bluuebunny/crossref_metadata_2025 huggingface dataset:
Telehealth system: A randomized controlled trial evaluating the impact of an internet‐based exercise intervention on quality of life, pain, muscle strength, and fatigue in breast cancer survivors
Authors: Galiano‐Castillo Noelia , Cantarero‐Villanueva Irene , Fernández‐Lao Carolina , Ariza‐García Angélica , Díaz‐Rodríguez Lourdes , Del‐Moral‐Ávila Rosario , Arroyo‐Morales Manuel
Published: June 2016

BACKGROUND

The chronicity status of breast cancer survivors suggests a growing need for cancer rehabilitation. Currently, the use of technology is a promising strategy for providing support, as reflected in the emergence of research interest in Web‐based interventions in cancer survivorship.

METHODS

A randomized controlled trial was conducted that included a total of 81 participants who had completed adjuvant therapy (except hormone treatment) for stage I to IIIA breast cancer. Participants were randomly assigned to an 8‐week Internet‐based, tailored exercise program (n = 40) or to a control group (n = 41).The instruments used at baseline, 8 weeks, and 6‐month follow‐up were the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire Core 30 and its breast cancer module, the Brief Pain Inventory, the handgrip dynamometer, the isometric abdominal test, the back dynamometer, the multiple sit‐to‐stand test, and the Piper Fatigue Scale.

RESULTS

After the intervention, the telerehabilitation group had significantly improved scores for global health status, physical, role, cognitive functioning, and arm symptoms (all P < .01) as well as pain severity (P = .001) and pain interference (P = .045) compared with the control group. Significant improvements also were observed favoring the telerehabilitation group for affected and nonaffected side handgrip (both P = .006), abdominal, back and lower body strength (all P < .01), and total fatigue (P < .001). These findings were maintained after 6 months of follow‐up, except for role functioning, pain severity, and nonaffected side handgrip. Analysis was based on an intention‐to‐treat principle.

CONCLUSIONS

This program may improve adverse effects and maintain benefits in breast cancer survivors. The results of this study have encouraging implications for cancer care. Cancer 2016;122:3166–74. © 2016 American Cancer Society.
Integration and scaling ofUV‐B radiation effects on plants: from molecular interactions to whole plant responses
Authors: Suchar Vasile Alexandru , Robberecht Ronald
Published: June 2016

A process based model integrating the effects ofUV‐B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed thatUV‐B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermalUV‐B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions betweenUV‐B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2–5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increasedUV‐B radiation through molecular level processes and their consequences to whole plant growth and development.
Dead or gone? Bayesian inference on mortality for the dispersing sex
Authors: Barthold Julia A. , Packer Craig , Loveridge Andrew J. , Macdonald David W. , Colchero Fernando
Published: June 2016

Estimates of age‐specific mortality are regularly used in ecology, evolution, and conservation research. However, estimating mortality of the dispersing sex, in species where one sex undergoes natal dispersal, is difficult. This is because it is often unclear whether members of the dispersing sex that disappear from monitored areas have died or dispersed. Here, we develop an extension of a multievent model that imputes dispersal state (i.e., died or dispersed) for uncertain records of the dispersing sex as a latent state and estimates age‐specific mortality and dispersal parameters in a Bayesian hierarchical framework. To check the performance of our model, we first conduct a simulation study. We then apply our model to a long‐term data set of African lions. Using these data, we further study how well our model estimates mortality of the dispersing sex by incrementally reducing the level of uncertainty in the records of male lions. We achieve this by taking advantage of an expert's indication on the likely fate of each missing male (i.e., likely died or dispersed). We find that our model produces accurate mortality estimates for simulated data of varying sample sizes and proportions of uncertain male records. From the empirical study, we learned that our model provides similar mortality estimates for different levels of uncertainty in records. However, a sensitivity of the mortality estimates to varying uncertainty is, as can be expected, detectable. We conclude that our model provides a solution to the challenge of estimating mortality of the dispersing sex in species with data deficiency due to natal dispersal. Given the utility of sex‐specific mortality estimates in biological and conservation research, and the virtual ubiquity of sex‐biased dispersal, our model will be useful to a wide variety of applications.
Multitrophic diversity effects of network degradation
Authors: Nichols Elizabeth , Peres Carlos A. , Hawes Joseph E. , Naeem Shahid
Published: June 2016

Predicting the functional consequences of biodiversity loss in realistic, multitrophic communities remains a challenge. No existing biodiversity–ecosystem function study to date has simultaneously incorporated information on species traits, network topology, and extinction across multiple trophic levels, while all three factors are independently understood as critical drivers of post‐extinction network structure and function. We fill this gap by comparing the functional consequences of simulated species loss both within (monotrophic) and across (bitrophic) trophic levels, in an ecological interaction network estimated from spatially explicit field data on tropical fecal detritus producer and consumers (mammals and dung beetles). We simulated trait‐ordered beetle and mammal extinction separately (monotrophic extinction) and the coextinction of beetles following mammal loss (bitrophic extinction), according to network structure. We also compared the diversity effects of bitrophic extinction models using a standard monotrophic function (the daily production or consumption of fecal detritus) and a unique bitrophic functional metric (the proportion of daily detritus production that is consumed). We found similar mono‐ and bitrophic diversity effects, regardless of which species traits were used to drive extinctions, yet divergent predictions when different measures of function were used. The inclusion of information on network structure had little apparent effect on the qualitative relationship between diversity and function. These results contribute to our growing understanding of the functional consequences of biodiversity from real systems and underscore the importance of species traits and realistic functional metrics to assessments of the ecosystem impacts of network degradation through species loss.
Phylogenetic test of speciation by host shift in leaf cone moths (Caloptilia) feeding on maples (Acer)
Authors: Nakadai Ryosuke , Kawakita Atsushi
Published: June 2016

