bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact on oncological outcomes after radical prostatectomy for prostate cancer of converting soft tissue margins at the apex and bladder neck from tumour‐positive to ‐negative
Authors: Pak Sahyun , Park Sejun , Kim Myong , Go Heounjeong , Cho Yong Mee , Ahn Hanjong
Published: July 2018

Objectives

To assess the impact of conversion from histologically positive to negative soft tissue margins at the apex and bladder neck on biochemical recurrence‐free survival (BCRFS) and distant metastasis‐free survival (DMFS) after radical prostatectomy (RP) for prostate cancer.

Materials and Methods

The records of 2 013 patients who underwent RP and intra‐operative frozen section (IFS) analysis between July 2007 and June 2016 were reviewed. IFS analysis of the urethra and bladder neck was performed, and if malignant or atypical cells remained, further resection with the aim of achieving histological negativity was carried out. Patients were divided into three groups according to the findings: those with a negative surgical margin (NSM), a positive surgical margin converted to negative (NCSM) and a persistent positive surgical margin (PSM).

Results

Among the 2 013 patients, rates of NSMs, NCSMs and PSMs were 75.1%, 4.9%, and 20.0%, respectively. The 5‐year BCRFS rates of patients with NSMs, NCSMs and PSMs were 89.6%, 85.1% and 57.1%, respectively (P < 0.001). In both pathological (p)T2 and pT3 cancers, the 5‐year BCRFS rate for patients with NCSMs was similar to that for patients with NSMs, and higher than for patients with PSMs. The 7‐year DMFS rates of patients with NSMs, NCSMs and PSMs were 97.8%, 99.1% and 89.4%, respectively (P < 0.001). Among patients with pT3 cancers, the 7‐year DMFS rate was significantly higher in the NCSM group than in the PSM group (98.0% vs 86.7%; P = 0.023), but not among those with pT2 cancers (100% vs 96.9%; P = 0.616). The 5‐year BCRFS rate for the NCSM group was not significantly different from that of the NSM group among the patients with low‐ (96.3% vs 95.8%) and intermediate‐risk disease (91.1% vs 82.8%), but was lower than that of the NSM group among patients in the high‐risk group (73.2% vs 54.7%).

Conclusions

Conversion of the soft tissue margin at the prostate apex and bladder neck from histologically positive to negative improved the BCRFS and DMFS after RP for prostate cancer; however, the benefit of conversion was not apparent in patients in the high‐risk group.
β3‐Adrenoceptor stimulation of perivascular adipocytes leads to increased fat cell‐derived NO and vascular relaxation in small arteries
Authors: Bussey Charlotte E , Withers Sarah B , Saxton Sophie N , Bodagh Neil , Aldous Robert G , Heagerty Anthony M
Published: July 2018

Background and Purpose

In response to noradrenaline, healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT‐derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the noradrenaline‐induced PVAT anticontractile effect.

Experimental Approach

In vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer.

Key Results

PVAT elicited an anticontractile effect in response to noradrenaline but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the β3‐adrenoceptor agonist, CL‐316243, reduced the vasoconstrictor effect of phenylephrine but not noradrenaline. Kv7 channel inhibition using XE 991 reversed the noradrenaline‐induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with noradrenaline and CL‐316243, but not phenylephrine, was associated with increased adipocyte‐derived NO production, and the contractile response to noradrenaline was augmented following incubation of exogenous PVAT with L‐NMMA. PVAT from eNOS−/− mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with noradrenaline stimulation implicating Gαs signalling in this process.

Conclusions and Implications

We have shown that adipocyte‐located β3‐adrenoceptor stimulation leads to activation of Gαs signalling pathways with increased cAMP and the release of adipocyte‐derived NO. This process is dependent upon Kv7 channel function. We conclude that adipocyte‐derived NO plays a central role in anticontractile activity when rodent PVAT is stimulated by noradrenaline.
MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25‐35‐induced anxiety and cognitive deficits in a mouse model
Authors: Huang Hei‐Jen , Huang Hsin‐Yu , Hsieh‐Li Hsiu Mei
Published: July 2018

Aims

Recently, histone deacetylase (HDAC) inhibitors are considered a possible therapeutic strategy in Alzheimer's disease (AD). However,HDACi treatments exhibit diverse functions with unfavorable effects inAD. Thus, the development of selectiveHDACi without side effects is urgently needed.

Methods

HDACi, namely,BML210,MGCD0103,PXD101, and Droxinostat, were screened in mouse hippocampal primary cultures incubated with oligomeric Aβ25‐35(50 μmol/L).MGCD0103 was chosen for in vivo tests and was intraperitoneally injected into C57BL/6J mice (0.5 mg/kg, once per day) for 4 weeks following an intrahippocampalCA1 injection of oligomeric Aβ25‐35. Brain samples were collected for pathological analyses after the behavioral analyses including open‐ field test (OFT), elevated plus maze (EPM), Y‐maze, and Morris water maze (MWM).

Results

Among theHDACi,MGCD0103 exhibited significant neuroprotection against the Aβ toxicity in primary cultures.MGCD0103 coattenuated cognitive deficits and anxiety against Aβ damage in mice.MGCD0103 further ameliorated pathological features such as the levels of acetylated histone 3 at Lys 9 site (H3K9) and α‐tubulin, synaptophysin, Aβ, tau protein phosphorylation, and serotonergic neuron loss against Aβ toxicity. Furthermore, chronicMGCD0103 treatment did not show liver or kidney toxicity in mice.

