bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Silencing of MLL5β Inhibits Tumor Growth and Promotes Gamma-Irradiation Sensitization in HPV16/18-Associated Cervical Cancers
Authors: Nin Dawn Sijin , Yew Chow Wenn , Tay Sun Kuie , Deng Lih-Wen 
Published: August 2014

Abstract
We previously identified a novel MLL5 isoform, MLL5β, which was essential for E6 and E7 transcriptional activation in HPV16/18-associated cervical cancers. In this report, we investigated the potential of RNAi-mediated silencing of MLL5β through the use of MLL5β-siRNA as a novel therapeutic strategy for HPV16/18-positive cervical cancer. We observed concurrent downregulation of E6 and E7 after MLL5β silencing, leading to growth inhibition via the activation of apoptosis and senescence in the HeLa cell model. This corresponded with the enhanced antitumor effects of MLL5β-siRNA compared with E6- or E7-siRNA single treatments. Significant reduction in tumor size after MLLβ-siRNA treatment in the HeLa xenograft tumor model further emphasized the importance of MLL5β in HPV16/18-associated tumor growth and the potential of RNAi therapeutics that target MLL5β. We also identified MLL5β as a modulator of gamma-irradiation (IR) sensitization properties of cisplatin. We observed that while MLL5β silencing alone was enough to evoke cisplatin-like IR sensitization in tumor cells in vitro, overexpression of MLL5β inhibited the ability of cisplatin to sensitize HeLa cells to IR-induced cytotoxicity. MLL5β-siRNA-IR cotreatment was also observed to enhance tumor growth inhibition in vivo. Taken together, our findings highlight the potential of targeted silencing of MLL5β via the use of MLL5β-siRNA as a novel therapeutic strategy and propose that MLL5β-siRNA could be a viable alternative for cisplatin in the current cisplatin-based chemotherapeutics for HPV16/18-associated cervical cancers. Mol Cancer Ther; 13(11); 2572–82. ©2014 AACR.
Delineating the mTOR Kinase Pathway Using a Dual TORC1/2 Inhibitor, AZD8055, in Multiple Myeloma
Authors: Cirstea Diana , Santo Loredana , Hideshima Teru , Eda Homare , Mishima Yuko , Nemani Neeharika , Mahindra Anuj , Yee Andrew , Gorgun Gullu , Hu Yiguo , Ohguchi Hiroto , Suzuki Rikio , Cottini Francesca , Guichard Sylvie M. , Anderson Kenneth C. , Raje Noopur 
Published: August 2014

Abstract
Despite promising preclinical results with mTOR kinase inhibitors in multiple myeloma, resistance to these drugs may arise via feedback activation loops. This concern is especially true for insulin-like growth factor 1 receptor (IGF1R), because IGF1R signaling is downregulated by multiple AKT and mTOR feedback mechanisms. We have tested this hypothesis in multiple myeloma using the novel selective mTOR kinase inhibitor AZD8055. We evaluated p-mTOR S2481 as the readout for mTORC2/Akt activity in multiple myeloma cells in the context of mTOR inhibition via AZD8055 or rapamycin. We next validated AZD8055 inhibition of mTORC1 and mTORC2 functions in multiple myeloma cells alone or in culture with bone marrow stroma cells and growth factors. Unlike rapamycin, AZD8055 resulted in apoptosis of multiple myeloma cells. AZD8055 treatment, however, induced upregulation of IGF1R phosphorylation in p-Akt S473–expressing multiple myeloma cell lines. Furthermore, exposure of AZD8055-treated cells to IGF1 induced p-Akt S473 and rescued multiple myeloma cells from apoptosis despite mTOR kinase inhibition and TORC2/Akt blockage. The addition of blocking IGF1R antibody resulted in reversing this effect and increased AZD8055-induced apoptosis. Our study suggests that combination treatment with AZD8055 and IGF1R-blocking agents is a promising strategy in multiple myeloma with potential IGF1R/Akt signaling–mediated survival. Mol Cancer Ther; 13(11); 2489–500. ©2014 AACR.
Cross-reactivity of insulin analogues with three insulin assays
Authors: Dayaldasani A , Rodríguez Espinosa M , Ocón Sánchez P , Pérez Valero V 
Published: August 2014