The traditional explanation for the exceptional diversity of herbivorous insects emphasizes host shift as the major driver of speciation. However, phylogenetic studies have often demonstrated widespread host plant conservatism by insect herbivores, calling into question the prevalence of speciation by host shift to distantly related plants. A limitation of previous phylogenetic studies is that host plants were defined at the family or genus level; thus, it was unclear whether host shifts predominate at a finer taxonomic scale. The lack of a statistical approach to test the hypothesis of host‐shift‐driven speciation also hindered studies at the species level. Here, we analyze the radiation of leaf cone moths (Caloptilia) associated with maples (Acer) using a newly developed, phylogeny‐based method that tests the role of host shift in speciation. This method has the advantage of not requiring complete taxon sampling from an entire radiation. Based on 254 host plant records for 14 Caloptilia species collected at 73 sites in Japan, we show that major dietary changes are more concentrated toward the root of the phylogeny, with host shift playing a minor role in recent speciation. We suggest that there may be other roles for host shift in promoting herbivorous insect diversification rather than facilitating speciation per se.
Electrostatic Properties of N‐Heterocyclic Carbenes Obtained by Experimental Charge‐Density Analysis of Two Selenium Adducts
Authors: Buhl Hannes , Verlinden Kathrin , Ganter Christian , Novaković Sladjana B. , Bogdanović Goran A.
Published: June 2016

High‐resolution X‐ray diffraction data and Hansen–Coppens multipole formalism have been used to obtain the charge density distribution in two selenium adducts with the N‐heterocyclic carbenes 1,3‐dimesitylimidazolidin‐2‐ylidene (1) and 1,3‐dimesityl‐4,5‐dioxoimidazolidin‐2‐ylidene (2). Application of Bader's quantum theory of atoms in molecules and calculation of the atomic charges by integration of the experimental electron density over the atomic basins showed that the main electrostatic difference between the Se adducts is in the significantly different accumulation of electron density in their C(carbene)–Se fragments (–0.10 vs. +0.30 e in1and2). Deformation electron density features along the C–Se bond and topological values at the bond critical point indicate that this bond has π character in both compounds but it is more pronounced in the case of2. This is in agreement with stronger C–N bonds and a larger N–C–N angle in1. The experimental charge density distribution also clearly indicates the important role of theN‐mesityl substituent as an electron‐donating group, which increases the electron density in the imidazole ring thus contributing to the electronic stabilization of the carbene C atom. Because theN‐mesityl substituents donate similar amounts of electron density in both molecules (0.75 and 0.64 e in1and2), it was concluded that the decisively different electronic properties of the two NHCs have to be attributed to their different backbone structures.
Synthesis of a Silylated Phosphorus Biradicaloid and Its Utilization in the Activation of Small Molecules
Authors: Hinz Alexander , Kuzora René , Rölke Anne‐Kristin , Schulz Axel , Villinger Alexander , Wustrack Ronald
Published: June 2016

Reduction of silylated 1,3‐dichloro‐1,3‐diphospha‐2,4‐diazane, [ClP(µ‐NHyp)]2 [Hyp = Si(SiMe3)3], with activated magnesium in dimethoxyethane allowed the isolation and full characterization of the first stable silylated biradicaloid, [P(µ‐NHyp)]2. The oxidation of [P(µ‐NHyp)]2 with selenium and sulfur was studied. Activation of molecules bearing double bonds was achieved in the reaction with acetone and carbon disulfide, yielding heteroatom cage compounds.
Iron(III)‐Triflate‐Catalyzed Multiple Glycosylations with Peracetylated β‐d‐Glucosamine
Authors: Xolin Amandine , Norsikian Stéphanie , Boyer François‐Didier , Beau Jean‐Marie
Published: June 2016

Direct multiple glycosylations of thioaryl and propargyl mannopyranosides with peracetylated β‐d‐glucosamine have been carried out using catalytic iron(III) triflate as a promoter in the presence of 2,4,6‐tri‐tert‐butylpyrimidine under microwave irradiation. This has led to the one‐step formation of various oligosaccharides with mannose at the branching point. Subsequent direct introduction of a linker through copper‐catalyzed azide–alkyne cycloaddition with the propargyl branched glycan and final deprotection gave rapid access to N‐glycan mimetics.
On end to end network slicing for 5G communication systems
Authors: An X. , Zhou C. , Trivisonno R. , Guerzoni R. , Kaloxylos A. , Soldani D. , Hecker A.
Published: June 2016

