bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence in Primary Health Care: Perceptions, Issues, and Challenges
Authors: Liyanage Harshana , Liaw Siaw-Teng , Jonnagaddala Jitendra , Schreiber Richard , Kuziemsky Craig , Terry Amanda L , de Lusignan Simon
Published: April 2019

Background: Artificial intelligence (AI) is heralded as an approach that might augment or substitute for the limited processing power of the human brain of primary health care (PHC) professionals. However, there are concerns that AI-mediated decisions may be hard to validate and challenge, or may result in rogue decisions.

Objective: To form consensus about perceptions, issues, and challenges of AI in primary care.

Method: A three-round Delphi study was conducted. Round 1 explored experts’ viewpoints on AI in PHC (n=20). Round 2 rated the appropriateness of statements arising from round one (n=12). The third round was an online panel discussion of findings (n=8) with the members of both the International Medical Informatics Association and the European Federation of Medical Informatics Primary Health Care Informatics Working Groups.

Results: PHC and informatics experts reported AI has potential to improve managerial and clinical decisions and processes, and this would be facilitated by common data standards. The respondents did not agree that AI applications should learn and adapt to clinician preferences or behaviour and they did not agree on the extent of AI potential for harm to patients. It was more difficult to assess the impact of AI-based applications on continuity and coordination of care.

Conclusion: While the use of AI in medicine should enhance healthcare delivery, we need to ensure meticulous design and evaluation of AI applications. The primary care informatics community needs to be proactive and to guide the ethical and rigorous development of AI applications so that they will be safe and effective.
Effectiveness of Compressive External Bracing in Patients with Flexible Pectus Carinatum Deformity: A Review
Authors: Hunt Ian , Patel Akshay Jatin
Published: April 2019

There has been a growing interest in the nonoperative treatment of chest wall deformities over the last few decades; with the advent of external compressive orthotics, similar outcomes have been reported compared with surgical intervention. There have been fewer major complications reported with dynamic compression bracing on the chest wall; however, the Achilles heel of this approach still lies with treatment tolerability and compliance. A Medline literature search was undertaken to evaluate the evidence concerning the techniques, modifications, and outcomes associated with external compressive bracing in the setting of pectus carinatum. Sixteen articles were integrated after literature review and data were collected on methods of assessing pectus carinatum (degree of severity as well as type), patient selection protocol (i.e., suitability for external compressive bracing), the bracing protocol itself, duration of treatment, metrics used to assess outcome, and success, compliance, and dropout rate, and length of long-term follow-up. Compressive external bracing appears to be a safe and well tolerated nonsurgical treatment option for young patients with flexible pectus carinatum deformities. However, there is still a need for robust level I randomized data from multiple centers with a clearly standardized bracing protocol, objective measurement of outcomes, and recording of results at the end of the bracing treatment program in sufficiently powered sample sizes over a significant follow-up period.
Accurate manipulation of optogenetic proteins with wavelength tunable femtosecond laser system
Authors: Ji Wanying , Wang Shaoyang , Zhao Jun , Tian Yu , Pan Huizhuo , Zheng Bin , Yang Minye , Tian Haochen , Hu Minglie , Wang Hanjie , Chang Jin
Published: April 2019

Photoactivated proteins controlled by optogenetic tools have broad application prospects in cell biology, neuroscience, and brain science. However, due to the narrow excitation wavelength width and the inflexibility of spatiotemporal operations, conventional sources such as visible light severely limit the further application of optogenetics. In this work, a femtosecond laser-operated system based on the optogenetic application was designed to address these limitations. The interaction between the photoreceptor and its partner protein can be triggered by a wavelength-tunable femtosecond laser. The results indicated that this process can be used to accurately manipulate optogenetic proteins in cells, which met spectral flexibility (700–1040 nm) and operational flexibility in time and space (a single cell to multiple cells). To demonstrate the practical applications of this process, the apoptotic signaling pathway of cancer cells was taken as an example. We believe that this wavelength-tunable femtosecond laser system will promote the development of optogenetics, making optics and even physics more powerful tools in biology.
A mass-selective ion transfer line coupled with a uniform supersonic flow for studying ion–molecule reactions at low temperatures
Authors: Joalland B. , Jamal-Eddine N. , Papanastasiou D. , Lekkas A. , Carles S. , Biennier L.
Published: April 2019

A new approach based on the uniform supersonic flow technique—a cold, thermalized de Laval expansion offering the advantage of performing experiments with condensable species—has been developed to study ion–molecule reactions at low temperatures. It employs a mass-selective radio frequency transfer line to capture and select ions from an adaptable ionization source and to inject the selected ions in the core of the supersonic expansion where rate coefficients and product branching can be measured from room temperature down to ∼15 K. The transfer line incorporates segmented ion guides combining quadrupolar and octapolar field orders to maximize transmission through the differential apertures and the large pressure gradients encountered between the ionization source (∼mbar), the quadrupole mass filter (∼10−5 mbar), and the de Laval expansion (∼mbar). All components were designed to enable the injection of cations and anions of virtually any m/z ratio up to 200 at near ground potential, allowing for a precise control over the momentum and thermalization of the ions in the flow. The kinetics and branching ratios of a selection of reactions have been examined to validate the approach. The technique will be instrumental in providing new insight on the reactivity of polyatomic ions and molecular cluster ions in astrophysical and planetary environments.
Solute transport in two-zone packed tube flow: Long-time asymptotic expansion
Authors: Jiang Weiquan , Chen Guoqian
Published: April 2019