Conclusions

These results revealMGCD0103 could be a potential therapeutic agent againstAD.
Worth the wait: Children trade off delay and reward in self‐ and other‐benefiting decisions
Authors: Liu Shari , Gonzalez Gorana , Warneken Felix
Published: July 2018

Human prosocial behaviors are supported by early‐emerging psychological processes that detect and fulfill the needs of others. However, little is known about the mechanisms that enable children to deliver benefits to others at costs to the self, which requires weighing other‐regarding and self‐serving preferences. We used an intertemporal choice paradigm to systematically study and compare these behaviors in 5‐year‐old children. Our results show that other‐benefiting and self‐benefiting behavior share a common decision‐making process that integrates delay and reward. Specifically, we found that children sought to minimize delay and maximize reward, and traded off delays against rewards, regardless of whether these rewards were for the children themselves or another child. However, we found that children were more willing to invest their time to benefit themselves than someone else. Together, these findings show that from childhood, other‐ and self‐serving decisions are supported by a general mechanism that flexibly integrates information about the magnitude of rewards, and the opportunity costs of pursuing them. A video abstract of this article can be viewed at: https://youtu.be/r8S0DGe7f8Q
Differences in health outcomes associated with initial adherence to oral antidiabetes medications among veterans with uncomplicated Type 2 diabetes: a 5‐year survival analysis
Authors: Gatwood J. D. , Chisholm‐Burns M. , Davis R. , Thomas F. , Potukuchi P. , Hung A. , Kovesdy C. P.
Published: July 2018

Aim

To determine the association of adherence to oral antidiabetes medication with macrovascular and microvascular complications, time to insulin therapy, revascularization, admissions, and death among veterans with uncomplicated diabetes.

Methods

This was a retrospective cohort study using the Veterans Affairs Corporate Data Warehouse to examine 159 032 veterans diagnosed with uncomplicated diabetes during 2002–2014 and starting oral antidiabetes therapy for the first time. The first uncomplicated diabetes diagnosis was identified and confirmed by subsequent oral antidiabetes therapy initiation. Adherence was calculated from outpatient pharmacy records using the proportion of days covered over the first year of therapy. Health outcomes were observed up to 5 years beyond the first oral antidiabetes agent fill, and compared according to adherence status using Cox proportional hazards models adjusted for baseline demographic and clinical characteristics.

Results

During the first 5 years of oral antidiabetes treatment, people initially non‐adherent to oral antidiabetes therapy were more likely to experience myocardial infarction (hazard ratio 1.14, 95% CI 1.03–1.27) and ischaemic stroke (hazard ratio 1.22, 95% CI 1.05–0.1.42), or to die (hazard ratio 1.21; 95% CI 1.15–1.28). Veterans with <20% adherence to oral antidiabetes therapy in the first year had particularly high hazards for ischaemic stroke (hazard ratio 1.78, 95% CI 1.27–2.49) and all‐cause death (hazard ratio 1.33, 95% CI 1.17–151). Adherent people were more likely to be diagnosed with a microvascular complication or chronic kidney disease.

Conclusions

People who are non‐adherent to treatment were more likely to experience detrimental health outcomes within the first 5 years of antidiabetes therapy. Adherence is paramount to disease management and this should be stressed from the time at which treatment is initiated.
Linking Talent Management to Traditional and Boundaryless Career Orientations: Research Propositions and Future Directions
Authors: Crowley‐Henry Marian , Benson Emily T. , Al Ariss Akram
Published: July 2018

Talent management (TM) is a growing field that concentrates on optimizing human resources so that they provide a sustained competitive advantage to organizations. While successful TM practices are widely understood to include career development, the topics of careers and TM remain largely disconnected in the human resource management (HRM) literature. In this conceptual paper, we review the traditional and boundaryless career literature from a multi‐level perspective, in order to theoretically develop TM, which to date has been consistently described as under‐theorized. We contend that consideration of the functioning of careers within and across individual, network, organization, industry, occupation, and national/global structures is important when developing effective TM practices. To further understand the relationship between careers and TM, this paper develops researchable propositions for future studies, supported by the existing literature.
Spared CA1 pyramidal neuron function and hippocampal performance following antisense knockdown of microRNA‐134
Authors: Morris Gareth , Brennan Gary P. , Reschke Cristina R. , Henshall David C. , Schorge Stephanie
Published: July 2018

Objective

Inhibition of microRNA‐134 by an oligonucleotide antagomir (ant‐134) has been shown to produce powerful antiseizure effects in multiple models of epilepsy. However, to successfully translate the treatment to the clinic, it is important to assess what potential adverse effects it may have on naive brain tissue.

Methods

To investigate this, adult male Sprague‐Dawley rats were treated with either ant‐134 or a scrambled control sequence. Animals were later assessed for spatial navigation, before ex vivo slices were taken to assess the effects of microRNA‐134 knockdown on well‐defined measures of intrinsic and synaptic properties.

Results

Hippocampal field potential recordings determined that silencing of microRNA‐134 by ant‐134 injection was associated with a reduction in epileptiform activity following application of 9 mmol/L K+. Nevertheless, rats performed normally in the novel object location test. Action potential waveforms and miniature excitatory synaptic currents recorded in CA1 pyramidal neurons were unaffected by ant‐134.