The heterogeneity in use cases and the need to support diverse requirements from vertical markets are the main drivers for new design principles of 5G communication systems. In this paper, we review the notion of plastic architecture and propose an end to end network slicing concept to serve new 5G capabilities and features in a flexible and efficient manner. Besides the concept definition, we address in particular the key issue of how 5G devices may be enabled to discover, select and access the most appropriate E2E network slices. To solve the issue, we developed a novel Device Triggered Network Control mechanism and evaluated its performance and implementation cost with respect to alternative available schemes, where the slicing concept was applied only to the core network domain of the communication system. Simulation results showed two digits gains in terms of attachment delay and signalling overhead. Copyright © 2016 John Wiley & Sons, Ltd.
Geomorphic fluvial markers reveal transient landscape evolution in tectonically quiescent southern Peninsular India
Authors: Mandal Sanjay Kumar , Burg Jean‐Pierre , Haghipour Negar
Published: June 2016

The morphology of 19 adjacent westward‐flowing and four eastward‐flowing major catchments draining across the Western Ghat escarpment in southern Peninsular India was studied to examine how the channel patterns and their longitudinal profiles reflect the landscape evolution. Field surveys were complemented with the quantitative morphometric analysis of fluvial channel profiles using digital topographic data. Results show distinctive differences between eastward‐ and westward‐flowing drainage systems. The channel profiles of eight westward‐flowing drainage basins show an apparent morphological equilibrium characterized by concave upward shape, whereas most channels from the other westward‐flowing basins display knickpoint(s). All studied eastward‐flowing drainage basins display the morphological signature of disequilibrium in the form of knickpoints. The eastern and western margins of southern Peninsular India have experienced major tectonic events ~120 and ~65 Ma ago, respectively, and are since then tectonically quiescent. All studied westward‐flowing basins share the same Arabian Sea base level, flow over comparable lithologies and developed under similar climatic conditions. The studied eastward‐flowing basins have the Bay of Bengal as base level and similar climatic conditions. Therefore, the spatial variations in catchment morphometry is interpreted as a dynamic response to complex interactions and feedbacks between (i) pre‐existing topography along and across the escarpment margins, and (ii) vigorous drainage piracy in more recent times. We hypothesize that the studied drainage basins have experienced different forcing magnitudes that can be quantified to a first order using the present day topography. Copyright © 2016 John Wiley & Sons, Ltd.
The impact of personality on memory function in older adults—results from the Longitudinal Aging Study Amsterdam
Authors: Klaming Ruth , Veltman Dick J. , Comijs Hannie C.
Published: June 2016

Objective

The aim of the study was to explore associations between memory function and the personality constructs mastery, self‐efficacy, and neuroticism in a large cohort of older adults over a 14‐year period.

Methods

Memory function and personality traits were assessed every three years for 14 years. Data was derived from the Longitudinal Aging Study Amsterdam (LASA). The study cohort included a total of 1966 men and women aged 65 and older at baseline. Episodic memory was assessed with a modified Dutch version of the Rey Auditory Verbal Learning Test. Personality was measured with Dutch versions of the Pearlin Mastery Scale, General Self‐Efficacy Scale, and an abbreviated version of the Dutch Personality Questionnaire. All three personality questionnaires are self‐rating instruments.

Results

Higher levels of mastery and self‐efficacy were associated with better memory function while high neuroticism was associated with poorer memory. Personality traits did not affect the rate of memory decline over time.

Conclusions

Results demonstrate the role personality constructs, in particular those related to control beliefs and proneness to psychological stress, play in cognitive function in older adults, and support the development of intervention programs. Targeted training has the potential to promote a sense of control over life outcomes and to lower stress in older adults who are at risk for impaired memory function.
Neuroanatomical and neurofunctional markers of social cognition in autism spectrum disorder
Authors: Patriquin Michelle A. , DeRamus Thomas , Libero Lauren E. , Laird Angela , Kana Rajesh K.
Published: June 2016

Social impairments in autism spectrum disorder (ASD), a hallmark feature of its diagnosis, may underlie specific neural signatures that can aid in differentiating between those with and without ASD. To assess common and consistent patterns of differences in brain responses underlying social cognition in ASD, this study applied an activation likelihood estimation (ALE) meta‐analysis to results from 50 neuroimaging studies of social cognition in children and adults with ASD. In addition, the group ALE clusters of activation obtained from this was used as a social brain mask to perform surface‐based cortical morphometry (SBM) in an empirical structural MRI dataset collected from 55 ASD and 60 typically developing (TD) control participants. Overall, the ALE meta‐analysis revealed consistent differences in activation in the posterior superior temporal sulcus at the temporoparietal junction, middle frontal gyrus, fusiform face area (FFA), inferior frontal gyrus (IFG), amygdala, insula, and cingulate cortex between ASD and TD individuals. SBM analysis showed alterations in the thickness, volume, and surface area in individuals with ASD in STS, insula, and FFA. Increased cortical thickness was found in individuals with ASD, the IFG. The results of this study provide functional and anatomical bases of social cognition abnormalities in ASD by identifying common signatures from a large pool of neuroimaging studies. These findings provide new insights into the quest for a neuroimaging‐based marker for ASD. Hum Brain Mapp 37:3957–3978, 2016. © 2016 Wiley Periodicals, Inc.
The activation of the caudate is associated with correct recollections in a reward‐based recollection task
Authors: Dong Guangheng , Wang Yifan , Potenza Marc N.
Published: June 2016

