bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio investigation of the formation of ZrO2-like structures upon the adsorption of Zrn on the CeO2(111) surface
Authors: Mucelini Johnatan , Costa-Amaral Rafael , Seminovski Yohanna , Da Silva Juarez L. F.
Published: December 2018

The adsorption of Zr on the CeO2 surfaces can lead to the formation of ZrO2-like structures, which can play a crucial role in the catalytic properties of CexZr1−xO2 as support for transition-metal catalysts; however, our atomistic understanding is far from satisfactory, and hence, it affects our capacity to engineer the combination of ZrO2–CeO2 for catalysis applications. Here, we investigate the adsorption of Zrn (n = 1 − 4) atoms on CeO2(111) surfaces through density functional theory with the Hubbard model and bring new insights into the Zr–CeO2 interaction and the formation of ZrO2-like structures on ceria. We found that the Zr atoms oxidize to Zr4+ and strongly interact with the O2− anions, reducing the surface Ce4+ cations to Ce3+ (4 Ce atoms per Zr adatom), which stabilizes the system by more than 10 eV per Zr. As more Zr is adsorbed, the O2− species migrate from the sub-surface to interact with the on-surface Zr adatoms in hcp sites, producing a full ZrO2-like monolayer, which contributes to reduce the strain induced by the increased size of the Ce3+ cations compared with Ce4+. The simulated partial and full ZrO2-like structure thicknesses agree with the experimental measurements. In addition, we found an unprecedented trend for the on-surface Zr atoms: our calculations show that they are less stable than Zr replacing Ce3+ atoms from the first cation layer. Therefore, under sufficiently high temperatures, one expects the formation of a Ce2O3-like/c-ZrO2/CeO2 structure, which may completely change the reactivity of the surface.
Thermal and caloric properties of fluids from non-equilibrium molecular dynamics simulations using the two-gradient method
Authors: Lautenschlaeger Martin P. , Hasse Hans
Published: December 2018

Transport properties of fluids can be determined efficiently from non-equilibrium molecular dynamics simulations using the two-gradient method which was introduced recently. It is shown here that thermal and caloric properties of fluids can also be determined accurately and efficiently along with the transport properties using this method. In a single run, all these properties are obtained for a series of state points at different temperatures and constant pressure. The truncated and shifted Lennard-Jones fluid is studied here as a test case. Data are reported for about 700 state points in the range of T = [0.7, 8.5] and ρ = [0.2, 1.0]. Besides data on the thermal conductivity, shear viscosity, and self-diffusion, the following thermal and caloric properties were measured: pressure p, internal energy u, enthalpy h, isobaric heat capacity cp, and thermal expansion coefficient αp. The results of the thermal and caloric properties agree very well with those from an accurate equation of state from the literature. Also the shear rate dependence of these properties can be studied easily with the two-gradient method.
Quantum dynamics studies of the dissociative chemisorption of CH4 on the steps and terraces of Ni(211)
Authors: Guo Han , Menzel Jan Paul , Jackson Bret
Published: December 2018

The dissociative chemisorption of CH4 on the stepped Ni(211) surface is explored. The H and CH3 fragments preferentially bind to the surface along the step edge, and the barriers to dissociation are lowest over the step edge atoms, with activation energies of 0.57 and 0.69 eV, depending upon the orientation of the dissociating bond. The activation energy for dissociation over a terrace atom is much larger, 0.99 eV. Quantum scattering calculations show that dissociation over the lowest barrier step edge site dominates the reactive scattering, except at very high collision energies, where the second step edge transition state becomes important. Even at incident energies of 1.0 eV, reaction over the terrace atoms contributes only about 3% to the total dissociative sticking. The symmetric stretch excitation has the largest efficacy for promoting reaction, with the other modes having somewhat smaller efficacies. While the vibrational properties of the step edge atoms are different from those on the terrace, reactions at both sites exhibit a similar variation with temperature. We find good agreement with experimental measurements of the thermally averaged sticking probability on a Ni step edge.
Exploring the challenges of computational enzyme design by rebuilding the active site of a dehalogenase
Authors: Jindal Garima , Slanska Katerina , Kolev Veselin , Damborsky Jiri , Prokop Zbynek , Warshel Arieh
Published: December 2018

Significance

The goal of rational computer-aided enzyme design is hampered by the lack of knowledge of the maximum possible rate enhancement. We address this problem by considering the enzyme DhlA, which is naturally adapted for the degradation of dihalogenated ethanes. Using empirical valence bond calculations, we determine the effect of finding mutations that reduce the catalysis and then introducing mutations that restore catalysis. One of our predicted cycles is confirmed experimentally, while the other attempt remains inconclusive. We believe that the proposed strategy provides a very powerful way of validating and refining approaches for computational enzyme design.
Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells
Authors: Tominaga Kana , Minato Hiroshi , Murayama Takahiko , Sasahara Asako , Nishimura Tatsunori , Kiyokawa Etsuko , Kanauchi Hajime , Shimizu Seiichiro , Sato Ayaka , Nishioka Kotoe , Tsuji Ei-ichi , Yano Masao , Ogawa Toshihisa , Ishii Hideshi , Mori Masaki , Akashi Koichi , Okamoto Koji , Tanabe Masahiko , Tada Kei-ichiro , Tojo Arinobu , Gotoh Noriko
Published: December 2018

