bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gliomas Promote Immunosuppression through Induction of B7-H1 Expression in Tumor-Associated Macrophages
Authors: Bloch Orin , Crane Courtney A. , Kaur Rajwant , Safaee Michael , Rutkowski Martin J. , Parsa Andrew T. 
Published: April 2013

AbstractPurpose: Gliomas are known to induce local and systemic immunosuppression, inhibiting T-cell–mediated cytotoxic responses to tumor growth. Tumor-associated macrophages are a significant component of the immune infiltrate in gliomas and may express immunosuppressive surface ligands, such as B7-H1.Experimental Design: Tumor and peripheral blood samples from patients with glioblastoma (GBM) were analyzed by flow cytometry to evaluate the expression of B7-H1 in circulating and tumor-infiltrating macrophages. Human monocytes from healthy patients were stimulated with conditioned media from glioma cells to evaluate B7-H1 expression. Production of interleukin (IL)-10 by stimulated monocytes was measured by ELISA, and stimulation with IL-10 alone was evaluated for the ability to induce B7-H1 expression. The effect of inhibiting IL-10 and its receptor on glioma-induced B7-H1 expression in monocytes was evaluated.Results: Circulating monocytes in patients with GBM had significantly increased expression of B7-H1 compared with healthy control patients. Tumor-associated macrophages from matched GBM tissue had even greater B7-H1 expression. Treatment of normal monocytes with glioma-conditioned media could significantly increase B7-H1 expression. Stimulation of monocytes with conditioned media resulted in substantial production of IL-10 and upregulation of the IL-10 receptor. Stimulation of monocytes with IL-10 alone could significantly increase B7-H1 expression, sufficient to induce T-cell apoptosis when cocultured with stimulated monocytes. Inhibition of IL-10 and the IL-10 receptor could knock down the effect of glioma media on B7-H1 by more than 50%.Conclusions: Gliomas can upregulate B7-H1 expression in circulating monocytes and tumor-infiltrative macrophages through modulation of autocrine/paracrine IL-10 signaling, resulting in an immunosuppressive phenotype. Clin Cancer Res; 19(12); 3165–75. ©2013 AACR.
Inhibition of Ron Kinase Blocks Conversion of Micrometastases to Overt Metastases by Boosting Antitumor Immunity
Authors: Eyob Henok , Ekiz Huseyin Atakan , DeRose Yoko S. , Waltz Susan E. , Williams Matthew A. , Welm Alana L. 
Published: April 2013

AbstractMany “nonmetastatic” cancers have spawned undetectable metastases before diagnosis. Eventual outgrowth of these microscopic lesions causes metastatic relapse and death, yet the events that dictate when and how micrometastases convert to overt metastases are largely unknown. We report that macrophage-stimulating protein and its receptor, Ron, are key mediators in conversion of micrometastases to bona fide metastatic lesions through immune suppression. Genetic deletion of Ron tyrosine kinase activity specifically in the host profoundly blocked metastasis. Our data show that loss of Ron function promotes an effective antitumor CD8+ T-cell response, which specifically inhibits outgrowth of seeded metastatic colonies. Treatment of mice with a Ron-selective kinase inhibitor prevented outgrowth of lung metastasis, even when administered after micrometastatic colonies had already been established. Our findings indicate that Ron inhibitors may hold potential to specifically prevent outgrowth of micrometastases in patients with cancer in the adjuvant setting.Significance: Our data shed new light on an understudied, yet critically important aspect of metastasis: the conversion of clinically undetectable micrometastatic tumor cells to overt metastases that eventually cause death of the patient. Our work shows that Ron inhibition can significantly reduce metastatic outgrowth, even when administered after metastatic colonies are established. Cancer Discov; 3(7); 751–60. ©2013 AACR.This article is highlighted in the In This Issue feature, p. 705
Ideal Cardiovascular Health in Adolescence
Authors: Pahkala Katja , Hietalampi Hanna , Laitinen Tomi T. , Viikari Jorma S.A. , Rönnemaa Tapani , Niinikoski Harri , Lagström Hanna , Talvia Sanna , Jula Antti , Heinonen Olli J. , Juonala Markus , Simell Olli , Raitakari Olli T. 
Published: April 2013

Background—
In the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study, repeated dietary counseling introduced in infancy and maintained until 20 years of age has led to lower intakes of saturated fat and serum low-density lipoprotein cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the American Heart Association. Additionally, we investigated the association between the concept and vascular intima-media thickness and elasticity in adolescence.