Previous studies of solute transport in two-zone packed tube flows focused only on the cross-sectional mean concentration, a Gaussian distribution with advection velocity and Taylor dispersivity. This work analytically investigates the complete spatial concentration distribution. The two-dimensional (longitudinal and transverse) concentration distribution is obtained, by Chatwin’s long-time asymptotic technique: Edgeworth expansion. Non-Gaussian distribution effects like skewness and kurtosis are included in the asymptotic solution. Three cases with different porosity distributions between zones are studied to illustrate the impact of heterogeneity of media distributions on solute dispersion. The variation of porosity distributions can lead to great changes in velocity profiles, positions of local maxima of the concentration distribution, and basic characteristics of the cross-sectional mean concentration distribution, such as dispersivity, skewness, and kurtosis. Additionally, zones have largely different in zone-cross-sectional mean concentration distributions in the initial stage of solute transport.
Beam splitting and unidirectional cloaking using anisotropic zero-index photonic crystals
Authors: Yang Yuting , Jia Ziyuan , Xu Tao , Luo Jie , Lai Yun , Hang Zhi Hong
Published: April 2019

We propose an anisotropic photonic crystal (PC) structure with close-to-zero effective parameters. The anisotropic zero-index property of PCs provides complex iso-frequency contours, where their shapes can change from ellipses or hyperbolae to a linear crossing. A mechanism of light beam splitting can be achieved by utilizing the linear crossing shaped iso-frequency curve. The manipulation of light beam propagations is verified by both numerical simulations and microwave experiments. By using pure dielectrics and scaling down to optical wavelengths, we also propose a design of nonperiodic PC structures to achieve optical unidirectional cloaking without size or shape limitation. Our design provides a promising platform for cloaking applications in the optical regime.
Data-assisted physical modeling of oxygen precipitation in silicon wafers
Authors: Yang Yi , Sattler Andreas , Sinno Talid
Published: April 2019

A quantitative continuum model for oxide precipitation in silicon is presented that accounts for vacancy absorption and shape change as mechanisms of precipitate stress relief. All model parameters except one, the Si/SiO2 interface free energy, are fixed at values established in prior studies of microdefect formation. The interface free energy is described by an 8-parameter function, whose functional form and dependencies were based on an analysis of electronic structure calculations of small oxide cluster thermodynamics. The interface energy function parameters are regressed, using global optimization, to an experimental benchmark consisting of 13 wafer thermal anneals, with different temperature-time histories and resulting in widely varying measured final oxide precipitate densities. We demonstrate that the model is able to capture the benchmark features well with multiple parameter combinations and that additional constraints are required to fully specify a unique solution. We also show that a simple, single-parameter, constant interface free energy model cannot fully capture the diverse experimental benchmark, highlighting the complexity of oxide precipitation. The precipitation model is used to analyze the mechanisms responsible for several features of oxide nucleation and growth during wafer annealing.
Dynamic evolution of resistive kink mode with electron diamagnetic drift in tokamaks
Authors: Zhang W. , Ma Z. W. , Zhang H. W. , Zhu J.
Published: April 2019

The dynamic evolution of the m/n = 1/1 resistive kink mode with electron diamagnetic drift is investigated by employing a three-dimensional toroidal Hall-MHD code CLT. It is found that the dependence of the linear growth rate of the resistive kink mode on the electron diamagnetic drift velocity is associated with thermal conductivity. For a large thermal conductivity, the linear growth rate of the resistive kink mode monotonically decreases with increasing electron diamagnetic drift velocity. But, for a small thermal conductivity, the linear growth rate increases first and then decreases with increasing electron diamagnetic drift velocity, which is different from previous studies. The saturation level of the resistive kink mode decreases with increasing electron diamagnetic drift velocity.
Negative refraction characteristics of a kind of concave metamaterial
Authors: Zhao Guozhi , Bi Shihua
Published: April 2019

This paper proposed a metamaterial with a high trough, high bandwidth, and high quality negative refraction band. It is composed of an axisymmetric concave sheet metal, an annular coil, and two parallel planar metal wires, and has passed the classical triangle verification. The influence of oblique incidence on the performance of the device was analyzed, and the relationship between plasma frequency and cell size was studied. By using an ingenious test scheme, the free space measurement of electromagnetic parameters was completed.
Photonic thermal conduction by infrared plasmonic resonators in semiconductor nanowires
Authors: Tervo Eric J. , Gustafson Michael E. , Zhang Zhuomin M. , Cola Baratunde A. , Filler Michael A.
Published: April 2019

