bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Regulation of CXCL12 Plays a Critical Role in Mediating Tumor Progression and the Immune Response In Osteosarcoma
Authors: Li Binghao , Wang Zhan , Wu Hao , Xue Mingfeng , Lin Peng , Wang Shengdong , Lin Nong , Huang Xin , Pan Weibo , Liu Meng , Yan Xiaobo , Qu Hao , Sun Lingling , Li Hengyuan , Wu Yan , Teng Wangsiyuan , Wang Zenan , Zhou Xingzhi , Chen Huabiao , Poznansky Mark C. , Ye Zhaoming 
Published: May 2018

Abstract
The mechanism by which osteosarcomas metastasize is elusive, and challenges remain regarding its treatment with modalities including immunotherapy. CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12. Here, we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and to impair cytotoxic T-cell homing to the tumor site. Analysis of human osteosarcoma cases further revealed that CXCL12 expression strongly correlated with overall survival. Evaluations on fresh human chemotherapy-free osteosarcoma samples also showed a positive correlation between CXCL12 concentration and the number of intratumoral lymphocytes. Critically, treatment targeting DNMT1 in immunocompetent mouse models significantly elevated expression of CXCL12 in tumors, resulting in a robust immune response and consequently eradicating early lung metastases in addition to suppressing subcutaneous tumor growth. These antitumor effects were abrogated by CXCL12–CXCR4 blockade or CD8+ T-cell depletion. Collectively, our data show that CXCL12 regulation plays a significant role in both tumor progression and immune response, and targeting CXCL12 is promising for therapeutics against osteosarcoma.
Significance: Epigenetic regulation of CXCL12 controls metastasis and immune response in osteosarcoma, suggesting epigenetic therapies or therapies targeting CXCL12 have potential for therapeutic intervention in osteosarcoma. Cancer Res; 78(14); 3938–53. ©2018 AACR.
Mechanistic Distinctions between CHK1 and WEE1 Inhibition Guide the Scheduling of Triple Therapy with Gemcitabine
Authors: Koh Siang-Boon , Wallez Yann , Dunlop Charles R. , Bernaldo de Quirós Fernández Sandra , Bapiro Tashinga E. , Richards Frances M. , Jodrell Duncan I. 
Published: May 2018

AbstractCombination of cytotoxic therapy with emerging DNA damage response inhibitors (DDRi) has been limited by tolerability issues. However, the goal of most combination trials has been to administer DDRi with standard-of-care doses of chemotherapy. We hypothesized that mechanism-guided treatment scheduling could reduce the incidence of dose-limiting toxicities and enable tolerable multitherapeutic regimens. Integrative analyses of mathematical modeling and single-cell assays distinguished the synergy kinetics of WEE1 inhibitor (WEE1i) from CHEK1 inhibitor (CHK1i) by potency, spatiotemporal perturbation, and mitotic effects when combined with gemcitabine. These divergent properties collectively supported a triple-agent strategy, whereby a pulse of gemcitabine and CHK1i followed by WEE1i durably suppressed tumor cell growth. In xenografts, CHK1i exaggerated replication stress without mitotic CDK hyperactivation, enriching a geminin-positive subpopulation and intratumoral gemcitabine metabolite. Without overt toxicity, addition of WEE1i to low-dose gemcitabine and CHK1i was most effective in tumor control compared with single and double agents. Overall, our work provides quantitative insights into the mechanisms of DDRi chemosensitization, leading to the rational development of a tolerable multitherapeutic regimen.Significance: Multiple lines of mechanistic insight regarding DNA damage response inhibitors rationally guide the preclinical development of a tolerable multitherapeutic regimen.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/11/3054/F1.large.jpg. Cancer Res; 78(11); 3054–66. ©2018 AACR.
Estimating the Marginal Causal Effect of Fish Consumption during Adolescence on Multiple Sclerosis: A Population-Based Incident Case-Control Study
Authors: Abdollahpour Ibrahim , Nedjat Saharnaz , Mansournia Mohammad Ali , Sahraian Mohammad Ali , Kaufman Jay S. 
Published: May 2018

