bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentially harmful excipients in neonatal medicines: a pan-European observational study
Authors: Nellis Georgi , Metsvaht Tuuli , Varendi Heili , Toompere Karolin , Lass Jana , Mesek Inge , Nunn Anthony J , Turner Mark A , Lutsar Irja 
Published: April 2015

ObjectivesWe aimed to describe administration of eight potentially harmful excipients of interest (EOI)—parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride—to hospitalised neonates in Europe and to identify risk factors for exposure.MethodsAll medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis.ResultsOverall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient.ConclusionsEuropean neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.
Associations between pentraxin 3 and severity of coronary artery disease
Authors: Liu Hua , Guan Shaofeng , Fang Weiyi , Yuan Fang , Zhang Min , Qu Xinkai 
Published: April 2015

ObjectiveTo investigate the associations between plasma levels of pentraxins 3 (PTX3) and C reactive protein (CRP) and the severity of coronary artery lesions.Design and methods60 patients with coronary heart disease (CHD) who underwent coronary angiography (CAG) in our hospital were included. Plasma was collected during CAG. The coronary Gensini score was used to evaluate the severity of coronary artery lesions. Associations between Gensini scores and plasma levels of PTX3 and CRP were analysed. Patients with estimated glomerular filtration rate <60 mL/min/1.73 m2were included in the chronic renal dysfunction subgroup.ResultsA linear correlation was observed between PTX3 and the Gensini score (r=0.513, p<0.001). One-way analysis of variance showed that PTX3 levels were significantly higher in patients with Gensini scores >90 compared with patients with scores of 46–90 or <45 (0–45:4.8±0.8, 46–90:6.7±1.2, >90:7.7±2.0, p<0.001). Stepwise multiple linear regression showed that PTX3 levels were significantly associated with Gensini score in patients with chronic renal dysfunction (p=0.012), while no significant association was found for CRP.ConclusionsPTX3 levers were positively associated with the severity of coronary artery lesions. PTX3 is closely associated with the severity of coronary artery stenosis in patients with chronic renal dysfunction.
Description and preliminary results from a structured specialist behavioural weight management group intervention: Specialist Lifestyle Management (SLiM) programme
Authors: Brown Adrian , Gouldstone Amy , Fox Emily , Field Annmarie , Todd Wendy , Shakher Jayadave , Bellary Srikanth , Teh Ming Ming , Azam Muhammad , John Reggie , Jagielski Alison , Arora Teresa , Thomas G Neil , Taheri Shahrad 
Published: April 2015

BackgroundSpecialist Lifestyle Management (SLiM) is a structured patient education and self-management group weight management programme. Each session is run monthly over a 6-month period providing a less intensive long-term approach. The groups are patient-centred incorporating educational, motivational, behavioural and cognitive elements. The theoretical background, programme structure and preliminary results of SLiM are presented.Subjects/methodsThe study was a pragmatic service evaluation of obese patients with a body mass index (BMI) ≥35 kg/m2with comorbidity or ≥40 kg/m2without comorbidity referred to a specialist weight management service in the West Midlands, UK. 828 patients were enrolled within SLiM over a 48-month period. Trained facilitators delivered the programme. Preliminary anonymised data were analysed using the intention-to-treat principle. The primary outcome measure was weight loss at 3 and 6 months with comparisons between completers and non-completers performed. The last observation carried forward was used for missing data.ResultsOf the 828 enrolled within SLiM, 464 completed the programme (56%). The mean baseline weight was 135 kg (BMI=49.1 kg/m2) with 87.2% of patients having a BMI≥40 kg/m2and 12.4% with BMI≥60 kg/m2. The mean weight change of all patients enrolled was −4.1 kg (95% CI −3.6 to −4.6 kg, p=0.0001) at the end of SLiM, with completers (n=464) achieving −5.5 kg (95% CI −4.2 to −6.2 kg, p=0.0001) and non-completers achieving −2.3 kg (p=0.0001). The majority (78.6%) who attended the 6-month programme achieved weight loss with 32.3% achieving a ≥5% weight loss.ConclusionsThe SLiM programme is an effective group intervention for the management of severe and complex obesity.
What matters to patients? A systematic review of preferences for medication-associated outcomes in mental disorders
Authors: Eiring Øystein , Landmark Brynjar Fowels , Aas Endre , Salkeld Glenn , Nylenna Magne , Nytrøen Kari 
Published: April 2015