Photons typically do not contribute to thermal transport within a solid due to their low energy density and tendency to be absorbed quickly. We propose a practical material system—infrared plasmonic resonators embedded in a semiconductor nanowire—that leverages near-field electromagnetic coupling to achieve photonic thermal transport comparable to the electronic and phononic contributions. We analytically show photonic thermal conductivities up to about 1 W m−1 K−1 for 10 nm diameter Si and InAs nanowires containing repeated resonators at 500 K. The nanowire system outperforms plasmonic particles in isotropic environments and presents a pathway for photonic thermal transport to exceed that of phonons and electrons.
Adding new capabilities to a neutron-scattering instrument to provide enhanced materials imaging
Authors: Marchand Mark
Published: April 2019

New modality introduces energy-resolved imaging to existing facility in Australia.
Godly Poland in godless Europe
Authors: Gomola Aleksander
Published: April 2019

This chapter investigates Catholic-nationalist discourse in Poland after 2004 when the country joined the European Union, combining elements of the Discourse Historical Approach with a Cognitive Linguistics perspective. It focuses on conceptual metaphors for the Polish nation to demonstrate how they serve the Catholic Church in shaping Polish national identity in opposition to the common European project, and how the discourse in question is able to absorb the most significant national trauma in post-war Polish history – the Smoleńsk plane crash. Discursive practices aimed at shaping Polish national identity as a part of a broader European identity were examined by Krzyżanowski (2009) and Grimstad (2012). The discourse discussed in this chapter depicts these identities as incompatible and thus is “the other side of the coin” of the processes of conceptualizing Polish nationality after 2004.
“Let’s work on our Serbian!”
Authors: Vervaet Stijn
Published: April 2019

This chapter explores the use of metaphors in the column “Let’s Safeguard Serbian” in the Serbian newspaper Politika in 2015. In this column, adherents of the standard language ideology offered advice about spelling, loanwords, and syntax as well as regarding the name of the language and preferred alphabet. Drawing on critical discourse analysis and metaphor analysis, I examine the link between prescriptivism and contemporary discourses on Serbian national identity. I argue that most metaphors appearing in texts that fall into “the complaint tradition” (Milroy and Milroy) do not reveal a clear-cut link between prescriptivism and nationalism. However, the complaint tradition also reactivates a rich repository of conventional(ized) metaphors and metonymies that reach back to Romanticism and have much more far-reaching implications ideologically.
Guidelines on how to construct a nation
Authors: Grassi Silvia
Published: April 2019

This chapter focuses on the analysis of metaphors employed in the first episode of the television series Gran Nord (2012–2013) (Great North) broadcast in prime time by Catalan television. The chapter demonstrates that these metaphors contribute to the construction of ideological meanings around the spaces which constitute the fictional universe of the series in relation to the apparently conflicting aspects of the protagonist's identity. In order to achieve this, Conceptual Metaphor Theory and, in particular, Lakoff and Johnson’s Metaphorical Representation Theory (1980) and Lera Boroditsky’s Metaphoric Structuring View (2000) are employed.
To automated generation of test questions on the basis of error annotations in EFL essays
Authors: Vinogradova Olga
Published: April 2019

The paper presents computer tools that were designed to increase the pedagogical value of a learner corpus for teachers and learners of English as a foreign language. The corpus used in the study is a collection of essays written by Russian learners of English – students from four different cities in Russia, studying at different Bachelor programmes at the Higher School of Economics. The paper describes how the tools we offer make use of manually annotated errors for the process of automated generation of questions for English tests, what editing the generated tests requires, and in the final section there is a discussion to what degree this process appears to be useful for EFL instructors.
Complexity and qualitative lexical knowledge
Authors: Biel Albert
Published: April 2019

This paper presents research that investigates differences in the use of the high-frequency verb TAKE between German learners of English and American English native speakers. This study examined 724 instances of TAKE and their respective lexical-syntactic structures in the German part of the ICLE and a comparable American English speaker corpus (LOCNESS). The sentences are classified according to a framework of complexity of lexical-syntactic structures adopted from Liu and Shaw (2001). The results of this research suggest that there are no significant differences in usage between both groups. The general conception that non-native speakers overuse simple verbs due to restricted vocabulary does not hold true for TAKE in the German learner data in this study.
Cohesion or coesione?
Authors: D’Arienzo Meredith
Published: April 2019

This paper presents an analysis of the use of linking adjuncts in academic essays by L1 Italian learners as compared to native speakers of English using the revised Contrastive Interlanguage Analysis (CIA 2) method. Concordance analyses were performed for selected linking adjuncts in academic essays from the Italian subset of the International Corpus of Learner English (ICLE) and the Louvain Corpus of Native English Essays (LOCNESS). Log-likelihood values were calculated to identify cases of significant overuse and underuse. Next, the phraseological context surrounding the linking adjuncts was examined qualitatively. Results reveal variation in the use of some linking adjuncts by L1 Italian speakers as compared to native English speakers and show evidence of cross-linguistic influence. Implications include proposed pedagogic materials aimed at facilitating Italian learners’ acquisition of these cohesive devices.
Researching learner language through POS keyword and syntactic complexity analyses
Authors: Pérez-Paredes Pascual , Díez-Bedmar María Belén
Published: April 2019

