bluuebunny/crossref_metadata_2025 huggingface dataset:
Plk1 Inhibition Enhances the Efficacy of BET Epigenetic Reader Blockade in Castration-Resistant Prostate Cancer
Authors: Mao Fengyi , Li Jie , Luo Qian , Wang Ruixin , Kong Yifan , Carlock Colin , Liu Zian , Elzey Bennet D. , Liu Xiaoqi
Published: May 2018

Polo-like kinase 1 (Plk1), a crucial regulator of cell-cycle progression, is overexpressed in multiple types of cancers and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that antineoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the β-catenin pathway and increased expression of c-MYC, eventually resulting in resistance to Plk1 inhibition. JQ1, a selective small-molecule inhibitor targeting the amino-terminal bromodomains of BRD4, has been shown to dramatically inhibit c-MYC expression and AR signaling, exhibiting antiproliferative effects in a range of cancers. Because c-MYC and AR signaling are essential for prostate cancer initiation and progression, we aim to test whether targeting Plk1 and BRD4 at the same time is an effective approach to treat prostate cancer. Herein, we show that a combination of Plk1 inhibitor GSK461364A and BRD4 inhibitor JQ1 had a strong synergistic effect on castration-resistant prostate cancer (CRPC) cell lines, as well as in CRPC xenograft tumors. Mechanistically, the synergistic effect is likely due to two reasons: (i) Plk1 inhibition results in the accumulation of β-catenin in the nucleus, thus elevation of c-MYC expression, whereas JQ1 treatment directly suppresses c-MYC transcription; (ii) Plk1 and BRD4 dual inhibition acts synergistically in inhibition of AR signaling. Mol Cancer Ther; 17(7); 1554–65. ©2018 AACR.
Nuclear Receptor CAR Suppresses GADD45B-p38 MAPK Signaling to Promote Phenobarbital-induced Proliferation in Mouse Liver
Authors: Hori Takeshi , Saito Kosuke , Moore Rick , Flake Gordon P. , Negishi Masahiko
Published: May 2018

Phenobarbital, a nongenotoxic hepatocarcinogen, induces hepatic proliferation and promotes development of hepatocellular carcinoma (HCC) in rodents. Nuclear receptor constitutive active/androstane receptor (NR1I3/CAR) regulates the induction and promotion activities of phenobarbital. Here, it is demonstrated that phenobarbital treatment results in dephosphorylation of a tumor suppressor p38 MAPK in the liver of C57BL/6 and C3H/HeNCrlBR mice. The molecular mechanism entails CAR binding and inhibition of the growth arrest and DNA-damage-inducible 45 beta (GADD45B)-MAPK kinase 6 (MKK6) scaffold to repress phosphorylation of p38 MAPK. Phenobarbital-induced hepatocyte proliferation, as determined by BrdUrd incorporation, was significantly reduced in both male and female livers of GADD45B knockout (KO) mice compared with the wild-type mice. The phenobarbital-induced proliferation continued until 48 hours after phenobarbital injection in only the C57BL/6 males, but neither in males of GADD45B KO mice nor in females of C57BL/6 and GADD45B KO mice. Thus, these data reveal nuclear receptor CAR interacts with GADD45B to repress p38 MAPK signaling and elicit hepatocyte proliferation in male mice.

Implications: This GADD45B-regulated male-predominant proliferation can be expanded as a phenobarbital promotion signal of HCC development in future studies.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/8/1309/F1.large.jpg. Mol Cancer Res; 16(8); 1309–18. ©2018 AACR.
Descobrindo a contínua realidade das mediações, ou redescobrindo a história de nosso campo de investigação
Authors: Couldry Nick
Published: May 2018

In this article, Nick Couldry author remember his encounter with the book De los medios a las mediaciones, highlighting points that mark the innovative character of the Jesus Martín-Barbero’s work. In his conclusion, the author indicates that Jesús Martín-Barbero and his work must be properly inserted in the global history of communication studies.
Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups
Authors: Breathett Khadijah , Leng Iris , Foraker Randi E. , Abraham William T. , Coker Laura , Whitfield Keith E. , Shumaker Sally , Manson JoAnn E. , Eaton Charles B. , Howard Barbara V. , Ijioma Nkechinyere , Cené Crystal W. , Martin Lisa W. , Johnson Karen C. , Klein Liviu , Rossouw Jacques , Ludlam Shari , Burwen Dale , McGowan Joan , Ford Leslie , Geller Nancy , Anderson Garnet , Prentice Ross , LaCroix Andrea , Kooperberg Charles , Stefanick Marcia L. , Jackson Rebecca , Thomson Cynthia A. , Wactawski-Wende Jean , Limacher Marian , Wallace Robert , Kuller Lewis
Published: May 2018

Background:

The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups.

