estimations is an opportunity to refine these estimates, because generalized estimates of palaeoclimate can often be deduced on the basis of sedimentological data such as palaeosol types, mineralogy and palaeohydraulics. This paper investigates how the relationship between catchment area and river discharge varies with four runoff categories (arid, semi‐arid, humid and wet), which are recognizable in the geological record, and modifies the coefficient and exponent of the above‐mentioned equation according to these classes. This modified model yields improved results in relating discharge to catchment area (R2 = 0·95 and error spanning one order of magnitude) when core, outcrop or regional palaeoclimate reconstruction data are available in non‐arid systems. Arid systems have an inherently variable water discharge, and catchment area is less important as a control due to downstream losses. The model here is sufficient for many geological applications and makes it possible to include variations in catchment humidity in mass‐flux estimates in ancient settings.
Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme
Authors: Rigas A. S. , Pedersen O. B. , Magnussen K. , Erikstrup C. , Ullum H. 
Published: October 2017

SUMMARYBlood components collected from blood donors are an invaluable part of modern‐day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self‐perceived mental and physical health.In general, the high proportion of iron‐deficient donors can be alleviated either by extending the inter‐donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.
Maternal control of embryogenesis by MPK6 and its upstream MKK4/MKK5 in Arabidopsis
Authors: Zhang Mengmeng , Wu Hongjiao , Su Jianbin , Wang Huachun , Zhu Qiankun , Liu Yidong , Xu Juan , Lukowitz Wolfgang , Zhang Shuqun 
Published: October 2017

SummaryIn flowering plants, developing embryos reside in maternal sporophytes. It is known that maternal generation influences the development of next‐generation embryos; however, little is known about the signaling components in the process. Previously, we demonstrated that Arabidopsis mitogen‐activated protein kinase 6 (MPK6) and MPK3 play critical roles in plant reproduction. In addition, we noticed that a large fraction of seeds from mpk6 single‐mutant plants showed a wrinkled seed coat or a burst‐out embryo phenotype. Here, we report that these seed phenotypes can be traced back to defective embryogenesis. The defective embryos have shorter suspensors and reduced growth along the longitudinal axis. Furthermore, the cotyledons fail to bend over to progress to the bent‐cotyledon stage. As a result of the uneven circumference along the axis, the seed coat wrinkles to develop raisin‐like morphology after dehydration. In more severe cases, the embryo can be pushed out from the micropylar end, resulting in the burst‐out embryo seed phenotype. Genetic analyses demonstrated that the defective embryogenesis of the mpk6 mutant is a maternal effect. Heterozygous or homozygous mpk6 embryos have defects only in mpk6 homozygous maternal plants, but not in wild‐type or heterozygous maternal plants. The loss of function of MKK4/MKK5 also results in the same phenotypes, suggesting that MKK4/MKK5 might act upstream of MPK6 in this pathway. The maternal‐mediated embryo defects are associated with changes in auxin activity maxima and PIN localization. In summary, this research demonstrates that the Arabidopsis MKK4/MKK5–MPK6 cascade is an important player in the maternal control of embryogenesis.
Quinolone Resistance Reversion by Targeting the SOS Response
Authors: Recacha E. , Machuca J. , Díaz de Alba P. , Ramos-Güelfo M. , Docobo-Pérez F. , Rodriguez-Beltrán J. , Blázquez J. , Pascual A. , Rodríguez-Martínez J. M. 
Published: October 2017

ABSTRACT

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of
Escherichia coli
representing multiple levels of quinolone resistance.
E. coli
mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate
in vivo
impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog
10
CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the
in vivo
efficacy of ciprofloxacin was significantly enhanced (Δlog
10
CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of
E. coli
phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the
in vivo
efficacy.

IMPORTANCE
The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this question, we have generated
E. coli
mutants that exhibited a spectrum of SOS activity, ranging from a natural SOS response to a hypoinducible or constitutively suppressed response. We tested the effects of these mutations on quinolone resistance reversion under therapeutic concentrations in a set of isogenic strains carrying different combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms with susceptible, low-level quinolone resistant, resistant, and highly resistant phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug resistance by targeting the SOS response.
An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in
Escherichia coli
Authors: Cleto Sara , Lu Timothy K. 
Published: October 2017

ABSTRACT

Peptides that are synthesized independently of the ribosome in plants, fungi, and bacteria can have clinically relevant anticancer, antihemochromatosis, and antiviral activities, among many other. Despite their natural origin, discovering new natural products is challenging, and there is a need to expand the chemical diversity that is accessible. In this work, we created a novel, compressed synthetic pathway for the heterologous expression and diversification of nonribosomal peptides (NRPs) based on homologs of siderophore pathways from
Escherichia coli
and
Vibrio cholerae
. To enhance the likelihood of successful molecule production, we established a selective pressure via the iron-chelating properties of siderophores. By supplementing cells containing our synthetic pathway with different precursors that are incorporated into the pathway independently of NRP enzymes, we generated over 20 predesigned, novel, and structurally diverse NRPs. This engineering approach, where phylogenetically related genes from different organisms are integrated and supplemented with novel precursors, should enable heterologous expression and molecular diversification of NRPs.

IMPORTANCE
Nonribosomal peptides (NRPs) constitute a source of bioactive molecules with potential therapeutic applications. However, discovering novel NRPs by rational engineering of biosynthetic pathways remains challenging. Here, we show that a synthetic compressed pathway in which we replaced biosynthetic genes with their ancestral homologs and orthologs enabled successful heterologous NRP expression. Polyamines added exogenously were incorporated into nascent NRPs, and molecular production was pressured by growing the host under conditions that make such NRPs beneficial for survival. This multilayered approach resulted in the assembly of over 20 distinct and novel molecules. We envision this strategy being used to enable the production of NRPs from heterologous pathways.
Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis
Authors: Liu Xiaoqian , Machado Gustavo C , Eyles Jillian P , Ravi Varshini , Hunter David J 
Published: October 2017

ObjectiveTo investigate the efficacy and safety of dietary supplements for patients with osteoarthritis.DesignAn intervention systematic review with random effects meta-analysis and meta-regression.Data sourcesMEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017.Study eligibility criteriaRandomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis.ResultsOf 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract,Curcuma longaextract,Boswellia serrataextract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size −0.30, –0.42 to −0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high.ConclusionsThe overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either ineffective or showed small and arguably clinically unimportant treatment effects. Supplements had no clinically important effects on pain and function at medium-term and long-term follow-ups.