Although specific brain regions have been implicated in long‐term memory processes, the brain function responsible for correctly recollecting information remains incompletely understood. This study used a remember–recollection–recognition task to explore brain activities specifically associated with correct recollection. Seventy‐eight subjects were first asked to remember 40 items and recollect them in the scanner. Comparison of correctly recollected trials to incorrectly recollected trials (when participants mistakenly believed they had recollected information correctly) identified greater activation of the caudate bilaterally. The involvement of caudate activation appears important in recollecting information correctly. Potential explanations and implications are discussed. Hum Brain Mapp 37:3999–4005, 2016. © 2016 Wiley Periodicals, Inc.
Fronto‐Parietal gray matter and white matter efficiency differentially predict intelligence in males and females
Authors: Ryman Sephira G. , Yeo Ronald A. , Witkiewitz Katie , Vakhtin Andrei A. , van den Heuvel Martijn , de Reus Marcel , Flores Ranee A. , Wertz Christopher R. , Jung Rex E.
Published: June 2016

While there are minimal sex differences in overall intelligence, males, on average, have larger total brain volume and corresponding regional brain volumes compared to females, measures that are consistently related to intelligence. Limited research has examined which other brain characteristics may differentially contribute to intelligence in females to facilitate equal performance on intelligence measures. Recent reports of sex differences in the neural characteristics of the brain further highlight the need to differentiate how the structural neural characteristics relate to intellectual ability in males and females. The current study utilized a graph network approach in conjunction with structural equation modeling to examine potential sex differences in the relationship between white matter efficiency, fronto‐parietal gray matter volume, and general cognitive ability (GCA). Participants were healthy adults (n = 244) who completed a battery of cognitive testing and underwent structural neuroimaging. Results indicated that in males, a latent factor of fronto‐parietal gray matter was significantly related to GCA when controlling for total gray matter volume. In females, white matter efficiency and total gray matter volume were significantly related to GCA, with no specificity of the fronto‐parietal gray matter factor over and above total gray matter volume. This work highlights that different neural characteristics across males and females may contribute to performance on intelligence measures. Hum Brain Mapp 37:4006–4016, 2016. © 2016 Wiley Periodicals, Inc.
Vemurafenib‐induced granulomatous hepatitis
Authors: Spengler Erin K. , Kleiner David E. , Fontana Robert J.
Published: June 2016

Vemurafenib (Zelboraf; Genentech, CA) is a highly effective oral chemotherapy agent for patients with metastatic melanoma who carry the BRAF V600E mutation. Side effects of this protein kinase inhibitor (PKI) include arthralgia, rash, and fatigue, which are reported in up to one third of treated patients. Mild abnormalities in liver biochemistries were reported with vemurafenib use in 30% of subjects, 11% developed severe laboratory abnormalities, and acute liver failure has been reported (Table 1). Herein, a case of severe vemurafenib‐induced granulomatous hepatitis leading to chronic cholestasis is reported along with a review of the hepatotoxicity of other PKIs.
Don't Believe the Hype: Hip‐Hop Literacies and English Education
Authors: Belle Crystal
Published: June 2016

Current scholarship suggests that many youths identify with hip‐hop, especially youths of color. Study of this artistic form has been suggested as a means of helping youths acquire and become fluent in literacy practices. This article explores how the use of a hip‐hop literacies curriculum addressed the literacy skills of urban ninth‐grade English students while helping them contextualize the significance of their in‐school and out‐of‐school literacy experiences. The article explains the connections between literacies and hip‐hop–based education, illustrates how hip‐hop can serve as a culturally responsive and rigorous pedagogical tool in the English classroom, and shares students' views on the use of such curriculum.
ZBTB16 as a Downstream Target Gene of Osterix Regulates Osteoblastogenesis of Human Multipotent Mesenchymal Stromal Cells
Authors: Onizuka Satoru , Iwata Takanori , Park Sung‐Joon , Nakai Kenta , Yamato Masayuki , Okano Teruo , Izumi Yuichi
Published: June 2016