Methods and Results:

In the WHI (Women’s Health Initiative; 1993–2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (
P
<0.0001, interaction of race/ethnicity and RF number
P
=0.18)—African-Americans 1 RF: 1.80 (1.01–3.20), 2 RFs: 3.19 (1.84–5.54), 3+ RFs: 7.31 (4.26–12.56); Whites 1 RF: 1.27 (1.04–1.54), 2 RFs: 1.95 (1.60–2.36), 3+ RFs: 4.07 (3.36–4.93); Hispanics 1 RF: 1.72 (0.68–4.34), 2 RFs: 3.87 (1.60–9.37), 3+ RFs: 8.80 (3.62–21.42). Risk of death before developing HF increased with subsequent RFs (
P
<0.0001) but differed by racial/ethnic group (interaction
P
=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (
P
=0.25; interaction
P
=0.48).

Conclusions:

Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.
Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy
Authors: Pradhan Aruna D. , Aday Aaron W. , Rose Lynda M. , Ridker Paul M
Published: May 2018

Background:

The combination of statin therapy and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain.

Methods:

We evaluated residual inflammatory risk among 9738 patients participating in the SPIRE-1 and SPIRE-2 cardiovascular outcomes trials (Studies of PCSK9 Inhibition and the Reduction in Vascular Events), who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRP
OT
) and LDL-C
OT
measured 14 weeks after drug initiation. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death.

Results:

At 14 weeks, the mean percentage change in LDL-C among statin-treated patients who additionally received bococizumab was −60.5% (95% confidence interval [CI], −61.2 to −59.8;
P
<0.001; median change, −65.4%) as compared to 6.6% (95% CI, −1.0 to 14.1;
P
=0.09; median change, 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to hsCRP
OT
<1, 1 to 3, and >3 mg/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI, 0.81–1.66), and 1.62 (95% CI, 1.14–2.30) (
P
-trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-C
OT
. Comparable adjusted hazard ratios for LDL-C
OT
(<30, 30–50, >50 mg/dL) were 1.0, 0.87, and 1.21, respectively (
P
-trend=0.16). Relative risk reductions with bococizumab were similar across hsCRP
OT
groups (
P
-interaction=0.87).

Conclusions:

In this post hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and proprotein convertase subtilisin-kexin type 9 inhibition.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT01975376, NCT01975389.
Hyperplane-Approximation-Based Method for Many-Objective Optimization Problems with Redundant Objectives
Authors: Li Yifan , Liu Hai-Lin , Goodman E. D.
Published: May 2018

For a many-objective optimization problem with redundant objectives, we propose two novel objective reduction algorithms for linearly and, nonlinearly degenerate Pareto fronts. They are called LHA and NLHA respectively. The main idea of the proposed algorithms is to use a hyperplane with non-negative sparse coefficients to roughly approximate the structure of the PF. This approach is quite different from the previous objective reduction algorithms that are based on correlation or dominance structure. Especially in NLHA, in order to reduce the approximation error, we transform a nonlinearly degenerate Pareto front into a nearly linearly degenerate Pareto front via a power transformation. In addition, an objective reduction framework integrating a magnitude adjustment mechanism and a performance metric [Formula: see text] are also proposed here. Finally, to demonstrate the performance of the proposed algorithms, comparative experiments are done with two correlation-based algorithms, LPCA and NLMVUPCA, and with two dominance-structure-based algorithms, PCSEA and greedy [Formula: see text]MOSS, on three benchmark problems: DTLZ5(I,M), MAOP(I,M), and WFG3(I,M). Experimental results show that the proposed algorithms are more effective.
Description of Tripylella jianjuni sp. n. (Nematoda: Tripylidae) from New Zealand
Authors: Xu Yumei , Leduc Daniel , Ye Weimin , Zhao Zengqi
Published: May 2018

Tripylella jianjunisp. n. (Tripylidae) is described from New Zealand. Females are characterised by a relatively long body (1743 (1675-1860)μm in the female and 1747 (1576-1979)μm in the male), outer labial setae (8-9μm long) and cephalic setae (4-5 μm long) in a single circle, two large subventral teeth in two adjacent stomatal chambers, relatively short pharynx (b = 5.5 (5.4-5.6) in the female and 5.7 (5.3-6.1) in the male), vulva located slightly anterior to mid-body (V = 44 (43-46)), protuberant lips, and long filiform tail (461 (398-531) μm, c = 3.8 (3.3-4.2) and c′ = 23.2 (18-29) in the female, and 450 (362-511)μm, c = 3.9 (3.6-4.4) and c′ = 19.0 (16.0-20.8) in the male), tail with three ventromedian caudal setae. Males have arcuate spicules 37 (35-41) μm long, gubernaculum straight, 14 (12-16) μm long, three ventromedian supplementary papillae located anterior to the cloacal aperture, and a single plus four pairs of subventral caudal setae located posterior to the cloacal aperture on the tail. Preliminary analyses of phylogenetic relationships within the Triplonchida were done using the SSU and D2-D3 region of LSU DNA sequences.
Lethal Violence, the Lack of Resonance and the Challenge of Forgiveness in Brazil
Authors: von Sinner Rudolf , Westphal Euler Renato
Published: May 2018

