bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methadone maintenance treatment programme reduces criminal activity and improves social well-being of drug users in China: a systematic review and meta-analysis
Authors: Sun Hua-Min , Li Xiao-Yan , Chow Eric P F , Li Tong , Xian Yun , Lu Yi-Hua , Tian Tian , Zhuang Xun , Zhang Lei 
Published: January 2015

ObjectiveMethadone maintenance treatment (MMT) has been implemented in China since 2004 and has expanded into a nationwide programme. This study aims to evaluate changes in social functioning, family relations and drug-related criminal behaviour among MMT clients in China.DesignSystematic review and meta-analysis.MethodsBoth English and Chinese literature databases, including PubMed, Chongqing VIP Chinese Science and Technology Journals Database (CQVIP), China National Knowledge Infrastructure (CNKI) and Wanfang Data, were comprehensively searched over the period 2004–2014 for studied indicators. Study selection, quality assessment and data extraction were conducted according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) Statement. Meta-analyses were conducted using Comprehensive Meta-Analysis Biostat software.ResultsThirty-eight articles were included in this review (1 in English and 37 in Chinese). The self-reported arrest rate decreased from 13.1% (95% CI 9.1% to 18.5%) at baseline to 3.4% (95% CI 1.5% to 7.7%) and 4.3% (95% CI 1.6% to 11.4%) after 6 and 12 months of MMT intervention, respectively. The rate of drug selling decreased from 7.6% (95% CI 3.8% to 14.8%) at baseline to 1.9% (95% CI 0.6% to 6.2%) and 3.0% (95% CI 1.0% to 8.9%) after 6 and 12 months of intervention, respectively. Similarly, the rates of selling sex for drugs and drug-related crime decreased from 5.3% (95% CI 2.4% to 11.1%) and 9.9% (95% CI 6.8% to 14.2%) at baseline to 1.1% (95% CI 0.5% to 2.3%) and 3.4% (95% CI 2.5% to 4.5%) at 6 months, then to 0.8% (95% CI 0.3% to 1.9%) and 3.4% (95% CI 0.8% to 13.1%) at 12 months after treatment initiation, respectively. In contrast, the rate of employment of clients and the proportion of clients having a good relationship with their family increased substantially from 26.4% (95% CI 22.9% to 30.1%) and 37.9% (95% CI 32.0% to 44.2%) to 41.6% (95% CI 36.6% to 48.0%) and 59.6% (95% CI 48.1% to 70.2%) at 6 months, then to 59.8% (95% CI 52.4% to 66.8%) and 75.0% (95% CI 69.0% to 80.2%) at 12 months after treatment initiation, respectively.ConclusionsMMT has significantly reduced criminal activity, and improved employment rate and social well-being, of clients of the MMT programme. MMT is an effective measure to help drug users to resume societal and familial functions in China.
Acupuncture for adults with overactive bladder: a systematic review protocol
Authors: Mo Qian , Wang Yang , Ye Yongming , Yu Jinna , Liu Zhishun 
Published: January 2015

IntroductionOveractive bladder (OAB) is a symptom syndrome defined by the International Continence Society (ICS) as ‘the presence of urinary urgency (both daytime and nighttime), usually accompanied by increased frequency and nocturia with or without urge urinary incontinence in the absence of a urinary tract infection or other obvious pathology’. Clinical studies indicate that acupuncture could reduce micturition over 24 h, urgency episodes over 24 h, and improve quality of life among people with OAB. This systematic review protocol details the proposed methods for evaluating the effectiveness and safety of acupuncture for OAB.Methods and analysisThe following databases will be searched for relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Incontinence Group Trials Register, MEDLINE, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP database), Wan-Fang Data, and China National Knowledge Infrastructure (CNKI) and will hand search a list of medical journals as a supplement. Any randomised controlled trials in English or Chinese without restriction of publication status will be included with treatment of OAB. Outcomes will mainly include number of micturition episodes over 24 h, number of urgency episodes over 24 h and number of incontinence episodes over 24 h. Two reviewers will independently screen the titles, abstracts or even full texts, and extract data. Two other reviewers will assess study quality. Revman 5.1 software will be used to conduct meta-analysis and calculate the risk ratio for dichotomous data. Weighted mean difference or standard mean difference will be calculated for continuous data. The Cochrane collaboration's tool will be used to assess the risk of bias.DisseminationThis systematic review protocol will provide information on acupuncture therapy for OAB. The results will be disseminated through peer-reviewed publication or conference presentations.Protocol registrationPROSPERO CRD42014010181.
Healthy Start vitamins—a missed opportunity: findings of a multimethod study
Authors: McFadden Alison , Green Josephine M , McLeish Jenny , McCormick Felicia , Williams Victoria , Renfrew Mary J 
Published: January 2015