Significance

These results demonstrate that ant‐134 confers a seizure‐protective effect without obvious interference with hippocampal neuronal properties or network function. These findings support further development of this novel approach to epilepsy treatment.
Combination of 5‐aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft‐versus‐host disease
Authors: Liu Chi , Yang Xue , Zhu Ping , Fujino Masayuki , Ito Hidenori , Takahashi Kiwamu , Nakajima Motowo , Tanaka Tohru , Wang Jiucun , Zhuang Jian , Zou Hejian , Li Xiao‐Kang
Published: July 2018

Scleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatological autoimmune disease affecting the skin, internal organs and blood vessels. There is at present no effective treatment for this condition. Our study investigated the effects of 5‐aminolevulinic acid (5‐ALA), which is a precursor of haem synthesis, on graft‐vs‐host disease (GvHD)‐induced SSc murine model. Lymphocytes were intravenously injected from donor mice (B10.D2) into recipient BALB/c mice (recombination‐activating gene 2 (Rag‐2)‐null mice) deficient in mature T and B cells to induce sclerodermatous GvHD (scl‐GvHD). To investigate the effect of 5‐ALA on scl‐GvHD, combination of 5‐ALA and sodium ferrous citrate (SFC) was orally administered to the recipient mice for 9 weeks. 5‐ALA/SFC treatment significantly reduced progressive inflammation and fibrosis in the skin and ears. Furthermore, 5‐ALA/SFC suppressed mRNA expression of transforming growth factor‐β, type I collagen and inflammatory cytokines. These results indicate that the 5‐ALA/SFC combination treatment has a protective effect against tissue fibrosis and inflammation in a murine scl‐GvHD‐induced skin and ear inflammation and fibrosis. Furthermore, the efficacy of 5‐ALA/SFC suggests important implications of HO‐1 protective activity in autoimmune diseases, and therefore, 5‐ALA/SFC may have promising clinical applications. These findings suggested that the 5‐ALA/SFC treatment may be the potential strategies for SSc.
“Celebrated, not just endured:” Rethinking Winter Cities
Authors: Stout Madeleine , Collins Damian , Stadler Sophie L. , Soans Ranon , Sanborn Emma , Summers Robert J.
Published: July 2018

A winter city is any urban centre that experiences a long, dark, cold, and/or snowy winter. The Winter Cities movement is a more precise concept, referring to cities taking an active role in becoming more appealing and functional in winter, primarily through physical interventions. The movement also has a social purpose, seeking to counter reclusion and “hibernation” in winter through greater use of the public realm. The movement is increasingly influential in policy, as part of a broader shift towards promoting livability and sustainability in cities. However, it has yet to receive sustained scholarly attention. This article brings the Winter City movement more fully into the academic sphere, describing its emergence, purpose, and key attributes, while also examining it critically for silences. Drawing on English‐ and German‐language publications, it places particular emphasis on the range of interventions and design approaches intended to promote greater use of outdoor public spaces, and an associated problematization of quasi‐public indoor environments.
Advantages, disadvantages and optimization of one‐stage and chromogenic factor activity assays in haemophilia A and B
Authors: Adcock D. M. , Strandberg K. , Shima M. , Marlar R. A.
Published: July 2018

Haemophilia A and B diagnosis and disease severity classification are determined on the basis of results from factor VIII (FVIII) and factor FIX (FIX) activity assays, respectively. These assays are also used for potency labelling, postinfusion monitoring of factor replacement products and testing for FVIII/FIX inhibitors. This review focuses on activated partial thromboplastin time (APTT)‐based one‐stage assays (OSAs) and two‐stage chromogenic substrate assays (CSAs). Currently, there is considerable inter‐laboratory variability in the results obtained using OSAs, which can be intensified in a reagent‐specific manner by the presence of the new modified recombinant factor replacement products that are entering the market. Furthermore, the use of CSAs, which tend to show less variability, especially with the new modified products, is recommended in a number of clinical scenarios. Clinical laboratories may, therefore, need to establish CSAs for routine use. In this review, we aim to improve understanding and help establish best practices by describing the methodology behind OSAs and CSAs and highlighting assay advantages and limitations. We argue that there can be value in offering both assay methodologies in clinical laboratories that contribute to the care of patients with haemophilia A or B. Educating both laboratory scientists and clinicians about the strengths and weaknesses of each type of assay will help to establish the necessary dialogue that is key to ensuring not only that the appropriate assays are used in the right clinical situations, but also that the results are interpreted correctly.
IPO underpricing in the second and main markets: The case of the London Stock Exchange
Authors: Acedo‐Ramírez Miguel Á. , Díaz‐Mendoza Ana C. , Ruiz‐Cabestre Francisco J.
Published: July 2018

This study contributes to a broader knowledge of initial public offerings (IPOs) underpricing in second and main markets. We analyse the particular case of the London Stock Exchange. In the second market, we distinguish between those companies that do not meet the main market listing requirements and those companies that, even though they meet the main market listing requirements, decide to float on the second market. The results show that there is less underpricing for firms that float on the main market than for companies listed on the second market regardless of whether those companies meet the main market listing requirements. Moreover, behind the underpricing, we find several variables related to firm and/or offering characteristics and market information and observe different behaviours in the explanatory variables for underpricing depending on the group to which the company belongs.
Effectiveness of high rate and delayed detection ICD programming by race: A MADIT‐RIT substudy
Authors: Jackson Larry R. , Thomas Kevin L. , Polonsky Bronislava , Zareba Wojciech , Lahiri Marc , Saba Samir , McNitt Scott , Schuger Claudio , Daubert James P. , Moss Arthur J. , Kutyifa Valentina
Published: July 2018

Introduction

Data on inappropriate and appropriate ICD therapy, and efficacy of ICD programing strategies by race are limited.