According to recent data there has been a considerable increase in lethal violence in Brazil as well as evidence of a growing brutality. Such data bears witness to the wide perception of impunity and the apparent commonality, even an acceptance of killing. The general political and economic insecurity reinforces a sense of abandonment among the population. The affluent hire private security services. The poor, with no alternative option, become victims of crime and drug trafficking wars. The police are often a part of organized crime rather than combatting such. They are understaffed and underequipped. The prison system is unfit to promote resocialization. What can the churches, theology and the state do to establish and foster justice worthy of the name? The purpose of this article is to analyse the situation in Brazil, referring to acclaimed interpreters as historian Sérgio Buarque de Holanda, to ponder possible reasons for violence using the sociological theory of resonance by Hartmut Rosa, and to reflect on a theology of justice that, rather than revenge, emphasises transformation, forgiveness and reconciliation. Through reference to Jürgen Moltmann, it seeks to show how a public theology can contribute to such transformation.
Democracy and Climate Justice: Public Theology in the Anthropocene
Authors: Fretheim Kjetil
Published: May 2018

Although controversial, the concept of the Anthropocene has gained prominence in the scholarly and political discourse on climate change, its effects and implications. This article presents key characteristics and dimensions of the Anthropocene with an emphasis on Bruno Latour’s interpretation and analysis of the term. This provides the background for a discussion of how religious actors and Christian theology have conceptualized climate change and the implications of the Anthropocene for public theology. I focus in particular on the interdisciplinary and normative dimensions of the field. The main argument is that public theology should acknowledge the conflicting interests and agendas in the climate change debate and promote democratic participation. I also highlight some of the implications of the Anthropocene to public theology in terms of the social analysis, politics and ethics, as well as language and voice used when participating in such debates. I conclude by arguing that public theology can give a unique contribution to climate justice by offering perspectives and insights from Christian narratives and imaginaries.
Race Rescue
Authors: Eves Richard
Published: May 2018

This paper examines Methodist missionary discourse in Papua at the turn of the nineteenth century, locating two themes: what I call a pathology of desire, to be found in the polemical missionary discourses directed at sexuality, immorality and licentiousness, and a pathology of culture, to be found in their polemical discourses against abortion, infanticide and child-rearing practices. Together, these pathologies were seen as the main causes of population decline. The two discourses, constantly at play, produce a doubled image of Papuan women – the fallen woman and the bad mother – which, it was considered, necessitated the intervention of “a civilising mission.” This involved race rescue – the isolation of those thought vulnerable (children and young women) on the mission station, away from the dangers of the villages, at the same time instilling in them their own notions of sexual morality, and above all the training of Papuan women in European models of motherhood and domesticity, so they would become good wives and mothers.
The Case for Hippos in Colombia
Authors: Dembitzer Jacob
Published: May 2018

Drug lord Pablo Escobar imported 4 Hippopotamuses (Hippopotamus amphibius) onto his private estate in Colombia in the 1980s. Since his arrest and assassination, the hippos have escaped the confines of the property and have begun to reproduce in the wild of Colombia. They now number approximately 60 individuals. The presence of such a large, and possibly dangerous, species in a new habitat raises several moral and ecological questions and dilemmas. It is unknown what effect these animals may have on their new environment, or the threat that they pose to the people living near them. In an effort to mitigate possible risks to the environment and local populations the Colombian government initiated an effort to castrate all males in the herd. However, it is unlikely that these efforts will be very effective in curbing the population growth of the animals. South America lost most of its large species of animals during the Quaternary Extinction and it is possible that the hippos are filling a gap that still exists in the ecology of the continent. The rewilding efforts occurring around the world aim to restore and protect natural processes and habitats by introducing (or reintroducing) apex predators or keystone species. Perhaps further research could shed light on possible positive influences that the Hippos have on the South American environment and responsible ways to avoid risks to local populations.
Is the prickly pear a ‘Tzabar’? Diversity and conservation of Israel’s migrant species
Authors: Wallach Arian D. , Lundgren Erick , Yanco Esty , Ramp Daniel
Published: May 2018

Human-assisted biotic migration is a hallmark of the Anthropocene. Populations introduced outside their native ranges (‘migrant species’) have commonly been viewed as a threat to be addressed with lethal control programs. Israel has a long history of anthropogenic changes, and conservation has typically focused on ameliorating direct human impacts rather than eradicating migrant species. However, this may be changing with the growing influence of invasion biology worldwide. We conducted a review of the diversity, conservation status, and academic attitudes toward Israel’s migrant species (IMS). We identified 199 plants and animals from 85 families that have immigrated into Israel from across the globe, and 122 species from 64 families considered native to Israel that have emigrated to every bioregion and to two oceans, although few species have become cosmopolitan. The conservation status of most immigrant (84.9%) and emigrant (55.7%) species has not been assessed, and even the native ranges of eleven immigrants (5.5%) remains unknown. Of those assessed, 27% of immigrants are threatened or decreasing in their native ranges, and 62% of emigrants are globally decreasing or locally threatened and extinct. After accounting for local extinctions, immigration has increased Israel’s plant and vertebrate richness by 104 species. Israel’s immigrants are increasingly being viewed from an invasion biology perspective, with 76% of studies published in the past decade, reaching over a quarter of local conservation publications. Incorporating principles of compassionate conservation could help foster a more socially acceptable and morally grounded approach to the immigrant wildlife of the Middle East.
Digital Religion and Media Economics: Concentration and Convergence in the Electronic Church
Authors: Ward Mark
Published: May 2018