ObjectiveTo investigate patients’ preferences for outcomes associated with psychoactive medications.Setting/designSystematic review of stated preference studies. No settings restrictions were applied.Participants/eligibility criteriaWe included studies containing quantitative data regarding the relative value adults with mental disorders place on treatment outcomes. Studies with high risk of bias were excluded.Primary and secondary outcome measuresWe restricted the scope of our review to preferences for outcomes, including the consequences from, attributes of, and health states associated with particular medications or medication classes, and process outcomes.ResultsAfter reviewing 11 215 citations, 16 studies were included in the systematic review. These studies reported the stated preferences from patients with schizophrenia (n=9), depression (n=4), bipolar disorder (n=2) and attention deficit hyperactive disorder (n=1). The median sample size was 81. Side effects and symptom outcomes outnumbered functioning and process outcomes. Severe disease and hospitalisation were reported to be least desirable. Patients with schizophrenia tended to value disease states as higher and side effects as lower, compared to other stakeholder groups. In depression, the ability to cope with activities was found to be more important than a depressed mood, per se. Patient preferences could not consistently be predicted from demographic or disease variables. Only a limited number of potentially important outcomes had been investigated. Benefits to patients were not part of the purpose in 9 of the 16 studies, and in 10 studies patients were not involved when the outcomes to present were selected.ConclusionsInsufficient evidence exists on the relative value patients with mental disorders place on medication-associated outcomes. To increase patient-centredness in decisions involving psychoactive drugs, further research—with outcomes elicited from patients, and for a larger number of conditions—should be undertaken.Trial registration numberPROSPERO CRD42013005685.
Infrequent DNA methylation ofmiR-9-1andmiR-9-3in multiple myeloma
Authors: Zhang Qi , Wang Lu Qian , Wong Kwan Yeung , Li Zhen Yu , Chim Chor Sang 
Published: April 2015

AimsThemiR-9family microRNAs (miRNAs) are tumour suppressor miRNAs implicated in carcinogenesis. We postulated thatmiR-9-1,miR-9-2andmiR-9-3may be inactivated by aberrant promoter methylation in multiple myeloma (MM).MethodsMethylation ofmiR-9-1,miR-9-2andmiR-9-3was studied by methylation-specific PCR (MSP) in six normal controls, including three each of healthy peripheral blood (PB) or bone marrow buffy coat, 10 MM cell lines, 62 primary MM marrow samples at diagnosis and 22 at relapse/progression.ResultsMSP, verified by quantitative pyrosequencing, showed that the promoters ofmiR-9-3andmiR-9-1were unmethylated in normal controls but methylated in 4 (40%) and 5 (50%) of 10 MM cell lines, respectively. However, the promoter ofmiR-9-2was methylated in three normal PB buffy coat controls and in CD138-sorted healthy marrow plasma cells, indicating possibly tissue specific rather than tumour-specific methylation ofmiR-9-2, which was thus not studied further. In WL-2 cells, which were completely methylated formiR-9-3, 5-aza-2′-deoxycytidine treatment causedmiR-9-3promoter demethylation andpri-miR-9-3re-expression. In primary samples, methylation ofmiR-9-3was detected in 1 of 62 patients at diagnosis and 1 of 22 patients at relapse/progression. However,miR-9-1methylation was absent in both primary samples at diagnosis and at relapse/progression.ConclusionsHypermethylation ofmiR-9-3andmiR-9-1is tumour-specific in MM, leading to reversible miRNA silencing. Frequent methylation ofmiR-9-3andmiR-9-1in cell lines, but not in primary samples, may be acquired duringin vitroculture, and indicates an unimportant role ofmiR-9methylation in myelomagenesis.
Intrauterine contraception in nulliparous women: a prospective survey
Authors: Hall Alexandra M , Kutler Beth A 
Published: April 2015