Methods and Results—

In adolescents participating in the longitudinal, randomized, atherosclerosis-prevention STRIP study, complete data on ideal cardiovascular health metrics were available at 15 (n=394), 17 (n=376), and 19 (n=298) years of age. Aortic intima-media thickness and elasticity were measured with ultrasonography at the same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5%, and 34.2% of the adolescents at 15, 17, and 19 years of age, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (≤3 metrics) compared with the intervention adolescents (risk ratio=1.35; 95% confidence interval=1.04–1.77). The number of ideal cardiovascular health metrics was inversely associated with aortic intima-media thickness (
P
<0.0001) and directly associated with elasticity (
P
=0.045). The risk of having high intima-media thickness (>85th percentile) was nearly 2-fold in adolescents with a low number of metrics (≤3) compared with those with a higher score (risk ratio=1.78; 95% confidence interval=1.31–2.43).

Conclusions—
Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence, supporting the relevance of targeting these metrics as part of primordial prevention.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00223600
PHA-543613 Preserves Blood–Brain Barrier Integrity After Intracerebral Hemorrhage in Mice
Authors: Krafft Paul R. , Caner Basak , Klebe Damon , Rolland William B. , Tang Jiping , Zhang John H. 
Published: April 2013

Background and Purpose—
Blood–brain barrier disruption and consequent vasogenic edema formation codetermine the clinical course of intracerebral hemorrhage (ICH). This study examined the effect of PHA-543613, a novel α7 nicotinic acetylcholine receptor agonist, on blood–brain barrier preservation after ICH.

Methods—
Male CD-1 mice, subjected to intrastriatal blood infusion, received PHA-543613 alone or in combination with α7 nicotinic acetylcholine receptor antagonist methyllycaconitine or phosphatidylinositol 3-kinase inhibitor wortmannin.

Results—
PHA-543613 alone, but not in combination with methyllycaconitine or wortmannin, inhibited glycogen synthase kinase-3β, thus, stabilizing β-catenin and tight junction proteins, which was paralleled by improved blood–brain barrier stability and ameliorated neurofunctional deficits in ICH animals.

Conclusions—
PHA-543613 preserved blood–brain barrier integrity after ICH, possibly through phosphatidylinositol 3-kinase-Akt–induced inhibition of glycogen synthase kinase-3β and β-catenin stabilization.
A 3-year retrospective cohort study of predictors of relapse in first-episode psychosis in Hong Kong
Authors: Hui Christy L-M , Tang Jennifer Y-M , Leung Chung-Ming , Wong Gloria H-Y , Chang Wing-Chung , Chan Sherry K-W , Lee Edwin H-M , Chen Eric Y-H 
Published: April 2013

Objective: Relapses in psychosis are costly and may have irreversible consequences. Relapse prevention is thus critical in the treatment of schizophrenia. Apart from medication discontinuation, a consistent relapse predictor has not been identified due to limitations in previous studies. We aim to investigate relapse predictors in a large cohort of patients with first-episode psychosis. Method: This is a retrospective cohort study designed to evaluate relapses in first-episode psychosis patients in 3 years. A total of 1400 patients’ case records were retrieved from a hospital database. Potential relapse predictors including demographic variables, baseline clinical measures, medication adherence, and residual positive symptoms upon clinical stabilization were collected. Results: The cumulative relapse rates were 19.3% by year 1, 38.4% by year 2, and 48.1% by year 3. Multivariate Cox-proportional hazards regression analysis revealed that medication non-adherence, smoking, schizophrenia diagnosis, younger age, and shorter baseline hospitalization were associated with an increased risk of relapse in 3 years. Conclusions: Nearly half of patients relapsed after 3 years following their first-episode psychosis. Smoking as a predictor of relapse is an intriguing new finding supportive of a link between nicotinic receptors and the dopamine system. Their relationship deserves further investigations with potential clinical implications for relapse prevention.
Impact of a district-wide diabetes prevention programme involving health education for children and the community
Authors: Sheeladevi Sethu , Sagar Jayanthi , Pujari Siddharth , Rani Padmaja Kumari 
Published: April 2013

