bluuebunny/crossref_metadata_2025 huggingface dataset:
Gentle Perineal Skin Stimulation for Control of Nocturia
Authors: Hotta Harumi , Watanabe Nobuhiro
Published: April 2019

One of the major causes of nocturia is overactive bladder (OAB). Somatic afferent nerve stimuli are used for treating OAB. However, clinical evidence for the efficacy of this treatment is insufficient due to the lack of appropriate control stimuli. Studies on anesthetized animals, which eliminate emotional factors and placebo effects, have demonstrated an influence of somatic stimuli on urinary bladder functions and elucidated the underlying mechanisms. In general, the effects of somatic stimuli are dependent on the modality, location, and physical characteristics of the stimulus. Recently we showed that gentle stimuli applied to the perineal skin using a soft elastomer roller inhibited micturition contractions to a greater extent than a roller with a hard surface. Studies aiming to elucidate the neural mechanisms of gentle stimulation‐induced inhibition reported that 1–10 Hz discharges of low‐threshold cutaneous mechanoreceptive Aβ, Aδ, and C fibers evoked during stimulation with an elastomer roller inhibited the micturition reflex by activating the spinal cord opioid system, thereby reducing both ascending and descending transmission between bladder and pontine micturition center. The present review will provide a brief summary of (1) the effect of somatic electrical stimulation on the micturition reflex, (2) the effect of gentle mechanical skin stimulation on the micturition reflex, (3) the afferent, efferent, and central mechanisms underlying the effects of gentle stimulation, and (4) a translational clinical study demonstrating the efficacy of gentle skin stimuli for treating nocturia in the elderly with OAB by using the two roller types inducing distinct effects on rat micturition contractions. Anat Rec, 302:1824–1836, 2019. © 2019 American Association for Anatomy
Modeling the online health information seeking process: Information channel selection among university students
Authors: Sbaffi Laura , Zhao Chen
Published: April 2019

This study investigates the influence of individual and information characteristics on university students' information channel selection (that is, search engines, social question & answer sites, online health websites, and social networking sites) of online health information (OHI) for three different types of search tasks (factual, exploratory, and personal experience). Quantitative data were collected via an online questionnaire distributed to students on various postgraduate programs at a large UK university. In total, 291 responses were processed for descriptive statistics, Principal Component Analysis, and Poisson regression. Search engines are the most frequently used among the four channels of information discussed in this study. Credibility, ease of use, style, usefulness, and recommendation are the key factors influencing users' judgments of information characteristics (explaining over 62% of the variance). Poisson regression indicated that individuals' channel experience, age, student status, health status, and triangulation (comparing sources) as well as style, credibility, usefulness, and recommendation are substantive predictors for channel selection of OHI.
Catalytic C−H Borylation Using Iron Complexes Bearing 4,5,6,7‐Tetrahydroisoindol‐2‐ide‐Based PNP‐Type Pincer Ligand
Authors: Kato Takeru , Kuriyama Shogo , Nakajima Kazunari , Nishibayashi Yoshiaki
Published: April 2019

Catalytic C−H borylation has been reported using newly designed iron complexes bearing a 4,5,6,7‐tetrahydroisoindol‐2‐ide‐based PNP pincer ligand. The reaction tolerated various five‐membered heteroarenes, such as pyrrole derivatives, as well as six‐membered aromatic compounds, such as toluene. Successful examples of the iron‐catalyzed sp3 C−H borylation of anisole derivatives were also presented.
Lipophilicity and bio‐mimetic properties determination of phytoestrogens using ultra‐high‐performance liquid chromatography
Authors: Lasić Kornelija , Bokulić Ana , Milić Astrid , Nigović Biljana , Mornar Ana
Published: April 2019

This paper presents lipophilicity and bio‐mimetic property determination of 15 phytoestrogens, namely biochanin A, daidzein, formononetin, genistein, genistein‐4,7‐dimethylether, prunetin, 3,4,7‐trihydroxyisoflavon, 4,6,7‐trihydroxyisoflavon, 4,6,7‐trimethoxyisoflavon, daidzin, genistin, ononin, sissotrin, coumestrol and coumestrol dimethylether. High‐performance liquid chromatography with fast gradient elution and Caco‐2 cell line were used to determine the physicochemical properties of selected phytoestrogens. Lipophilicity was determined on octadecyl‐sylane stationary phase using pH 2.0 and pH 7.4 buffers. Immobilized artificial membrane chromatography was used for prediction of interaction with biological membranes. Protein binding was measured on human serum albumin and α‐1‐acid‐glycoprotein (AGP) stationary phases. Caco‐2 assay was used as a gold standard for assessing in vitro permeability. The obtained results differentiate phytoestrogens according to their structure where aglycones show significantly higher lipophilicity, immobilized artificial membrane partitioning, AGP binding and Caco‐2 permeability compared with glucosides. However, human serum albumin binding was very high for all investigated compounds. Furthermore, a good correlation between experimentally obtained chromatographic parameters and in silico prediction was obtained for lipophilicity and human serum albumin binding, while the somewhat greater difference was obtained for AGP binding and Caco‐2 permeability.
A clinical case–control comparison of epidermal innervation density in Rett syndrome
Authors: Symons Frank J. , Barney Chantel C. , Byiers Breanne J. , McAdams Brian D. , Foster Shawn X. Y. L. , Feyma Timothy J. , Wendelschafer‐Crabb Gwen , Kennedy William R.
Published: April 2019

Introduction

Rett syndrome (RTT), a rare neurodevelopmental disorder occurring primarily in females (1:10–15,000 female live births), is most often caused by loss‐of‐function mutations in the X‐linked methyl‐CpG‐binding protein 2 gene (MECP2). Clinical observations and preclinical findings indicate apparent abnormal sensory and nociceptive function. There have been no direct investigations of epidermal sensory innervation in patients with RTT.