The economics that push every medium toward market concentration have historically done likewise to every religious medium. “Online religion” is now, in its turn, colonized by an “electronic church” industry that, due to media deregulation, is dominated by religious media conglomerates—through whom North Americans are most likely to engage in digital religion. The largest conglomerate alone generates 110 million computer sessions and 79 million mobile sessions per month. This study reviews the economics of media concentration and applications to religious media, surveys the digital footprint of the institutional electronic church, and advocates integration of media practices into Digital Religion Studies.
Helminthosporium submersum sp. nov. (Massarinaceae) from submerged wood in north-western Yunnan Province, China
Authors: ZHAO NA , LUO ZONG-LONG , HYDE KEVIN D , SU HONG-YAN , BHAT DARBHE J. , LIU JIAN-KUI , BAO DAN-FENG , HAO YU-E
Published: May 2018

The diversity of lignicolous freshwater fungi of China is currently being studied. In this paper, we report on nine collections of asexual morphs of Helminthosporium from submerged wood in rivers and streams in west to north-west Yunnan Province, China. The taxa are characterized based on morphology and phylogenetic analyses of ITS, LSU, SSU, RPB2 and TEF1α sequence data. A new species, Helminthosporium submersum, is described and illustrated with notes on taxonomy and phylogeny. Molecular data for Helminthosporium aquaticum and H. velutinum are provided.
The Deflection of the China Coastal Current over the Taiwan Bank in Winter
Authors: Liao Enhui , Oey Lie Yauw , Yan Xiao-Hai , Li Li , Jiang Yuwu
Published: May 2018

In winter, an offshore flow of the coastal current can be inferred from satellite and in situ data over the western Taiwan Bank. The dynamics related to this offshore flow are examined here using observations as well as analytical and numerical models. The currents can be classified into three regimes. The downwind (i.e., southward) cold coastal current remains attached to the coast when the northeasterly wind stress is stronger than a critical value depending on the upwind (i.e., northward) large-scale pressure gradient force. By contrast, an upwind warm current appears over the Taiwan Bank when the wind stress is less than the critical pressure gradient force. The downwind coastal current and upwind current converge and the coastal current deflects offshore onto the bank during a moderate wind. Analysis of the vorticity balance shows that the offshore transport is a result of negative bottom stress curl that is triggered by the positive vorticity of the two opposite flows. The negative bottom stress curl is reinforced by the gentle slope over the bank, which enhances the offshore current. Composite analyses using satellite observations show cool waters with high chlorophyll in the offshore current under moderate wind. The results of composite analyses support the model findings and may explain the high productivity over the western bank in winter.
Development of a Rapid Coal Analyzer Using Laser-Induced Breakdown Spectroscopy (LIBS)
Authors: Yao Shunchun , Mo Juehui , Zhao Jingbo , Li Yuesheng , Zhang Xiang , Lu Weiye , Lu Zhimin
Published: May 2018

Determination of coal quality plays a major role in coal-fired power plants and coal producers for optimizing the utilization efficiency and controlling the quality. In this work, a rapid coal analyzer based on laser-induced breakdown spectroscopy (LIBS) was developed for rapid quality analysis of pulverized coal. The structure of the LIBS apparatus was introduced in detail. To avoid time-consuming and complicated sample preparation, a pulverized feeding machine was designed to form a continuously stable coal particle flow. The standard deviation (SD) of characteristic peaks was used to estimate the spectral valid data in this experiment. Coupled with cluster analysis, artificial neural networks and genetic algorithm are employed as a nonlinear regression method in order to indicate the relationship between coal quality and the corresponding plasma spectra. It is shown that the average absolute error of ash, volatile matter, fixed carbon, and gross calorific value for the validation set is 0.82%, 0.85%, 0.96%, and 0.48 MJ/kg. The average standard deviation of repeated samples is 1.64%, 0.92%, 1.08%, and 0.86 MJ/kg, showing a high sample-to-sample repeatability. This rapid coal analyzer is capable of performing reliable and accurate analysis of coal quality.
The (dis)advantages of sector-level bargaining: Outsourcing of cleaning work and the segmentation of the Israeli industrial relations system
Authors: Bondy Assaf S
Published: May 2018

This article examines the segmentation of the corporatist industrial relations system through a historical analysis of the public-sector outsourcing process in Israel, which occurred in the 1960s and 1970s. Emphasizing the intersection of class, race/ethnicity and gender in Israeli society, the article analyses outsourcing of cleaning work as the adoption of labour market vulnerability into the industrial relations system. It uses intersectionality to demonstrate how the promotion of outsourcing through sector-level bargaining acted as a means of labour market control and industrial relations centralization, thus legitimizing precarious employment forms. Stressing the links between intersectionality and outsourcing practices in the Israeli corporatist system sheds light upon structural segmentation and differential representation of vulnerable workers in a centralized industrial relations system.
Proton therapy technology evolution in the clinic: impact on radiation protection
Authors: Depuydt T.
Published: May 2018