Human multipotent mesenchymal stromal cells (hMSCs) possess the ability to differentiate into osteoblasts, and they can be utilized as a source for bone regenerative therapy. Osteoinductive pretreatment, which induces the osteoblastic differentiation of hMSCs in vitro, has been widely used for bone tissue engineering prior to cell transplantation. However, the molecular basis of osteoblastic differentiation induced by osteoinductive medium (OIM) is still unknown. Therefore, we used a next‐generation sequencer to investigate the changes in gene expression during the osteoblastic differentiation of hMSCs. The hMSCs used in this study possessed both multipotency and self‐renewal ability. Whole‐transcriptome analysis revealed that the expression of zinc finger and BTB domain containing 16 (ZBTB16) was significantly increased during the osteoblastogenesis of hMSCs. ZBTB16 mRNA and protein expression was enhanced by culturing the hMSCs with OIM. Small interfering RNA (siRNA)‐mediated gene silencing of ZBTB16 decreased the activity of alkaline phosphatase (ALP); the expression of osteogenic genes, such as osteocalcin (OCN) and bone sialoprotein (BSP), and the mineralized nodule formation induced by OIM. siRNA‐mediated gene silencing of Osterix (Osx), which is known as an essential regulator of osteoblastic differentiation, markedly downregulated the expression of ZBTB16. In addition, chromatin immunoprecipitation (ChIP) assays showed that Osx associated with the ZBTB16 promoter region containing the GC‐rich canonical Sp1 sequence, which is the specific Osx binding site. These findings suggest that ZBTB16 acts as a downstream transcriptional regulator of Osx and can be useful as a late marker of osteoblastic differentiation. J. Cell. Biochem. 117: 2423–2434, 2016. © 2016 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.
HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression
Authors: Micheli Laura , D'Andrea Giorgio , Leonardi Luca , Tirone Felice
Published: June 2016

PC3/Tis21 is a transcriptional cofactor that inhibits proliferation in several cell types, including neural progenitors. Here, we report that PC3/Tis21 associates with HDAC1, HDAC4, and HDAC9 in vivo, in fibroblast cells. Furthermore, when HDAC1, HDAC4, or HDAC9 are silenced in fibroblasts or in a line of cerebellar progenitor cells, the ability of PC3/Tis21 to inhibit proliferation is significantly reduced. Overexpression of HDAC1, HDAC4, or HDAC9 in fibroblasts and in cerebellar precursor cells synergizes with PC3/Tis21 in inhibiting the expression of cyclin D1, a cyclin selectively inhibited by PC3/Tis21. Conversely, the depletion of HDAC1 or HDAC4 (but not HDAC9) in fibroblasts and in cerebellar precursor cells significantly impairs the ability of PC3/Tis21 to inhibit cyclin D1 expression. An analysis of HDAC4 deletion mutants shows that both the amino‐terminal moiety and the catalytic domain of HDAC4 associate to PC3/Tis21, but neither alone is sufficient to potentiate the inhibition of cyclin D1 by PC3/Tis21. As a whole, our findings indicate that PC3/Tis21 inhibits cell proliferation in a way dependent on the presence of HDACs, in fibroblasts as well as in neural cells. Considering that several reports have demonstrated that HDACs can act as transcriptional corepressors on the cyclin D1 promoter, our data suggest that the association of PC3/Tis21 to HDACs is functional to recruit them to target genes, such as cyclin D1, for repression of their expression. J. Cell. Physiol. 232: 1696–1707, 2017. © 2016 Wiley Periodicals, Inc.
Low Incubation Temperature Induces DNA Hypomethylation in Lizard Brains
Authors: Paredes Ursula , Radersma Reinder , Cannell Naomi , While Geoffrey M. , Uller Tobias
Published: June 2016

Developmental stress can have organizational effects on suites of physiological, morphological, and behavioral characteristics. In lizards, incubation temperature is perhaps the most significant environmental variable affecting embryonic development. Wall lizards (Podarcis muralis) recently introduced by humans from Italy to England experience stressfully cool incubation conditions, which we here show reduce growth and increase the incidence of scale malformations. Using a methylation‐sensitive AFLP protocol optimized for vertebrates, we demonstrate that this low incubation temperature also causes hypomethylation of DNA in brain tissue. A consistent pattern across methylation‐susceptible AFLP loci suggests that hypomethylation is a general response and not limited to certain CpG sites. The functional consequences of hypomethylation are unknown, but it could contribute to genome stability and regulation of gene expression. Further studies of the effects of incubation temperature on DNA methylation in ectotherm vertebrates may reveal mechanisms that explain why the embryonic thermal environment often has physiological and behavioral consequences for offspring.
An Efficient and Facile Synthesis of 5‐Amino‐3‐methyl‐7‐aryl‐1,3‐dihydroisobenzofuran‐4,6‐dicarbonitrile Derivatives Under Mild Conditions
Authors: Yin Zehan , Wang Zhansheng , Xu Jing , Hao Ganlu , Gao Xu , Rong Liangce
Published: June 2016

This article describes an efficient approach for the synthesis of 5‐amino‐3‐methyl‐7‐aryl‐1,3‐dihydroisobenzofuran‐4,6‐dicarbonitrile derivatives from the reaction of aromatic aldehyde, 2‐methyltetrahydrofuran‐3‐one, and malononitrile under mild conditions. This is a simple and facile process to structure this important heterocyclic compounds. The other advantages of this approach are rapid reaction rate, high yield, and simple procedure. This article provided a good method for the synthesis of 1,3‐dihydroisobenzofuran derivatives.
Visiting professorship in hospital medicine: An innovative twist for a growing specialty
Authors: Cumbler Ethan , Herzke Carrie , Smalligan Roger , Glasheen Jeffrey J. , O'Malley Cheryl , Pierce J. Rush
Published: June 2016

INTRODUCTION

As an emerging and rapidly growing specialty, academic hospitalists face unique challenges in career advancement. Key mentoring needs, especially developing reputation and relationships outside of their institution are often challenging.