Methods

We compared 3 mm epidermal punch biopsy specimens from adolescent female RTT patients (N = 4, aged 12–19 years) against an archived approximate age‐, sex‐, body‐site matched comparison sample of healthy adolescent females (N = 8, ages 11–17).

Results

Confocal imaging revealed, on average, statistically significant increased epidermal nerve fiber (ENF) peptidergic (co‐stained calcitonin gene‐related protein [CGRP]) innervation density compared with healthy female control individuals.

Conclusions

Given the clinical phenotype of disrupted sensory function along with diagnostic criteria specific to cold hands/feet and insensitivity to pain, our preliminary observations of ENF peptidergic fiber density differences warrants further investigation of the peripheral neurobiology in RTT.
Association of Pollinators of Different Species of Oil Palm with the Metabolic Profiling of Volatile Organic Compounds
Authors: Alves Filho Elenilson G. , Brito Rafaela S. , Rodrigues Tigressa Helena S. , Silva Lorena Mara A. , de Brito Edy S. , Canuto Kirley M. , Krug Cristiane , Zocolo Guilherme J.
Published: April 2019

The development of studies on emissions of volatile organic compounds (VOCs) by inflorescence of oil palms deserves a special attention regarding the importance to reproduction success and for increase of production. This study aimed to evaluate metabolic profiling of VOCs expelled by male and female inflorescences of different oil palm species (African oil palm, Amazonian Caiaué and the interspecific hybrid BRS‐Manicoré), associating the composition variability with main pollinators to improve the comprehension of the plant−insect relationship. The phenylpropanoids, terpenoids and the aliphatic hydrocarbons were predominant classes detected in inflorescences of oil palms and the major compound was estragole. This result may be correlated with attraction of Elaidobius pollinators, since these insects were not attracted by Caiaué, which emitted estragole only in trace amounts. However, Caiaué and the hybrid species were visited by other native species whose frequencies were low and their success as pollinators could not be expected.
Synthesis and Biochemical Evaluation of an Artificial, Fluorescent Glucosinolate (GSL)
Authors: Glindemann Carina Patrizia , Backenköhler Anita , Strieker Matthias , Wittstock Ute , Klahn Philipp
Published: April 2019

The synthesis of the first example of a fluorescent glucosinolate (GSL)–BODIPY conjugate based on an azide‐containing artificial GSL precursor (GSL‐N3) is reported. Biochemical evaluation of the artificial GSLs revealed that the compounds are converted to the corresponding isothiocyanates in the presence of myrosinase. Furthermore, myrosinase‐catalyzed hydrolysis in the presence of plant specifier proteins yielded the expected alternative products, namely nitriles. The easy assembly of the fluorescent GSL–BODIPY conjugate by click chemistry from GSL‐N3 holds potential for application as a fluorescence labeling tool to investigate GSL‐associated processes.
Construction of Pd/BiOCl Catalyst for Highly‐selective Synthesis of Benzoin Ethyl Ether by Chlorine Promoted Coupling Reaction
Authors: Yuan Qinglin , Gong Wanbing , Ye Yixing , Liu Jun , Lin Yue , Chen Chun , Zhang Haimin , Li Pengfei , Cheng Weiren , Wei Xiangjun , Liang Changhao
Published: April 2019

Exploring novel catalyst supports with unique performance creates more opportunity for transforming organic chemicals in heterogeneous catalysis. In this paper, BiOCl is first presented as an effective support for Pd nanoparticles (NPs) toward application in the coupling reaction of benzaldehyde. The Cl− ion dissociates from BiOCl, which forms nucleophile with Pd nanoparticles; this is key for the one‐step synthesis of benzoin ethyl ether, the conversion and selectivity of which can reach to 100 % and 97.9 % at 100 °C, respectively. DFT calculations reveal that Cl− ions can be stabilized by stronger Bi−Cl bonds through doping of Fe ions in substituting Bi sites in BiOCl. The parallel catalytic evaluation using Pd/Fe‐doped BiOCl catalyst shows the suppression of coupling reaction, conversely, demonstrating the crucial role of nucleophile. This work provides new insights into support tailoring for the synthesis of vital organic chemicals in heterogeneous catalysis by changing chemical reaction pathway.
Tape casting of preceramic polymers toward advanced ceramics: A review
Authors: Hotza Dachamir , Nishihora Rafael K. , Machado Ricardo A. F. , Geffroy Pierre‐Marie , Chartier Thierry , Bernard Samuel
Published: April 2019