Methods

In MADIT‐RIT, we evaluated the risk of ICD therapy by race, and the efficacy of high rate cut‐off ventricular tachycardia (VT) zone ≥200 beats per minute (bpm) (Arm B), or 60 seconds delay in VT zone 170–199 bpm (Arm C), compared to 2.5 seconds delay at 170 bpm (Arm A) among black and white patients.

Results

MADIT‐RIT enrolled 272 (20%) black and 1119 (80%) white patients. The risk of inappropriate therapy was similar among blacks and whites, HR 1.25, 95% CI (0.82–1.93), P  =  0.30. High rate cut‐off or delayed VT therapy was associated with significant reductions in inappropriate therapy among whites, Arm B versus Arm A, HR 0.15, 95% CI (0.08–0.29), P < 0.0001, Arm C versus Arm A, HR 0.19, 95% CI (0.11–0.33), P < 0.001, and black individuals Arm B versus Arm A, HR 0.24, 95% CI (0.01–0.56), P  =  0.0001, Arm C versus Arm A, HR 0.30, 95% CI (0.13–0.68), P  =  0.004, P interaction > 0.10). However, delayed VT therapy was associated with a trend toward greater reduction in appropriate therapy in black individuals, HR 0.08, 95% CI (0.03–0.27), P < 0.0001 relative to white individuals, HR 0.27, 95% CI (0.16–0.43), P < 0.0001, P interaction  =  0.077.

Conclusion

In MADIT‐RIT, high rate and delayed detection ICD programming provided similar benefit with reductions in both inappropriate therapy and unnecessary appropriate therapy among black and white individuals.

Clinicaltrials.gov identifier

NCT00947310
EU Investors versus EU States: International Arbitration of Investment Disputes
Authors: Donaubauer Julian , Nunnenkamp Peter
Published: July 2018

Recent information on investor‐state dispute settlement, collected by UNCTAD, suggests that European investors are more litigious than non‐European investors. Most of the intra‐EU claims for financial compensation are directed at relatively poor respondent states in Central Europe. However, private investors win surprisingly few intra‐EU disputes. The appointment bias of arbitrators and the composition of tribunals appear to matter for the outcome of investor‐state dispute settlement.
Misidentification of istiophorid billfishes by fisheries observers raises uncertainty over stock status
Authors: Williams Samuel M. , Pepperell Julian G. , Bennett Michael , Ovenden Jennifer R.
Published: July 2018

We investigated whether commercially landed black marlin Istiompax indica were being misidentified by fisheries observers operating throughout the Pacific Ocean. Of 83 samples reported by observers as I. indica, 77% were genetically identified to be blue marlin Makaira nigricans and 2% to be striped marlin Kajikia audax. The high rate of misidentification by observers places considerable uncertainty over historic catch ratios of Indo‐Pacific marlin and stock assessments relying on the validity of these data.
Pain in labor assessed from two discomfort aspects: Physical pain intensity and psychological stress state
Authors: Iizuka Yukie , Masaoka Naoki , Ohashi Kazutomo
Published: July 2018

Aim

To assess two discomfort aspects of pain in labor, physical pain intensity and psychological stress state, we analyzed the association between the two parameters.

Methods

Twenty‐nine pregnant Japanese women with a singleton in 37–40 weeks of gestation were analyzed. Physical pain intensity was examined by the Numeric Rating Scale (NRS). Psychological stress state was measured by chromogranin A (CgA) in saliva. Data were collected thrice during labor (at 4–6 cm and 10 cm of cervical dilatation and immediately after delivery) and were accumulated from 4–6 cm and 10 cm of cervical dilatation. The study was approved by the Ethics Committees of Osaka University and Tokyo Women's Medical University.

Results

The median NRS score (10, IQR = 10–18) and the median CgA in saliva (8.0, IQR = 4.3–12.0) pmol/mg at 10 cm of cervical dilatation were significantly higher than those at the other two time points (P < 0.05). Although there were no correlations between NRS scores and concentrations of CgA in saliva at the three time points, there was a significant correlation between accumulated NRS and accumulated CgA in saliva (r = 0.68, P = 0.000). There was a significant difference in the accumulated NRS scores (P = 0.005) but not in the accumulated concentrations of CgA between primiparae and multiparae.

Conclusion

Women in labor perceived severe pain and psychological stress with similar patterns during labor. However, these parameters were independent and need to be measured to evaluate these two discomfort aspects.
Pain management of surgical abortion using transcutaneous acupoint electrical stimulation: An orthogonal prospective study
Authors: Wang Zedong , Chen Yong , Chen Chong , Zhao Liang , Chen Pinjie , Zeng Linchai , Xie Wenxia
Published: July 2018

Aim

This study aimed to evaluate the optimal combination of parameters for the management of pain during surgical abortion using transcutaneous acupoint electrical stimulation (TEAS).

Methods

This study recruited patients scheduled for surgical abortion between October 2014 and August 2015. The treatment protocol was created using three levels for each factor (stimulating time, acupoints, age, and parity). The primary outcomes were intraoperative visual analog scale (VAS), postoperative VAS, cervical relaxation degree and intraoperative blood loss. The secondary outcomes were the vital signs.