METHODS

We describe the structure of a novel Visiting Professorship in Hospital Medicine Program. It utilizes reciprocal exchanges of hospitalist faculty at the rank of late assistant to early associate professor. The program is designed explicitly to facilitate spread of innovation between institutions through a presentation by the visiting professor and exposure to an innovation at the host hospital medicine group. It provides a platform to advance the career success of both early‐ and midcareer hospitalist faculty through 1‐on‐1 coaching sessions between the visiting professor and early‐career faculty at the host institution and commitment by visiting professors to engage in mentoring after the visit.

RESULTS

Five academic hospitalist groups participated. Seven visiting professors met with 29 early‐career faculty. Experience following faculty exchange visits demonstrates program effectiveness, as perceived by both early‐career faculty and the visiting professors, in advancing the goals of mentorship and career advancement. One‐year follow‐up suggests that 62% of early‐career faculty will engage in subsequent interactions with the visiting professor, and half report spread of innovation between academic hospital medicine groups.

CONCLUSIONS

The Visiting Professorship in Hospital Medicine offers a low‐cost framework to promote collaboration between academic hospital medicine groups and facilitate interinstitutional hospitalist mentoring. It is reported to be effective for the goal of professional development for midcareer hospitalists. Journal of Hospital Medicine 2016;11:714–718. © 2016 Society of Hospital Medicine
Rotavirus vaccine strain transmission by vaccinated infants in the foster home
Authors: Miura Hiroki , Kawamura Yoshiki , Sugata Ken , Koshiyama Nozomi , Yoshikawa Akiko , Komoto Satoshi , Taniguchi Koki , Ihira Masaru , Yoshikawa Tetsushi
Published: June 2016

Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real‐time reverse transcription polymerase chain reaction (RT‐PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real‐time RT‐PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79–84, 2017. © 2016 Wiley Periodicals, Inc.
Effect of phosphorus management in rice–mungbean rotations on sandy soils of Cambodia
Authors: Ro Sophoanrith , Becker Mathias , Manske Günther
Published: June 2016

Nitrogen (N) and phosphorus (P) deficiencies are key constraints in rainfed lowland rice (Oryza sativa L.) production systems of Cambodia. Only small amounts of mineral N and P or of organic amendment are annually applied to a single crop of rainfed lowland rice by smallholder farmers. The integration of leguminous crops in the pre‐rice cropping niche can contribute to diversify the production, supply of C and N, and contribute to soil fertility improvement for the subsequent crop of rice. However, the performance of leguminous crops is restricted even more than that of rice by low available soil P. An alternative strategy involves the application of mineral P that is destined to the rice crop already to the legume. This P supply is likely to stimulate legume growth and biological N2 fixation, thus enhancing C and N inputs and recycling N and P upon legume residue incorporation. Rotation experiments were conducted in farmers' fields in 2013–2014 to assess the effects of P management on biomass accumulation and N2 fixation (δ15N) by mungbean (Vigna radiata L.) and possible carry‐over effects on rice in two contrasting representative soils (highly infertile and moderately fertile sandy Fluvisol). In the traditional system (no legume), unamended lowland rice (no N, + 10 kg P ha−1) yielded 2.8 and 4.0 t ha−1, which increased to 3.5 and 4.7 t ha−1 with the application of 25 kg ha−1 of urea‐N in the infertile and the moderately fertile soil, respectively. The integration of mungbean as a green manure contributed up to 9 kg of biologically fixed N (17% Nfda), increasing rice yields only moderately to 3.5–4.6 t ha−1. However, applying P to mungbean stimulated legume growth and enhanced the BNF contribution up to 21 kg N ha−1 (36% Nfda). Rice yields resulting from legume residue incorporation (“green manure use”–all residues returned and “grain legume use”–only stover returned) increased to 4.2 and 4.9 t ha−1 in the infertile and moderately fertile soil, respectively. The “forage legume use” (all above‐ground residues removed) provided no yield effect. In general, legume residue incorporation was more beneficial in the infertile than in the moderately fertile soil. We conclude that the inclusion of mungbean into the prevailing low‐input rainfed production systems of Cambodia can increase rice yield, provided that small amounts of P are applied to the legume. Differences in the attributes of the two major soil types in the region require a site‐specific targeting of the suggested legume and P management strategies, with largest benefits likely to accrue on infertile soils.
Assessing the plant minimal exchangeable potassium of a soil
Authors: Schneider André , Augusto Laurent , Mollier Alain
Published: June 2016