Background Immunometric assays have recently shown higher specificity in the detection of human insulin than radioimmunoassays with almost no cross-reaction with proinsulin or C peptide. The introduction of the new insulin analogues on the market, however, has raised the need to define their cross-reactivity in these assays. Several studies have been published in this regard with different results. Methods The analogues studied were insulins lispro, aspart, glargine, detemir, and glulisine. Insulin concentrations were measured in Immulite® 2000 and Advia Centaur® XP (Siemens Healthcare Diagnostics), and Elecsys® Modular Analytics E170 (Roche). All samples were processed 15 times in the same analytical run following a random sequence. Those samples which showed statistically and clinically significant changes in insulin concentration were reprocessed using increasing concentrations of analogue, and this was done twice, using two different serum pools, one with a low concentration of insulin and one with a high concentration of insulin. Results In the Elecsys® E170 analyser, glargine showed statistical changes (comparison of mean concentrations with p < 0.05) and clinically significant changes in measured insulin (percentage difference 986.2% > reference change value: 59.8%), and the interference increased with increasing concentrations of analogue; the differences were not significant in the case of the other analogues. In the Advia Centaur® and Immulite® 2000 only the results for glulisine did not present significance (percentage difference 44.7% < reference change value 103.5%). Increasing concentrations of aspart, glargine, and lispro showed increased interference in Immulite® 2000. Conclusions In the Elecsys® E170 assay, relevant cross-reactivity was only detected with insulin glargine, whereas in the other analysers all analogues except glulisine showed significant interference.
Educating consumers in self-testing: The development of an online decision aid
Authors: Ickenroth Martine HP , Grispen Janaica EJ , Ronda Gaby , Dinant Geert-Jan , de Vries Nanne K , van der Weijden Trudy 
Published: August 2014

Context and objective: Diagnostic self-tests have become available worldwide. The most frequently performed self-tests in the Netherlands are tests to detect high cholesterol and diabetes. Since these tests can be performed without professional guidance, potential consumers need to receive independent information on the pros and cons of self-testing. The aim of this study was to develop a decision aid (DA) on cholesterol and glucose self-testing to encourage informed choice and to meet consumers’ needs and expectations. Methods: A DA was developed based on previous research and medical practice guidelines. The first prototype was assessed for content by means of semi-structured interviews with experts ( n = 13), followed by usability tests with users ( n = 10), leading to improvements to the DA in an iterative process. Results: Comments of the experts were grouped into four categories: general comments, textual remarks, technical errors and lay-out. User comments were mainly consistent with the experts’ opinions. Important considerations that were identified concerned the safety of providing this information without direct professional counselling, whether a ranking of available tests should be provided and how strong a warning about self-testing should be. Conclusion: Important considerations on how to inform consumers about self-testing were discussed, and led to important changes in the DA. Future research will have to assess the actual use of the DA once it is accessible to the general public, as well as its effects on knowledge and attitude towards self-testing.
Evaluation of True Vocal Fold Growth as a Function of Age
Authors: Rogers Derek J. , Setlur Jennifer , Raol Nikhila , Maurer Rie , Hartnick Christopher J. 
Published: August 2014

ObjectiveTo evaluate change in true vocal fold length as a function of age.Study DesignProspective study.SettingTertiary aerodigestive center.Subjects and MethodsIn total, 205 patients (aged 1 month to 20 years), of whom 87 (42.4%) were female and 118 (57.6%) male, were included. Lengths of the total vocal fold (TVFL), membranous vocal fold (MVFL), and cartilaginous vocal fold (CVFL) were measured during direct laryngoscopy. Membranous‐to‐cartilaginous (M/C) ratios were calculated.ResultsFor patients younger than 1 year, mean (SD) MVFL was 4.4 (1.3) mm for females and 4.9 (1.8) mm for males. At age 17 years, mean (SD) MVFL was 12.3 (2.1) mm for females and 14.0 (1.4) mm for males. Mean TVFL, MVFL, and CVFL increased an average of 0.7 mm, 0.5 mm, and 0.2 mm per year in linear fashion, respectively (linear regression, P <. 0001). The M/C ratio did not significantly change with age (P =. 33). Mean TVFL, MVFL, and CVFL showed no statistical difference between males and females (P =. 27,. 11, and. 75, respectively).ConclusionThis is the largest longitudinal pediatric study specifically examining vocal fold length as a function of age. Each length of the true vocal fold appeared to linearly increase for both females and males. The M/C ratio remained relatively constant, unlike previously reported data, possibly due to in vivo vs cadaveric measurements. These findings suggest that critical periods of development in females and males are not explainable by changes in vocal fold length alone, and other factors such as vocal fold layers need further exploration.
A study of the reliability of the Nociception Coma Scale
Authors: Riganello F , Cortese MD , Arcuri F , Candelieri A , Guglielmino F , Dolce G , Sannita WG , Schnakers C 
Published: August 2014