Objective: To present results from a district-wide diabetes prevention programme involving health education for school children and the local community. Method: The model of health education that was utilized aimed to secure lifestyle changes and the identification of diabetes risk by school children (aged 9–12 years). The children acted as health messengers in their families as well as in the neighbouring community. Health education sessions were also held for school teachers, non-governmental organizations, primary health centre physicians, self-help groups and laypeople in the district. All were trained in diabetes risk assessment by using the standardized Indian diabetic risk score and were trained to estimate urine glucose. Results: Over a four-year period (2005–2009) the programme trained 8288 teachers and 119,743 schoolchildren in 679 schools and 30,915 people working in the health and development sectors. Trained school children reached out to 2.4 million people in over 500,000 families, covering 80% of the district population (3 million). The project identified 83,907 (3.5%) people as being at high risk of developing diabetes and these were counselled regarding risk reduction and lifestyle modifications. Among those identified with diabetes risk, 15,868 (19%) people were identified as having positive urine glucose. There were 10,522 (0.4%) people with known diabetes who were referred to identified diabetes care centres in the district. Conclusion: This child-to-family-based lifestyle change and health education intervention, along with community participation, offers a novel approach with substantial coverage of district populations in India.
A cross-national cross-sectional survey of the attitudes and perceived competence of final-year medicine, nursing and pharmacy students in relation to end-of-life care in dementia
Authors: De Witt Jansen Bannin , Weckmann Michelle , Nguyen Christopher M , Parsons Carole , Hughes Carmel M 
Published: April 2013

Background: Little is known about the attitudes of healthcare professional students’ perceived competence and confidence in treating those with dementia who are at the end of life. Aim: To explore the attitudes of final year medical, nursing and pharmacy students towards people with dementia and to evaluate their perceived competence and confidence dealing with biomedical and psychosocial issues within the context of palliative care provision to patients with dementia. Design: Cross-sectional survey using a questionnaire. Setting/participants: Final-year students in each profession from Queen’s University Belfast (Northern Ireland) and the University of Iowa (USA) were recruited. Method: Three versions of an online questionnaire (containing the Attitudes to Dementia Questionnaire and a series of questions on end-of-life care in dementia) were distributed. Results: A total of 368 responses were received (response rate 42.3%). All respondents reported positive attitudes towards people with dementia. US nursing students reported significantly more positive attitudes than the medical students of United States and Northern Ireland. Medical students were more likely to report low confidence in discussing non-medical aspects of dying, whereas nursing students were most likely to feel prepared and confident to do this. Medical and nursing students reported low confidence with aspects of medication-related care; however, data from the pharmacy samples of Northern Ireland and United States suggested that these students felt confident in advising other healthcare professionals on medication-related issues. Conclusions: While healthcare students hold positive attitudes towards people with dementia, some clinical tasks remain challenging and further basic training may be of benefit.
Identification of α1-antitrypsin as a potential prognostic biomarker for advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors by proteomic analysis
Authors: Zhao Wei , Yang Zhen , Liu Xingchen , Tian Qing , Lv Yongzhuang , Liang Yuan , Li Chunsun , Gao Xiaofang , Chen Liangan 
Published: April 2013