The use of proton therapy as a treatment modality is becoming more widespread in conventional radiation therapy practice. Commercialisation and introduction of compact systems has led to embedding of proton therapy facilities in existing hospital environments. In addition, technologically, proton therapy is currently undergoing an important evolution, moving from passive scattering delivery techniques to active pencil beam scanning, adopting image guidance techniques from conventional radiotherapy and introducing various range verification techniques in the clinic. An overview is given of today’s technological evolution of proton therapy in clinical environments, and its impact on aspects of radiation protection.
The Irish approach to postaccident preparedness
Authors: McMahon C.A. , Smith V. , Leonard K. , Ryan R.
Published: May 2018

Ireland does not have any nuclear installations, but a nuclear accident at a site elsewhere, particularly in Europe, could result in widespread but low-level contamination of the Irish environment. Ireland’s National Emergency Plan for Nuclear Accidents was established, following the Chernobyl accident, for the national response to a nuclear accident abroad affecting Ireland. It has since been extended to also cover domestic radiological emergencies for which a national-level input is required to support the local response. This paper describes the approach taken to developing and maintaining arrangements for a nuclear accident abroad. The use of hazard assessments to prioritise resource use and planned protective actions, and the specifics of Ireland’s situation in terms of location, governance, economy, and available resources have heavily influenced the preparedness arrangements. In particular, the importance of the ingestion pathway to projected doses, together with the significance of agricultural exports to the Irish economy, has had a key influence on the arrangements in place.
Sulodexide Monotherapy in Chronic Idiopathic Subjective Tinnitus: A Randomized Controlled Trial
Authors: El Beaino Marc , McCaskey Meghan K. , Eter Elie
Published: May 2018

Objective

To report the therapeutic value of sulodexide monotherapy in the management of patients with chronic subjective idiopathic tinnitus.

Study Design

Randomized double‐blinded controlled trial.

Setting

Single tertiary care institution.

Subjects and Methods

Observations from 124 patients who received either sulodexide or placebo were collected from the patients’ medical records. Computer‐generated tables were used to allocate treatments. Patients took 1 tablet of the drug or placebo each morning and evening for 40 consecutive days. The response was assessed by the Tinnitus Handicap Inventory and the Mini‐Tinnitus Questionnaire.

Results

Between 2014 and 2017, 124 patients were divided into 2 treatment arms. The sulodexide group encompassed 63 patients, whereas the placebo arm contained 61 patients. Tinnitus Handicap Inventory and Mini‐Tinnitus Questionnaire scores were more decreased in the sulodexide arm compared to the placebo group (P =. 03 and P <. 01, respectively).

Conclusions

Sulodexide monotherapy decreases chronic subjective idiopathic tinnitus.
Intermittent Esotropia in 4 Patients With Allan-Herndon-Dudley Syndrome
Authors: Swiston Cole J. , Nash David L.
Published: May 2018

Allan-Herndon-Dudley syndrome is a rare X-linked neurologic condition caused by mutations in monocarboxylate transporter 8 ( MCT8), which leads to deficient thyroid hormone transport. Typical features include severe cognitive impairment, truncal hypotonia, spastic paraplegia, weakness, and speech difficulties. Minimal literature exists describing the ocular findings in patients with Allan-Herndon-Dudley syndrome. We describe 4 male siblings affected with Allan-Herndon-Dudley syndrome with a novel nonsense mutation (Q90X) in the MCT8 protein. All affected siblings presented with classic findings of Allan-Herndon-Dudley syndrome, and each of the siblings also developed intermittent esotropia. This group of affected siblings represents the first consistent documentation of strabismus in Allan-Herndon-Dudley syndrome, suggesting a possible association between this clinical finding and the neurologic syndrome.
Information creation and models of information behavior: Grounding synthesis and further research
Authors: Gorichanaz Tim
Published: May 2018

This paper contributes to the conceptualization of information creation in the field of information behavior. To do so, it synthesizes discussions and conceptual models on information creation and related topics, such as communication, design and documentation, which to date have been disconnected. A number of models are discussed, as well as some of the strengths, weaknesses and unique contributions of each with respect to information creation. This discussion leads to a number of paths for further research, both conceptual and empirical, on information creation. In particular, one fruitful site for further research in information creation is art. Drawing on the ground-breaking work of Tidline, it is clear that art is informative, and that the activities involved in and surrounding the creation of art showcase the aspects of information creation that have been highlighted in theoretical models of information behavior. Further research should consider the information behavior involved in an artistic task from start to finish.
Discrimination and the Health of African Americans: The Potential Importance of Intersectionalities
Authors: Lewis Tené T. , Van Dyke Miriam E.
Published: May 2018