The plant minimal exchangeable K (EPl,min) defines the lower accessible limit of the most available pool of soil K to plants. It is also an index of long‐term K reserve in soils. However, its estimation by the classical method of exhaustion cropping is laborious. This study aimed at comparing EPl,min values obtained by the exhaustion cropping method with EPl,min values estimated by an alternative approach based on the cationic exchange capacity (CEC) of the infinitely high selective sites for K (i.e., always saturated with K) in the K‐Ca exchange (EK‐Ca,min). A set of 45 soil samples, corresponding to the various fertilization K treatments of 15 long‐term K fertilization trials, was used in this study. The selected soil samples presented a wide range of texture, CEC, and exchangeable K. The plant minimal exchangeable K was found more or less independent of the K treatment, whereas EK‐Ca,min increased when the soil exchangeable K content increased. The plant minimal exchangeable K was systematically lower than EK‐Ca,min, showing that EK‐Ca,min is at least partially available to the plant. Hence, EK‐Ca,min is not a surrogate of EPl,min. Conversely, the plant minimal exchangeable K was strongly, positively correlated to soil CEC (measured at soil pH; r2 = 0.90***). This soil property can consequently be used as a proxy of EPl,min.
Aerobic gammaproteobacterial methanotrophs mitigate methane emissions from oxic and anoxic lake waters
Authors: Oswald Kirsten , Milucka Jana , Brand Andreas , Hach Philipp , Littmann Sten , Wehrli Bernhard , Kuypers Marcel M.M. , Schubert Carsten J.
Published: June 2016

Freshwater lakes represent a substantial natural source of methane to the atmosphere and thus contribute to global climate change. Microbial methane oxidation is an important control on methane release from these systems, where oxygen appears to be the most essential electron acceptor for this process. However, there is extensive geochemical evidence that methane is also oxidized under anoxic conditions in lakes, though the details about the exact mechanism have still not been resolved. Here, we investigated the fate of methane in the water column of meromictic Lake Zug. We provide evidence for ongoing methane oxidation at the oxic/anoxic boundary and also in the anoxic hypolimnion, both apparently mediated by aerobic methane‐oxidizing bacteria. Gammaproteobacterial methanotrophs (gamma‐MOB) dominated the indigenous methanotrophic community and were active under all investigated conditions—oxic, sub‐oxic and anoxic. Methane oxidation was stimulated by the additions of oxygen or iron and manganese oxides under anoxic conditions. In the latter case, trace amounts of oxygen may have still been required for methane activation, yet these findings indicate that gamma‐MOB in Lake Zug might be able to respire electron acceptors other than oxygen. We propose that gamma‐MOB are actively removing methane also in anoxic lake waters, thus contributing to methane mitigation from these habitats.
How to Tackle the Challenge of siRNA Delivery with Sequence‐Defined Oligoamino Amides
Authors: Reinhard Sören , Wagner Ernst
Published: June 2016

RNA interference (RNAi) as a mechanism of gene regulation provides exciting opportunities for medical applications. Synthetic small interfering RNA (siRNA) triggers the knockdown of complementary mRNA sequences in a catalytic fashion and has to be delivered into the cytosol of the targeted cells. The design of adequate carrier systems to overcome multiple extracellular and intracellular roadblocks within the delivery process has utmost importance. Cationic polymers form polyplexes through electrostatic interaction with negatively charged nucleic acids and present a promising class of carriers. Issues of polycations regarding toxicity, heterogeneity, and polydispersity can be overcome by solid‐phase‐assisted synthesis of sequence‐defined cationic oligomers. These medium‐sized highly versatile nucleic acid carriers display low cytotoxicity and can be modified and tailored in multiple ways to meet specific requirements of nucleic acid binding, polyplex size, shielding, targeting, and intracellular release of the cargo. In this way, sequence‐defined cationic oligomers can mimic the dynamic and bioresponsive behavior of viruses.

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Sustainable Electrochemically‐Mediated Atom Transfer Radical Polymerization with Inexpensive Non‐Platinum Electrodes
Authors: Fantin Marco , Lorandi Francesca , Isse Abdirisak A. , Gennaro Armando
Published: June 2016

Electrochemically‐mediated atom transfer radical polymerization (eATRP) of oligo(ethylene oxide) methyl ether methacrylate in water is investigated on glassy carbon, Au, Ti, Ni, NiCr and SS304. eATRPs are performed both in divided and undivided electrochemical cells operating under either potentiostatic or galvanostatic mode. The reaction is fast, reaching high conversions in ≈4 h, and yields polymers with dispersity <1.2 and molecular weights close to the theoretical values. Most importantly, eATRP in a highly simplified setup (undivided cell under galvanostatic mode) with inexpensive nonnoble metals, such as NiCr and SS304, as cathode is well‐controlled. Additionally, these electrodes neither release harmful ions in solution nor react directly with the CX chain end and can be reused several times. It is demonstrated that Pt can be replaced with cheaper, and more readily available materials without negatively affecting eATRP performance.

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Sequestration of Methylene Blue into Polyelectrolyte Complex Coacervates
Authors: Zhao Mengmeng , Zacharia Nicole S.
Published: June 2016

Polyelectrolyte complex coacervation is a process that has been proposed as a model for protocell formation due to its ability to compartmentalize chemicals in solution without a membrane. During the liquid–liquid phase separation that results in water rich and polyelectrolyte rich phases, small molecules present in solution selectively partition to one phase over the other. This sequestration is based on relative affinities. Here, a study of the sequestration of methylene blue (MB) into the complex coacervate phase of three pairs of synthetic polyelectrolytes is presented; branched polyethylene imine with polyacrylic acid, polyvinyl sulfonate, or poly(4‐styrenesulfonic acid). These materials are characterized with UV–vis, zeta potential measurements, and dynamic light scattering. The branched polyethylene imine/poly(4‐styrenesulfonic acid) system is shown to have a significantly higher sequestration capacity for the MB as compared to either of the other two systems, based on π–π interactions which are not possible in the other systems.