Results

Stimulation time was associated with intraoperative VAS scores (P < 0.001), acupoints were associated with postoperative VAS scores (P = 0.037), and age was associated with postoperative VAS scores (P < 0.043). Parity (P = 0.025) was associated with heart rate. A comprehensive analysis of the parameters revealed the best levels for each (stimulation time: from 15 min before operation to immediate postoperative; acupoints: SP 6 and LR 3; patient age 25.1–30.0 years; and parity: G≥2P0A≥1). Seven patients did not complete follow‐up. The remaining 135 subjects did not show continuous vaginal bleeding, abdominal pain, fever or any other adverse effect.

Conclusion

During surgical abortion, TEAS stimulation from 15 min before operation to immediate postoperative, SP 6 and LR 3, age 25.1–30.0 years and G≥2P0A≥1 were associated with the best analgesic effect.
Prediction of the efficacy of dinoprostone slow release vaginal insert (Propess) for cervical ripening: A prospective cohort study
Authors: Daykan Yair , Biron‐Shental Tal , Navve Daniella , Miller Netanella , Bustan Mor , Sukenik‐Halevy Rivka
Published: July 2018

Aim

To evaluate factors predictive of the success of dinoprostone slow release vaginal insert for cervical ripening.

Methods

A total of 169 women who underwent cervical ripening with dinoprostone slow release vaginal insert were included in the study cohort. The correlation between parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes were analyzed.

Results

Dinoprostone slow release vaginal insert was successful in achieving vaginal delivery in 148 of 169 (87.6%), while sufficient ripening was achieved in 140 (83%) cases. Factors associated with successful vaginal delivery were multiparity and younger gestational age at delivery. Factors predictive of the success of cervical ripening with dinoprostone slow release vaginal insert were lower body mass index (BMI), higher parity and perceived contractions prior to insertion. Intrauterine growth restriction was associated with a significant risk for dinoprostone insert removal. Neonatal outcomes were similar in cases of successful or failed ripening.

Conclusion

The success of cervical ripening with dinoprostone slow release vaginal insert can be predicted by factors that can be recognized at admission.
Pigment epithelium-derived factor: a key mediator in bone homeostasis and potential for bone regenerative therapy
Authors: Baxter-Holland Mia , Dass Crispin R
Published: July 2018

Objectives

Pigment epithelium-derived factor (PEDF), a multifunctional endogenous glycoprotein, has a very wide range of biological actions, notably in bone homeostasis. The question has been raised regarding the place of PEDF in the treatment of bone disorders and osteosarcoma, and its potential for tumour growth suppression.

Methods

The PubMed database was used to compile this review.

Key findings

Pigment epithelium-derived factor's actions in osteoid tissues include promoting mesenchymal stem cell commitment to osteoblasts, increasing matrix mineralisation, and promoting osteoblast proliferation. It shows potential to improve therapeutic outcomes in treatment of multiple cancer types and regrowth of bone after trauma or resection in animal studies. PEDF may possibly have a reduced adverse effect profile compared with current osteo-regenerative treatments; however, there is currently very limited evidence regarding the safety or efficacy in human models.

Pigment epithelium-derived factor is very active within the body, particularly in osseous tissue, and its physiological actions give it potential for treatment of both bone disorders and multiple tumour types. Further research is needed to ascertain the adverse effects and safety profile of PEDF as a therapeutic agent.
The morphogenetic approach and immanent causality: A spinozian perspective
Authors: Knio Karim
Published: July 2018

The morphogenetic approach as powered by analytical dualism offers an appealing account of the processes whereby people – through their reflexivities – reflect back on structures and cultures during the double and triple morphogenesis of agency. However, in order to further specify an account of social change, this paper argues that it would be helpful to provide an account of what occurs in the other direction as well: from the direction of structures and cultures, between each other and towards people, also at the points of double and triple morphogenesis of agency. This article is therefore a theoretical piece that proposes a reading of the morphogenetic model imbued with an enlightened understanding of immanent causality, driven by the Spinozian doctrine of parallelism and operationalized by his understanding of the two expressive roles of ideas.
Effects of deoxynivalenol exposure time and contamination levels on rainbow trout
Authors: Gonçalves Rui A. , Menanteau‐Ledouble Simon , Schöller Mélanie , Eder Alexander , Schmidt‐Posthaus Heike , Mackenzie Simon , El‐Matbouli Mansour
Published: July 2018

The trend toward using plant‐based ingredients in aquafeeds is set to intensify; however, mycotoxin contamination might be a challenge. Two diets, with deoxynivalenol (DON) levels of 1,166 μg/kg (1.1 DON) and 2,745 μg/kg (2.7 DON), were prepared for short‐term DON exposure (50 days). A third diet with a low DON level of 367 μg/kg (0.3 DON) was prepared for long‐term DON exposure (168 days). Ingestion of DON by trout during both short‐term/high‐dosage exposure (50 days; 1,166 μg/kg and 2,700 μg/kg DON) and long‐term/low‐dosage exposure (168 days; 367 μg/kg DON) impacted growth performance and, to a lesser extent, liver enzyme parameters (2.7 DON). Histopathology showed mild to moderate changes in the liver but not in the other sampled tissues (intestine and kidney). Despite these effects, short‐term exposure of rainbow trout to high doses of DON did not result in increased susceptibility to Yersinia ruckeri. In both the short‐ and long‐term studies, the effects of DON showed a high interindividual variability. The present study confirms that subclinical levels of mycotoxins affect rainbow trout. The effects of such low mycotoxin levels could be masked by other production challenges while still negatively affecting productivity.
Seed morphology and seed coat anatomy of Fraxinus, Ligustrum and Syringa (Oleeae: Oleaceae) and its systematic implications
Authors: Ghimire Balkrishna , Jeong Mi Jin , Suh Gang Uk , Heo Kweon , Lee Cheul Ho
Published: July 2018