Significance

Tumors are composed of both cancer stem-like cells (CSCs) and differentiated cancer cells. Each CSC can undergo either a symmetric cell division to produce two CSCs or an asymmetric cell division to produce one CSC and one differentiated cancer cell. It is believed that the rate of symmetric division increases as more CSCs become malignant; however, underlying molecular mechanisms remain elusive. Here we show that stimulation with a cytokine, semaphorin (Sema), activates monooxygenase of MICAL3, a cytoplasmic signal transducer, through the neuropilin (NP) receptor that is specifically expressed on the breast CSC plasma membrane. The activation of MICAL3 induces symmetric division of CSCs. Each molecule in this signaling pathway represents a promising therapeutic target for eliminating CSCs.
Climate network percolation reveals the expansion and weakening of the tropical component under global warming
Authors: Fan Jingfang , Meng Jun , Ashkenazy Yosef , Havlin Shlomo , Schellnhuber Hans Joachim
Published: December 2018

Significance

Climate change could threaten our society through impacts on social, cultural, and natural resources. Here, we develop an approach based on percolation theory and climate network frameworks to detect and quantify the impacts of past and future climate change. Our method of analysis provides a perspective on the evolution of climate systems in response to global warming and can potentially be used for predicting the consequences of future climate changes. Furthermore, our study may also enrich and facilitate the understanding of discontinuous phase transitions.
Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti–CTLA-4 antibody
Authors: Ha Danbee , Tanaka Atsushi , Kibayashi Tatsuya , Tanemura Atsushi , Sugiyama Daisuke , Wing James Badger , Lim Ee Lyn , Teng Karen Wei Weng , Adeegbe Dennis , Newell Evan W. , Katayama Ichiro , Nishikawa Hiroyoshi , Sakaguchi Shimon
Published: December 2018

Significance

Anti–CTLA-4 mAb is able to augment tumor immunity despite CTLA-4 expression by functionally opposing T cell populations: activated effector T (Teff) cells and FOXP3+CD4+Treg cells. Here we show that anti–CTLA-4 mAb engineered to be cytotoxic depleted Treg cells effectively in vitro in humans and in vivo in mice. It expanded antigen-specific CD8+Teff cells when tumor-antigen stimulation was delayed several days to protect them from killing by the mAb. Anti–CTLA-4 mAb modified to exhibit a lesser or no cell-depleting activity failed to show such effects. This strategy of differentially controlling Treg and Teff cells by cytotoxic anti–CTLA-4 mAb to evoke effective tumor immunity will help in designing cancer immunotherapy targeting other molecules commonly expressed by Treg and Teff cells.
IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses
Authors: Santana Carrero Rosa M. , Beceren-Braun Figen , Rivas Sarai C. , Hegde Shweta M. , Gangadharan Achintyan , Plote Devin , Pham Gabriel , Anthony Scott M. , Schluns Kimberly S.
Published: December 2018

Significance

Expression and regulation of IL-15 in the tumor microenvironment are poorly understood and are important as studies have provided correlative data that IL-15 expression within human tumors is a critical factor dictating antitumor responses. Moreover, IL-15 utilizes unique mechanisms that preclude typical expression analyses. Herein we demonstrate using multiple tumor models that soluble (s) IL-15/IL-15Rα complexes are expressed in tumors and regulate tumor-infiltrating lymphocyte numbers. While the levels of sIL-15 complexes are low in established tumors, IL-15–expressing myeloid cells are abundant. Nonetheless, providing a local inflammatory signal upregulates sIL-15 complexes within the tumor and drives tumor regression in an IL-15–dependent manner. Thus, our findings reveal a strategy for unleashing a natural resource within tumors that enhances antitumor responses.
Modular reconfiguration of an auditory control brain network supports adaptive listening behavior
Authors: Alavash Mohsen , Tune Sarah , Obleser Jonas
Published: December 2018

Speech comprehension in noisy, multitalker situations poses a challenge. Successful behavioral adaptation to a listening challenge often requires stronger engagement of auditory spatial attention and context-dependent semantic predictions. Human listeners differ substantially in the degree to which they adapt behaviorally and can listen successfully under such circumstances. How cortical networks embody this adaptation, particularly at the individual level, is currently unknown. We here explain this adaptation from reconfiguration of brain networks for a challenging listening task (i.e., a linguistic variant of the Posner paradigm with concurrent speech) in an age-varying sample of
n
= 49 healthy adults undergoing resting-state and task fMRI. We here provide evidence for the hypothesis that more successful listeners exhibit stronger task-specific reconfiguration (hence, better adaptation) of brain networks. From rest to task, brain networks become reconfigured toward more localized cortical processing characterized by higher topological segregation. This reconfiguration is dominated by the functional division of an auditory and a cingulo-opercular module and the emergence of a conjoined auditory and ventral attention module along bilateral middle and posterior temporal cortices. Supporting our hypothesis, the degree to which modularity of this frontotemporal auditory control network is increased relative to resting state predicts individuals’ listening success in states of divided and selective attention. Our findings elucidate how fine-tuned cortical communication dynamics shape selection and comprehension of speech. Our results highlight modularity of the auditory control network as a key organizational principle in cortical implementation of auditory spatial attention in challenging listening situations.
Toward understanding cancer stem cell heterogeneity in the tumor microenvironment
Authors: Bocci Federico , Gearhart-Serna Larisa , Boareto Marcelo , Ribeiro Mariana , Ben-Jacob Eshel , Devi Gayathri R. , Levine Herbert , Onuchic José Nelson , Jolly Mohit Kumar
Published: December 2018