Research examining associations between self-reported experiences of discrimination overall (e.g., potentially due to race, gender, socioeconomic status, age) and health—particularly among African Americans—has grown rapidly over the past two decades. Yet recent findings suggest that self-reported experiences of racism alone may be less impactful for the health of African Americans than previously hypothesized. Thus, an approach that captures a broader range of complexities in the study of discrimination and health among African Americans may be warranted. This article presents an argument for the importance of examining intersectionalities in studies of discrimination and physical health in African Americans and provides an overview of research in this area.
Book review: Angela Willey (2016), Undoing Monogamy: The Politics of Science and the Possibilities of Biology
Authors: Subramaniam Banu
Published: May 2018

Angela Willey (2016), Undoing Monogamy: The Politics of Science and the Possibilities of Biology. Durham: Duke University Press. 216 pp., 9 illustrations. $89.95 (Cloth), ISBN: 978-0-8223-6140-4; $23.95 (Paperback), ISBN: 978-0-8223-6159-6.
Book review: Aaron Panofsky (2014), Misbehaving Science: Controversy and the Development of Behavior Genetics
Authors: Rodríguez-Muñiz Michael
Published: May 2018

Aaron Panofsky (2014), Misbehaving Science: Controversy and the Development of Behavior Genetics. Chicago, IL: University of Chicago Press. 321 pp., $27.50 (Paperback), ISBN: 9780226058450. $89.00 (Hardcover), ISBN: 9780226058313.
Intentions to Use Social Networking Sites (SNS) Using Technology Acceptance Model (TAM)
Authors: Dixit Ruchi V. , Prakash Gyan
Published: May 2018

This article intends to empirically test and analyse Social Networking Sites (SNS) usage pattern applying Technology Acceptance Model (TAM) and predict user’s intention to use SNS. This information would help in understanding better its remarkable marketing potential in India to practice and to create user value. The researchers explored intentions to use SNS using Davis (1985) TAM in Indian context and applied confirmatory factor analysis using structural equation modelling (SEM) technique to check the model fitness. To commensurate this, a survey was carried out through a well-structured questionnaire of 172 respondents of North India, particularly from western UP covering different age groups, income level, educational background and professions. To explore the degree of fitness of TAM factors in SNS, six hypotheses were formulated and tested, where four were accepted and two were rejected. Findings revealed that the TAM fits with the data to interpret and analyse intentions to use SNS in the target population. Since the survey was conducted in and around Mathura (UP), this work could be extended to further research covering bigger geographical areas and sample size to have more accurate predictions regarding diversified SNS usage pattern in India. To evaluate the integration of new technologies, traditional TAM is extensively used. The ‘Intention to Use SNS’ is studied comparatively less in Indian context. This study explores and underlines the diversified potential of these networks. To gauge detailed information, the researcher added five items in ‘Perceived Usefulness’ construct and one item in ‘Intention to Use’ construct of TAM. The objective is to critically analyse and interpret respondent’s viewpoints regarding diversified SNS usage intentions, in addition to viewing and communicating with old and new friends.
The Production of Corporate Research to Manufacture Doubt About the Health Hazards of Products: An Overview of the Exponent Bakelite® Simulation Study
Authors: Egilman David
Published: May 2018

Although corporate sponsorship of research does not necessarily lead to biased results, in some industries, it has resulted in the publication of inaccurate and misleading data. Some companies have hired scientific consulting firms to retrospectively calculate exposures to hazardous products during use that are no longer manufactured or sold. As an example, this paper reviews one such study—a litigation-generated study of Union Carbide Corporation’s asbestos-containing product, Bakelite®. This analysis is based on previously secret documents, produced as a result of litigation. The study generated asbestos fiber exposure measurements which resulted in underestimates of actual exposures to create doubt about the hazards associated with manufacture and manipulation of Bakelite®.
Lesson Planning With Engagement in Mind: Proactive Classroom Management Strategies for Curriculum Instruction
Authors: Nagro Sarah A. , Fraser Dawn W. , Hooks Sara D.
Published: May 2018

Teacher success is critical to student success, yet teachers are challenged daily to meet their students’ diverse learning and behavioral needs. Of major concern is the time many teachers spend managing student behaviors, which takes time away from instruction. One way to reduce time spent managing student behavior and increase student engagement is to use proactive classroom management strategies. Teachers can embed proactive research-based strategies within their lesson plans to reduce behavior problems and improve achievement for all students, including students with disabilities. This article highlights four research-based proactive strategy categories including whole-group response systems, movement integration, visual supports, and student choice. This article illustrates how teachers can embed strategies from these categories in their lesson planning and includes a lesson plan template with teacher-created examples.
Ameloblastic Carcinoma In Situ: Review of Literature and a Case Presentation in a Pediatric Patient
Authors: Fahradyan Artur , Odono Lauren , Hammoudeh Jeffrey A. , Howell Lori Kathryn
Published: May 2018