Objective This retrospective study attempted to identify serum biomarkers that could help to indicate treatment response in advanced nonsmall-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods Two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to identify proteins expressed in serum samples from NSCLC patients with long (>6-month) progression-free survival (PFS) periods, following EGFR-TKI treatment. Results Serum amyloid P component (APCS), α1-antitrypsin (AAT), fibrinogen-α (FGA), keratin type I cytoskeletal 10 (KRT10) and serotransferrin (TF) expression differed between samples taken from 18 patients before treatment (baseline) and when progressive disease (PD) was observed, during treatment. Changes in AAT, KRT10 and APCS levels were validated by Western blot analysis in the sample pool; findings were further validated by Western blot analysis in a random sample of four patients. These proteins were also present in serum samples obtained from the same patients at the partial response (PR) timepoint during EGFR-TKI treatment. AAT was upregulated at PD compared with baseline, but downregulated during the PR phase. Conclusion These observations suggest that AAT could be used as a serological biomarker for predicting the utility of EGFR-TKI treatment for advanced NSCLC.
Contact behaviour of children and parental employment behaviour during school closures against the pandemic influenza A (H1N1-2009) in Japan
Authors: Mizumoto Kenji , Yamamoto Taro , Nishiura Hiroshi 
Published: April 2013

Objectives To identify epidemiological determinants of the contact behaviour of children and their impact on parental employment, during school closures that took place over the course of the 2009 pandemic influenza (H1N1-2009) in Japan. Methods A retrospective survey was conducted in Japanese households between October 2009 and May 2010 by administration of a standardized questionnaire. Demographic and behavioural variables were explored, in association with the frequency with which children left the home and the risk of parents being absent from work during school closures. Results Data from 882 eligible households were analysed. A total of 181/882 (20.5%) of households reported that children left the home for nonessential reasons during school closures. No impact on parental working hours was reported by 742/882 (84.1%) of households. Univariate analyses showed that the frequency with which children left the home was dependent on age, extent of school closure and requirement for special childcare arrangements. Conclusions A greater understanding of age-dependent behaviours, during school closures as a consequence of a pandemic, is required. Consideration of a public policy to permit a paid leave of absence from work for parents during school closures may be beneficial; the cost-effectiveness of such a measure should be assessed in future.
Anti-IFI16 antibodies and their relation to disease characteristics in systemic lupus erythematosus
Authors: Caneparo V , Cena T , De Andrea M , Dell'Oste V , Stratta P , Quaglia M , Tincani A , Andreoli L , Ceffa S , Taraborelli M , Magnani C , Landolfo S , Gariglio M 
Published: April 2013

Objective Several studies have shown the presence of anti-IFI16 antibodies in systemic lupus erythematosus (SLE), Sjögren Syndrome (SjS), systemic sclerosis (SSc) and other autoimmune diseases. However, the significance of anti-IFI16 antibodies in SLE has not been fully characterized. The aim of this study was to investigate associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE. Methods An enzyme-linked immunosorbent assay (ELISA) kit was used to measure anti-IFI16 antibodies in the sera of 168 SLE patients, 46 patients with any type of primary glomerulonephritis (GN) and 182 healthy controls (HCs). Associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE were statistically evaluated using both univariate and multivariate analysis. Results Significantly higher anti-IFI16 titres were observed in SLE patients compared to both non-SLE GN and HCs (median levels: 270.1 U/ml vs 132.1 U/ml, p = 0.001, and 52.9 U/ml, p < 0.0001, respectively). With cut-off levels corresponding to the 95th percentile of the control population (113 U/ml), 63% of the SLE patients tested positive for anti-IFI16 autoantibodies, compared to just 24% of patients with primary non-SLE GN and 5% of HCs. The presence of anti-IFI16 antibodies inversely correlated with proteinuria (univariate analysis) and C3 hypocomplementaemia (univariate and multivariate analyses). Conclusions The inverse correlations observed between anti-IFI16 positivity, proteinuria and C3 hypocomplementaemia suggest that anti-IFI16 antibodies do not contribute to renal inflammation in SLE; indeed they may even prevent complement consumption. Anti-IFI16 antibodies hold the potential to serve as a new biomarker of disease activity in SLE.
Plantar Forces in Flexor Hallucis Longus Versus Flexor Digitorum Longus Transfer in Adult Acquired Flatfoot Deformity
Authors: Spratley E. Meade , Arnold John M. , Owen John R. , Glezos Christopher D. , Adelaar Robert S. , Wayne Jennifer S. 
Published: April 2013