ObjectiveTo evaluate and provide a real-life view of the operation of the Healthy Start vitamins scheme.SettingThe study took place in primary care and community settings that served rural, urban and ethnically diverse populations, in two sentinel sites: London, and Yorkshire and the Humber. An online consultation and stakeholder workshops elicited views from across England.Participants669 health and social care practitioners including health visitors, midwives, public health practitioners, general practitioners, paediatricians and support staff participated in focus group discussions (n=49) and an online consultation (n=620). 56 participants representing health and social care practitioners, policymakers, service commissioners, and voluntary and independent sectors took part in stakeholder workshops.MethodsThree-phase multimethod study comprising focus group discussions, an online consultation and stakeholder workshops. Qualitative data were analysed thematically and quantitative data from the online survey were analysed using descriptive statistics.ResultsStudy participants were concerned about the low uptake of Healthy Start vitamin supplements and the consequences of this for health outcomes for women and young children. They experienced Healthy Start vitamin distribution as logistically complex, requiring the time, resources and creative thinking of a range of local and regional practitioners from senior strategists to administrative support workers. In the light of this, many participants argued that moving to universal provision of vitamin supplements would be more cost-effective than the current system.ConclusionsThere is consistency of views of health practitioners that the current targeted system of providing free vitamin supplements for low-income childbearing women and young children via the Healthy Start programme is not fulfilling its potential to address vitamin deficiencies. There is wide professional and voluntary sector support for moving from the current targeted system to provision of free vitamin supplements for all pregnant and new mothers, and children up to their fifth birthday.
Correct recognition and management of anaphylaxis: not much change over a decade
Authors: Plumb Benjamin , Bright Philip , Gompels Mark M , Unsworth David Joe 
Published: January 2015

ABSTRACT

Background
Anaphylaxis is increasing in incidence. This potentially fatal condition requires immediate intramuscular adrenaline as a vital part of early treatment. A 2002 survey of UK Senior House Officers showed a lack of knowledge regarding the recognition and management of anaphylaxis. Since then major changes in medical education and updated national guidelines have aimed to ensure that doctors can recognise and treat anaphylaxis appropriately.

Objectives
To determine current knowledge concerning the recognition and management of anaphylaxis among junior doctors compared to their predecessors.

Methods
Using the same methodology as in 2002, we asked 68 Foundation doctors to read five clinical scenarios potentially suggesting anaphylaxis and indicate how they would respond to each case. Their results were compared to those of Senior House Officers in 2002.

Results
68 of 107 (64%) junior doctors completed the questionnaire. All recognised the need for adrenaline in anaphylaxis, but only 74% selected the correct intramuscular route, and 34% the correct route and dose. 82% of junior doctors would inappropriately give adrenaline to the patient who had inhaled a foreign body (case 2). A higher percentage of the 2013 cohort indicated the correct route and dose of adrenaline in anaphylaxis than their 2002 colleagues. However, a greater percentage also selected adrenaline treatment inappropriately in non-anaphylactic case scenarios.