In the last 20 years, tape casting, a standard wet‐shaping process to produce thin ceramics, has been applied to manufacture polymer‐derived ceramics (PDCs). Si‐based polymers, such as polysiloxanes and polysilazanes, also known as preceramic polymers (PCPs), have been used as precursors/binders replacing conventional raw materials and additives for tape casting process. Thermal processing of PCPs is carried out at lower temperatures in comparison with classical ceramic sintering, particularly of carbides and nitrides. Furthermore, polymeric precursors can be converted into hybrid or composite ceramics, when parts of the polymers remain unreacted. Inert or reactive fillers might be used to reduce both shrinkage and porosity inherently caused by the weight loss occurring during polymer pyrolysis while forming new ceramic phases in the final materials. Alternatively, pore formers might also be added to tailor pore shape, connectivity, and volume (macroporosity). Nevertheless, current equipment and process parameters for tape casting‐based products must be eventually adjusted to fit the characteristics of ceramic precursors. Therefore, the aim of this review is focused on listing and discussing the efforts to produce PDCs using tape casting as a shaping technique. Interactions of system components and effects of treatment, particularly thermal stages, on final microstructure and properties are stressed out. Gaps in the literature concerning processing optimization are pointed out, and suggestions are given for further development of PDCs produced by tape casting.
Putting a New Spin on It: Gradient Centrifugation for Analytical and Preparative Applications
Authors: Spinnrock Andreas , Cölfen Helmut
Published: April 2019

Gradient centrifugation is an important technique in chemistry, biology, materials science and engineering. It has big potential beyond the well‐known centrifugation for separation of molecules and particles. Various possibilities for special analysis and separation of particles, but also preparative applications like the production of gradient materials and controlled polymerizations exist. In all examples, a gradient of physical and/or chemical properties is generated by centrifugation and used for the further application. In this Concept article, selected examples of gradient centrifugation are presented, to show important developments in the field and discuss their applications, potential, and limitations. It concludes by analysing future trends of gradient centrifugation that are relevant for academic and industrial usage.
Two‐Photon‐Induced CO‐Releasing Molecules as Molecular Logic Systems in Solution, Polymers, and Cells
Authors: Ramu Vadde , Upendar Reddy Gandra , Liu Jingjing , Hoffmann Patrick , Sollapur Rudrakant , Wyrwa Ralf , Kupfer Stephan , Spielmann Christian , Bonnet Sylvestre , Neugebauer Ute , Schiller Alexander
Published: April 2019

Phototherapeutic applications of carbon monoxide (CO)‐releasing molecules are limited because they require harmful UV and blue light for activation. We describe two‐photon excitation with NIR light (800 nm)‐induced CO‐release from two MnI tricarbonyl complexes bearing 1,8‐naphthalimide units (1, 2). Complex 2 behaves as a logic OR gate in solution, nonwovens, and in HeLa cells. CO release, indicated by fluorescence enhancement, was detected in solution, nonwoven, and HeLa cells by single‐ (405 nm) and two‐photon (800 nm) excitation. The photophysical properties of 1 and 2 have been measured and supported by DFT and TDDFT quantum chemical calculations. Both photoCORMs are stable in the dark in solution and noncytotoxic, leading to promising applications as phototherapeutics with NIR light.
Near‐Infrared Circularly Polarized Luminescence through Intramolecular Excimer Formation of Oligo(p‐phenyleneethynylene)‐Based Double Helicates
Authors: Miki Koji , Noda Takeru , Gon Masayuki , Tanaka Kazuo , Chujo Yoshiki , Mizuhata Yoshiyuki , Tokitoh Norihiro , Ohe Kouichi
Published: April 2019

Carbon‐based double helicates consisting of two anthracene‐containing oligo(p‐phenyleneethynylene) units and two flexible chiral 1,1′‐binaphthyl units or two rigid chiral 9,9′‐spirobifluorene units were developed. The curved oligo(p‐phenyleneethynylene) fragments in the double helicates were successfully constructed by tin‐mediated reductive aromatization. Helical oligo(p‐phenyleneethynylene) double strands fixed by two rigid spirobifluorene units showed little structural change under photoirradiation, thereby emitting circularly polarized luminescence (CPL) in the visible region with a high quantum yield (ΦPL=0.93). In contrast, flexible binaphthyl units induced dynamic structural change of the oligo(p‐phenyleneethynylene) luminophores under photoirradiation, leading to strong CPL (|glum|=1.1×10−2) in the near‐infrared (NIR) region. UV/Vis, circular dichroism (CD), CPL and NMR spectroscopic analyses of the binaphthyl‐hinged double helicate suggested excimer formation between two π‐conjugated strands in the excited state. Theoretical calculations highlight the importance of the tightly interlocked excimer structure of the carbon‐based double helicate in controlling the angle between the electric and magnetic transition dipole moments for strong NIR CPL generation.
Photogenerated Neutral Nitrogen Radical Catalyzed Bifunctionalization of Alkenes
Authors: Zhao Quan‐Qing , Chen Jun , Zhou Xue‐Song , Yu Xiao‐Ye , Chen Jia‐Rong , Xiao Wen‐Jing
Published: April 2019

Alkene bifunctionalizations are powerful tools for the rapid construction of structurally complex and valuable scaffolds, and such reactions typically involve the use of transition‐metal catalysts or organocatalysts. Here, we report for the first time a photogenerated neutral nitrogen radical catalyzed intermolecular alkene bifunctionalization by using allyl sulfones as the source of both the carbon and the sulfone functionalities under mild conditions. The key to the success of this protocol involves the visible‐light‐mediated photocatalytic in situ generation of a nitrogen‐centered radical from the N‐(2‐acetylphenyl) benzenesulfonamide catalyst, and its activation of the allyl sulfones to generate reactive species. The preliminary control experiments supported the postulated mechanism.
Price bias and common practice in option pricing
Authors: Bégin Jean‐François , Gauthier Geneviève
Published: April 2019