We have carried out a morphological and anatomical study of the seeds of 19 taxa representing two subtribes and three genera of the tribe Oleeae (Fraxinus, Ligustrum, and Syringa) and two species of Forsythia (Forsythieae) using scanning electron and light microscopy to evaluate the usefulness of seed characteristics for the identification of systematic relationships. Considerable differences were found in seed coat morphology both among and within genera. Three types of seed coat pattern – reticulate, colliculate, and tuberculate – were recognized. The shape of the testa epidermal cells was either elongated rectangular or polygonal with smooth, striated, or infolded secondary ornamentations. The seed coat was thickest in Ligustrum spp. and thinnest in Syringa spp. The exotesta of Fraxinus species was discontinuous due to the presence of longitudinal grooves on its surface. Based on 22 seed morphological characters, cladistic analysis resolved three well‐supported clades that matched the three genera well, with Forsythia species considered as an outgroup. Ligustrum foliosum, with reticulate ornamentation, concave periclinal walls, and raised anticlinal walls, was the most distinct species within the genus, whereas the flat periclinal and sunken anticlinal walls in Syringa fauriei were unique in Syringa. Similarly, infolded secondary ornamentation was only observed in Fraxinus rhynchophylla var. densata. Although the investigated specimens represent a limited sample, the results provide valuable support for the characterization of several taxa, particularly at the species level. Moreover, surface ornamentation, epidermal cell shape, periclinal and anticlinal wall structure, and the nature and structure of the exotesta are shown to be potentially useful for cladistic analysis and for identification of species in this alliance.
Methanogenic Archaea dominate mature heartwood habitats of Eastern Cottonwood (Populus deltoides)
Authors: Yip Daniel Z. , Veach Allison M. , Yang Zamin K. , Cregger Melissa A. , Schadt Christopher W.
Published: July 2018

While recent reports demonstrate that the direct emission of methane from living tree trunks may be a significant terrestrial emission source, there has been debate whether tree emissions are due to transport from soils or produced in the wood environment itself. Reports of methanogens from wood of trees were prominent in the literature 40 years ago but have not been revisited with molecular ecology approaches.

We examined communities associated with Populus deltoides using rRNA gene sequence analyses and how these vary with tree and wood properties.

Our data indicate that wood environments are dominated by anaerobic microbiomes. Methanogens are prominent in heartwood (mean 34% relative abundance) compared to sapwood environments (13%), and dominant operational taxonomic units (OTUs) were classified as the Methanobacterium sp. Members of the Firmicutes phylum comprised 39% of total sequences and were in 42% greater abundance in sapwood over heartwood niches. Tree diameter was the strongest predictor of methanogen abundance, but wood moisture content and pH were also significant predictors of taxon abundance and overall community composition.

Unlike microbiomes of the soil, rhizosphere and phyllosphere, wood associated communities are shaped by unique environmental conditions and may be prominent and overlooked sources of methane emissions in temperate forest systems.
Leaf rehydration capacity: Associations with other indices of drought tolerance and environment
Authors: John Grace P. , Henry Christian , Sack Lawren
Published: July 2018

Clarifying the mechanisms of leaf and whole plant drought responses is critical to predict the impacts of ongoing climate change. The loss of rehydration capacity has been used for decades as a metric of leaf dehydration tolerance but has not been compared with other aspects of drought tolerance. We refined methods for quantifying the percent loss of rehydration capacity (PLRC), and for 18 Southern California woody species, we determined the relative water content and leaf water potential at PLRC of 10%, 25%, and 50%, and, additionally, the PLRC at important stages of dehydration including stomatal closure and turgor loss. On average, PLRC of 10% occurred below turgor loss point and at similar water status to 80% decline of stomatal conductance. As hypothesized, the sensitivity to loss of leaf rehydration capacity varied across species, leaf habits, and ecosystems and correlated with other drought tolerance traits, including the turgor loss point and structural traits including leaf mass per area. A new database of PLRC for 89 species from the global literature indicated greater leaf rehydration capacity in ecosystems with lower growing season moisture availability, indicating an adaptive role of leaf cell dehydration tolerance within the complex of drought tolerance traits.
Divine Foundationalism
Authors: Bohn Einar Duenger
Published: July 2018

Divine Foundationalism (DF) is the thesis that God is the existential source of all things apart from God hirself. In this paper, I provide some contemporary structure to a debate over DF. I first discuss what the thesis is more exactly, before I discuss some main arguments for and against it.
Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,
Authors: Ashwood Brennan , Pollum Marvin , Crespo‐Hernández Carlos E.
Published: July 2018

