bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia
Authors: Gao Yang , O'Caoimh Rónán , Healy Liam , Kerins David M , Eustace Joseph , Guyatt Gordon , Sammon David , Molloy D William 
Published: July 2013

ObjectivesThere is growing evidence that antihypertensive agents, particularly centrally acting ACE inhibitors (CACE-Is), which cross the blood–brain barrier, are associated with a reduced rate of cognitive decline. Given this, we compared the rates of cognitive decline in clinic patients with dementia receiving CACE-Is (CACE-I) with those not currently treated with CACE-Is (NoCACE-I), and with those who started CACE-Is, during their first 6 months of treatment (NewCACE-I).DesignObservational case–control study.Setting2 university hospital memory clinics.Participants817 patients diagnosed with Alzheimer's disease, vascular or mixed dementia. Of these, 361 with valid cognitive scores were included for analysis, 85 CACE-I and 276 NoCACE-I.MeasurementsPatients were included if the baseline and end-point (standardised at 6 months apart) Standardised Mini-Mental State Examination (SMMSE) or Quick Mild Cognitive Impairment (Qmci) scores were available. Patients with comorbid depression or other dementia subtypes were excluded. The average 6-month rates of change in scores were compared between CACE-I, NoCACE-I and NewCACE-I patients.ResultsWhen the rate of decline was compared between groups, there was a significant difference in the median, 6-month rate of decline in Qmci scores between CACE-I (1.8 points) and NoCACE-I (2.1 points) patients (p=0.049), with similar, non-significant changes in SMMSE. Median SMMSE scores improved by 1.2 points in the first 6 months of CACE treatment (NewCACE-I), compared to a 0.8 point decline for the CACE-I (p=0.003) group and a 1 point decline for the NoCACE-I (p=0.001) group over the same period. Multivariate analysis, controlling for baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups, p=0.002.ConclusionsCognitive scores may improve in the first 6 months after CACE-I treatment and use of CACE-Is is associated with a reduced rate of cognitive decline in patients with dementia.
The diagnostic accuracy of pleural effusion and plasma samples versus tumour tissue for detection of EGFR mutation in patients with advanced non-small cell lung cancer: comparison of methodologies
Authors: Liu Xiaoqing , Lu Yachao , Zhu Guanshan , Lei Yao , Zheng Li , Qin Haifeng , Tang Chuanhao , Ellison Gillian , McCormack Rose , Ji Qunsheng 
Published: July 2013

AimsTo evaluate the suitability of malignant pleural effusion (MPE) and plasma as surrogate samples for epidermal growth factor receptor (EGFR) mutation detection, and compare three different detection methods.MethodsMatched tissue and plasma samples were collected from patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB/IV adenocarcinoma/adenosquamous carcinoma), with matched MPE samples collected from a subgroup. DNA was extracted from tissue, MPE cell block, MPE supernatant and plasma before mutation detection by amplification refractory mutation system (ARMS) (all samples), Sanger sequencing and mutant-specific immunohistochemistry (IHC) (tissue and MPE cell blocks only).ResultsSensitivity of MPE cell block, MPE supernatant and plasma versus tissue: 81.8% (9/11), 63.6% (7/11) and 67.5% (27/40); specificity was 80.0% (8/10), 100% (10/10) and 100% (46/46), respectively. Sensitivity of Sanger sequencing versus ARMS: 81.8% (27/33) for tissue, 40% (4/10) for MPE cell blocks; specificity was 100% (36/36 and 12/12) for both. Sensitivity of mutant-specific IHC versus ARMS: 54.8% (17/31) for tissue, 50.0% (6/12) for MPE cell blocks; specificity was 97.1% (34/35) and 100% (14/14), respectively.ConclusionsMPE and plasma are valid surrogates for NSCLC tumour EGFR mutation detection when tissue is not available. ARMS is most suitable for mutation detection in tissue and MPE cell blocks; however, mutant-specific IHC could be a complementary method when DNA-based molecular testing is unavailable.
Pattern and cause of fractures in patients who abuse alcohol: what should we do about it?
Authors: Kelly Kieran Nial , Kelly Clive 
Published: July 2013