Significance

The presence of heterogeneous subsets of cancer stem cells (CSCs) remains a clinical challenge. These subsets often occupy different regions in the primary tumor and have varied epithelial–mesenchymal phenotypes. Here, we devise a theoretical framework to investigate how the tumor microenvironment (TME) modulates this spatial patterning. We find that a spatial gradient of EMT-inducing signal, coupled with juxtacrine Notch-JAG1 signaling triggered by inflammatory cytokines in TME, explains this spatial heterogeneity. Finally, in vitro JAG1 knockdown in triple-negative breast cancer SUM149 cells severely restricts the growth of tumor organoid, hence validating the association between JAG1 and CSC fraction. Our results offer insights into principles of spatiotemporal patterning in TME and identify a relevant target to alleviate multiple CSC subsets: JAG1.
The textual colligation of stance phraseology in cross-disciplinary academic discourse
Authors: Dong Jihua , Buckingham Louisa
Published: December 2018

This study investigates the textual colligation of stance phrases at the levels of sentence, paragraph and text in empirical research articles from agriculture and economics. We extracted the textual positions of stance phrases with the softwareWordskew(Barlow, 2016) in two purpose-built corpora of around three million tokens. The results show that stance phrases display similar distribution patterns in the two disciplinary corpora; however, we found significant differences with respect to the frequency of stance phrases in particular textual positions in each corpus. The findings consolidateHoey’s (2005)premise that certain expressions are primed to occur in particular textual positions. We contend that the textual positions of stance phrases may be a result of the routinised discourse function that they serve, and that the appropriate timing of stance-taking is of particular communicative importance.
Solving contradictions in semantic prosody analysis with prosody concord
Authors: Tang Xuri , Liu Gaixiang
Published: December 2018

Using collocation-based approaches, semantic prosody analyses of lemmas likealleviateandcureyield judgments of negative prosody, which contradict common sense. This poses a challenge to the concept of semantic prosody and the principle of co-occurrence. To solve such contradictions, this paper proposes a new approach to semantic prosody analysis named ‘prosody concord’. The approach adopts collostruction as the locus of analysis on the basis of the explication of the unit of meaning model, and uses a mechanism for semantic prosody determination that incorporates multiple sources of information such as interactions of words, collocations, colligations and semantic preferences. Case studies of the lemmasbudge, credibility, causeandalleviateshow that the proposed approach can solve the contradictions and provide a consistent means for semantic prosody analysis.
Academic lexical bundles
Authors: Hyland Ken , Jiang Feng (Kevin)
Published: December 2018

An important component of fluent linguistic production and a key distinguishing feature of particular modes,
registers and genres is the multi-word expressions referred to as ‘lexical bundles’. These are extended collocations which appear
more frequently than expected by chance, helping to shape meanings and contributing to our sense of coherence and distinctiveness
in a text. These strings have been studied extensively, particularly in academic writing in English, but little is known about how
they may have changed over time. In this paper we explore changes in their use and frequency over the past 50 years, drawing on a
corpus of 2.2 million words taken from top research journals in four disciplines. We find that bundles are not static and
invariant markers of research writing but change in response to new conditions and contexts, with the most interesting changes
within disciplines. The paper also discusses methodological approaches to studying bundles diachronically.
An analysis of morphosyntactic variation in the Old Spanish future and conditional
Authors: Graham Lamar A.
Published: December 2018

The presence of two forms of the future and conditional paradigms in Old Spanish is well-attested. The analytic form, which was marked by a mesoclitic, was more syntactically restricted, while the synthetic form, which surfaced with either a proclitic or an enclitic, was essentially free to appear in any syntactic context. It is notable that the analytic form was only acceptable in contexts in which finite verbs obligatorily hosted enclitics. In this article, I test various morphosyntactic factors to determine the level of variation among the analytic and synthetic future and conditional forms across six centuries of Old Spanish. The factors of verb tense, preverbal constituent, and verb stem morphology significantly affect the emergence of mesoclisis or enclisis, as does the century during which the verb is produced; however, subject expression is not a significant factor.
Re-evaluating the reconstruction of Proto-Eskimo-Aleut
Authors: Berge Anna
Published: December 2018

The relationship between Unangam Tunuu (Aleut) and Eskimo was established in the early 19th century, and the 20th century especially saw a number of efforts on the reconstruction of Proto-Eskimo-Aleut (PEA). Reconstruction has supported assumptions of a largely genealogical relationship between the EA languages, assumptions which include a long history of independent development in isolation from other languages and language families. The reconstruction of PEA, however, is incomplete; many apparent cognates have irregular or imperfectly understood sound correspondences. Furthermore, advances in archaeology and genetics have called into question many assumptions about EA prehistory and about the isolation or lack thereof of Unangam Tunuu. In this study, I re-examine the proposed cognates and evaluate them based on the strength of their correspondences and their distribution within the lexicon, with reference to new findings regarding technological innovations and periods of cultural contact. Several patterns emerge, including a large group of proposed cognates with overly-specific semantic correlations relating to technologies or cultural practices post-dating the split of EA languages, a gender-based difference in the number of cognates relating to cultural activities, and a correlation between known borrowings and high levels of cognates in certain semantic domains. Results suggest extensive language contact, especially in the past millennium.
The discourse functions ofcertainlyand its Spanish counterparts in journalistic opinion discourse
Authors: Pérez Blanco María
Published: December 2018