BackgroundIntrauterine contraception is a first-line option for young women, yet relatively few prospective studies have been performed in nulliparous women using currently available devices, and many providers are still reluctant to provide this option.MethodsBetween January 2012 and June 2014, 109 nulliparous women, aged 18–30 years, who had an intrauterine device (IUD) placed at a student health clinic [88 levonorgestrel-intrauterine system (LNG-IUS) users and 21 Cu T 380A (IUD) users] were surveyed at 1, 6, 12 and 18 months after insertion.ResultsOverall satisfaction was high; at follow-up survey 83% of 100 women (mean use 13.4 months) were ‘happy’ or ‘very happy’ with their IUD, and there were no differences in satisfaction between the two IUD types. Some 75% of participants stated that the insertion procedure went ‘very well’, despite 78% rating insertion pain as moderate to severe, and 46% experiencing vasovagal symptoms. The 12-month continuation rate was 89%, with discontinuations for expulsion (3%), side effects (6%), lack of anticipated benefit (1%) and pregnancy (1%). Users of the Cu T 380A were more likely to have heavy menses (74% vs 2%;p<0.0001) or moderate to severe cramping (68% vs 20%;p=0.0002) compared with LNG-IUS users. There were no uterine perforations or diagnoses of pelvic inflammatory disease. The rate of failed insertions during the study period was 6.2%.ConclusionsDespite significant symptoms with insertion, intrauterine contraception is safe, effective and ultimately well tolerated in nulliparous women and should be provided to this population in both university and community health settings.
Amino Acid Transporters in Cancer and Their Relevance to “Glutamine Addiction”: Novel Targets for the Design of a New Class of Anticancer Drugs
Authors: Bhutia Yangzom D. , Babu Ellappan , Ramachandran Sabarish , Ganapathy Vadivel 
Published: April 2015

Abstract
Tumor cells have an increased demand for amino acids because of their rapid proliferation rate. In addition to their need in protein synthesis, several amino acids have other roles in supporting cancer growth. There are approximately two-dozen amino acid transporters in humans, and tumor cells must upregulate one or more of these transporters to satisfy their demand for amino acids. If the transporters that specifically serve this purpose in tumor cells are identified, they can be targeted for the development of a brand new class of anticancer drugs; the logical basis of such a strategy would be to starve the tumor cells of an important class of nutrients. To date, four amino acid transporters have been found to be expressed at high levels in cancer: SLC1A5, SLC7A5, SLC7A11, and SLC6A14. Their induction occurs in a cancer type–specific manner with a direct or indirect involvement of the oncogene c-Myc. Further, these transporters are functionally coupled, thus maximizing their ability to promote cancer growth and chemoresistance. Progress has been made in preclinical studies, exploiting these transporters as drug targets in cancer therapy. These transporters also show promise in development of new tumor-imaging probes and in tumor-specific delivery of appropriately designed chemotherapeutic agents. Cancer Res; 75(9); 1782–8. ©2015 AACR.
Decreased Ferroportin Promotes Myeloma Cell Growth and Osteoclast Differentiation
Authors: Gu Zhimin , Wang He , Xia Jiliang , Yang Ye , Jin Zhendong , Xu Hongwei , Shi Jumei , De Domenico Ivana , Tricot Guido , Zhan Fenghuang 
Published: April 2015

Abstract
Iron homeostasis is disrupted in multiple myeloma, a difficult-to-cure plasma cell malignancy with lytic bone lesions. Here, we systematically analyzed iron gene expression signature and demonstrated that mRNA expression of iron exporter ferroportin (FPN1) is significantly downregulated in myeloma cells and correlates negatively with clinic outcome. Restoring expression of FPN1 reduces intracellular liable iron pool, inhibits STAT3-MCL-1 signaling, and suppresses myeloma cells growth. Furthermore, we demonstrated that mRNA of FPN1 is also downregulated at the initial stages of osteoclast differentiation and suppresses myeloma cell–induced osteoclast differentiation through regulating iron regulator TFRC, NF-κB, and JNK pathways. Altogether, we demonstrated that downregulation of FPN1 plays critical roles in promoting myeloma cell growth and bone resorption in multiple myeloma. Cancer Res; 75(11); 2211–21. ©2015 AACR.
Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer
Authors: Kageyama Shinichi , Ikeda Hiroaki , Miyahara Yoshihiro , Imai Naoko , Ishihara Mikiya , Saito Kanako , Sugino Sahoko , Ueda Shugo , Ishikawa Takeshi , Kokura Satoshi , Naota Hiroaki , Ohishi Kohshi , Shiraishi Taizo , Inoue Naoki , Tanabe Masashige , Kidokoro Tomohide , Yoshioka Hirofumi , Tomura Daisuke , Nukaya Ikuei , Mineno Junichi , Takesako Kazutoh , Katayama Naoyuki , Shiku Hiroshi 
Published: April 2015