Sulfur‐substituted nucleobases (a.k.a., thiobases) are among the world's leading prescriptions for chemotherapy and immunosuppression. Long‐term treatment with azathioprine, 6‐mercaptopurine and 6‐thioguanine has been correlated with the photoinduced formation of carcinomas. Establishing an in‐depth understanding of the photochemical properties of these prodrugs may provide a route to overcoming these carcinogenic side effects, or, alternatively, a basis for developing effective compounds for targeted phototherapy. In this review, a broad examination is undertaken, surveying the basic photochemical properties and excited‐state dynamics of sulfur‐substituted analogs of the canonical DNA and RNA nucleobases. A molecular‐level understanding of how sulfur substitution so remarkably perturbs the photochemical properties of the nucleobases is presented by combining experimental results with quantum‐chemical calculations. Structure‐property relationships demonstrate the impact of site‐specific sulfur substitution on the photochemical properties, particularly on the population of the reactive triplet state. The value of fundamental photochemical investigations for driving the development of ultraviolet‐A chemotherapeutics is showcased. The most promising photodynamic agents identified thus far have been investigated in various carcinoma cell lines and shown to decrease cell proliferation upon exposure to ultraviolet‐A radiation. Overarching principles have been elucidated for the impact that sulfur substitution of the carbonyl oxygen has on the photochemical properties of the nucleobases.
Factors associated with additional time dental hygienists spent on educating patients with diabetes
Authors: Yuen Hon K.
Published: July 2018

Aims

To investigate what dental hygienists’ practice characteristics and oral health topics are associated with additional time dental hygienists spent on educating patients with diabetes.

Methods

A one‐page survey was mailed to 2237 registered dental hygienists in South Carolina. Survey questions focused on perceptions of dental hygienists regarding their oral health preventive education for patients with diabetes. After two follow‐up mails, we received 995 usable questionnaires.

Results

Multivariable logistic regression modeling showed dental hygienist respondents who spent additional time educating patients with diabetes about oral health felt they had adequately covered the topics on effects of periodontal disease related to diabetes, effects of uncontrolled diabetes on periodontal disease, and nutrition and dietary counseling. In addition, a higher number of patients with diabetes treated per week, and a shorter recall interval for patients were also associated with more likelihood of respondents spending additional time educating patients with diabetes.

Conclusion

Results suggest that the additional time that dental hygienist respondents spent on educating patients with diabetes was related to oral health issues associated with diabetes, not just repetition of routine oral hygiene and plaque control instructions.
Oxygen therapy improves cerebral oxygen delivery and neurovascular function in hypoxaemic chronic obstructive pulmonary disease patients
Authors: Hoiland Ryan L. , Mladinov Suzana , Barak Otto F. , Willie Christopher K. , Mijacika Tanja , Stembridge Mike , Dujic Zeljko , Ainslie Philip N.
Published: July 2018

New Findings

What is the central question of this study?

How does oxygen therapy influence cerebral blood flow, cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients?

What is the main finding and its importance?

Oxygen therapy improves cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients. This improvement in cerebral oxygen delivery and neurovascular function might provide a physiological link between oxygen therapy and a reduced risk of cerebrovascular disease (e.g. stroke, mild cognitive impairment and dementia) in chronic obstructive pulmonary disease.

We investigated the role of hypoxaemia in cerebral blood flow (CBF), oxygen delivery (CDO2) and neurovascular coupling (coupling of CBF to neural activity; NVC) in hypoxaemic chronic obstructive pulmonary disease (COPD) patients (n = 14). Resting CBF (duplex ultrasound), peripheral oxyhaemoglobin saturation (; pulse‐oximetry) and NVC (transcranial Doppler) were assessed before and after a 20 min wash‐in of supplemental oxygen (∼3 l min−1). The peripheral oxyhaemoglobin saturation increased from 91.0 ± 3.3 to 97.4 ± 3.0% (P < 0.01), whereas CBF was unaltered (593.0 ± 162.8 versus 590.1 ± 138.5 ml min−1; P = 0.91) with supplemental O2. In contrast, both CDO2 (98.1 ± 25.7 versus 108.7 ± 28.4 ml dl−1; P = 0.02) and NVC were improved. Specifically, the posterior cerebral artery cerebrovascular conductance was increased to a greater extent after O2 normalization (+40%, from 20.4 ± 9.9 to 28.0 ± 10.4% increase in conductance; P = 0.04), whereas the posterior cerebral artery cerebrovascular resistance decreased to a greater extent during O2 normalization (+22%, from −16.7 ± 7.3 to −21.4 ± 6.6% decrease in resistance; P = 0.04). The cerebral vasculature of COPD patients appears insensitive to oxygen, because CBF was unaltered in response to O2 supplementation leading to improved CDO2. In patients, the improvements in CDO2 and neurovascular function with supplemental O2 may underlie the cognitive benefits associated with O2 therapy.
Nano-optical imaging of monolayer MoSe2-WSe2 lateral heterostructure with subwavelength domains
Authors: Xue Wenjin , Sahoo Prasana K. , Liu Jiru , Zong Haonan , Lai Xiaoyi , Ambardar Sharad , Voronine Dmitri V.
Published: July 2018

Atomically thin two-dimensional (2D) transition metal dichalcogenides (TMDs) are the materials of recent interest to study the spatial confinement of charge carriers, photons, and phonons. Heterostructures based on TMD monolayers, especially composed of Mo and W, form type-II band alignment, and hence, the optically excited carriers can be easily separated for applications pertaining to optoelectronics. Mapping the spatially confined carriers or photons in lateral heterostructures with nanoscale resolution as well as their recombination behavior at the heterointerfaces is necessary for the effective use of 2D materials in optoelectronic devices. Near-field (NF) optical microscopy has been used as a viable route to understand the nanoscale material properties below the diffraction limit. The authors performed tip-enhanced photoluminescence (TEPL) imaging with a spatial resolution of 40 nm of multijunction monolayer MoSe2-WSe2 lateral heterostructures with subwavelength domains grown by chemical vapor deposition. Monolayer MoSe2 and WSe2 domains were identified by atomic force microscopy (AFM) through the topography and phase mapping. Far-field (FF) and NF techniques were used for the optical imaging of the WSe2 ↔ MoSe2 multijunction heterostructure correlated with AFM phase imaging. Near-field TEPL imaging was able to successfully distinguish the presence of distinct crystalline boundaries across the WSe2 ↔ MoSe2 interfaces in 2D lateral heterostructures with a higher spatial resolution, as compared to the far-field imaging, which failed to resolve the interfaces on one of the crystal sides due to the asymmetric FF excitation.
Acoustic characterization of exploration drilling in the Chukchi and Beaufort seas
Authors: Austin Melanie E. , Hannay David E. , Bröker Koen C.
Published: July 2018