This paper explores the discourse functions ofcertainlyand its Spanish equivalents in the genre of newspaper opinion discourse. Certainty markers seem to have a presence intrinsic to the opinion genre and, therefore, are expected to “exhibit a certain uniformity across languages” (Dafouz, 2008, p. 110). Whereas the non-correspondence betweencertainlyandciertamentesoon becomes apparent, the results of earlier studies (Ramón, 2009;Carretero, 2012) might well lead to the hypothesis that the PPssin dudaanddesde luegorealize in Spanish opinion articles the same discourse functions ascertainlydoes in English newspapers. Drawing on naturally-occurring linguistic data from a corpus of English and Spanish opinion texts (C-OPRES), this study (1) investigates the non-correspondence between cognates and (2) explores the aforesaid research hypothesis. Finally, a translation corpus is used (P-ACTRES) to address the complex relationships between seemingly equivalent words, filling in the gaps of the contrastive analysis. The findings reveal a partial overlap betweencertainlyand its Spanish counterparts as epistemic markers or in concessive contexts; whereas there are also significant differences in the distribution of other discourse functions, mainly regarding the emphasizing use ofcertainlyand the grammaticalization of its so-called equivalents in Spanish as textual and/or interpersonal discourse markers.
Understanding bilingualism in La Mancha schools
Authors: Relaño Pastor Ana María
Published: December 2018

This article discusses narratives of bilingualism told in parental group interviews conducted as part of the critical sociolinguistic ethnography carried out in public and semi-private bilingual schools of the autonomous region of Castilla-La Mancha (Spain). School stakeholders in this region are still adapting to the rapid implementation of bilingual programs in this region, which are transforming classroom linguistic practices and circulating discourses about bilingualism, bilingual education, and the bilingual subject. Among them, families are trying to reconcile their language desires and aspirations for English and bilingualism with the understanding of the type of bilingual education their children are receiving. By taking a social interactional approach to narrative combined with anthropological approaches to the study of conversational narrative, this article analyzes parents’ emotional and moral stancetaking in narratives of bilingualism. The narrative analysis will shed light on how families in Castilla-La Mancha are appropriating bilingualism as ideology and practice in the highly commodified global market of English.
Correlates of health in adolescent elite athletes and adolescents: A cross‐sectional study of 1016 adolescents
Authors: von Rosen Philip , Olofsson Oskar , Väsbom Sebastian , Heijne Annette
Published: December 2018

The primary aim of this cross‐sectional study was to compare subjective correlates of health, such as nutrition, self‐esteem, sleep and stress, between adolescent elite athletes (n = 625) and a reference group of adolescents (n = 391) not involved in elite sports. A secondary aim was to study predictors for self‐perceived stress. A questionnaire was e‐mailed to all participants containing valid questions about competence‐based self‐esteem, nutrition, self‐perceived stress and sleep. Our results show that adolescent elite athletes reported significantly (p < .001) lower self‐perceived stress, competence‐based self‐esteem, a more varied diet and more time of sleep, compared to adolescents not involved in elite sports (Hedges'g 0.31–0.82). Female adolescent elite athletes and female adolescents, compared to their male peer group, reported poorer values for competence‐based self‐esteem (elite, Hedges'g 0.29; adolescents, Hedges'g 0.30) and self‐perceived stress (elite, Hedges'g 0.63; adolescents, Hedges'g 0.60). The linear mixed effect model revealed several significant (p < .05) predictors (sex, general well‐being, competence‐based self‐esteem, sleep during weekdays, BMI, training volume) associated with self‐perceived stress in adolescent elite athletes. In conclusion, differences in correlates of health with a moderate to strong effect sizes were found between the two groups, where elite athletes surprisingly reported less stress, competence‐based self‐esteem, a more varied diet and more time of sleep. Even if injury risk is high in adolescent elite athletes and pressure from multiple stakeholders is evident, it appears that the athletes still have better conditions for a good subjective health, based on self‐reported measures, compared to adolescents not involved in elite sports.
Optimizing recovery to support multi‐evening cycling competition performance
Authors: Richard Normand A , Koehle Michael S
Published: December 2018