Ameloblastic carcinomas are rare malignant lesions with 3 mandibular pediatric cases reported in the literature. We present a case of ameloblastic carcinoma in situ in a 15-year-old male with a right mandibular cystic lesion on computed tomography. The incisional biopsy revealed plexiform ameloblastoma. Due to the infiltrating and aggressive nature of the tumor, the patient underwent hemimandibulectomy and immediate reconstruction with a vascularized osteocutaneous fibula free flap. The final pathology was read as ameloblastic carcinoma in situ. Given the rarity of this disease in the pediatric population, this case report may be a valuable addition to the current literature.
Short-term outcomes of endoscopic submucosal dissection for superficial cecal tumors: a comparison between extension and nonextension into the appendiceal orifice
Authors: Boda Kazuki , Oka Shiro , Tanaka Shinji , Tanaka Hidenori , Matsumoto Kenta , Yamashita Ken , Sumimoto Kyoku , Hirano Daiki , Tamaru Yuzuru , Ninomiya Yuki , Hayashi Nana , Chayama Kazuaki
Published: May 2018

Background:

Few studies have investigated the use of endoscopic submucosal dissection (ESD) for cecal tumors extending into the appendiceal orifice. Herein, we assessed the feasibility and safety of ESD for cecal tumors extending into the appendiceal orifice.

Methods:

We retrospectively examined the outcomes of ESD for 78 patients with 78 cecal tumors (male/female ratio, 40/38; mean [standard deviation, SD] age, 67 [9] years; mean [SD] tumor size, 32 [15] mm), who underwent ESD at the Hiroshima University Hospital between October 2008 and March 2016. The indication for ESD in cecal tumors extending into the appendiceal orifice was recognition of the distal edge of the lesion in the appendix. They were classified into two groups: patients with cecal tumors extending (Group A: 29 patients, 29 tumors) and not extending (Group B: 49 patients, 49 tumors) into the appendiceal orifice. We compared the outcomes of ESD between both groups.

Results:

No significant differences in clinicopathological characteristics were observed between both groups. The rate of severe submucosal fibrosis in Group A (48%) was significantly higher than that in Group B (24%) ( p < 0.05). The mean (SD) procedure speed in Group A (14 [10] mm2/min) was significantly slower than that in Group B (23 [16] mm2/min) ( p < 0.01). The en bloc resection rates in Groups A and B were 90% and 96%, respectively. There were no significant differences in adverse events reported between both groups.

Conclusions:

ESD for cecal tumors with extension into the appendiceal orifice is effective and safe.
Value Creation and Efficiency: Incompatible or Inseparable?
Authors: Davidow Moshe
Published: May 2018

The efficiency/value creation (effectiveness) debate has been mostly one sided through the years in favor of efficiency. However, a new way of looking at things has started to even out the balance. In this article, we will discuss both sides of the debate, state the underlying problem at the base of the debate, and give examples of how this debate actually destroys value. In most cases, this failure is not really a failure, but was designed into the system by misguided managerial choices. We then present our solution based on thinking holistically about productivity and efficiency in a world of co-creation, and discuss ways for managers to implement it in their organizations. This implementation is based on current examples from the literature, as well as a discussion as to why these ways are so effective. In a sense, in a world of co-creation, efficiency becomes less important, as the customer is willing to pay more money for a higher value product, thus covering the cost of a slightly less efficient process.
Complement C5 but not C3 is expendable for tissue factor activation by cofactor-independent antiphospholipid antibodies
Authors: Müller-Calleja Nadine , Ritter Svenja , Hollerbach Anne , Falter Tanja , Lackner Karl J. , Ruf Wolfram
Published: May 2018

Key Points

Cofactor-independent aPLs cause PDI- and complement-dependent monocyte TF activation. C3, but not C5, is required for TF activation and aPL-induced thrombosis.
Doctors, suicide and mental illness
Authors: Gerada Clare
Published: May 2018

This article focuses on doctors and suicide. It provides real examples to illustrate why doctors die by their own hand. These reasons are replicated in the general population, but also include a host of additional risk factors related to being a doctor. In each case, information about the doctor is in the public domain or, as in one case, consent from the next of kin has been obtained for a detail not in the public domain. The author is a doctors' doctor, heading up a confidential health service for doctors with mental illness or addiction, the National Health Service Practitioner Health Programme. Mortality data from the programme (January 2008–January 2017) will also be included. For the sake of confidentiality, data is collated and details regarding age and gender have been approximated.

Declaration of interest

None.
Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial
Authors: Stilgenbauer Stephan , Eichhorst Barbara , Schetelig Johannes , Hillmen Peter , Seymour John F. , Coutre Steven , Jurczak Wojciech , Mulligan Stephen P. , Schuh Anna , Assouline Sarit , Wendtner Clemens-Martin , Roberts Andrew W. , Davids Matthew S. , Bloehdorn Johannes , Munir Talha , Böttcher Sebastian , Zhou Lang , Salem Ahmed Hamed , Desai Monali , Chyla Brenda , Arzt Jennifer , Kim Su Young , Verdugo Maria , Gordon Gary , Hallek Michael , Wierda William G.
Published: May 2018

Purpose

Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported.