This paper characterizes underwater sound levels produced by three drilling units during offshore exploration drilling at three sites in the Beaufort and Chukchi seas. Received levels and spectra are reported as functions of distance during drilling and excavation of mudline cellars (MLCs). Sound levels emitted during MLC excavation exceeded those during drilling at all three sites, although this operation was much shorter in duration. Drilling sounds exhibited tones below 2 kHz, with harmonics present to 10 kHz, while MLC excavation sounds were broadband in character. Drilling sounds varied substantially between the three operations, whereas MLC excavation sounds were more consistent in amplitude and spectral distribution. Estimates of broadband and 1/3-octave band source levels were computed from measurements at 1 km range. The broadband drilling source levels were 168.6 dB re 1 μPa m for the Kulluk drilling unit, 174.9 dB re 1 μPa m for the drillship Noble Discoverer, and 170.1 dB re 1 μPa m for the semi-submersible Polar Pioneer. The received levels measured at 1 km during MLC excavation yielded source level estimates that were more consistent among sources: 191.8, 193.0, and 193.3 dB re 1 μPa for the Discoverer, Kulluk, and Polar Pioneer, respectively.
A crossbar network for silicon quantum dot qubits
Authors: Li Ruoyu , Petit Luca , Franke David P. , Dehollain Juan Pablo , Helsen Jonas , Steudtner Mark , Thomas Nicole K. , Yoscovits Zachary R. , Singh Kanwal J. , Wehner Stephanie , Vandersypen Lieven M. K. , Clarke James S. , Veldhorst Menno
Published: July 2018

Quantum dots take a shortcut toward practical quantum information.
Revisiting IL-2: Biology and therapeutic prospects
Authors: Abbas Abul K. , Trotta Eleonora , R. Simeonov Dimitre , Marson Alexander , Bluestone Jeffrey A.
Published: July 2018

Deeper insights into the biology of interleukin-2 and its receptors are leading to therapeutic strategies for selective T
reg
stimulation.
Celebrating twoness at
Science Immunology
Authors: Williams Ifor R.
Published: July 2018

Science Immunology
’s second anniversary invites a pause for editorial reflections.
cROSs-presentation in pDCs: An energetic (m)CAT and mouse game
Authors: Joshi Sunil , Pillai Asha
Published: July 2018

pDC cross-presentation of antigens to CD8
+
T cells depends on mitochondrial generation of reactive oxygen species.
Multiclonal Expansion and High Prevalence of β-Lactamase-Negative Haemophilus influenzae with High-Level Ampicillin Resistance in Japan and Susceptibility to Quinolones
Authors: Honda Hiroyuki , Sato Toyotaka , Shinagawa Masaaki , Fukushima Yukari , Nakajima Chie , Suzuki Yasuhiko , Shiraishi Tsukasa , Kuronuma Koji , Takahashi Satoshi , Takahashi Hiroki , Yokota Shin-ichi
Published: July 2018

β-Lactam-resistant
Haemophilus influenzae
is a clinical concern. A high prevalence (>40%) of β-lactamase-negative high-level ampicillin-resistant
H. influenzae
(high-BLNAR) isolates in Japan has been reported.
The Fungal Cyp51 Inhibitor VT-1129 Is Efficacious in an Experimental Model of Cryptococcal Meningitis
Authors: Wiederhold Nathan P. , Najvar Laura K. , Garvey Edward P. , Brand Stephen R. , Xu Xin , Ottinger Elizabeth A. , Alimardanov Asaf , Cradock Jim , Behnke Mark , Hoekstra William J. , Schotzinger Robert J. , Jaramillo Rosie , Olivo Marcos , Kirkpatrick William R. , Patterson Thomas F.
Published: July 2018

Cryptococcal meningitis is a significant cause of morbidity and mortality in immunocompromised patients. VT-1129 is a novel fungus-specific Cyp51 inhibitor with potent
in vitro
activity against
Cryptococcus
species.
A Lytic Bacteriophage for Controlling Pseudomonas lactis in Raw Cow's Milk
Authors: Tanaka Chikage , Yamada Kohsuke , Takeuchi Honami , Inokuchi Yoshio , Kashiwagi Akiko , Toba Takahiro
Published: July 2018

Suppression of bacterial growth in raw milk under cold storage is crucial for the quality control of commercially supplied milk. The use of lytic phages as low-cost microbicides is an attractive prospect. Due to strict host specificities, phages must be isolated from the raw milk where the host bacteria are growing. We first isolated the
P. lactis
bacterial strain and then the phage infecting that strain. Partial phage genomic analysis showed that this is a newly isolated phage, different from any previously reported. This study reports a lytic phage for
P. lactis
, and we have presented evidence here that this phage reduced viable bacterial cell counts not only in rich medium but also in skim and whole milk. As a result, we have concluded that the phage reported in this study would be useful in milk processing.