Abstract
Alcohol abuse is increasing in the UK and contributes significantly to the rising number of acute hospital admissions. The effects are increasingly seen among younger people who binge drink. The effects of excess alcohol on the skeleton have attracted far less attention than those on other organs, but the risk of fractures at important sites, such as the hips and vertebrae, is greatly increased in alcoholics. This is partly owing to reductions in bone mineral density, but other factors such as an increased rate of falls play an important part. The contribution of excess alcohol consumption to the risk of fractures is recognised in the widely available fracture assessment tool (FRAX). The mechanisms of fracture in alcohol abusers are complex and involve direct effects on bone cells, and indirect effects, mediated by alcohol, on the endocrine system, pancreas and cytokine system. Poor nutrition, with a reduction in body mass index and vitamin D levels, often contributes significantly. Prevention and treatment of fractures in alcohol abusers has received limited attention, and there are surprisingly few therapeutic trials to guide clinical intervention. Abstinence has been shown to improve markers of bone turnover within 2 months. However, compliance with oral therapeutic agents is often poor, and bisphosphonates may be contraindicated in patients with alcoholic liver disease and varices. The emergence of newer therapeutic options may facilitate controlled prospective studies of the role of parenteral agents in providing protection against both primary and secondary osteoporotic fractures among patients with alcohol abuse.
A Road Map to Comprehensive Androgen Receptor Axis Targeting for Castration-Resistant Prostate Cancer
Authors: Mitsiades Nicholas 
Published: July 2013

Abstract
Gonadal androgen suppression (castration via orchiectomy or gonadotropin-releasing hormone analogues) suppresses circulating testosterone levels but does not achieve adequate androgen ablation within the prostate cancer microenvironment because it does not address adrenal and intratumoral steroid contributions. These residual extragonadal sources of androgens allow prostate cancer cells to survive, adapt, and evolve into castration-resistant prostate cancer (CRPC). The persistent significance of the androgen receptor (AR) axis in CRPC was recently validated by the clinical efficacy of androgen synthesis inhibitors (abiraterone) and novel, second-generation AR antagonists (enzalutamide). The appreciation that conventional therapeutic approaches achieve a suboptimal ablation of intratumoral androgens and AR axis signaling output opens transformative therapeutic opportunities. A treatment paradigm of comprehensive AR axis targeting at multiple levels (androgen synthesis, metabolism, and action) and at all relevant sites (gonadal, adrenal, intratumoral) simultaneously at the time of initiation of endocrine therapy (instead of the current approach of sequentially adding one agent at a time and only after disease progression) deserves examination in clinical trials to explore whether maximal first-line AR axis suppression via combination therapy can achieve maximal induction of cancer cell apoptosis (before they have the chance to adapt and evolve into CRPC) and thus, improve patient outcomes. Cancer Res; 73(15); 4599–605. ©2013 AACR.
PDK1 Signaling Toward PLK1–MYC Activation Confers Oncogenic Transformation, Tumor-Initiating Cell Activation, and Resistance to mTOR-Targeted Therapy
Authors: Tan Jing , Li Zhimei , Lee Puay Leng , Guan Peiyong , Aau Mei Yee , Lee Shuet Theng , Feng Min , Lim Cheryl Zihui , Lee Eric Yong Jing , Wee Zhen Ning , Lim Yaw Chyn , Karuturi R.K. Murthy , Yu Qiang 
Published: July 2013