In this paper, we explore the affordances of two different research methods that may be instrumental in analysing learner language complexity: standard corpus linguistics methodology and automatic syntactic complexity analysers. Our results suggest that POS keyword analysis and automatic syntactic analysis are both effective for the identification of linguistic features at different levels of development in instructed SLA. In particular, countable nouns, prepositional phrases, verbs and general adverbs are criterial features that define the transition from lower to higher secondary school language learning in the Spanish component of the ICCI corpus. We suggest that the analysis of complexity in noun phrases is of great interest for researchers and teachers in terms of identifying development milestones in language acquisition.
English intonation of advanced learners
Authors: Puga Karin
Published: April 2019

Adopting a corpus-based approach within the autosegmental-framework, this paper reports on a study on L2 learners’ intonational deviances of edge tones within intonational units in spontaneous speech in monologues and dialogues derived from a “Contrastive Interlanguage Analysis” (CIA) (cf. Granger 1996, 2015). The analysis reveals that German, Spanish, and British speakers of English deviate from each other in their intonational phrasing and pitch heights in utterance-final and -medial position. The learners break their utterances into considerably more intonation phrases (IP) and intermediate phrases (ip) than native-speakers. While the British native-speakers (n = 10) mainly stick to the usage of falls within IPs and ips, the German learners (n = 10) frequently use rising tones and the Spanish learners (n = 10) frequently use falling tones.
Song of Songs and Ecclesiastes
Authors: Givón T.
Published: April 2019

This book is a new English translation of the two shortest, most controversial and perhaps most vibrant books in the Hebrew Old Testament – Song of Songs (Song of Solomon) and Qohelet (Ecclesiastes). The two books slipped into the Jewish – and eventually Christian – Canon by a series of misrepresentations. The first, Song of Songs, is linguistically the latest book along the Biblical Hebrew dialect continuum, perhaps as late as 300–100 BC to judge by its language, which closely resembles Mishnaic Hebrew (2nd Cent. AD). The book is a lush, carnal poetic account of an illicit love affair, where lusty exchanges between the female beloved and her male lover are interspersed with rustic love songs. The ultimate provenance of the text may be older than the time it was recruited into the Canon, or the time suggested by its late dialect.The second book, Qohelet, is linguistically earlier on the Biblical Hebrew dialect continuum, though still following the return from the Babylonian exile (ca. 550 BC). Unlike Song of Songs, which is linguistically coherent and bears all the marks of having been produced by a native speaker (or speakers), Qohelet is replete with non-native lexical and grammatical usage, and was most likely produced by a speaker (or speakers) of Aramaic, the lingua franca of the Persian empire and the returning exiles. Multiple English translations of the two books exist. Nonetheless, in one way or another all previous translations suffer from two main drawbacks: First, their interpretation of the grammar – and on occasion also the vocabulary – of Biblical Hebrew is sometimes questionable. And second, the poetic quality of their English leaves much to be desired, paling in comparison with the stark beauty of the Hebrew original.This book attempts to do justice to both the contents and form of these two magnificent, deliciously subversive poetic works. The Hebrew texts and their English translation are preceded by two scholarly chapters, the first about the Biblical Hebrew dialect continuum , the second about the science and art of translation.
Chrysin reduces the activity and protein level of mature forms of sterol regulatory element-binding proteins
Authors: Iwase Masamori , Watanabe Kyoko , Shimizu Makoto , Suzuki Tsukasa , Yamamoto Yuji , Inoue Jun , Sato Ryuichiro
Published: April 2019

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of genes involved in fatty acid and cholesterol biosynthetic pathways. The present study showed that the flavonoid chrysin impairs the fatty acid synthase promoter. Chrysin reduces the expression of SREBP target genes, such as fatty acid synthase, in human hepatoma Huh-7 cells and impairs de novo synthesis of fatty acids and cholesterol. Moreover, it reduces the endogenous mature, transcriptionally active forms of SREBPs, which are generated by the proteolytic processing of precursor forms. In addition, chrysin reduces the enforced expressing mature forms of SREBPs and their transcriptional activity. The ubiquitin–proteasome system is not involved in the chrysin-mediated reduction of SREBPs mature forms. These results suggest that chrysin suppresses SREBP activity, at least partially, via the degradation of SREBPs mature forms.

Abbreviations: ACC1: acetyl-CoA carboxylase 1; DMEM: Dulbecco’s modified Eagle’s medium; FAS: fatty acid synthase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; 25-HC: 25-hydroxycholesterol; HMGCS: HMG-CoA synthase; LDH: lactate dehydrogenase; LPDS: lipoprotein-deficient serum; PI3K: phosphatidylinositol 3-kinase; SCD1: stearoyl-CoA desaturase; SREBPs: sterol regulatory element-binding proteins.
Structural basis for the nuclear import and export functions of the biportin Pdr6/Kap122
Authors: Aksu Metin , Trakhanov Sergei , Vera Rodriguez Arturo , Görlich Dirk
Published: April 2019