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Data Analytics from Enroll‐HD, a Global Clinical Research Platform for Huntington's Disease
Authors: Landwehrmeyer Georg B. , Fitzer‐Attas Cheryl J. , Giuliano Joseph D. , Gonçalves Nilza , Anderson Karen E. , Cardoso Francisco , Ferreira Joaquim J. , Mestre Tiago A. , Stout Julie C. , Sampaio Cristina
Published: June 2016

Background

The study of complex neurodegenerative diseases is moving away from hypothesis‐driven biological methods toward large scale multimodal approaches, requiring standardized collaborative efforts. Enroll‐HD exemplifies such an integrated clinical research platform, designed and implemented to meet the research and clinical needs of Huntington's disease (HD). The aim of this study was to describe the unique organization of Enroll‐HD and report baseline data analyses of its core study.

Methods

The Enroll‐HD platform incorporates electronic data capture, biosampling, and a longitudinal observational study spanning four continents (ClinicalTrials.gov Identifier: NCT01574053). The primary study population includes HD gene expansion carriers (HDGECs; CAG expansion ≥36), subdivided into manifest/premanifest HD. The control population consists of genotype‐negative first‐degree relatives and family controls not genetically related. The study includes 10 core clinical assessments covering motor, cognitive, and behavioral domains.

Results

This data set comprises 1,534 participants (HDGEC = 1,071; controls = 463). Participant retention was high; 42 participants prematurely withdrew from the study. Mean ± standard deviation SD CAG repeat size was 43.5 ± 3.5 for HDGECs and 19.8 ± 3.4 for controls. Motor and behavioral assessments identified numerical differences between controls and HDGECs (manifest > premanifest > controls). Functional and independence assessments were generally similar for the premanifest and control groups with overlap in range of scores obtained. For the majority of cognitive tests, there were large differences between participants with manifest HD and all other groups.

Conclusions

These first data from the Enroll‐HD clinical research platform demonstrate the maturity and potential of the platform in collecting high‐quality, clinically relevant data. Future data sets will be substantially larger as the platform expands longitudinally and regionally.
An allosteric antibody to the leptin receptor reduces body weight and reverses the diabetic phenotype in the Lepob/Lepob mouse
Authors: Bhaskar Vinay , Goldfine Ira D. , Gerstner Resi , Michelson Kristen , Tran Catarina , Nonet Genevieve , Bohmann David , Pongo Elizabeth , Zhao Jingsong , Horwitz Arnold H. , Takeuchi Toshihiko , White Mark , Corbin John A.
Published: June 2016

Objective

Leptin (LEP) deficiency results in major metabolic perturbations, including obesity, dyslipidemia, and diabetes. Although LEP deficiency can be treated with daily injections of a recombinant LEP, generation of an antibody activating the LEP receptor (LEPR) that has both an intrinsically long half‐life and low immunogenicity could be useful in the treatment of this condition.

Methods

Phage display technology coupled with flow cytometry and cell‐based in vitro assays were employed to identify an allosteric agonist of the mouse LEPR. LEP‐deficient Lepob/Lepob mice were used to compare in vivo effects of LEP to antibody administration. To evaluate hypothalamic effects of treatment, changes in mRNA levels of neuropeptide Y and proopiomelanocortin were measured.

Results

XPA.80.037 is a monoclonal antibody that demonstrates allosteric agonism of the mouse LEPR. Treatment of Lepob/Lepob mice with XPA.80.037 markedly reduced hyperphagia and body weight, normalized blood glucose and plasma insulin levels, and corrected dyslipidemia. These metabolic alterations correlated with changes in mRNA levels of neuropeptide Y and proopiomelanocortin, suggesting that XPA.80.037 had hypothalamic effects.

Conclusions

Agonist allosteric monoclonal antibodies to the LEPR can correct metabolic effects associated with LEP deficiency in vivo and thereby have the potential to treat conditions of LEP deficiency.
How Do Nonprofits Respond to Regulatory Thresholds: Evidence From New York's Audit Requirements
Authors: St. Clair Travis
Published: June 2016

Nonprofits in the United States must comply with various state and federal regulations to maintain their tax‐exempt status. Despite persistent calls to increase accountability in the nonprofit sector, there is little research examining the burden imposed by existing regulatory requirements, especially at the state level. This paper uses a bunching design to estimate the avoidance behavior exhibited by tax‐exempt charities in response to New York State's audit requirements. There is clear evidence of bunching in response to the requirement that nonprofits above certain revenue thresholds file financial statements reviewed by or audited by an independent certified public accountant. Measuring the extent of bunching around the revenue notches yields estimates of the average revenue that nonprofits either forego or fail to report in avoidance of the requirements. Results from dynamic estimation show that charities near the threshold for a review engagement report approximately $1,300 less revenue than otherwise predicted by a counterfactual; charities near the threshold for a full audit report approximately $1,400 less. The results have implications for the optimal design of state‐level financial regulations.