Generally, the semiclosed‐form option pricing formula for complex financial models depends on unobservable factors such as stochastic volatility and jump intensity. A popular practice is to use an estimate of these latent factors to compute the option price. However, in many situations this plug‐and‐play approximation does not yield the appropriate price. This article examines this bias and quantifies its impacts. We decompose the bias into terms that are related to the bias on the unobservable factors and to the precision of their point estimators. The approximated price is found to be highly biased when only the history of the stock price is used to recover the latent states. This bias is corrected when option prices are added to the sample used to recover the states' best estimate. We also show numerically that such a bias is propagated on calibrated parameters, leading to erroneous values. The Canadian Journal of Statistics 48: 8–35; 2020 © 2019 Statistical Society of Canada
Family communication and patient distress after germline genetic testing in individuals with pancreatic ductal adenocarcinoma
Authors: Peters Mary Linton B. , Stobie Lindsey , Dudley Beth , Karloski Eve , Allen Kyle , Speare Virginia , Dolinsky Jill S. , Tian Yuan , DeLeonardis Kim , Krejdovsky Jill , Button Arlene , Lim Cynthia , Borazanci Erkut , Brand Randall , Tung Nadine
Published: April 2019

Background

Germline genetic testing currently is recommended for patients with pancreatic ductal adenocarcinoma (PDAC). In the current study, the authors assessed how often results are communicated to first‐degree relatives within 3 months and the emotional impact of testing on patients.

Methods

A total of 148 patients who were newly diagnosed with PDAC and who had undergone testing of 32 cancer susceptibility genes at 3 academic centers were selected; 71% participated. Subjects completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) and a family communication survey. The results of both surveys were assessed at 3 months according to the genetic test result (positive, negative, or variant of unknown significance [VUS]) and whether a patient met criteria for genetic testing.

Results

A total of 99 patients completed the MICRA survey and 104 completed the family communication survey. The average age of the patients was 67 years, 47% were female, 29% had stage III/IV (AJCC 8th edition) disease, and 42% met genetic testing criteria. Approximately 80% of patients told at least 1 first‐degree relative about their result. There was a trend toward greater disclosure among patients who tested positive (93% vs 77% for those with a VUS result [P = .149] and 74% for those who tested negative [P = .069]). Patients not meeting genetic testing criteria were less likely to disclose results (69% vs 93%; P = .003). MICRA scores did not differ by test result, age, stage of disease, or sex.

Conclusions

The rate of result communication was high, although it was lower among patients who did not meet genetic testing criteria, those who tested negative, or those who had a VUS result. Testing‐associated distress was similar across patient groups, and was comparable to that reported by other patients with cancer. Improved communication for all patients is crucial given the prognosis of PDAC, which limits time for disclosure.
Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013
Authors: Shiels Meredith S. , Engels Eric A. , Yanik Elizabeth L. , McGlynn Katherine A. , Pfeiffer Ruth M. , O’Brien Thomas R.
Published: April 2019

Background

In the United States, incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in older individuals. Chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) are important causes of HCC; however, the contribution of viral hepatitis to recent trends in HCC incidence among older Americans is unclear.

Methods

Data from the Surveillance, Epidemiology, and End Results–Medicare linkage (SEER‐Medicare) for the years 2001 through 2013 were used to identify HCC cases among individuals aged ≥66 years and Medicare files were used to assess the HCV and HBV status of these HCC cases. Age‐standardized incidence rates of HCV‐attributable, HBV‐attributable, and HCV/HBV‐unrelated HCC were estimated overall and by age group, sex, and race/ethnicity. The authors also calculated annual percent changes (APCs) in HCC incidence.

Results

Between 2001 and 2013, a total of 15,300 HCC cases occurred in this population. Overall HCC rates increased 43% from 16.3 to 23.3 per 100,000 population (APC, 3.40% per year), whereas HCV‐attributable HCC rates nearly doubled from 4.2 to 8.2 per 100,000 population (APC, 5.62% per year). HCC rates increased more slowly for HBV‐attributable HCC (1.3 to 1.8 per 100,000 population; APC, 3.17% per year) and HCV/HBV‐unrelated HCC (11.3 to 14.1 per 100,000 population; APC, 2.35% per year). The percentage of HCC cases with evidence of HCV infection increased from 25.7% in 2001 through 2004 to 32.3% in 2011 through 2013, whereas the percentage with HBV remained stable at 8%. In 2013, higher rates for both HCV‐attributable and HBV‐attributable HCC were noted among individuals aged 66 to 75 years, men, and individuals of Asian ancestry.

Conclusions

Among Americans aged ≥66 years, HCC rates increased rapidly between 2001 and 2013. Although HCV‐attributable cases contributed substantially to this increase, rates of HBV‐attributable and HCV/HBV‐unrelated HCC also rose during this period.
Central connections of the trigeminal motor command system in the weakly electric Elephantnose fish (Gnathonemus petersii)
Authors: Amey‐Özel Monique , Anders Stefanie , Grant Kirsty , von der Emde Gerhard
Published: April 2019