Road criterium and track bicycle racing occur at high speeds, demand repeated high power outputs, last 10–90 min, and offer little chance for recovery after the event. Consecutive evenings of criterium and track racing are respectively known as speed‐week or six‐day events and take place in evening hours over the course of a week. Given the schedule and timing of these competitions, return to homeostasis can be compromised. No recommendations exist on how to optimize recovery for cyclists participating in these types of repeated evening competitions. Criterium and track cyclists spend considerable time, near and above the individual lactate threshold and therefore mostly utilize carbohydrate as their chief energy substrate. Henceforth, pre – and post‐race nutrition and hydration is examined and recommendations are brought forward for carbohydrate, protein, and fluid intake. As evening high‐intensity exercise perturbs sleep, strategies to optimize sleep are discussed and recommendations for an optimal sleep environment are given. Active recovery is examined, and the benefits of a short duration low intensity exercise reviewed. Passive recovery methods such as compression garments and cold water immersion are recommended, while evidence for massage, pneumatic compression devices, and neuromuscular electrical stimulation is still lacking. Optimizing recovery strategies will facilitate a return to the resting state following strenuous night competition.
An external focus of attention promotes flow experience during simulated driving
Authors: Harris David J. , Vine Samuel J. , Wilson Mark R.
Published: December 2018

Achieving a state of flow is associated with positive experiences and improved sporting performance (Jackson & Csikszentmihalyi, 1999). Focused attention is a fundamental component of the flow experience, but to date there has been little investigation of whether attention plays a causal role in creating flow, or is a product of it. Consequently, this study aimed to test the effect of an attentional focus manipulation on flow and performance in a simulated driving task. It was predicted that an external focus would lead to improved visuomotor control, greater flow experience and improved performance. Thirty‐three participants from a student population completed the driving task under both internal and external focus instructions. Eye movements and steering wheel movements were recorded during each race. Participants reported greater flow experience (p < .001, d = 1.78) and enhanced outcome expectancies (p = .02, d = 0.41) under external, compared to internal focus conditions, however, there was no effect on visuomotor control (gaze‐steering coordination and steering entropy) or racing performance (ps > 0.28). These findings suggest that adopting an external focus of attention may contribute to positive performance states such as flow.
A high-avidity biosensor reveals plasma membrane PI(3,4)P2 is predominantly a class I PI3K signaling product
Authors: Goulden Brady D. , Pacheco Jonathan , Dull Allyson , Zewe James P. , Deiters Alexander , Hammond Gerald R.V.
Published: December 2018

Class I phosphoinositide 3-OH kinase (PI3K) signaling is central to animal growth and metabolism, and pathological disruption of this pathway affects cancer and diabetes. However, the specific spatial/temporal dynamics and signaling roles of its minor lipid messenger, phosphatidylinositol (3,4)-bisphosphate (PI(3,4)P2), are not well understood. This owes principally to a lack of tools to study this scarce lipid. Here we developed a high-sensitivity genetically encoded biosensor for PI(3,4)P2, demonstrating high selectivity and specificity of the sensor for the lipid. We show that despite clear evidence for class II PI3K in PI(3,4)P2-driven function, the overwhelming majority of the lipid accumulates through degradation of class I PI3K-produced PIP3. However, we show that PI(3,4)P2 is also subject to hydrolysis by the tumor suppressor lipid phosphatase PTEN. Collectively, our results show that PI(3,4)P2 is potentially an important driver of class I PI3K-driven signaling and provides powerful new tools to begin to resolve the biological functions of this lipid downstream of class I and II PI3K.
Enhancement of tristable energy harvesting using stochastic resonance
Authors: Jin Yanfei , Xiao Shaoming , Zhang Yanxia
Published: December 2018

In this paper, stochastic resonance (SR) is exploited within a tristable electromechanical coupled system to enhance energy harvesting. Assuming that the effective capacitance of the piezoelectric element can be neglected, the coupled electromechanical equations are converted to a second-order stochastic differential equation. Using the adiabatic approximation and the linear response theory, the spectral amplification of the equivalent tristable mechanical system is obtained to characterize the SR. It is observed that the spectral amplification exhibits a maximum as a function of the nonlinear stiffness coefficients and noise intensity. That is, both parameter-optimized SR and traditional SR are found in this system, which can be used to amplify the amplitude of the system response and enhance the performance of nonlinear vibration energy harvesting. Moreover, the efficiency in power conversion and the RMS voltage obtained under the SR effect are much higher than those harvested under ambient random vibration alone. The theoretical results are well verified through the numerical simulations of the original electromechanical coupled system.
Correspondence Between Objective and Self-reported Endocrine Therapy Adherence Among Women With Breast Cancer
Authors: Bright Emma E , Stanton Annette L
Published: December 2018

Background

Among the approximately 70% of women with hormone receptor-positive breast cancer, endocrine therapies lower the likelihood of recurrence. Nonadherence to endocrine therapy predicts lower survival.

Purpose

We examined concordance between self-reported and objective indicators of adherence and predictors of over-reporting endocrine therapy adherence among survivors of breast cancer.

Methods

Women with breast cancer (N = 112) receiving their initial endocrine therapy prescription completed three assessments at prescription initiation (Time 1), 1 month (Time 2), and 4 months later (Time 3). At Time 1, participants were provided a medication event monitoring system (MEMS) cap to assess adherence; it was collected at Time 3. Women completed items regarding self-reported adherence, depressive symptoms, cancer-related coping processes, and the patient–physician relationship.

Results

MEMS was significantly negatively correlated with the self-reported nonadherence measurements of occasionally forgetting (Time 2, ρ = −.29, p < .01; Time 3, ρ = −.24, p < .01), nonadherence in the past week (Time 2, ρ = −.53, p < .01; Time 3, ρ = −.45, p < .01), and nonadherence in an average week in the past month (Time 2, ρ = −.38, p < .01; Time 3, ρ = −.39, p < .01). Concordance in objective and self-reported adherence measures was evident in 83% of women at Time 2 and 73% at Time 3. Older age was significantly associated (p < .01) with discordance.