Abstract
Purpose: Preparative lymphodepletion, the temporal ablation of the immune system, has been reported to promote persistence of transferred cells along with increased rates of tumor regression in patients treated with adoptive T-cell therapy. However, it remains unclear whether lymphodepletion is indispensable for immunotherapy with T-cell receptor (TCR) gene–engineered T cells.
Experimental Design: We conducted a first-in-man clinical trial of TCR gene-transduced T-cell transfer in patients with recurrent MAGE-A4–expressing esophageal cancer. The patients were given sequential MAGE-A4 peptide vaccinations. The regimen included neither lymphocyte-depleting conditioning nor administration of IL2. Ten patients, divided into 3 dose cohorts, received T-cell transfer.
Results: TCR-transduced cells were detected in the peripheral blood for 1 month at levels proportional to the dose administered, and in 5 patients they persisted for more than 5 months. The persisting cells maintained ex vivo antigen-specific tumor reactivity. Despite the long persistence of the transferred T cells, 7 patients exhibited tumor progression within 2 months after the treatment. Three patients who had minimal tumor lesions at baseline survived for more than 27 months.
Conclusions: These results suggest that TCR-engineered T cells created by relatively short-duration in vitro culture of polyclonal lymphocytes in peripheral blood retained the capacity to survive in a host. The discordance between T-cell survival and tumor regression suggests that multiple mechanisms underlie the benefits of preparative lymphodepletion in adoptive T-cell therapy. Clin Cancer Res; 21(10); 2268–77. ©2015 AACR.
Efficacy and Safety of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent
Authors: Kereiakes Dean J. , Meredith Ian T. , Windecker Stephan , Lee Jobe R. , Mehta Shamir R. , Sarembock Ian J. , Feldman Robert L. , Stein Bernardo , Dubois Christophe , Grady Timothy , Saito Shigeru , Kimura Takeshi , Christen Thomas , Allocco Dominic J. , Dawkins Keith D. 
Published: April 2015

Background—
Drug eluting stents with durable polymers may be associated with hypersensitivity, delayed healing, and incomplete endothelialization, which may contribute to late/very late stent thrombosis and the need for prolonged dual antiplatelet therapy. Bioabsorbable polymers may facilitate stent healing, thus enhancing clinical safety. The SYNERGY stent is a thin-strut, platinum chromium metal alloy platform with an ultrathin bioabsorbable Poly(D,L-lactide-co-glycolide) abluminal everolimus-eluting polymer. We performed a multicenter, randomized controlled trial for regulatory approval to determine noninferiority of the SYNERGY stent to the durable polymer PROMUS Element Plus everolimus-eluting stent.

Methods and Results—

Patients (n=1684) scheduled to undergo percutaneous coronary intervention for non–ST-segment–elevation acute coronary syndrome or stable coronary artery disease were randomized to receive either the SYNERGY stent or the PROMUS Element Plus stent. The primary end point of 12-month target lesion failure was observed in 6.7% of SYNERGY and 6.5% PROMUS Element Plus treated subjects by intention-to-treat (
P
=0.83 for difference;
P
=0.0005 for noninferiority), and 6.4% in both the groups by per-protocol analysis (
P
=0.0003 for noninferiority). Clinically indicated revascularization of the target lesion or definite/probable stent thrombosis were observed in 2.6% versus 1.7% (
P
=0.21) and 0.4% versus 0.6% (
P
=0.50) of SYNERGY versus PROMUS Element Plus–treated subjects, respectively.