The highly mobile chin appendage of Gnathonemus petersii, the Schnauzenorgan, is used to actively probe the environment and is known to be a fovea of the electrosensory system. It receives an important innervation from both the trigeminal sensory and motor systems. However, little is known about the premotor control pathways that coordinate the movements of the Schnauzenorgan, or about central pathways originating from the trigeminal motor nucleus. The present study focuses on the central connections of the trigeminal motor system to elucidate premotor centers controlling Schnauzenorgan movements, with particular interest in the possible connections between the electrosensory and trigeminal systems. Neurotracer injections into the trigeminal motor nucleus revealed bilateral, reciprocal connections between the two trigeminal motor nuclei and between the trigeminal sensory and motor nuclei by bilateral labeling of cells and terminals. Prominent afferent input to the trigeminal motor nucleus originates from the nucleus lateralis valvulae, the nucleus dorsalis mesencephali, the cerebellar corpus C1, the reticular formation, and the Raphe nuclei. Retrogradely labeled cells were also observed in the central pretectal nucleus, the dorsal anterior pretectal nucleus, the tectum, the ventroposterior nucleus of the torus semicircularis, the gustatory sensory and motor nuclei, and in the hypothalamus. Labeled terminals, but not cell bodies, were observed in the nucleus lateralis valvulae and the reticular formation. No direct connections were found between the electrosensory system and the V motor nucleus but the central connections identified would provide several multisynaptic pathways linking these two systems, including possible efference copy and corollary discharge mechanisms.
Open and Reproducible Research on Open Science Framework
Authors: Sullivan Ian , DeHaven Alexander , Mellor David
Published: April 2019

By implementing more transparent research practices, authors have the opportunity to stand out and showcase work that is more reproducible, easier to build upon, and more credible. Scientists gain by making work easier to share and maintain within their own laboratories, and the scientific community gains by making underlying data or research materials more available for confirmation or making new discoveries. The following protocol gives authors step‐by‐step instructions for using the free and open source Open Science Framework (OSF) to create a data management plan, preregister their study, use version control, share data and other research materials, or post a preprint for quick and easy dissemination. © 2019 by John Wiley & Sons, Inc.
Loss of function of Kmt2d, a gene mutated in Kabuki syndrome, affects heart development in Xenopus laevis
Authors: Schwenty‐Lara Janina , Nürnberger Annika , Borchers Annette
Published: April 2019

Background

Kabuki syndrome is a haploinsufficient congenital multi‐organ malformation syndrome, which frequently includes severe heart defects. Mutations in the histone H3K4 methyltransferase KMT2D have been identified as the main cause of Kabuki syndrome, however, the role of KMT2D in heart development remains to be characterized.

Results

Here we analyze the function of Kmt2d at different stages of Xenopus heart development. Xenopus Kmt2d is ubiquitously expressed at early stages of cardiogenesis, with enrichment in the anterior region including the cardiac precursor cells. Morpholino‐mediated knockdown of Kmt2d led to hypoplastic hearts lacking the three‐chambered structure. Analyzing different stages of cardiogenesis revealed that development of the first and second heart fields as well as cardiac differentiation were severely affected by loss of Kmt2d function.

Conclusion

Kmt2d loss of function in Xenopus recapitulates the hypoplastic heart defects observed in Kabuki syndrome patients and shows that Kmt2d function is required for the establishment of the primary and secondary heart fields. Thus, Xenopus Kmt2d morphants can be a valuable tool to elucidate the etiology of the congenital heart defects associated with Kabuki syndrome.
The role of endothelial cilia in postembryonic vascular development
Authors: Elworthy Stone , Savage Aaron M. , Wilkinson Robert N. , Malicki Jarema J. , Chico Timothy J.A.
Published: April 2019

Abstrct

Background

Cilia are essential for morphogenesis and maintenance of many tissues. Loss‐of‐function of cilia in early Zebrafish development causes a range of vascular defects, including cerebral hemorrhage and reduced arterial vascular mural cell coverage. In contrast, loss of endothelial cilia in mice has little effect on vascular development. We therefore used a conditional rescue approach to induce endothelial cilia ablation after early embryonic development and examined the effect on vascular development and mural cell development in postembryonic, juvenile, and adult Zebrafish.

Results

ift54(elipsa)‐mutant Zebrafish are unable to form cilia. We rescued cilia formation and ameliorated the phenotype of ift54 mutants using a novel Tg(ubi:loxP‐ift54‐loxP‐myr‐mcherry,myl7:EGFP)sh488 transgene expressing wild‐type ift54 flanked by recombinase sites, then used a Tg(kdrl:cre)s898 transgene to induce endothelial‐specific inactivation of ift54 at postembryonic ages. Fish without endothelial ift54 function could survive to adulthood and exhibited no vascular defects. Endothelial inactivation of ift54 did not affect development of tagln‐positive vascular mural cells around either the aorta or the caudal fin vessels, or formation of vessels after tail fin resection in adult animals.

Conclusions

Endothelial cilia are not essential for development and remodeling of the vasculature in juvenile and adult Zebrafish when inactivated after embryogenesis.
Ecosystem service change caused by climatological and non‐climatological drivers: a Swiss case study
Authors: Braun Daniela , de Jong Rogier , Schaepman Michael E. , Furrer Reinhard , Hein Lars , Kienast Felix , Damm Alexander
Published: April 2019