Background: Flexor hallucis longus (FHL) and flexor digitorum longus (FDL) tendon transfers are frequently used to restore the function of a deficient tibialis posterior tendon in stage II adult acquired flatfoot deformity (AAFD). Either transfer causes some loss in toe flexion force, although the decision to tenodese the cut tendon to restore associated function remains controversial. This study quantified changes in plantar force before and after tendon transfer and with or without distal tenodesis in a cadaveric model. Methods: The plantar force distribution of 10 matched pairs of statically loaded cadaveric lower extremities was investigated. Each foot was tested when it was intact, after FDL/FHL tendon transfer, and after tendon transfer + tenodesis. Results: Transfer of either FHL or FDL showed a statistically significant decrease in flexion force of the great toe ( P < .01) and lesser toes ( P < .001), respectively. Subsequent tenodesis in either tendon demonstrated an ability to restore flexion force in the great ( P < .05) and lesser ( P < .01) toes, respectively, with the FHL transfer + tenodesis restoring great toe loading to near pretransfer levels. Following either transfer, plantar force increased in the medial forefoot; this was sustained with FDL transfer + tenodesis but reduced under FHL transfer + tenodesis. Lateral forefoot force increased modestly (8%) with FHL transfer ( P < .05) but returned to near intact levels with tenodesis. FDL transfer + tenodesis resulted in increased medial midfoot and heel loading. Discussion: FHL or FDL transfer notably reduces associated toe flexion force. This loss can be restored to near normal levels with tenodesis for FHL transfer. As increased lateral forefoot loading is commonly associated with AAFD corrective procedures, FHL tenodesis may mitigate the unintended increases caused by the tendon transfer. The medial midfoot and heel loading with FDL transfer + tenodesis underscores that tendon transfers alone do not reestablish the passive architecture of the foot but augment deficient subtalar inversion force. Clinical Relevance: This cadaveric study shows that the FHL is more biomechanically suitable for tibialis posterior tendon insufficiency than the FDL, which may be a basis for a study to investigate whether it is superior in a clinical situation.
Conversion Arthrodesis for Failed First Metatarsophalangeal Joint Hemiarthroplasty
Authors: Garras David N. , Durinka Joel B. , Bercik Michael , Miller Adam G. , Raikin Steven M. 
Published: April 2013

Background: Arthrodesis is currently the most commonly performed surgical procedure for the treatment of arthritis of the first metatarsophalangeal (MTP) joint. Hemiarthroplasty of the first MTP joint has been shown to have inferior clinical results and higher revision rates. The objective of this study was to assess the clinical outcome of the salvage of failed hallux phalangeal hemiarthroplasty with conversion to arthrodesis. Methods: A retrospective review of patients who underwent salvage of the first MTP joint hemiarthroplasty with conversion to arthrodesis was performed. Preoperative assessment included the visual analog pain (VAP) scale and AOFAS Hallux Metatarsophalangeal Interphalangeal scoring system (AOFAS-HMI). Postoperative outcomes were graded via AOFAS-HMI, VAP, and Foot and Ankle Ability Measure (FAAM). Results: Twenty-one hemiarthroplasties were converted to arthrodesis in 21 patients, with 18 available for follow-up included in the study. There were 13 women and 5 men. Local autologous bone graft was used in 12 cases, while 6 patients required tricortical iliac crest bone graft for the treatment of extensive bone loss. At final follow-up, at a mean of 4.3 years, the average VAS pain score had diminished to 0.75 from 7.8 preoperatively out of 10, while the mean AOFAS-HMI improved from 36.2 out of 100 preoperatively to 85.3 out of 90 (modified to exclude first MTP motion). The mean FAAM ADL/sports were 97.3/91.3, respectively. All patients achieved fusion although at a longer interval than primary fusions. Conclusions: Conversion from a failed hallux phalangeal hemiarthroplasty to arthrodesis showed similar success to primary arthrodesis which was achieved in the majority of cases with the use of regional bone graft for small defects. However, the time to fusion was longer than that of primary arthrodesis, and it sometimes required structural bone graft for augmentation. Level of Evidence: Level IV, retrospective case series.