Conclusions

Findings reveal moderate correspondence between objective and self-report measures, with self-report overestimating objective adherence. Clinicians should be aware when treating older breast cancer survivors that they are more likely to over self-report their endocrine therapy adherence.
Lapatinib-induced annexin A6 upregulation as an adaptive response of triple-negative breast cancer cells to EGFR tyrosine kinase inhibitors
Authors: Widatalla Sarrah E , Korolkova Olga Y , Whalen Diva S , Goodwin J Shawn , Williams Kevin P , Ochieng Josiah , Sakwe Amos M
Published: December 2018

The epidermal growth factor receptor (EGFR) is a major oncogene in triple-negative breast cancer (TNBC), but the use of EGFR-targeted tyrosine kinase inhibitors (TKI) and therapeutic monoclonal antibodies is associated with poor response and acquired resistance. Understanding the basis for the acquired resistance to these drugs and identifying biomarkers to monitor the ensuing resistance remain a major challenge. We previously showed that reduced expression of annexin A6 (AnxA6), a calcium-dependent membrane-binding tumor suppressor, not only promoted the internalization and degradation of activated EGFR but also sensitized TNBC cells to EGFR-TKIs. Here, we demonstrate that prolong (>3 days) treatment of AnxA6-low TNBC cells with lapatinib led to AnxA6 upregulation and accumulation of cholesterol in late endosomes. Basal extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation was EGFR independent and significantly higher in lapatinib-resistant MDA-MB-468 (LAP-R) cells. These cells were more sensitive to cholesterol depletion than untreated control cells. Inhibition of lapatinib-induced upregulation of AnxA6 by RNA interference (A6sh) or withdrawal lapatinib from LAP-R cells not only reversed the accumulation of cholesterol in late endosomes but also led to enrichment of plasma membranes with cholesterol, restored EGFR-dependent activation of ERK1/2 and sensitized the cells to lapatinib. These data suggest that lapatinib-induced AnxA6 expression and accumulation of cholesterol in late endosomes constitute an adaptive mechanism for EGFR-expressing TNBC cells to overcome prolong treatment with EGFR-targeted TKIs and can be exploited as an option to inhibit and/or monitor the frequently observed acquired resistance to these drugs.
Is quality of life impairment associated with chronic diseases dependent on educational level?
Authors: Galenkamp Henrike , van Oers Hans A M , Kunst Anton E , Stronks Karien
Published: December 2018

Background

Previous research indicates that quality of life impairment as a result of chronic diseases differs between socioeconomic groups, but the pattern seems to vary between health-related quality of life (HRQOL) outcomes. We tested for a one-item and a multi-item outcome whether associations between diseases and HRQOL varied between educational levels.

Methods

Data come from Dutch participants of HELIUS (N =4615, aged 18–70). Education was defined as low, middle or high. Myocardial infarction, angina pectoris, hypertension, diabetes, obesity and depressed mood were measured using physical examination and/or self-report. Outcomes were fair/poor self-rated health (SRH) and physical (PCS) and mental (MCS) SF-12 scores. Interaction terms and relative excess risk due to interaction (RERI) were used as measures of additive interaction.

Results

SRH and PCS were worst in lower educated participants, whereas MCS was worst in middle educated participants. Out of thirty-six interactions tested, four were statistically significant, with risks of poor HRQOL being both larger and smaller in low vs. high education groups. Obesity was associated with smaller risk of fair/poor SRH in low vs. high educated [RERI=−2.49 (−4.66; −0.33)]. Depressed mood was associated with more [b=−3.34 (−6.14; −0.54)] and hypertension with less reduction in PCS [b=1.23 (0.18; 2.27)] in middle vs. high educated. Depressed mood was highly associated with MCS, but less so in middle vs. high educated [b=4.09 (0.72; 7.47)].

Conclusion

Despite a higher prevalence of diseases in low education groups, if measured in absolute terms, most diseases were not associated with larger impairment of HRQOL in lower vs. higher educated groups, regardless of the outcome measure used.
Assessment of temperature-dependent proteomes of Pythium insidiosum by using the SWISS-PROT database
Authors: Krajaejun Theerapong , Reamtong Onrapak , Lohnoo Tassanee , Yingyong Wanta , Thammasudjarit Ratchainant
Published: December 2018

Pythium insidiosum causes the life-threatening disease, called pythiosis. Information on microbial pathogenesis could lead to an effective method of infection control. This study aims at assessing temperature-dependent proteomes, and identifying putative virulence factors of P. insidiosum. Protein extracts from growths at 25°C and 37°C were analyzed by mass spectrometry and SWISS-PROT database. A total of 1052 proteins were identified. Upon exposure to increased temperature, 219 proteins were markedly expressed, eight of which were putative virulence factors of P. insidiosum. These temperature-dependent proteins should be further investigated for their roles in pathogenesis, and some of which could be potential therapeutic targets.
Stimulation of the Tractography-Defined Subthalamic Nucleus Regions Correlates With Clinical Outcomes
Authors: Avecillas-Chasin Josue M , Alonso-Frech Fernando , Nombela Cristina , Villanueva Clara , Barcia Juan A
Published: December 2018

BACKGROUND

Although deep brain stimulation (DBS) of the dorsolateral subthalamic nucleus (STN) is a well-established surgical treatment for patients with Parkinson disease (PD), there is still controversy about the relationship between the functional segregation of the STN and clinical outcomes.