<b><i>Background:</i></b> Adolescence is considered as a critical time period in multiple sclerosis (MS) etiology. Nonetheless, there are insufficient reports regarding the potential role of fresh and canned fish consumptions during adolescence in MS etiology. The authors investigated the association between fresh and canned fish consumptions and MS. <b><i>Methods:</i></b> This was a population-based incident case-control study conducted in Tehran. Cases (<i>n</i> = 547) identified from Iranian Multiple Sclerosis Society between August 7, 2013, and November 17, 2015 were included in the study. Population-based controls (<i>n</i> = 1,057) were recruited by random digit telephone dialing without any matching. Inverse-probability-of-treatment weighing (IPTW) using 2 sets of propensity scores and model-based standardization were used to separately estimate the marginal odds ratio between fresh and canned fish consumptions in adolescence and MS. <b><i>Results:</i></b> The marginal OR for fresh fish was 0.72 (95% CI 0.58–0.90; <i>p</i> = 0.005) in both IPTW analyses. Similarly, the marginal OR for canned fish consumption was 0.75 (95% CI 0.60–0.95; <i>p</i> = 0.014).The model-based standardized OR was 0.72 (95% CI 0.58–0.91; <i>p</i> = 0.008) for fresh and 0.73 (95% CI 0.59–0.94; <i>p</i> = 0.006) for canned fish consumption in adolescence. <b><i>Discussion:</i></b> Subject to limitation of case-control studies in interpreting associations causally, this study suggests that both fresh and canned fish consumptions in adolescence can decrease the risk of MS.
Orthostatic Hypotension and Risk of Clinical and Subclinical Cardiovascular Disease in Middle‐Aged Adults
Authors: Juraschek Stephen P. , Daya Natalie , Appel Lawrence J. , Miller Edgar R. , McEvoy John William , Matsushita Kunihiro , Ballantyne Christie M. , Selvin Elizabeth 
Published: May 2018

Background

Although orthostatic hypotension (
OH
) is a well‐recognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease (
CVD
) risk is controversial.

Methods and Results

Participants with
OH
, defined as a decrease in blood pressure (systolic ≥20 mm Hg or diastolic ≥10 mm Hg) from the supine to standing position, were identified during the first visit of the ARIC (Atherosclerosis Risk in Communities) Study (1987–1989) within 2 minutes of standing. All participants were followed up for the development of myocardial infarction, heart failure, stroke, fatal coronary heart disease (
CHD
), any
CHD
(combination of silent, nonfatal, and fatal
CHD
or cardiac procedures), and all‐cause mortality. Participants were assessed for carotid intimal thickness and plaque during the first visit. Detectable high‐sensitivity troponin T (≥5 ng/L) and elevated NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; ≥100 pg/mL) were determined in blood collected during the second visit (1990–1992). All associations were adjusted for known
CVD
risk factors. In 9139 participants (57% women; 23% black; mean age, 54±5.7 years), 3% had
OH
. During follow‐up (median, 26 years),
OH
was associated with myocardial infarction (hazard ratio [
HR
], 1.88; 95% confidence interval [
CI
], 1.44–2.46), congestive heart failure (
HR
, 1.65; 95%
CI
, 1.34–2.04), stroke (
HR
, 1.83; 95%
CI
, 1.35–2.48), fatal
CHD
(
HR
, 2.77; 95%
CI
, 1.93–3.98), any
CHD
(
HR
, 2.00; 95%
CI
, 1.64–2.44), and all‐cause mortality (
HR
, 1.68; 95%
CI
, 1.45–1.95).
OH
was also associated with carotid intimal thickness (β, 0.05 mm; 95%
CI
, 0.04–0.07 mm), carotid plaque (odds ratio, 1.51; 95%
CI
, 1.18–1.93), detectable high‐sensitivity troponin T (odds ratio, 1.49; 95%
CI
, 1.16–1.93), and elevated
NT
‐pro
BNP
(odds ratio, 1.92; 95%
CI
, 1.48–2.49).