Understanding the drivers of ecosystem change and their effects on ecosystem services are essential for management decisions and verification of progress towards national and international sustainability policies (e.g., Aichi Biodiversity Targets, Sustainable Development Goals). We aim to disentangle spatially the effect of climatological and non‐climatological drivers on ecosystem service supply and trends. Therefore, we explored time series of three ecosystem services in Switzerland between 2004 and 2014: carbon dioxide regulation, soil erosion prevention, and air quality regulation. We applied additive models to describe the spatial variation attributed to climatological (i.e., temperature, precipitation and relative sunshine duration) and non‐climatological drivers (i.e., random effects representing other spatially structured processes) that may affect ecosystem service change. Obtained results indicated strong influences of climatological drivers on ecosystem service trends in Switzerland. We identified equal contributions of all three climatological drivers on trends of carbon dioxide regulation and soil erosion prevention, while air quality regulation was more strongly influenced by temperature. Additionally, our results showed that climatological and non‐climatological drivers affected ecosystem services both negatively and positively, depending on the regions (in particular lower and higher altitudinal areas), drivers, and services assessed. Our findings highlight stronger effects of climatological compared to non‐climatological drivers on ecosystem service change in Switzerland. Furthermore, drivers of ecosystem change display a spatial heterogeneity in their influence on ecosystem service trends. We propose an approach building on an additive model to disentangle the effect of climatological and non‐climatological drivers on ecosystem service trends. Such analyses should be extended in the future to ecosystem service flow and demand to complete ecosystem service assessments and to demonstrate and communicate more clearly the benefits of ecosystem services for human well‐being.
Patterns of local species richness and their associations with functional traits in a 60‐ha tropical forest dynamics plot
Authors: Zang Lipeng , Xu Han , Lin Mingxian , Zang Runguo
Published: April 2019

Understanding the underlying mechanisms of diversity maintenance in tropics remains a challenge for ecologists. To reveal the underlying mechanism from a plant‐eye‐view perspective, we examined the patterns of local species richness which was defined as the number of species around individuals of a target species within circles of different radii and their correlations with major plant functional traits in a tropical montane rainforest. In 2012, we established a 60‐ha forest dynamics plot (FDP) in tropical montane rainforest on Hainan Island, China. In 2013, we measured eight functional traits (specific leaf area [SLA], leaf dry matter content [LDMC], wood density, potential maximum height, leaf carbon content [LCC], leaf nitrogen content [LNC], leaf phosphorus content [LPC], and leaf potassium content) of all the species in the FDP. Based on all the mapped individuals that had a diameter at breast height ≥10 cm, we utilized individual species–area relationships function (ISARs(r)) combined with the heterogeneous Poisson null model to quantify the patterns of local species richness at scales from 1 to 50 m. Regression analysis was used to determine which functional traits could influence the local diversity pattern. Results showed that the 123 ISARs(r) curves were relatively similar and no species seemed to be extremely higher or lower than the average of all the ISARs(r) curves. The percentage of species that behaved predominantly as accumulators or repellers or neutrally was 42.23%, 13.82%, and 43.9% at scale of <30 m, respectively. But at scales ≥30 m, more than 70% of all species behaved neutrally suggesting that facilitative interactions probably occurred when neighborhoods were <30 m apart. Among the eight measured traits, the SLA, LNC, and LPC were negatively associated with local species richness. Our results indicated that (1) the spatial community structure was not controlled by key species; (2) facilitative interactions played an important role in local diversity maintenance; (3) species with conservative functional trait syndromes were more likely to have relatively high local species richness in the tropical montane rainforest on Hainan Island, China.
Linking tree physiological constraints with predictions of carbon and water fluxes at an old‐growth coniferous forest
Authors: Jiang Yueyang , Kim John B. , Trugman Anna T. , Kim Youngil , Still Christopher J.
Published: April 2019

Old‐growth coniferous forests of the Pacific Northwest are among the most productive temperate ecosystems and have the capacity to store large amounts of carbon for multiple centuries. To date, there are considerable gaps in modeling ecosystem fluxes and their responses to physiological constraints in these old‐growth forests. These model shortcomings limit our ability to understand and project how the old‐growth forests of the Pacific Northwest will respond to global climate change. This study applies the cohort‐based Ecosystem Demography Model 2 (ED2) to the Wind River Experimental Forest (Washington, USA), a well‐studied old‐growth Douglas‐fir–western hemlock ecosystem. ED2 is calibrated and validated using an extensive suite of forest inventory, eddy covariance, and biophysical observations. ED2 is able to reproduce observed forest composition and canopy structure, and carbon, water, and energy fluxes at the site. In the simulations, the effect of limited water supply on ecosystem carbon fluxes is mediated primarily by the forest's gross primary productivity (GPP) response, rather than its heterotrophic respiration response. The simulation indicates that stomatal conductance is mainly determined by soil moisture during periods of low vapor pressure deficit (VPD). However, when VPD is high, stomatal conductance is greatly reduced regardless of soil moisture status. During summer droughts, reduced soil moisture and increased VPD result in considerable stomatal closure and GPP reduction, which in turn decreases net carbon uptake. Cohort‐based scheme integrates all canopy layers (species) that have distinct sensitivity to microclimate and respond distinctly to drought. This study is an initial first step to explore the potential importance of cohort‐based model in simulating forest with complex structure, and to lay the foundation for applying cohort‐based model at regional scales across the Pacific Northwest.
The Reaction of Ethylenediamine with 1,4‐Bis(trimethylsilyl)butadiyne and the Role of Water: A Qualitative Method for the Determination of Water Impurities in Ethylenediamine
Authors: Frischhut Sabine , Bentlohner Manuel M. , Fässler Thomas F.
Published: April 2019