Patients and Methods

Overall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up. Responses were based on 2008 International Workshop on Chronic Lymphocytic Leukemia criteria, with monthly physical exams and blood counts. Computed tomography scan was mandatory at week 36, after which assessment made was by clinical evaluation. Marrow biopsy was performed when complete remission was suspected. MRD was assessed by flow cytometry.

Results

Patients had a median of two prior therapies (range, zero to 10 therapies), 71% had TP53 mutation, and 48% had nodes that were ≥ 5 cm. Median time on venetoclax was 23.1 months (range, 0 to 44.2 months) and median time on study was 26.6 months (range, 0 to 44.2 months). For all patients, investigator-assessed objective response rate was 77% (122 of 158 patients; 20% complete remission) and estimated progression-free survival at 24 months was 54% (95% CI, 45% to 62%). For 16 patients who received prior kinase inhibitors, objective response rate was 63% (10 of 16 patients) and 24-month progression-free survival estimate was 50% (95% CI, 25% to 71%). By intent-to-treat analysis, 48 (30%) of 158 patients achieved MRD below the cutoff of 10−4 in blood. Common grade 3 and 4 adverse events were hematologic and managed with supportive care and/or dose adjustments.

Conclusion

Venetoclax achieves durable responses and was well tolerated in patients with del(17p) CLL. A high rate of blood MRD < 10−4 was achieved in this high-risk population.
SMART Cancer Navigator: A Framework for Implementing ASCO Workshop Recommendations to Enable Precision Cancer Medicine
Authors: Warner Jeremy L. , Prasad Ishaan , Bennett Makiah , Arniella Monica , Beeghly-Fadiel Alicia , Mandl Kenneth D. , Alterovitz Gil
Published: May 2018

Purpose

Data standards and interoperability are critical for improving care for patients with cancer. Recent efforts by ASCO include the Data Standards and Interoperability Summit in 2016, which led to the Omics and Precision Oncology and Advancing Interoperability workshops. To facilitate improved patient care, several recommendations for data sharing and standardization were made to the community.

Methods

To address these recommendations, we developed SMART Cancer Navigator, a Web application that uses application programming interfaces to gather clinical and genomic data from 11 public knowledge bases ranging from basic to clinical content coverage; three (CIViC, ClinVar, and OncoKB) explicitly linked genomic variants to clinical factors such as prognosis and treatment selection. We illustrated the utility of this application by selecting one of the monthly case studies presented by the ASCO University Molecular Oncology Tumor Board: Ovarian Cancer (BRCA Mutation). We also performed analyses on information from the three clinico-genomic knowledge bases to corroborate previous work and illustrate the state of data sharing among publicly available resources.

Results

SMART Cancer Navigator aggregates and contextualizes data from 11 different knowledge bases and stores user queries in a lightweight Web application that can link into Fast Healthcare Interoperability Resources–enabled electronic health records. Potentially relevant clinical trials and/or approved treatments were identified for three mutations found in a hypothetical patient with advanced ovarian cancer. A comparison of the three clinico-genomic knowledge bases indicated substantial differences in coverage at the gene and variant levels.

Conclusion

SMART Cancer Navigator has immediate relevance to practicing oncologists and others. Additional knowledge bases can be added without undue effort. As a first step toward utility, we generalized and disseminated the resulting implementation ( https://smart-cancer-navigator.github.io ) and data sets.
Embryonic bone morphogenetic protein and nodal induce invasion in melanocytes and melanoma cells
Authors: Sinnberg Tobias , Niessner Heike , Levesque Mitch P. , Dettweiler Christoph , Garbe Claus , Busch Christian
Published: May 2018

Despite recent progress in melanoma therapy via inhibition of activated oncogenes or immune stimulation, most stage IV melanoma patients still have limited survival times. Both therapeutic approaches eventually fail to prevent further invasion and metastasis, which is driven by a morphological process termed epithelial-mesenchymal transition (EMT). We previously demonstrated that inhibition of EMT in melanoma cells via antagonizing the bone morphogenetic protein (BMP)-pathway abrogated EMT and neural crest migration of melanoma cells in the chick embryo.

Here, we show that BMP-2 is highly expressed in invasive melanoma cells and is elevated in the serum of stage IV melanoma patients compared to stage IB-IIC patients and healthy controls. Highly BMP-2-expressing melanoma cells display enhanced invasion in the rhombencephalon of the chick embryo. In addition to driving neural crest migration in the zebrafish embryo, the agonists BMP-2, BMP-7 and nodal induce EMT/invasion in radial growth phase melanoma cells and in human melanocytes in skin reconstructs. Blocking either BMP or nodal-signaling by antagonists (noggin, lefty) or the Alk4/5/7-receptor inhibitor SB431542 decreases EMT and invasion of melanoma cells in human epidermal skin reconstructs. Together, our data suggest that inhibition of EMT-inducing pathways in melanoma might be a therapeutic approach to attenuate melanoma cell invasiveness.