Objective: In this study, we investigated the reliability of the Nociception Coma Scale which has recently been developed to assess nociception in non-communicative, severely brain-injured patients. Design: Prospective cross-sequential study. Setting: Semi-intensive care unit and long-term brain injury care. Subjects: Forty-four patients diagnosed as being in a vegetative state ( n=26) or in a minimally conscious state ( n=18). Interventions: Patients were assessed by two experts (rater A and rater B) on two consecutive weeks to measure inter-rater agreement and test-retest reliability. Main measures: Total scores and subscores of the Nociception Coma Scale. Results: We performed a total of 176 assessments. The inter-rater agreement was moderate for the total scores (k = 0.57) and fair to substantial for the subscores (0.33 ≤ k ≤ 0.62) on week 2. The test-retest reliability was substantial for the total scores (k = 0.66) and moderate to almost perfect for the subscores (0.53 ≤ k ≤ 0.96) for rater A. The inter-rater agreement was weaker on week 1, whereas the test-retest reliability was lower for the least experienced rater (rater B). Conclusions: This study provides further evidence of the psychometric qualities of the Nociception Coma Scale. Future studies should assess the impact of practical experience and background on administration and scoring of the scale.
Factors describing community ambulation after stroke: a mixed-methods study
Authors: Barclay Ruth , Ripat Jacquie , Mayo Nancy 
Published: August 2014

Objective: To develop a model of community ambulation after stroke based on: Canadian data from community-dwelling individuals post-stroke; the experiences and opportunities for community ambulation expressed by individuals with stroke; and current literature. The model presents a visual depiction of the relationships between the different factors of community ambulation after stroke. Design: A quantitative/qualitative explanatory sequential mixed-methods design was utilized. Secondary data analysis with structural equation modeling resulted in a community ambulation model. Two focus groups of individuals with stroke were conducted to verify and explain the model. Setting: Community. Subjects: Quantitative data from 227 participants: 142 (63%) male; 63.4 (12.0) years of age and 2.6 (2.5) years post stroke. Eleven individuals participated in the focus groups: 6 (55%) male; 61.4 (6.9) years of age and 5.8 (3.3) years since stroke. Main measures: Model variables: items from the EuroQol, Preference Based Stroke Index, gait speed, Reintegration to Normal Living Index, the Community Health Activities Model Program for Seniors, and the Geriatric Depression Scale. Results: The model had reasonable fit with three latent variables: ambulation, gait speed, and health perceptions (normed χ2 = 1.8, root mean square error of approximation = 0.060 (0.043; 0.075)). Depression was also a component of community ambulation. Participants verified the model and added endurance and the environment as additional components. Participants used self-awareness and knowledge of the environment to engage in cognitive strategies related to community ambulation. Conclusions A model of community ambulation after stroke was developed and verified. Recognizing important components of community ambulation may assist physiotherapists in determining community ambulation goals, needs, and opportunities in partnership with clients.
Does adding a 12-month exercise programme to usual care after a rotator cuff repair effect disability and quality of life at 12 months? A randomized controlled trial
Authors: Piitulainen Kirsi , Häkkinen Arja , Salo Petri , Kautiainen Hannu , Ylinen Jari 
Published: August 2014