OBJECTIVE

To correlate motor and neuropsychological (NPS) outcomes with the overlap between the volume of activated tissue (VAT) and the tractography-defined regions within the STN.

METHODS

Retrospective study evaluating 13 patients with PD treated with STN-DBS. With the aid of tractography, the STN was segmented into 4 regions: smaSTN (supplementary motor area STN), m1STN (primary motor area STN), mSTN (the sum of the m1STN and the smaSTN segments), and nmSTN (non-motor STN). We computed the overlap coefficients between these STN regions and the patient-specific VAT. The VAT outside of the STN was also calculated. These coefficients were then correlated with motor (Unified Parkinson's Disease Rating Scale, UPDRS III) and NPS outcomes.

RESULTS

Stimulation of the mSTN segment was significantly correlated with UPDRS III and bradykinesia improvement. Stimulation of the smaSTN segment, but not the m1STN one, had a positive correlation with bradykinesia improvement. Stimulation of the nmSTN segment was negatively correlated with the improvement in rigidity. Stimulation outside of the STN was correlated with some beneficial NPS effects.

CONCLUSION

Stimulation of the tractography-defined motor STN, mainly the smaSTN segment, is positively correlated with motor outcomes, whereas stimulation of the nmSTN is correlated with poor motor outcomes. Further validation of these results might help individualize and optimize targets prior to STN-DBS.
Microsurgical Strategies for the Treatment of Compression Neuropathies Secondary to Vertebrobasilar Dolichoectasia: From Simple Decompression to Sling Transposition
Authors: Barrow Daniel L , Ellis Jason A
Published: December 2018

BACKGROUND

Vertebrobasilar artery dolichoectasia may result in neural element compression anywhere along its course within the cervical region, the craniocervical junction or in the posterior fossa. The clinical syndromes most often observed include cranial neuropathy, bulbar dysfunction, myelopathy and cervical radiculopathy. When indicated, the operative techniques utilized to address vertebrobasilar artery dolichoectasia must be individually tailored, can be technically challenging, and have been rarely expounded.

OBJECTIVE

To share selected cases that demonstrate the variety of pathological states caused by vertebrobasilar artery dolichoectasia as well as our experience in managing this condition.

METHODS

Here we review examples of pathological impingement of neural elements compressed by ectasia within the vertebrobasilar arterial system throughout its anatomic course. The surgical techniques we have employed to alleviate the compression, including simple decompression as well as sling-assisted arterial transposition, are described. The evolution and refinement of our transposition technique are detailed.

RESULTS

A wide range of pathological conditions may result from compression of neural structures throughout the course of the vertebrobasilar system. Compression of cervical nerve roots, the spinal cord, brainstem, and cranial nerves can be seen. Microsurgical management may be indicated in selected cases with gratifying results.

CONCLUSION

Pathological compression of neural structures throughout the course of the vertebrobasilar system should be recognized. When indicated, microsurgical decompression must be tailored to the individual symptomology and the unique anatomic relationship in each case with the potential to prevent neurological worsening and, in many cases, improve functional outcome.
Tomato Stress-Associated Protein 4 Contributes Positively to Immunity Against Necrotrophic Fungus Botrytis cinerea
Authors: Liu Shixia , Yuan Xi , Wang Yuyan , Wang Hui , Wang Jiali , Shen Zhihui , Gao Yizhou , Cai Jiating , Li Dayong , Song Fengming
Published: December 2018

Stress-associated proteins (SAPs) are A20 and AN1 domain–containing proteins, some of which play important roles in plant stress signaling. Here, we report the involvement of tomato SlSAP family in immunity. SlSAPs responded with different expression patterns to Botrytis cinerea and defense signaling hormones. Virus-induced gene silencing of each of the SlSAP genes and disease assays revealed that SlSAP4 and SlSAP10 play roles in immunity against B. cinerea. Silencing of SlSAP4 resulted in attenuated immunity to B. cinerea, accompanying increased accumulation of reactive oxygen species and downregulated expression of jasmonate and ethylene (JA/ET) signaling-responsive defense genes. Transient expression of SlSAP4 in Nicotiana benthamiana led to enhanced resistance to B. cinerea. Exogenous application of methyl jasmonate partially restored the resistance of the SlSAP4-silenced plants against B. cinerea. SlSAP4 interacted with three of four SlRAD23 proteins. The A20 domain in SlSAP4 and the Ub-associated domains in SlRAD23d are critical for SlSAP4-SlRAD23d interaction. Silencing of SlRAD23d led to decreased resistance to B. cinerea, but silencing of each of other SlRAD23s did not affect immunity against B. cinerea. Furthermore, silencing of SlSAP4 and each of the SlRAD23s did not affect immunity to Pseudomonas syringae pv. tomato DC3000. These data suggest that SlSAP4 contributes positively to tomato immunity against B. cinereal through affecting JA/ET signaling and may be involved in the substrate ubiquitination process via interacting with SlRAD23d.
Problem Setting and Problem Solving in the Case of Olive Quick Decline Syndrome in Apulia, Italy: A Sociological Approach
Authors: Colella Christian , Carradore Roberto , Cerroni Andrea
Published: December 2018