Conclusions
Despite updated guidelines, junior doctors continue to have poor knowledge about the recognition and management of anaphylaxis, with some still considering inappropriate intravenous adrenaline. More effort should be given to the recognition of anaphylaxis in early medical training.
Hot clasts and cold blasts: thermal heterogeneity in boiling-over pyroclastic density currents
Authors: Rader Erika , Geist Dennis , Geissman John , Dufek Joe , Harpp Karen 
Published: January 2015

Abstract
Partial thermal remanent magnetization data from clasts in pyroclastic density current (PDC) deposits provide information on the emplacement temperatures of both lithic and juvenile magmatic clasts contained in the deposits. We collected palaeomagnetic data from clasts in PDC deposits emplaced during historical eruptions of two volcanoes in Ecuador, the 2006 eruption at Tungurahua and the 1877 eruption at Cotopaxi. These eruptions were characterized by emplacement of PDCs mainly related to boiling-over activity. The deposits of these eruptions are similar and are characterized by cauliflower-textured juvenile scoria clasts up to 1 m in diameter and a diverse assemblage of lithic clasts surrounded by an unwelded ashy matrix. On the basis of progressive thermal demagnetization experiments, we infer that emplacement temperatures for most of the lithic clasts in PDC deposits are below 90 °C. In contrast, palaeomagnetic data from juvenile clasts from the same deposits provide emplacement temperatures higher than 540 °C. These data indicate the PDC were thermally heterogeneous over short length scales (decimetres) also after deposition. We hypothesize that PDCs emplaced by the boiling-over mechanism cool quickly owing to atmosphere entrainment, causing the juvenile clasts to form a rind that retains heat and that also prevents lithic clasts from appreciable heating. Several deposits on Cotopaxi, despite being morphologically similar to the PDC deposits, contain both cold lithic and juvenile clasts, which we interpret to be lahar deposits formed by PDCs travelling across glacial ice and snow. Rare deposits containing both hot lithic and hot juvenile clasts are classified as well-mixed, hot PDCs, and were erupted during a more energetic phase at Tungurahua.
From planet Earth to society: a new dynamic in Portugal concerning geoscience education and outreach activities
Authors: Silva Elizabeth , Sá Artur A. , Roxo Maria J. 
Published: January 2015

Abstract
Since the United Nations declared 2008 as the International Year of Planet Earth (IYPE) (during the triennium of 2007–2009), under the motto ‘Earth Sciences for Society’, many impacts and changes were generated in Portuguese society. Particular attention was given to educational activities concerning geosciences and these were promoted by several entities in Portugal.
The Portuguese National Commission for United Nations Educational, Scientific and Cultural Organization (UNESCO) has assumed an increasing role in the science sector with the promotion of initiatives and the creation of several scientific committees acting as national branches of UNESCO scientific programmes. This is the case of the National Committee for the International Geosciences Programme (NC–IGCP), which has been responsible for multiple initiatives that have been promoted and implemented in the area of geosciences and that contribute to the improvement of scientific literacy.
The work developed by NC–IGCP has contributed to developing new ways of promoting geosciences and to creating awareness about the role of geoscientists for a better world based in a sustainable development guided by ethical principles.
The use of tools such as itinerant exhibitions, educational training courses, school contests and information available on the website have allowed closer support and visibility to the development of fundamental science projects and outreach activities in Earth sciences.
A Novel CDC25B Promoter–Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models
Authors: Weber Helga L. , Gidekel Manuel , Werbajh Santiago , Salvatierra Edgardo , Rotondaro Cecilia , Sganga Leonardo , Haab Gabriela Acosta , Curiel David T. , Cafferata Eduardo G. , Podhajcer Osvaldo L. 
Published: January 2015

Abstract
Purpose: We decided to construct a novel oncolytic adenovirus whose replication was driven by the CDC25B promoter for its use in preclinical models of pancreatic cancer.
Experimental Design: We placed the essential E1A gene under control of the CDC25B promoter. Based on preliminary data, we pseudotyped the adenovirus with a chimeric fiber of serotypes 5/3. We investigated the in vitro lytic effect and the in vivo therapeutic efficacy in combination with gemcitabine on human pancreatic tumor xenografts orthotopically growing in nude mice and in tumors growing in Syrian hamsters. We also assessed biochemical markers of hepatic toxicity and CA19.9 levels.
Results: AV25CDC exhibited a strong in vitro lytic effect on pancreatic cancer cells. In vivo administration of AV25CDC combined with gemcitabine in mice harboring subcutaneously growing SW1990 pancreatic tumors almost abrogated tumor growth. Nude mice harboring 15-day-old orthotopic tumors, treated intratumorally or systemically with AV25CDC combined with gemcitabine, exhibited 70% to 80% reduction in tumor size compared with control mice that lasted for at least 60 days. Chemovirotherapy treatment induced a return to normal levels of biochemical parameters of hepatic toxicity; these mice exhibited more than 90% reduction in CA19.9 serum levels compared with control. Chemovirotherapy efficacy was confirmed in mice harboring Mia PaCa-2 tumors and in Syrian hamster harboring HaP-T1 tumors. We observed that viral treatment disrupted tumor architecture and induced an increase in MMP-9 activity that might facilitate gemcitabine penetrability.
Conclusion: These data demonstrate that AV25CDC is an effective oncolytic agent candidate for pancreatic cancer chemovirotherapy combination. Clin Cancer Res; 21(7); 1665–74. ©2015 AACR.
Differential Effects of Tyrosine Kinase Inhibitors on Normal and Oncogenic EGFR Signaling and Downstream Effectors
Authors: Kim Youngjoo , Apetri Mihaela , Luo BeiBei , Settleman Jeffrey E. , Anderson Karen S. 
Published: January 2015