Objective: To compare a 12-month home-based exercise programme with usual care for disability and health-related quality of life after rotator cuff repair. Design: Randomized controlled trial. Setting: Outpatient physical and rehabilitation medicine clinic. Subjects: Consecutive patients ( n = 67, mean age 54 years) who underwent rotator cuff repairs were randomized into an experimental group (EG) or a usual care group (UCG). Interventions: The UCG received ordinary postoperative instructions, while the EG were given advice and instructions on a shoulder muscle strengthening programme to be undertaken at home. Main measures: Disability was assessed with the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and quality of life with the Short-Form 36 Health Survey (SF-36). Results: At the follow-up, no between-group differences were observed in any of the outcomes. The mean (SD) ASES score improved by 21 points (95% CI, 16 to 26, p < 0.001) in the EG from the baseline 74 (14) and by 25 points (95% CI, 20 to 31, p < 0.001) in the UCG from the baseline 70 (18). Both groups exhibited significant improvements ( p < 0.001) in the SF-36 physical component score. In the UCG, improvements were observed in the Social Functioning ( p = 0.034) and Role Emotional ( p = 0.003) dimensions. In the EG, 57% of the patients completed the exercises twice weekly for the first six months, after which training adherence declined. Conclusions: The home exercise programme and usual care were equally effective in improving disability and quality of life after rotator cuff repair. The extra time involved in teaching the home exercise programme is not warranted.
Assessing child bilingualism: Direct assessment of bilingual syntax amends caretaker report
Authors: Lust Barbara , Flynn Suzanne , Blume María , Park Seong Won , Kang Carissa , Yang Sujin , Kim Ah-Young 
Published: August 2014

Aims and objectives: In this paper we investigate measures for the evaluation of a child’s bilingualism. Methodology: We compare a caretaker report on the estimated quantity and quality of a child’s bilingualism to results from direct assessment of the bilingual child’s production of complex sentences in Korean and English. We adopt an integrated methodology in which two case studies, closely matched on caretaker report and general background, are investigated directly through an elicited imitation task, for their knowledge of syntactic factors underlying development of coordinate sentence structure in both languages. Data and analysis: The participants are two four-year-old Korean-English bilingual children. We compare the caretaker report on the estimated quantity and quality of the children’s bilingualism to results from the direct assessment of their production of comparable complex sentences in both languages. We adopt an integrated methodology in which the two case studies, closely matched on caretaker report and general background, are investigated directly through an elicited imitation task for their knowledge of syntactic factors underlying development of coordinate sentence structure in both languages. Findings: Direct assessment reveals significant differences between the two children in the quantity and quality of their bilingualism, in spite of commonalities in caretaker reports. Limitations: This study compared only two children and two languages, and focused on language production. Replication with a larger number of subjects, including variation in child age, and measurement through other tasks, for example, tests of language comprehension, are merited. Implications: Results are interpreted as motivating both the refinement of caretaker report questionnaires and the necessity for direct assessment of bilingual participants, and suggest the elicited imitation task as a valuable method for conducting such direct assessment.
The M235T polymorphism in the angiotensinogen gene and atrial fibrillation: A meta-analysis
Authors: Wang HuiXuan , Teng Yi , Wang Ke , Xia ZhengWu , Tian YuanYuan , Li CuiJuan 
Published: August 2014

Objective: The M235T polymorphism in the angiotensinogen gene has been reported to be associated with the development of atrial fibrillation (AF).However, results from observational studies are conflicting. Methods: PubMed, google scholar and China National Knowledge Infrastructure database(2000.1–2013.4) were searched for eligible articles; four separate studies with 2580 subjects on the relationship between M235T polymorphism and AF were analyzed by meta-analysis. The associations between M235T polymorphism and AF risk were estimated by pooled odds ratio (OR) and 95% confidence interval (CI) using a fixed or random-effects model. Results: There was a significant association between M235T polymorphism and AF. The pooled OR for the recessive model in the total population was 2.17 (95% CI: 1.39–3.38, I2=0%). In a subgroup analysis by nationality, the pooled OR for TT vs. MM genotype was 0.55 (95% CI: 0.32–0.95, I2=0%) and the pooled OR for the recessive model was 1.86 (95% CI: 1.08–3.20, I2=0%) in Asians. Conclusions: The current meta-analysis suggested that the M235T polymorphism in the angiotensinogen gene might be related to the increased risk of AF in Asians. Conclusive evidence on the effects of the variants in AF should be addressed in further studies.
Association of polymorphisms in AGTR1 and AGTR2 genes with primary aldosteronism in the Chinese Han population
Authors: Wu Zhun , Huang Chao , Zhou Tingting , Lin Jinglai , Zhang Kaiyan , Li Wei , Zheng Jiaxin , Chen Bin , Wang Baojun , Zhang Xu , Xing Jinchun 
Published: August 2014