This article gives an account of the social construction of phytopathological knowledge in the case of olive quick decline syndrome (OQDS) in Apulia, Italy. Due to the economic, cultural, and social importance of the olive crop, the spread of this disease has been characterized by a social debate over the implementation of mandatory phytosanitary policies, the etiological role played by the bacterium Xylella fastidiosa, the role of scientific experts, and the unexplored research trajectories (“undone science”) proposed by social and environmental movements. We examine how the disease has generated different approaches to problem setting and problem solving, one focused on OQDS as a complex of symptoms uniquely caused by X. fastidiosa, and the other framing the study of “complesso del disseccamento rapido dell’olivo” (CoDiRO) as a complex of causes. Drawing on a 2-year ethnographic study among researchers, policymakers, agricultural stakeholders, and social movements, this article uses theoretical concepts from the sociology of knowledge, sociology of scientific knowledge, and sociology of ignorance to examine the case and to reconstruct the 360° approach proposed by social movements as an alternative to the epistemic and political reductionism of official phytosanitary and science policies.
“I didn’t want to be on Suboxone at first…” – Ambivalence in Perinatal Substance Use Treatment
Authors: Ostrach Bayla , Leiner Catherine
Published: December 2018

Objectives:

The objectives of this article are to present findings from recent qualitative research with patients in a combined perinatal substance use treatment program in Central Appalachia, and to describe and analyze participants’ ambivalence about medication-assisted treatment for opioid use disorder (OUD), in the context of widespread societal stigma and judgement.

Methods:

We conducted research in a comprehensive outpatient perinatal substance use treatment program housed in a larger obstetric practice serving a large rural, Central Appalachian region. The program serves patients across the spectrum of substance use disorders but specifically offers medication-assisted treatment to perinatal patients with OUD. We purposively and opportunistically sampled patients receiving prescriptions for buprenorphine or buprenorphine-naloxone dual product, along with prenatal care and other services. Through participant-observation and semi-structured interviews, we gathered qualitative data from 27 participants, in a total of 31 interviews. We analyzed transcripts of interviews and fieldnotes using modified Grounded Theory.

Results:

Participants in a combined perinatal substance use treatment program value supportive, non-judgmental care but report ambivalence about medication, within structural and institutional contexts of criminalized, stigmatized substance use and close scrutiny of their pregnancies. Women are keenly aware of the social and public consequences for themselves and their parenting, if they begin or continue medication treatment for OUD.

Conclusions:

Substance use treatment providers should consider the social consequences of medication treatment, as well as the clinical benefits, when presenting treatment options and recommendations to patients. Patient-centered care must include an understanding of larger social and structural contexts.
Quantitative Assessment of Muscle Strength Following “Slow” Surgical Lengthening of the Medial Hamstring Muscles in Children With Cerebral Palsy
Authors: Davids Jon R. , Cung Nina Q. , Sattler Kelly , Boakes Jennette L. , Bagley Anita M.
Published: December 2018

Background:

Classic teaching for surgical lengthening of muscle contractures in children with cerebral palsy (CP) has emphasized complete correction of the deformity acutely, with immobilization of the targeted muscles in the fully corrected position. Clinical experience has led to the impression that the muscles are invariably weakened by this approach. We have developed an alternative technique for correction of contractures called slow surgical lengthening (SSL). The goal of the study was to determine the physical examination, kinematic, and muscle strength outcomes following SSL of the medial hamstring muscles in children with CP.

Methods:

The study group included 41 children with CP who underwent SSL of the medial hamstring muscles as part of a comprehensive single-event multilevel surgery, who had preoperative and 1-year postoperative evaluations in our Motion Analysis Center, which included quantitative assessment of isometric and isokinetic muscle strength.

Results:

All subjects were Gross Motor Function Classification System I and II. Mean age at the time of surgery was 10.8 years. The mean popliteal angle improved by 16.2 degrees (P<0.001) following SSL of the medial hamstrings. Sagittal plane kinematics following SSL of the medial hamstrings showed improvement of knee extension at initial contact of 10.2 degrees (P<0.001), decrease of peak knee flexion in mid-swing of 3.6 degrees (P=0.014), improved minimum knee flexion in stance of 4.9 degrees (P=0.002), and no significant change in mean anterior pelvic tilt (P=0.123). Mean peak isometric knee flexion torque remained unchanged from preoperative to postoperative studies (P=0.154), whereas mean peak isokinetic knee flexion torque significantly increased by 0.076 Nm/kg (P=0.014) following medial hamstring SSL.

Discussion:

SSL was developed based upon clinical experience and improved understanding of the pathophysiology of skeletal muscle in children with CP. The SSL technique allows the tendinous tissue to separate spontaneously at the time of recession, but does not force further acute lengthening by intraoperative manipulation, thereby minimizing the damage to the underlying muscle. It is broadly believed that muscle weakness is inevitable following surgical lengthening. The current study shows that the SSL technique does not cause weakness.

Level of Evidence:

Level IV—therapeutic.