Importins ferry proteins into nuclei while exportins carry cargoes to the cytoplasm. In the accompanying paper in this issue (Vera Rodriguez et al. 2019. J. Cell Biol. https://doi.org/10.1083/jcb.201812091), we discovered that Pdr6 is a biportin that imports, e.g., the SUMO E2 ligase Ubc9 while depleting the translation factor eIF5A from the nuclear compartment. In this paper, we report the structures of key transport intermediates, namely, of the Ubc9•Pdr6 import complex, of the RanGTP•Pdr6 heterodimer, and of the trimeric RanGTP•Pdr6•eIF5A export complex. These revealed nonlinear transport signals, chaperone-like interactions, and how the RanGTPase system drives Pdr6 to transport Ubc9 and eIF5A in opposite directions. The structures also provide unexpected insights into the evolution of transport selectivity. Specifically, they show that recognition of Ubc9 by Pdr6 differs fundamentally from that of the human Ubc9-importer Importin 13. Likewise, Pdr6 recognizes eIF5A in a nonhomologous manner compared with the mammalian eIF5A-exporter Exportin 4. This suggests that the import of Ubc9 and active nuclear exclusion of eIF5A evolved in different eukaryotic lineages more than once and independently from each other.
Key comparison BIPM.RI(I)-K2 of the air-kerma standards of the NPL, UK, and the BIPM in low-energy x-rays
Authors: Burns D T , Kessler C , Kelly M , Maughan D J , Sander T
Published: April 2019

A key comparison has been made between the air-kerma standards of the NPL, UK and the BIPM in the low-energy x-ray range. The results indicate a progressive drift of the NPL standard, now lower than the BIPM standard by around 1 part in 102. The expanded uncertainty (k = 2) of the comparison is 4.2 parts in 103. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
A decomposition theorem for projective manifolds with nef anticanonical bundle
Authors: Cao Junyan , Höring Andreas
Published: April 2019

Let

X
X

be a simply connected projective manifold with nef anticanonical bundle. We prove that

X
X

is a product of a rationally connected manifold and a manifold with trivial canonical bundle. As an application we describe the MRC-fibration of any projective manifold with nef anticanonical bundle.
The message of Methodism
Authors: Abraham William J.
Published: April 2019

‘The message of Methodism’ refers to the complex network of doctrines that became essential to the teachings and identity of Methodism and considers its canonical sermons and crucial elements. Methodism is not a cult of John Wesley; it is a whole new vision of Christianity. While it clearly bears the imprint of John Wesley and the early leaders, it had to develop the doctrinal and intellectual resources to carry it across space and time. Its initial message was certainly furnished by Wesley, but it was not limited to Wesley. Moreover, given its mission to spread Christianity near and far, it necessarily made adjustments as best it could as it spread across the world.
The search for credible alternatives
Authors: Abraham William J.
Published: April 2019

The search for a viable alternative to classical Methodist teaching was taken up in earnest in the first half of the 20th century. If there was a failure of nerve in the effort to sustain the riches of the tradition, there was no lack of confidence in pursuing the quest for a better future intellectually. The basic strategy was to reach outside the boundaries of Methodism and find fitting materials that would replace the earlier orthodoxy. ‘The search for credible alternatives’ describes the work and impact of Albert Outler in the 1960s, new developments over the last fifty years, and present-day disputes and problems within Methodism.
1. What is reading?
Authors: Jack Belinda
Published: April 2019

What do we mean by reading? To understand reading we need to appeal to a wide range of disciplines: myriad forms of history, literary and textual studies, psychology, phenomenology, and sociology. What is now widely accepted is that reading is far more than the decoding of messages that have been previously encoded. ‘What is reading?’ considers the world’s earliest readers and the earliest examples of writing. It explains how the invention of paper in 105 ce triggered the extraordinary expansion of reading throughout East Asia. It also discusses the processes of learning to read and explains how literacy allows for the assimilation of useful knowledge and the means to communicate it.
4. The American century?
Authors: Preston Andrew
Published: April 2019

Despite rejecting the internationalist marriage Woodrow Wilson had arranged for it with the world, America was still the strongest state in the international system. ‘The American century?’ explains how the myth of isolationism emerged in this period, and why it was so powerful. The Depression did more damage to America’s role in the world than anything in the decades before it, yet in the late 1930s Franklin D. Roosevelt began rebuilding the structures of American power. Thanks to Roosevelt, during World War II the United States transitioned from a major, but often peripheral actor on the world scene, to one of the most powerful states the world has ever seen.
Use of Antihypertensive Medications and Survival Rates for Breast, Colorectal, Lung, or Stomach Cancer
Authors: Cui Yong , Wen Wanqing , Zheng Tao , Li Honglan , Gao Yu-Tang , Cai Hui , You Mingrong , Gao Jing , Yang Gong , Zheng Wei , Xiang Yong-Bing , Shu Xiao-Ou
Published: April 2019