Abstract
Although 3-phosphoinositide–dependent protein kinase-1 (PDK1) has been predominately linked to the phosphoinositide 3-kinase (PI3K)–AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1–PLK1–MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency. Intriguingly, PDK1–PLK1–MYC signaling induces an embryonic stem cell–like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self-renewal. Finally, we show that a PLK1 inhibitor synergizes with an mTOR inhibitor to induce synergistic antitumor effects in colorectal cancer by antagonizing compensatory MYC induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting MYC-associated tumorigenesis and therapeutic resistance.
Significance: This work identifies PDK1–PLK1–MYC signaling as a new oncogenic pathway driving oncogenic transformation and CSC self-renewal. Targeted inhibition of PDK1/PLK1 is robust in targeting MYC dependency in cancer cells. Thus, our findings provide important insights into cancer and CSC biology and have significant therapeutic implications. Cancer Discov; 3(10); 1156–71. ©2013 AACR.
See related commentary by Cunningham and Ruggero, p. 1099
This article is highlighted in the In This Issue feature, p. 1083
Endothelin-1 Overexpression Exacerbates Atherosclerosis and Induces Aortic Aneurysms in Apolipoprotein E Knockout Mice
Authors: Li Melissa W. , Mian Muhammad Oneeb Rehman , Barhoumi Tlili , Rehman Asia , Mann Koren , Paradis Pierre , Schiffrin Ernesto L. 
Published: July 2013

Objective—

Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet–induced atherosclerosis in apolipoprotein E
−/−
(
Apoe
−/−
) mice. ET-1–induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development.

Approach and Results—

Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1),
Apoe
−/−
mice, and eET-1/
Apoe
−/−
mice were fed high-fat diet for 8 weeks. eET-1/
Apoe
−/−
had a 45% reduction in plasma high-density lipoprotein (
P
<0.05) and presented ≥2-fold more aortic atherosclerotic lesions compared with
Apoe
−/−
(
P
<0.01). AAAs were detected only in eET-1/
Apoe
−/−
(8/21;
P
<0.05). Reactive oxygen species production was increased ≥2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/
Apoe
−/−
compared with
Apoe
−/−
(
P
<0.05). Monocyte/macrophage infiltration was enhanced ≥2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/
Apoe
−/−
compared with
Apoe
−/−
(
P
<0.05). CD4
+
T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/
Apoe
−/−
(
P
<0.05). The percentage of spleen proinflammatory Ly-6C
hi
monocytes was enhanced 26% by ET-1 overexpression in
Apoe
−/−
(
P
<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/
Apoe
−/−
(
P
<0.05) compared with
Apoe
−/−
.

Conclusions—
ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.
Unequal Access to Treatment With Intravenous Alteplase for Women With Acute Ischemic Stroke
Authors: de Ridder Inger , Dirks Maaike , Niessen Louis , Dippel Diederik 
Published: July 2013

Background and Purpose—
A recent meta-analysis showed that women with acute ischemic stroke are less likely to receive treatment with intravenous alteplase than men. The aim of this study was to assess sex differences in treatment with intravenous alteplase and to explore the reasons for these differences.

Methods—
We analyzed data from the Promoting Acute Thrombolysis for Ischaemic Stroke (PRACTISE) study. We applied a multiple logistic regression model and expressed the association between sex and treatment with an age-adjusted odds ratio with 95% confidence interval.

Results—
In total, 5515 patients were included in PRACTISE. Women were an average of 4 years older than men. The median National Institutes of Health Stroke Scale score was 6 in women and 5 in men. Fewer women were treated with intravenous alteplase (11% versus 14%; adjusted odds ratio, 0.8; 95% confidence interval, 0.7–1.0). However, fewer women arrived within 4 hours after onset (27% versus 33%; adjusted odds ratio, 0.8; 95% confidence interval, 0.7–0.9).