Conclusions

OH
identified in community‐dwelling middle‐aged adults was associated with future
CVD
events and subclinical
CVD
. Further research is necessary to establish a causal role for
OH
in the pathogenesis of
CVD
.
Dynamical Properties of the North Atlantic Atmospheric Circulation in the Past 150 Years in CMIP5 Models and the 20CRv2c Reanalysis
Authors: Rodrigues David , Alvarez-Castro M. Carmen , Messori Gabriele , Yiou Pascal , Robin Yoann , Faranda Davide 
Published: May 2018

AbstractIt is of fundamental importance to evaluate the ability of climate models to capture the large-scale atmospheric circulation patterns and, in the context of a rapidly increasing greenhouse forcing, the robustness of the changes simulated in these patterns over time. Here we approach this problem from an innovative point of view based on dynamical systems theory. We characterize the atmospheric circulation over the North Atlantic in the CMIP5 historical simulations (1851–2000) in terms of two instantaneous metrics: local dimension of the attractor and stability of phase-space trajectories. We then use these metrics to compare the models to the Twentieth Century Reanalysis version 2c (20CRv2c) over the same historical period. The comparison suggests that (i) most models capture to some degree the median attractor properties, and models with finer grids generally perform better; (ii) in most models the extremes in the dynamical systems metrics match large-scale patterns similar to those found in the reanalysis; (iii) changes in the attractor properties observed for the ensemble-mean 20CRv2c are artifacts resulting from inhomogeneities in the standard deviation of the ensemble over time; and (iv) the long-term trends in local dimension observed among the 56 members of the 20CR ensemble have the same sign as those observed in the CMIP5 multimodel mean, although the multimodel trend is much weaker.
Evaluation of CMIP5 Earth System Models for the Spatial Patterns of Biomass and Soil Carbon Turnover Times and Their Linkage with Climate
Authors: Wu Donghai , Piao Shilong , Liu Yongwen , Ciais Philippe , Yao Yitong 
Published: May 2018

AbstractEarth system models (ESMs) from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were diagnosed as having large discrepancies in their land carbon turnover times, which partly explains the differences in the future projections of terrestrial carbon storage from the models. Carvalhais et al. focused on evaluation of model-based ecosystem carbon turnover times τeco in relation with climate factors. In this study, τeco from models was analyzed separately for biomass and soil carbon pools, and its spatial dependency upon temperature and precipitation was evaluated using observational datasets. The results showed that 8 of 14 models slightly underestimated global biomass carbon turnover times τveg (modeled median of 8 yr vs observed 11 yr), and 11 models grossly underestimated the soil carbon turnover time τsoil (modeled median of 16 yr vs observed 26 yr). The underestimation of global carbon turnover times in ESMs was mainly due to values for τveg and τsoil being too low in the high northern latitudes and arid and semiarid regions. In addition, the models did not capture the observed spatial climate sensitivity of carbon turnover time in these regions. Modeled τveg and τsoil values were generally weakly correlated with climate variables, implying that differences between carbon cycle models primarily originated from structural differences rather than from differences in atmospheric climate models (i.e., related to temperature and precipitation). This study indicates that most models do not reproduce the underlying processes driving regional τveg and τsoil, highlighting the need for improving the model parameterization and adding key processes such as biotic disturbances and permafrost–carbon climate responses.
Treatment of Patients With Benign Paroxysmal Positional Vertigo and Severe Immobility Using the Particle Repositioning Chair: A Retrospective Cohort Study
Authors: Luryi Alexander L. , Lawrence Juliana , LaRouere Michael , Babu Seilesh , Bojrab Dennis I. , Zappia John , Sargent Eric W. , Schutt Christopher A. 
Published: May 2018