Using time-dependent Cox regression models, we examined associations of common antihypertensive medications with overall cancer survival (OS) and disease-specific survival (DSS), with comprehensive adjustment for potential confounding factors. Participants were from the Shanghai Women’s Health Study (1996–2000) and Shanghai Men’s Health Study (2002–2006) in Shanghai, China. Included were 2,891 incident breast, colorectal, lung, and stomach cancer cases. Medication use was extracted from electronic medical records. With a median 3.4-year follow-up after diagnosis (interquartile range, 1.0–6.3), we found better outcomes among users of angiotensin II receptor blockers with colorectal cancer (OS: adjusted hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.44, 0.86; DSS: adjusted HR = 0.61, 95% CI: 0.43, 0.87) and stomach cancer (OS: adjusted HR = 0.62, 95% CI: 0.41, 0.94; DSS: adjusted HR = 0.63, 95% CI: 0.41, 0.98) and among users of β-adrenergic receptor blockers with colorectal cancer (OS: adjusted HR = 0.50, 95% CI: 0.35, 0.72; DSS: adjusted HR = 0.50, 95% CI: 0.34, 0.73). Better survival was also found for calcium channel blockers (DSS: adjusted HR = 0.67, 95% CI: 0.47, 0.97) and diuretics (OS: adjusted HR = 0.66, 95% CI: 0.45, 0.96; DSS: adjusted HR = 0.57, 95% CI: 0.38, 0.85) with stomach cancer. Our findings suggest angiotensin II receptor blockers, β-adrenergic receptor blockers, and calcium channel blockers might be associated with improved survival outcomes of gastrointestinal cancers.
Functional and chemical characterization of XAF: a heat-stable plant polymer that activates xyloglucan endotransglucosylase/hydrolase (XTH)
Authors: Nguyen-Phan Tu C , Fry Stephen C
Published: April 2019

Background and Aims

Xyloglucan endotransglucosylase/hydrolase (XTH) proteins that possess xyloglucan endotransglucosylase (XET) activity contribute to cell-wall assembly and remodelling, orchestrating plant growth and development. Little is known about in-vivo XET regulation, other than at the XTH transcriptional level. Plants contain ‘cold-water-extractable, heat-stable polymers’ (CHPs) which are XTH-activating factors (XAFs) that desorb and thereby activate wall-bound XTHs. Because XAFs may control cell-wall modification in vivo, we have further explored their nature.

Methods

Material was cold-water-extracted from 25 plant species; proteins were precipitated by heat-denaturation, then CHP was ethanol-precipitated. For XAF assays, CHP (or sub-fractions thereof) was applied to washed Arabidopsis thaliana cell walls, and the enzymes thus solubilized were assayed radiochemically for XET activity. In some experiments, the CHP was pre-treated with trifluoroacetic acid (TFA), alkali (NaOH) or glycanases.

Key Results

CHP specifically desorbed wall-bound XTHs, but not β-glucosidases, phosphatases or peroxidases. CHP preparations from 25 angiosperms all possessed XAF activity but had no consistent monosaccharide composition. Of 11 individual plant polymers tested, only gum arabic and tamarind xyloglucan were XAF-active, albeit less so than CHP. On gel-permeation chromatography, XAF-active cauliflower CHP eluted with a molecular weight of ~7000–140 000, although no specific sugar residue(s) co-eluted exactly with XAF activity. Cauliflower XAF activity survived cold alkali and warm dilute TFA (which break ester and glycofuranosyl linkages, respectively), but was inactivated by hot 2 m TFA (which breaks glycopyranosyl linkages). Cauliflower XAF activity was remarkably stable to diverse glycanases and glycosidases.

Conclusions

XAFs are naturally occurring heat-stable polymers that specifically desorb (thereby activating) wall-bound XTHs. Their XAF activity considerably exceeds that of gum arabic and tamarind xyloglucan, and they were not identifiable as any major plant polysaccharide. We propose that XAF is a specific, minor, plant polymer that regulates xyloglucan transglycosylation in vivo, and thus wall assembly and restructuring.
The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD)
Authors: Banovcin Peter , Duricek Martin , Zatko Tomas , Liptak Peter , Hyrdel Rudolf , Kollarik Marian
Published: April 2019

Recent studies in animal models have reported that some afferent fibers innervating the esophagus express the cold receptor TRPM8. In the somatosensory system the stimulation of TRPM8 leads to cold sensations and in certain circumstances alleviates pain. It is therefore hypothesized in this paper that the esophageal infusion of the TRPM8 activator menthol evokes cold sensations from the esophagus and alleviates heartburn in humans. The esophageal infusion of menthol (3 mM, 20 min) evoked cold sensations in 11 of 12 healthy subjects. In striking contrast, the esophageal infusion of menthol evoked heartburn in 10 of 10 patients with gastroesophageal reflux disease (GERD). In healthy subjects the cold sensation evoked by menthol was perceived only as a minor discomfort as evaluated by the visual analog scale (VAS score 1.9 ± 0.3 on the scale 1–10). However, in patients with GERD the menthol-induced heartburn was perceived as painful (VAS score 5.6 ± 0.6, P < 0.01 compared to healthy subjects). It is concluded that the sensations evoked by esophageal infusion of menthol change from relatively nonpainful cold sensations in healthy subjects to painful heartburn sensations in patients with GERD. These qualitative and quantitative changes indicate substantial alterations in afferent signaling mediating sensations from the esophagus in patients with GERD.
It’s not ageing, stupid: why population ageing won’t bankrupt health systems
Authors: Jayawardana Sahan , Cylus Jonathan , Mossialos Elias
Published: April 2019