Hypothesis: Polymorphisms in angiotensin II type-1/2 receptor genes ( AGTR1/ AGTR2) may be involved in the pathogenesis of primary aldosteronism. The present study aims to reveal some loci susceptible to the disease on the genes in a group of Chinese Han nationality. Materials and methods: A case-control study was conducted in 202 patients and 188 controls. Ten tagging SNPs on AGTR1/ AGTR2 were genotyped for all subjects via the method of multiplex PCR-ligase detection reaction. Statistical analysis was performed with chi-square test and logistic regression analysis. Results: rs3772616 on the AGTR1 gene was a factor for susceptibility to primary aldosteronism ( p<0.001), and the TT genotype significantly decreased the risk of primary aldosteronism compared with the CC homozygote ( p=0.008, adjusted OR=0.13; 95%CI: 0.03–0.59). The rs3772616 polymorphism was associated with primary aldosteronism under the additive and dominant models. The female carriers of the G allele in rs5193 showed a significant difference compared with the T allele. Conclusions: The AGTR1 rs3772616 polymorphism can be considered as a hereditary marker for primary aldosteronism, and in the Chinese Han population the rs5193 G allele seems to predispose to it only in women.
The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin–angiotensin–aldosterone system
Authors: Wang Huishu , Zhang Siduo , Xu Shiyuan , Zhang Liangcheng 
Published: August 2014

Introduction: Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α2-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigated whether dexmedetomidine induces cardioprotection against myocardial apoptosis injury. Methods: In order to assess the role of dexmedetomidine on myocardial apoptosis, we established a grave scalding rat model. Blood and myocardial tissue from the ventriculus sinister were harvested, then troponin, myocardial apoptosis, and expression of caspase-12, GRP78, and CHOP were assessed. Results: Dexmedetomidine significantly reduced myocardial apoptosis, improved functional recovery, and reversed myocardial injury induced by grave scalding. The heart rate in the five groups studied was significantly different ( p < 0.05). The number of buffy-stained nucleoli in the myocardial cell was highest in the simple scald group. The expression of caspase-12 obviously increased in the simple scald group. The expression of GRP78 and CHOP increased in the simple scald and scald and 50 μg/kg dexmedetomidine groups ( p < 0.05). Conclusions: The results show that dexmedetomidine (DEX) produces cardioprotection against myocardial apoptosis injury. DEX is not only a useful sedative, but also plays a pivotal role in anesthetic cardioprotection. The potential benefits of DEX protection in high risk cardiovascular patients undergoing surgery are enormous.
Lay and health care professional understandings of self-management: A systematic review and narrative synthesis
Authors: Sadler Euan , Wolfe Charles DA , McKevitt Christopher 
Published: August 2014

Objectives: Self-management is widely promoted but evidence of effectiveness is limited. Policy encourages health care professionals to support people with long-term conditions to learn self-management skills, yet little is known about the extent to which both parties share a common understanding of self-management. Thus, we compared health care professional and lay understandings of self-management of long-term conditions. Methods: Systematic review and narrative synthesis of qualitative studies identified from relevant electronic databases, hand-searching of references lists, citation tracking and recommendations by experts. Results: In total, 55 studies were included and quality was assessed using a brief quality assessment tool. Three conceptual themes, each with two subthemes were generated: traditional and shifting models of the professional–patient relationship (self-management as a tool to promote compliance; different expectations of responsibility); quality of relationship between health care professional and lay person (self-management as a collaborative partnership; self-management as tailored support) and putting self-management into everyday practice (the lived experience of self-management; self-management as a social practice). Conclusion: Self-management was conceptualised by health care professionals as incorporating both a biomedical model of compliance and individual responsibility. Lay people understood self-management in wider terms, reflecting biomedical, psychological and social domains and different expectations of responsibility. In different ways, both deviated from the dominant model of self-management underpinned by the concept of self-efficacy. Different understandings help to explain how self-management is practised and may help to account for limited evidence of effectiveness of self-management interventions.