Conclusions—
Fewer women present themselves within 4 hours from stroke onset than men and consequently less often receive thrombolytic treatment. This difference may be caused by the older age of women on average and consequently women more often living alone.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN20405426.
Fighting for a Democratic Police: Politics, Experts and Bureaucrats in the Transformation of the Police in Post-Authoritarian Chile and Argentina
Authors: Hathazy Paul 
Published: July 2013

Abstract
Through a comparative field analysis, I explain why, after being subjected to the same reform projects and rationalities in the democratic period, police bureaucracies changed in Chile but remained unchanged in Argentina. In doing so I advance a field theory account of police bureaucratic change that (a) overcomes the limitations of Late-modern, Post-modern and Governmentality theories of police change, and (b) emphasizes positionality, agency and a plurality of interests in processes of administrative change. I demonstrate that the proliferation of new experts and their reconversion strategies within the field led to the emergence of specific demands for reform while the historical structures and location of the policing field and the outcomes of struggles within them determined the differential evolution of police organizations in democratic times.
Democratisation, State and Society in the Middle East and North Africa
Authors: García-Rivero Carlos 
Published: July 2013

Abstract
The so-called “Arab spring” has swept throughout Middle East and North Africa against authoritarian forms of government, overthrowing regimes from West to East. After several aborted and repressed attempts, by Islamic parties, to access the institutions through the elections, mainly in the early 2000, the society rose in arms against the Arab State. In the forms of revolt, anger against the State repression has shaken the whole region. This article analyses the bases of confidence in the State institutions in five Arab countries in an attempt to evaluate if the current events are taking the region in the correct direction for democratic stability, according to citizens expectations about state reforms.
The study is a quantitative analysis making extensive use of survey data gathered from the region. Conclusions reached indicate that, more than Islamisation of societies, citizens demand more respect for human rights and a higher participation and development of civil society.
Human Freedom and the Freedom of Natural Processes: On Omnicausality, A-Causality and God’s Omnipotence
Authors: du Toit Cornel W. 
Published: July 2013

Abstract
The article traces the development of causality in physical science and examines its functioning in theology, as well as its demand for a different approach to power, especially the omnipotence and omnicausality of God. The three main phases in the development of causality is briefly mentioned with special reference to some applicable notions of Hume, Newton and Kant. Some examples are given of developments that contributed to the erosion of the causality concept in the sciences during the nineteenth century. The possibility of thinking of God in a-causal terms is proposed. The idea of an omni-causal God is build upon a pre-modern monarchical view. The question whether the importance of God as an omni-causal agent forms part of our regulative thinking, is dealt with. Special attention is given to the way Karl Barth interprets our knowledge of God as well as God’s power. We take the stance that the idea of God’s omnipotence does not imply his omnicausality. This implies that he respect the freedom (autopoeticism) of nature as he respect the freedom of humans. This stance obviates the need to prove God as the magical force in or behind natural and physical events. The action of God is seen on the consequential side of events and not on its causal side.
Who’s the Fool, and Why? Paul on Wisdom from a South African Perspective
Authors: Punt Jeremy 
Published: July 2013

Abstract
South Africa is a young democracy but with colonial and Apartheid legacies fresh in the minds of many, the lasting impact and consequences of hegemony still tangible and measurable in a new, democratic dispensation with its own problems and concerns. This is the context within which Paul’s appeal for a different understanding of wisdom and appearance to insist on breaking through the conventions of the day (1 Cor 1:18–31) is considered. Since Empire largely defined wisdom in the first century, Paul’s rhetoric of foolishness can be interpreted as a critique of the imperial discourse of wisdom and power. But Paul simultaneously invoked a new discourse of power through his rhetoric which inter alia depended on scriptural appeal for endorsement or authority. A postcolonial optic enables one to see Paul’s discourse as mimicry, negotiating power as much with discursive Roman colonialism as with the recipients of his letters, and also with the Scriptures of Israel. Such use of discursive power and ambiguity resonates in interesting ways in the South African context.
Religious Pluralism in the Thinking of Three Qurʾānic Scholars of the Indian Subcontinent
Authors: Dadoo Yousuf 
Published: July 2013