An ageing population is often viewed as a factor that will increase healthcare expenditures (HCE) to unsustainable levels. With nearly half the disease burden in high-income countries arising in older people, there are concerns that caring for a burgeoning older population that is sick and dependent on support will not be possible. The aim of this narrative review is to examine how population ageing is likely to affect future HCE growth. We find that despite the increasing share of older people over the next few decades, the changing age-mix will not be a significant driver of HCE growth. While older people, on average, incur higher per person healthcare spending than younger people, the proportions of the population at the oldest and most costly age groups increase very slowly over time. In the European Union, we estimate the changing age-mix to result in the increase of the average annual growth in per person health spending by no more than 0.6 additional percentage points per year between 2015 and 2050. Therefore, price growth and technological advancements, independent of population ageing, will be the main contributors to future HCE growth.
Strategy instruction for successful language tandems
Authors: Webster Simon
Published: April 2019

Educational institutions are placing increased value on language tandems owing to the language development opportunities they offer for learners of modern languages. Where these learners lack autonomous language learning strategies, however, the results can be disappointing, with limited linguistic development taking place. This paper reports on recent research into the language tandem experiences of international study abroad students during their period of study at a British university. When it became apparent that the students lacked skills in managing their language tandems to meet their learning needs, strategy instruction was introduced to facilitate more effective language learning strategy use. The findings suggest that such an intervention can significantly increase learners’ ability to create a language tandem which meets their learning needs.
Women have lower chances than men to be resuscitated and survive out-of-hospital cardiac arrest
Authors: Blom Marieke T , Oving Iris , Berdowski Jocelyn , van Valkengoed Irene G M , Bardai Abdenasser , Tan Hanno L
Published: April 2019

Aims

Previous studies on sex differences in out-of-hospital cardiac arrest (OHCA) had limited scope and yielded conflicting results. We aimed to provide a comprehensive overall view on sex differences in care utilization, and outcome of OHCA.

Methods and results

We performed a population-based cohort-study, analysing all emergency medical service (EMS) treated resuscitation attempts in one province of the Netherlands (2006–2012). We calculated odds ratios (ORs) for the association of sex and chance of a resuscitation attempt by EMS, shockable initial rhythm (SIR), and in-hospital treatment using logistic regression analysis. Additionally, we provided an overview of sex differences in overall survival and survival at successive stages of care, in the entire study population and in patients with SIR. We identified 5717 EMS-treated OHCAs (28.0% female). Women with OHCA were less likely than men to receive a resuscitation attempt by a bystander (67.9% vs. 72.7%; P < 0.001), even when OHCA was witnessed (69.2% vs. 73.9%; P < 0.001). Women who were resuscitated had lower odds than men for overall survival to hospital discharge [OR 0.57; 95% confidence interval (CI) 0.48–0.67; 12.5% vs. 20.1%; P < 0.001], survival from OHCA to hospital admission (OR 0.88; 95% CI 0.78–0.99; 33.6% vs. 36.6%; P = 0.033), and survival from hospital admission to discharge (OR 0.49, 95% CI 0.40–0.60; 33.1% vs. 51.7%). This was explained by a lower rate of SIR in women (33.7% vs. 52.7%; P < 0.001). After adjustment for resuscitation parameters, female sex remained independently associated with lower SIR rate.

Conclusion

In case of OHCA, women are less often resuscitated by bystanders than men. When resuscitation is attempted, women have lower survival rates at each successive stage of care. These sex gaps are likely explained by lower rate of SIR in women, which can only partly be explained by resuscitation characteristics.
Less dementia and stroke in low-risk patients with atrial fibrillation taking oral anticoagulation
Authors: Friberg Leif , Andersson Tommy , Rosenqvist Mårten
Published: April 2019

Aims

To investigate if patients with atrial fibrillation (AF) without clear indication for oral anticoagulant (OAC) due to perceived low stroke risk may benefit from OAC treatment when also dementia and intracerebral bleeding risks are considered.

Methods and results

Retrospective study of cross-matched national registries of all individuals in Sweden with a hospital diagnosis of AF between 2006 and 2014 (n = 456 960). Exclusion was made of patients with a baseline CHA2DS2-VASc score >1, not counting female sex, and of patients with previous diagnosis of dementia or intracranial bleeding. After exclusions, 91 254 patients remained in the study of whom 43% used OAC at baseline. Propensity score matching and falsification endpoints were used. Treatment with OAC was associated with lower risk of dementia after adjustment for death as a competing risk [subhazard ratio (sHR) 0.62 with 95% confidence interval (CI) 0.48–0.81]. Regarding the composite brain protection endpoint, OAC treatment was associated with an overall 12% lower risk (sHR 0.88, CI 0.72–1.00). This apparent benefit was restricted to patients aged >65 years, whereas OAC treatment of patients <60 years of age without risk factors appeared to do more harm than good.

Conclusion

Low-risk AF patients who take OAC have lower risk of dementia than those who do not use OAC. Patients age >65 years appear to benefit from OAC treatment irrespective of stroke risk score.
Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction
Authors: Li Ziwen , Solomonidis Emmanouil G , Meloni Marco , Taylor Richard S , Duffin Rodger , Dobie Ross , Magalhaes Marlene S , Henderson Beth E P , Louwe Pieter A , D’Amico Gabriela , Hodivala-Dilke Kairbaan M , Shah Ajay M , Mills Nicholas L , Simons Benjamin D , Gray Gillian A , Henderson Neil C , Baker Andrew H , Brittan Mairi
Published: April 2019

Aims

A better understanding of the pathways that regulate regeneration of the coronary vasculature is of fundamental importance for the advancement of strategies to treat patients with heart disease. Here, we aimed to investigate the origin and clonal dynamics of endothelial cells (ECs) associated with neovascularization in the adult mouse heart following myocardial infarction (MI). Furthermore, we sought to define murine cardiac endothelial heterogeneity and to characterize the transcriptional profiles of pro-angiogenic resident ECs in the adult mouse heart, at single-cell resolution.