Alkenylation of [Ge9]4– and formation of the vinylated species [Ge9(CH=CH2)n](4–n)– proceed only in ethylenediamine (en) as a solvent. Variation of the alkyne leads to coupling products between the alkyne and en. Herein, we investigated the coupling reactions between 1,4‐bis(trimethylsilyl)butadiyne and en and showed that a water impurity in en plays a decisive role in the outcome of the reaction. NMR spectroscopic investigations revealed that 1‐trimethylsilyl‐7‐amino‐5‐aza‐hepta‐3‐en‐1‐yne is formed by addition of en at 1,4‐bis(trimethylsilyl)butadiyne. Addition of another amino‐functionality of en giving both the cyclization product and 1,9‐di‐amino‐4‐methyl‐3,7‐di‐aza‐nonadiene is only possible in presence of water. 1,9‐Di‐amino‐4‐methyl‐3,7‐di‐aza‐nonadiene is also formed by the reaction of deprotonated en with 1‐trimethylsilyl‐7‐amino‐5‐aza‐hepta‐3‐en‐1‐yne. Based on these results, we developed a simple method to detect water in en, supported by 1H NMR spectroscopy. The finding that 1,9‐di‐amino‐4‐methyl‐3,7‐di‐aza‐nonadiene is also formed by reaction of 1‐trimethylsilyl‐7‐amino‐5‐aza‐hepta‐3‐en‐1‐yne with deprotonated en was exploited to indirectly proof the deprotonation of en upon the nucleophilic reaction of [Ge9]4– with alkynes in the solvent en.
Health‐related quality of life change in patients treated at a multidisciplinary pain clinic
Authors: Vartiainen Pekka , Heiskanen Tarja , Sintonen Harri , Roine Risto P. , Kalso Eija
Published: April 2019

Background

Multidisciplinary pain management (MPM) is a generally accepted method for treating chronic pain, but heterogeneous outcome measures provide only limited conclusions concerning its effectiveness. Therefore, further studies on the effectiveness of MPM are needed to identify subgroups of patients who benefit, or do not benefit, from these interventions. Our aim was to analyse health‐related quality of life (HRQoL) changes after MPM and to identify factors associated with treatment outcomes.

Methods

We carried out a real world observational follow‐up study of chronic pain patients referred to a tertiary multidisciplinary outpatient pain clinic to describe, using the validated HRQoL instrument 15D, the HRQoL change after MPM and to identify factors associated with this change. 1,043 patients responded to the 15D HRQoL questionnaire at baseline and 12 months after the start of treatment. Background data were collected from the pre‐admission questionnaire of the pain clinic.

Results

Fifty‐three percent of the patients reported a clinically important improvement and, of these, 81% had a major improvement. Thirty‐five percent reported a clinically important deterioration, and 12% had no change in HRQoL. Binary logistic regression analysis revealed that major improvement was positively associated with shorter duration of pain (<3 years), worse baseline HRQoL, higher education levels and being employed.

Conclusions

The majority of the patients reported significant HRQoL improvement after multidisciplinary pain management. Better understanding of the factors associated with treatment outcomes is needed to meet the needs of those who had unfavourable outcomes.

Significance

Multidisciplinary pain management (MPM) increases the health‐related quality of life (HRQoL) in most patients. More research into factors associated with HRQoL change is needed to understand why not all patients benefit from MPM and how MPM approaches could be improved to meet the needs of these patients.
The European Semester: Democratic Weaknesses as Limits to Learning
Authors: Papadopoulos Yannis , Piattoni Simona
Published: April 2019

In this contribution to the symposium “What's the problem? Multilevel governance and problem‐solving,” we discuss possible reasons that make difficult for the European Semester to achieve the goals of developing mutual learning and the acquisition of “ownership” over fiscal restraint, budgetary coordination and structural reforms. We underscore the uneasy coupling of a “soft” multilevel governance mode with “hard” forms of governance associated with power politics and domination. We claim that four major problems undermine the Semester's credibility and effectiveness: (1) a democratic deficit resulting from executive dominance, the relative sidelining of parliaments and the marginalization of the public, which confine learning to governmental and administrative circles; (2) the constitutionalization of budgetary policy choices, which constrains the available policy options and preempts reflection and discussion; (3) the “disciplinary logic” imposed through asymmetric intergovernmentalism, which invites noncompliance or bargaining, and (4) the “tough” treatment of debtor Eurozone members outside the Semester.
Individual differences in sustained attention are associated with cortical thickness
Authors: Mitko Alex , Rothlein David , Poole Victoria , Robinson Meghan , McGlinchey Regina , DeGutis Joseph , Salat David , Esterman Michael
Published: April 2019

Several studies have examined how individual differences in sustained attention relate to functional brain measures (e.g., functional connectivity), but far fewer studies relate sustained attention ability, or cognition in general, to individual differences in cortical structure. Functional magnetic resonance imaging meta‐analyses and patient work have highlighted that frontoparietal regions, lateralized to the right hemisphere, are critical for sustained attention, though recent work implicates a broader expanse of brain regions. The current study sought to determine if and where variation in cortical thickness is significantly associated with sustained attention performance. Sustained attention was measured using the gradual onset continuous performance task and the Test of Variables of Attention in 125 adult Veteran participants after acquiring two high‐resolution structural MRI scans. Whole‐brain vertex‐wise analyses of the cortex demonstrated that better sustained attention was associated with increased thickness in visual, somatomotor, frontal, and parietal cortices, especially in the right hemisphere. Network‐based analyses revealed relationships between sustained attention and cortical thickness in the dorsal attention, ventral attention, somatomotor, and visual networks. These results indicate cortical thickness in multiple regions and networks is associated with sustained attention, and add to the growing knowledge of how structural MRI can help explain individual differences in cognition.
Crumbs3 is a critical factor that regulates invasion and metastasis of colon adenocarcinoma via the specific interaction with FGFR1
Authors: Iioka Hidekazu , Saito Ken , Sakaguchi Masakiyo , Tachibana Taro , Homma Keiichi , Kondo Eisaku
Published: April 2019