Conclusions—
In this randomized trial, the SYNERGY bioabsorbable polymer everolimus-eluting stent was noninferior to the PROMUS Element Plus everolimus-eluting stent with respect to 1-year target lesion failure. These data support the relative safety and efficacy of SYNERGY in a broad range of patients undergoing percutaneous coronary intervention.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01665053.
A panel data analysis of the impacts of institutional differences on local governments' budgetary decisions
Authors: Kim Soojin , Eom Tae Ho 
Published: April 2015

This study provides empirical evidence on how institutional differences influence school budget decisions by using panel data from 178 K-12 New Jersey school districts for the period 1996 to 2007. The findings obtained by the Newey-West model, correcting heteroskedasticity and serial correlation, support our hypothesis that school districts with elected school boards (Type II districts) are more likely to be effective at lowering school spending than ones with appointed school boards (Type I districts). Viewing school systems through the lens of new institutional economics, this study argues that institutional differences in governance are critical in leading to differences in budgetary decisions by affecting incentive structures faced by public officials, along with transaction costs and agency costs. Points for practitioners To date, the issue of the impact of institutional differences on local budgetary decisions has been an ongoing topic of debate among many scholars and practitioners in the public administration field. This implies that as an effective incentive structure as well as constraint mechanism, direct electoral institutions in school districts can be a valuable tool to control growing education spending by placing clear accountability on school boards in shaping school budget decisions. Policy makers should consider feasible strategies accompanied by institutional changes in a situation in which local governments are challenged to manage their budget effectively under fiscal stress.
The Role of Parotidectomy in the Treatment of Auricular Squamous Cell Carcinoma
Authors: Kadakia Sameep , Saman Masoud , Gordin Eli , Marra Diego , Ducic Yadranko 
Published: April 2015

ObjectiveWe analyze parotid specimens in patients treated with prophylactic parotidectomy for squamous cell carcinoma of the auricle greater than or equal to 2 cm to determine rates of metastasis and the efficacy of elective resection.Study DesignCase series with chart review.SettingCancer treatment center in Fort Worth, Texas, from 1998 to 2013.Subjects and MethodsThe study included 104 patients between ages 36 and 97 years with primary auricular squamous cell carcinoma greater than or equal to 2 cm, with no evidence of adenopathy or parotid involvement on imaging. Patients underwent local excision and ipsilateral parotidectomy. The primary cancer was analyzed for vascular involvement, perineural invasion, and cartilage involvement, while the parotid specimen was analyzed for cancer positivity.ResultsThirty‐nine parotid (37.5%) samples were positive for carcinoma. Of these, 16 patients had primary auricular carcinomas with vascular involvement, 17 had perineural invasion, and 4 had cartilage involvement. Thirty‐two of 77 affected men and 7 of 27 affected women had positive parotid specimen. Vascular involvement (P =. 0006) and perineural invasion (P =. 0027) of the primary lesion were significantly higher in patients with a positive parotid specimen. Cartilage involvement and sex were not statistically significant.ConclusionsElective parotidectomy is beneficial in patients with squamous cell carcinoma of the auricle at least 2 cm in size, especially in lesions having perineural invasion and vascular involvement. For patients with positive parotid specimens, we recommend postoperative external beam radiation therapy and close surveillance.
The association between thyroid autoantibodies in serum and abnormal function and structure of the thyroid
Authors: Yan Yue-Rong , Gao Xi-Lian , Zeng Jing , Liu Yang , Lv Qing-Guo , Jiang Jing , Huang Hui , Tong Nan-Wei 
Published: April 2015

Objectives To evaluate the association between thyroid autoantibodies and abnormalities in thyroid function and structure, and to investigate any risk factors. Methods A cross-sectional survey was undertaken in Chengdu residents ≥18 years with no previous thyroid disease. The study participants provided demographic and clinical data. Thyroid function and serum concentrations of the thyroid autoantibodies antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) were measured. Results A total of 1334 subjects were included in this study. The prevalence of TPOAb and TgAb positivity was significantly higher in female than in male subjects. The prevalence of thyroid autoantibodies in those with subclinical hypothyroidism and clinical hyper- and hypothyroidism was significantly greater than in euthyroid subjects. The concentration of TPOAb and TgAb in subjects with both TPOAb and TgAb was significantly higher than in those who exhibited only one type of thyroid autoantibody. Using multivariate logistic regression analysis, female sex, thyroid volume, thyroid hypo- and heteroechogenicity were found to be risk factors for the presence of autoantibodies. Conclusions Thyroid autoantibodies were common in the general population. Women with thyroid enlargement, hypoechogenicity and heteroechogenicity might benefit from routine screening for thyroid autoantibodies and thyroid function.