Methods and results

An EC-specific multispectral lineage-tracing mouse (Pdgfb-iCreERT2-R26R-Brainbow2.1) was used to demonstrate that structural integrity of adult cardiac endothelium following MI was maintained through clonal proliferation by resident ECs in the infarct border region, without significant contributions from bone marrow cells or endothelial-to-mesenchymal transition. Ten transcriptionally discrete heterogeneous EC states, as well as the pathways through which each endothelial state is likely to enhance neovasculogenesis and tissue regeneration following ischaemic injury were defined. Plasmalemma vesicle-associated protein (Plvap) was selected for further study, which showed an endothelial-specific and increased expression in both the ischaemic mouse and human heart, and played a direct role in regulating human endothelial proliferation in vitro.

Conclusion

We present a single-cell gene expression atlas of cardiac specific resident ECs, and the transcriptional hierarchy underpinning endogenous vascular repair following MI. These data provide a rich resource that could assist in the development of new therapeutic interventions to augment endogenous myocardial perfusion and enhance regeneration in the injured heart.
Time-to-isolation-guided cryoballoon ablation reduces oesophageal and mediastinal alterations detected by endoscopic ultrasound: results of the MADE-PVI trial
Authors: Cordes Friederike , Ellermann Christian , Dechering Dirk G , Frommeyer Gerrit , Kochhäuser Simon , Lange Philipp S , Pott Christian , Lenze Frank , Schmidt Hartmut , Ullerich Hansjoerg , Eckardt Lars
Published: April 2019

Aims

Cryoballoon ablation is safe and efficient for achieving pulmonary vein isolation (PVI) in atrial fibrillation. Structural oesophago-mediastinal lesions, which seem to be associated with an increased risk of the lethal complication of an atrio-oesophageal fistula, have been described. MADE-PVI (Mediastino-oesophageal Alterations Detected by Endosonography after PVI) aimed at evaluating safety of cryoballoon PVI in relation to two different freeze protocols. As time-to-isolation-(TTI)-guided protocol has been reported to be as effective as conventional ‘two freeze protocol’, we hypothesized a TTI-guided protocol causes less oesophago-mediastinal lesions.

Methods and results

Seventy consecutive patients were scheduled for cryoballoon (2nd generation) PVI employing either a conventional protocol (n = 35: 2 × 180 s per vein) or a TTI-guided approach (n = 35: TTI + 120 s per vein or 1 × 180 s in case TTI could not be measured). Oesophagogastroduodenoscopy and endoscopic ultrasound, assessing oesophago-mediastinal alterations (e.g. ulceration, oedema) were performed blinded prior and post-ablation. Post-interventional mediastinal oedematous alterations were detected in 70% with a mean diameter of 14 mm (±0.9 mm), while only 15% revealed large mediastinal oedema >20 mm. Oesophageal lesions due to PVI occurred in 5%. Freeze protocols had a distinct impact on oesophago-mediastinal alterations as mean diameter and frequency of large oedema were significantly increased in patients after conventional protocol PVI (17 mm vs. 11 mm; 26% vs. 6%). Furthermore, every oesophageal lesion was detected in patients with conventional protocol (9%). No major complication occurred in either group.

Conclusion

The present prospective study demonstrates a significant impact of freeze protocol on oesophago-mediastinal alterations. A TTI-guided protocol reduces mediastino-oesophageal lesions and may reduce short- and long-term complications of cryoballoon PVI.
Nitrogen dynamics of decomposing Scots pine needle litter depends on colonizing fungal species
Authors: Baskaran Preetisri , Ekblad Alf , Soucémarianadin Laure N , Hyvönen Riitta , Schleucher Jürgen , Lindahl Björn D
Published: April 2019

In boreal ecosystems plant production is often limited by low availability of nitrogen. Nitrogen retention in below-ground organic pools plays an important role in restricting recirculation to plants and thereby hampers forest production. Saprotrophic fungi are commonly assigned to different decomposer strategies, but how these relate to nitrogen cycling remains to be understood. Decomposition of Scots pine needle litter was studied in axenic microcosms with the ligninolytic litter decomposing basidiomycete Gymnopus androsaceus or the stress tolerant ascomycete Chalara longipes. Changes in chemical composition were followed by 13C CP/MAS NMR spectroscopy and nitrogen dynamics was assessed by the addition of a 15N tracer. Decomposition by C. longipes resulted in nitrogen retention in non-hydrolysable organic matter, enriched in aromatic and alkylic compounds, whereas the ligninolytic G. androsaceus was able to access this pool, counteracting nitrogen retention. Our observations suggest that differences in decomposing strategies between fungal species play an important role in regulating nitrogen retention and release during litter decomposition, implying that fungal community composition may impact nitrogen cycling at the ecosystem level.