Epithelial cell polarity regulator Crumbs3 (Crb3), a mammalian homolog within the Drosophila Crb gene family, was initially identified as an essential embryonic development factor. It is recently implicated in tumor suppression, though its specific functions are controversial. We here demonstrate that Crb3 strongly promotes tumor invasion and metastasis of human colon adenocarcinoma cells. Crb3 centrality to tumor migration was supported by strong expression at invasive front and metastatic foci of colonic adenocarcinoma of the patient tissues. Accordingly, two different Crb3‐knockout (KO) lines, Crb3‐KO (Crb3 −/−) DLD‐1 and Crb3‐KO WiDr from human colonic adenocarcinomas, were generated by the CRISPR‐Cas9 system. Crb3‐KO DLD‐1 cells exhibited loss of cellular mobility in vitro and dramatic suppression of liver metastases in vivo in contrast to the wild type of DLD‐1. Unlike DLD‐1, Crb3‐KO WiDr mobility and metastasis were unaffected, which were similar to wild‐type WiDr. Proteome analysis of Crb3‐coimmunopreciptated proteins identified different respective fibroblast growth factor receptor (FGFR) isotypes specifically bound to Crb3 isoform a through their intracellular domain. In DLD‐1, Crb3 showed membranous localization of FGFR1 leading to its functional activation, whereas Crb3 bound to cytoplasmic FGFR4 in WiDr without FGFR1 expression, leading to cellular growth. Correlative expression between Crb3 and FGFR1 was consistently detected in primary and metastatic colorectal cancer patient tissues. Taking these together, Crb3 critically accelerates cell migration, namely invasion and metastasis of human colon cancers, through specific interaction to FGFR1 on colon cancer cells.
Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis
Authors: Seliger Corinna , Genbrugge Els , Gorlia Thierry , Chinot Olivier , Stupp Roger , Nabors Burt , Weller Michael , Hau Peter ,   for the EORTC Brain Tumor Group
Published: April 2019

Metformin has been linked to improve survival of patients with various cancers. There is little information on survival of glioblastoma patients after use of metformin. We assessed the association between metformin use and survival in a pooled analysis of patient data from 1,731 individuals from the randomized AVAglio, CENTRIC and CORE trials. We performed multivariate Cox analyses for overall survival (OS) and progression‐free survival (PFS) comparing patients' use of metformin at baseline and/or during concomitant radiochemotherapy (TMZ/RT). Further exploratory analyses investigated the effect of metformin with a history of diabetes and nonfasting glucose levels in relation to OS or PFS of glioblastoma patients. Metformin alone or in any combination was not significantly associated with OS or PFS (at baseline, hazard ratio [HR] for OS = 0.87; 95% confidence interval [CI] = 0.65–1.16; HR for PFS = 0.84; 95% CI = 0.64–1.10; during TMZ/RT HR for OS = 0.97; 95% CI = 0.68–1.38; HR for PFS = 1.02; 95% CI = 0.74–1.41). We found a statistically nonsignificant association of metformin monotherapy with glioblastoma survival at baseline (HR for OS = 0.68; 95% CI = 0.42–1.10; HR for PFS = 0.57; 95% CI = 0.36–0.91), but not during the TMZ/RT period (HR for OS = 0.90; 95% CI = 0.51–1.56; HR for PFS = 1.05; 95% CI = 0.64–1.73). Diabetes mellitus or increased nonfasting glucose levels were not associated with a difference in OS or PFS in our selected study population. Metformin did not prolong survival of patients with newly diagnosed glioblastoma in our analysis. Additional studies may identify patients with specific tumor characteristics that are associated with potential benefit from treatment with metformin, possibly due to metabolic vulnerabilities.
Overuse of antianaerobic drug is associated with poor postchemotherapy prognosis of patients with hepatocellular carcinoma
Authors: Iida Noriho , Mizukoshi Eishiro , Yamashita Tatsuya , Terashima Takeshi , Arai Kuniaki , Seishima Jun , Kaneko Shuichi
Published: April 2019

Overuse of antibiotic drugs alters the composition of gut microbiota and has detrimental effects on the host. In our study, we investigated association of gut flora and antibiotics in the prognosis of patients with liver cancer who have undergone chemotherapy by analyzing two independent clinical studies. We retrospectively subanalyzed a previously reported randomized controlled trial (RCT) on hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma (HCC) to investigate the association between use of antibiotics and prognosis. In the other study, we prospectively determined the abundance of specific bacterial genus in patients with HCC by sequencing 16S ribosomal RNA and assessed its association with survival. Subanalysis of the RCT data showed that, of 26 types of antibiotics used, administration of carbapenem before or during chemotherapy was associated with poor progression‐free survival (PFS) and overall survival (OS) of patients with HCC (carbapenem + vs. −; median PFS, 78 days vs. 154 days, p = 0.0053; median OS, 177 days vs. 475 days, p = 0.0003). Multivariate analysis revealed that antianaerobic drug use is an independent predictor of poor prognosis. In the prospective study, the abundance of Blautia in fecal microbiota correlated positively with both PFS and OS of patients with HCC who underwent chemotherapy. Use of antibiotics targeting anaerobes is associated with a poor prognosis in patients with HCC who have undergone chemotherapy, whereas the intestinal anaerobic bacteria, Blautia is associated with a good prognosis. These findings might indicate the need for caution regarding overuse of broad‐spectrum antibiotics targeting anaerobes in patients with HCC.