Abstract
Constitutive activation of EGFR due to overexpression or mutation in tumor cells leads to dysregulated downstream cellular signaling pathways. Therefore, EGFR as well as its downstream effectors have been identified as important therapeutic targets. The FDA-approved small-molecule inhibitors of EGFR, gefitinib (Iressa) and erlotinib (Tarceva), are clinically effective in a subset of patients with non–small cell lung cancer (NSCLC) whose tumors harbor activating mutations within the kinase domain of EGFR. The current study examined effects of these drugs in 32D cells expressing native (WT) or oncogenic (L858R) EGFR as well as in cancer cell lines A431 and H3255. Distinct patterns for gefitinib and erlotinib inhibition of EGFR autophosphorylation at individual tyrosines were revealed for wild-type (WT) and L858R EGFR. Phosphorylation of Y845 has been shown to be important in cancer cells and Y1045 phosphorylation is linked to Cbl-mediated ubiquitination and degradation. Dramatic differences were observed by greater potency of these drugs for inhibiting downstream effectors for L858R EGFR including Cbl and STAT5. Selective targeting of Cbl may play a role in oncogene addiction and effects on STAT5 identify features of signaling circuitry for L858R EGFR that contribute to drug sensitivity and clinical efficacy. These data provide new understanding of the EGFR signaling environment and suggest useful paradigms for predicting patient response to EGFR-targeted therapy as well as combination treatments.
Implications: This study offers fundamental insights for understanding molecular mechanisms of drug sensitivity on oncogenic forms of EGFR and downstream signaling components as well as considerations for further drug optimization and design of combination therapy. Mol Cancer Res; 13(4); 765–74. ©2015 AACR.
Combined Inhibition of MAP Kinase and KIT Signaling Synergistically Destabilizes ETV1 and Suppresses GIST Tumor Growth
Authors: Ran Leili , Sirota Inna , Cao Zhen , Murphy Devan , Chen Yuedan , Shukla Shipra , Xie Yuanyuan , Kaufmann Michael C. , Gao Dong , Zhu Sinan , Rossi Ferdinando , Wongvipat John , Taguchi Takahiro , Tap William D. , Mellinghoff Ingo K. , Besmer Peter , Antonescu Cristina R. , Chen Yu , Chi Ping 
Published: January 2015

Abstract
Gastrointestinal stromal tumor (GIST), originating from the interstitial cells of Cajal (ICC), is characterized by frequent activating mutations of the KIT receptor tyrosine kinase. Despite the clinical success of imatinib, which targets KIT, most patients with advanced GIST develop resistance and eventually die of the disease. The ETS family transcription factor ETV1 is a master regulator of the ICC lineage. Using mouse models of Kit activation and Etv1 ablation, we demonstrate that ETV1 is required for GIST initiation and proliferation in vivo, validating it as a therapeutic target. We further uncover a positive feedback circuit where MAP kinase activation downstream of KIT stabilizes the ETV1 protein, and ETV1 positively regulates KIT expression. Combined targeting of ETV1 stability by imatinib and MEK162 resulted in increased growth suppression in vitro and complete tumor regression in vivo. The combination strategy to target ETV1 may provide an effective therapeutic strategy in GIST clinical management.
Significance: ETV1 is a lineage-specific oncogenic transcription factor required for the growth and survival of GIST. We describe a novel strategy of targeting ETV1 protein stability by the combination of MEK and KIT inhibitors that synergistically suppress tumor growth. This strategy has the potential to change first-line therapy in GIST clinical management. Cancer Discov; 5(3); 304–15. ©2015 AACR.
See related commentary by Duensing, p. 231
This article is highlighted in the In This Issue feature, p. 213
Complement-Mediated Macrophage Polarization in Perivascular Adipose Tissue Contributes to Vascular Injury in Deoxycorticosterone Acetate–Salt Mice
Authors: Ruan Cheng-Chao , Ge Qian , Li Yan , Li Xiao-Dong , Chen Dong-Rui , Ji Kai-Da , Wu Yong-Jie , Sheng Li-Juan , Yan Chen , Zhu Ding-Liang , Gao Ping-Jin 
Published: January 2015