Abstract
This article explores the attitude of three scholars of the Indian subcontinent to this phenomenon, namely, Muḥammad ʿAlī, ʿAbdullāh Yūsuf ʿAlī and Abu l-Kalām Āzād. Their outlooks on this subject differed, sometimes quite substantively, from those of institutionalized religious leaders. Yet their standpoints on religious pluralism were multifarious. Initially, the concept of religious pluralism is interrogated; followed by an overview of the cultural milieu during which they lived in order to contextualize our appraisal. The views of each scholar is then separately analysed before concluding remarks about the similarities and differences in their standpoints.
A Judaeo-Syriac Medical Fragment from the Cairo Genizah
Authors: Bhayro Siam 
Published: July 2013

This article presents an edition and analysis of a hitherto unpublished leaf from the Cairo Genizah (Cambridge University Library, T-S K 14.22) that contains part of a list of simples and their uses. The text is remarkable because, although it is written in Jewish Aramaic script, the language is clearly Syriac. Other features of the text, such as the use of Palestinian vocalisation and medical abbreviations, are discussed, as well as the wider significance of this fragment for our understanding of the Syriac medical tradition.
High-Resolution Topography-Following Chemical Mapping of Ocean Hypoxia by Use of an Autonomous Underwater Vehicle: The Santa Monica Basin Example
Authors: Hofmann Andreas F. , Walz Peter M. , Thomas Hans , Peltzer Edward T. , Brewer Peter G. 
Published: July 2013

AbstractThis paper reports on the execution of a combined chemical sensing/high-resolution terrain-following autonomous underwater vehicle (AUV) survey to explore the fine structure and functional boundaries of the Santa Monica Basin suboxic zone and its relationship to topography. An AUV mapping vehicle is used in a novel configuration—combining the mapping vehicle tail section, with precision inertial navigation and acoustic communications systems, with CTD/O2, NO3 sensing, and Gulper water sampling systems. The challenge was to perform a long-distance near-bottom physical/chemical survey in deep water without any intermediate surfacing to disrupt the survey or require the vehicle to surface in areas of heavy ship traffic. Some 210 km of AUV cruise track at ≈10 m above bottom were accomplished during a 3-day survey. The dissolved oxygen concentration [O2] data are combined with temperature T, salinity S, and hydrostatic pressure P to produce maps of oxygen partial pressure pO2 that help define the limits at which the oceanic supply of O2 can match the O2 demands required to sustain various forms of marine life. The chemical NO3 sensing was included to define the critical pO2 boundary at which NO3 reduction occurs. The combination of a high-resolution terrain-following AUV with chemical sensors is important for a diverse array of investigations, including the study of vent sites, and for locating the source of chemical signals originating from the seafloor. The hypoxic basin example here permits better discrimination between general climate/circulation controls on hypoxia and more specific point-source-driven processes.
Improving Social Connection Through a Communities-of-Practice-Inspired Cognitive Work Analysis Approach
Authors: Euerby Adam , Burns Catherine M. 
Published: July 2013

Objective: Increasingly, people work in socially networked environments. With growing adoption of enterprise social network technologies, supporting effective social community is becoming an important factor in organizational success. Background: Relatively few human factors methods have been applied to social connection in communities. Although team methods provide a contribution, they do not suit design for communities.  Wenger’s community of practice concept, combined with cognitive work analysis, provided one way of designing for community. Method: We used a cognitive work analysis approach modified with principles for supporting communities of practice to generate a new website design. Over several months, the community using the site was studied to examine their degree of social connectedness and communication levels. Results: Social network analysis and communications analysis, conducted at three different intervals, showed increases in connections between people and between people and organizations, as well as increased communication following the launch of the new design. Conclusion: In this work, we suggest that human factors approaches can be effective in social environments, when applied considering social community principles. Application: This work has implications for the development of new human factors methods as well as the design of interfaces for sociotechnical systems that have community building requirements.