Objective: To report treatment of benign paroxysmal positional vertigo (BPPV) in patients unable to undergo traditional canalith repositioning maneuvers (CRMs) using a particle repositioning chair (PRC). Methods: A retrospective chart review was conducted at a single high-volume otology practice of patients diagnosed with BPPV from 2007 to 2017 with immobility prohibiting use of traditional CRMs. Patients were diagnosed and treated using a PRC, and outcome measures including resolution, recurrence, and number of treatment visits were recorded. Results: A total of 34 patients meeting criteria were identified, 24 of whom had cervical spine disease and 10 of whom had other prohibitive immobility. Symptoms were present for between 5 days and 11 years at presentation, with mean and median of 552 and 90 days, respectively. Symptoms resolved in 68% of patients and recurred in 13% of those patients. Most patients required 1 treatment visit. Conclusions: Successful treatment of patients with BPPV and concomitant immobility prohibiting traditional CRMs is reported using the PRC. Benign paroxysmal positional vertigo in the setting of immobility is an indication for treatment with a PRC if available.
Disparities in the impact of a community hypertension education programme across age, gender, race and housing type
Authors: Lwin May O , Malik Shelly , Kang Vernon Beng Tat , Chen Grace Peimin 
Published: May 2018

Objective: This study investigated the extent to which the efficacy of a hypertension awareness programme in Singapore may differ based on age, gender, race and housing type (as proxy for income). Method: Pre- and post-programme survey responses on blood pressure (BP) knowledge and beliefs from 9,960 grade 5 students were assessed. Post-programme responses from 5,361 adult family members were also evaluated. Results: Female students were more likely to show better BP knowledge and beliefs. As compared to Chinese students, Malay students had lower levels of BP knowledge and attitudes, while Indian students possessed stronger attitudes. Programme efficacy among students in the most affordable housing was the least favourable. In the adult family member sample, Malay and Indian adults had higher self-confidence and intention to measure their BP in the future than the Chinese. Adult respondents in the most affordable housing possessed the least favourable beliefs towards BP measurement. Older adults, men, Malays and residents in affordable housing types had higher odds of being found with hypertension when tested at home. Conclusion: Despite the same hypertension education programme being implemented, disparities in programme impact were apparent in both student and adult sample across race, housing type and, to a lesser extent, gender. Future interventions should consider these disparities when developing health education programmes.
Academic Entrepreneurs, Public Policy, and the Growth of Latin American Studies in Britain during the Cold War
Authors: Miller Rory M. 
Published: May 2018

The initial development of Latin American studies in Britain in the early 1960s resulted from the interest of pioneering academics in London and Cambridge and the Royal Institute of International Affairs. Alongside these academic efforts, the government’s concerns about the declining role of British business in the region triggered the establishment of the Parry Committee in 1962. Reporting in 1965, this committee recommended the establishment of five government-financed Latin American centers, together with investment in training new Ph.D. students, especially in the social sciences. These younger scholars, who took the opportunity to do research and travel in Latin America, soon began to react more strongly against U.S. policy, economic inequality, and human rights abuses. In the 1970s, tensions between the older and newer generations became acute with the Pinochet coup and the “dirty wars.” Many academics thus distanced themselves from business and government in a way that the pioneers had not anticipated. El desarrollo inicial de los estudios latinoamericanos en Gran Bretaña a principios de la década de 1960 se debió al interés de académicos pioneros en Londres, Cambridge y el Instituto Real de Asuntos Internacionales. Junto con estas iniciativas académicas, la preocupación gubernamental ante el declive de los negocios británicos en la región dio lugar a la fundación del Comité Parry en 1962. En su informe de 1965, dicho comité recomendó el establecimiento de cinco centros latinoamericanos financiados por el gobierno, así como la formación de nuevos estudiantes doctorales, sobre todo en el área de ciencias sociales. Estos académicos más jóvenes, que aprovecharon la oportunidad de estudiar en y viajar por América Latina, pronto comenzaron a reaccionar con mayor fuerza contra la política de EE.UU., la desigualdad económica y los abusos contra los derechos humanos. En la década de 1970, las tensiones entre las generaciones más viejas y las nuevas se agudizaron con el golpe de estado de Pinochet y las “guerras sucias.” Muchos académicos se distanciaron entonces de los negocios y los asuntos del gobierno de una manera que los pioneros no habían previsto.
Predictors of Exclusive Breastfeeding for 6 Months in a National Sample of US Children
Authors: Odar Stough Cathleen , Khalsa Amrik S. , Nabors Laura A. , Merianos Ashley L. , Peugh James 
Published: May 2018