Objective—
We have previously shown an increased expression of complement 3 (C3) in the perivascular adipose tissue (PVAT) in the deoxycorticosterone acetate (DOCA)–salt hypertensive model. This study aims to examine the role and underlying mechanism of C3 in PVAT for understanding the pathogenesis of hypertensive vascular remodeling further.

Approach and Results—
The role of C3 in macrophage polarization was investigated using peritoneal macrophages from wild-type and C3-deficient (C3KO) mice because we found that C3 was primarily expressed in macrophages in PVAT of blood vessels from DOCA-salt mice, and results showed a decreased expression of M1 phenotypic marker in contrast to an increased level of M2 marker in the C3KO macrophages. Bone marrow transplantation studies further showed in vivo that DOCA-salt recipient mice had fewer M1 but more M2 macrophages in PVAT when the donor bone marrows were from C3KO compared with those from wild-type mice. Of note, this macrophage polarization shift was accompanied with an ameliorated vascular injury. Furthermore, we identified the complement 5a (C5a) as the major C3 activation product that was involved in macrophage polarization and DOCA-salt–induced vascular injury. Consistently, in vivo depletion of macrophages prevented the induction of C3 and C5a in PVAT, and ameliorated hypertensive vascular injury as well.

Conclusions—
The presence and activation of bone marrow–derived macrophages in PVAT are crucial for complement activation in hypertensive vascular inflammation, and C5a plays a critical role in DOCA-salt–induced vascular injury by stimulating macrophage polarization toward a proinflammatory M1 phenotype in PVAT.
Association of Rare Loss-Of-Function Alleles in
HAL
, Serum Histidine
Authors: Yu Bing , Li Alexander H. , Muzny Donna , Veeraraghavan Narayanan , de Vries Paul S. , Bis Joshua C. , Musani Solomon K. , Alexander Danny , Morrison Alanna C. , Franco Oscar H. , Uitterlinden André , Hofman Albert , Dehghan Abbas , Wilson James G. , Psaty Bruce M. , Gibbs Richard , Wei Peng , Boerwinkle Eric 
Published: January 2015

Background—
Histidine is a semiessential amino acid with antioxidant and anti-inflammatory properties. Few data are available on the associations between genetic variants, histidine levels, and incident coronary heart disease (CHD) in a population-based sample.

Methods and Results—

By conducting whole exome sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3 novel rare LoF variants in
HAL
, a gene that encodes histidine ammonia-lyase in the first step of histidine catabolism. These LoF variants had large effects on blood histidine levels (
β
=0.26;
P
=1.2×10
−13
). The positive association with histidine levels was replicated by genotyping an independent sample of 718 ARIC African Americans (minor allele frequency=1%;
P
=1.2×10
−4
). In addition, high blood histidine levels were associated with reduced risk of developing incident CHD with an average of 21.5 years of follow-up among African Americans (hazard ratio=0.18;
P
=1.9×10
−4
). This finding was validated in an independent sample of European Americans from the Framingham Heart Study (FHS) Offspring Cohort. However, LoF variants in
HAL
were not directly significantly associated with incident CHD after meta-analyzing results from the CHARGE Consortium.

Conclusions—

Three LoF mutations in
HAL
were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. Future investigations on the association between
HAL
gene variation and CHD are warranted.