Purpose: To explore predictors of breastfeeding behavior and seek to replicate prior findings using a recent nationally representative United States (US) sample, which has not been done previously. Design: Secondary data analysis using the National Survey of Children’s Health 2011 to 2012. Setting: Households in the 50 US states, the District of Columbia, and the US Virgin Islands. Participants: Caregivers with a child between 6 months and 6 years of age (n = 26 552). Measures: Caregiver-reported child breastfeeding behavior, child birth weight, child/maternal/family demographics, maternal physical and mental health, and household tobacco exposure. Analysis: A multinomial logistic regression explored whether child, maternal, and family characteristics predicted exclusive breastfeeding for 6 months or breastfeeding for a suboptimal duration. Results: Approximately 79% and 17% of the sample-initiated breastfeeding and exclusively breastfed for 6 months, respectively. Child ethnicity/race, maternal education, household tobacco exposure, family composition, and family income predicted odds of both exclusive breastfeeding for 6 months and breastfeeding for a suboptimal duration or not exclusively. Normal or high child birth weight and better maternal physical health predicted greater odds of exclusive breastfeeding for 6 months. Conclusion: Rates of exclusive breastfeeding for 6 months remain low in the United States. Single-parent and step-families, lower income families, non-Hispanic black children, children with exposure to tobacco, and children of mothers with lower education are at greatest risk.
Development and Initial Psychometric Properties of a Questionnaire to Assess Competence in Palliative Care: Palliative Care Competence Framework Questionnaire
Authors: Connolly Michael , McLean Sarah , Guerin Suzanne , Walsh Gillian , Barrett Aileen , Ryan Karen 
Published: May 2018

Background: Although the provision of palliative care (PC) is fundamental to the role of the physician, little research has assessed the competence of trainee and experienced physicians in PC. Aim: To describe the development of a competence questionnaire and assess the level of competence of medical doctors in Ireland to provide PC to individuals with life-limiting conditions and their families. Design: A survey-based cohort study was employed using a questionnaire based on the Palliative Care Competence Framework, developed specifically for this study. Setting: The sample was accessed via the Royal College of Physicians of Ireland. All specialties in adult medical care and direct patient contact were included. Results: A pilot study demonstrated comprehensiveness and ensured face validity. In the main study, all subscales showed internal reliability and evidence of a normal distribution. Strong correlation was noted between knowledge and behavior while moderate correlations were noted between attitudes and behavior and attitudes and knowledge, respectively. As expected, palliative-trained participants scored significantly higher in attitudes, behavior, and knowledge. Conclusions: The study provides baseline data on the level of competence of PC of doctors working in Ireland. The study also offers a novel assessment tool that has the potential to be used for future research.
Educating intensive care unit nurses to use central venous catheter infection prevention guidelines: effectiveness of an educational course
Authors: Aloush Sami 
Published: May 2018

Background Nurses' knowledge of central venous catheter-related infection (CVC-RI) prevention guidelines is poor, indicating that nurses do not receive proper education about these guidelines. Aim The aim of this study was to evaluate the effectiveness of an educational course that aimed to improve nurses' knowledge about CVC-RI prevention guidelines. Method A sample of 131 nurses were randomly assigned to the experimental group (received an educational course) or control group (received no education). Pre-Post data were collected using a structured questionnaire that included a 23-item knowledge assessment. Results In the pre-test, all participants demonstrated poor knowledge, with mean scores of 8.2 (standard deviation = 3.6). After completion of the course, knowledge was significantly improved in the experimental group, whereas the control group showed no change ( t(106,3) = 25.1, p = 0.00). Conclusions An educational course on CVC-RI prevention guidelines had an encouraging effect. Decision makers are recommended to implement such courses in their settings to improve nurses' competency.