18F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y1R for PET Imaging of mammary carcinoma

NeuropeptideYY(1) receptors (Y1R) have been found to be overexpressed in a number of different tumours, such as breast, ovarian or renal cell cancer. In mammary carcinoma the highY(1)R density together with its high incidence of 85% in primary human breast cancers and 100% in breast cancer derived lymph node metastases attracted special attention. Therefore, the aim of this study was the development of radioligandsforY(1)R imaging by positron emission tomography (PET) with a special emphasis on imaging agents with reduced lipophilicity to provide a PET ligand with improved biodistribution in comparison with previously published tracers targeting theY(1)R. Three new radioligands based on BIBP3226, bearing an F-18-fluoroethoxy linker (12), an F-18-PEG-linker (13) or an F-18-fluoroglycosyl moiety (11) were radiosynthesised in high radioactivity yields. The new radioligands displayedY(1)R affinities of 2.8 nM (12), 29 nM (13) and 208 nM (11) and were characterised in vitro regarding binding to human breast cancer MCF-7-Y1 cells and slices of tumour xenografts. In vivo, small animal PET studies were conducted in nude mice bearing MCF-7-Y1 tumours. The binding to tumours, solid tumour slices and tumour cells correlated well with theY(1)R affinities. Although 12 and 13 showed displaceable and specific binding toY(1)R in vitro and in vivo, the radioligands still need to be optimised to achieve higher tumour-to-background ratios forY(1)R imaging by PET.Yet the present study is another step towards an optimized PET radioligand for imaging ofY(1)R in vivo

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Standard and limit values for the symmetry of articulation parameters in the temporomandibular joint area - evaluations of the associated project of the SHIP study

The articulation parameters, especially the horizontal condylar inclination angle (HCI), the Bennett angle (BA), and the immediate side shift (ISS) were determined in 259 subjects (100 males; 159 females) of the associated project with reference to the population-representative baseline study (Study of Health in Pomerania, SHIP 0). The evaluations were based on a clinical functional status and electronic motion recording with the ultrasonic measuring system Jaw Motion Analyser (JMA, Zebris, Isny, Germany). The reference plane, to which all measured values were represented and the HCI calculated, was the hinge axis infraorbital plane (HA-IOP). The HCI was determined after an excursive movement with a length of 4 mm to the HA-IOP in the sagittal view and the BA after a mediotrusive excursion movement of 6 mm in the horizontal view to the midsagittal plane. For the standard and limit values, the average value in addition to the standard deviation and the 10th and 90th percentile value (10th percentile value, 90th percentile value) were determined: HCI right 52.1 +/- 10.14 degrees (39.4 degrees, 64.0 degrees), HCI left 53.1 +/- 9.67 degrees (42.3 degrees, 67.0 degrees), BA right 15.2 +/- 7.53 degrees (6.7 degrees, 25.0 degrees), BA left 14.2 +/- 7.84 degrees (5.4 degrees, 24.1 degrees). The HCI was approximately 2 to 3 degrees larger in females (males: right 50.5 +/- 9.47 degrees, left 51.9 +/- 8.99 degrees; females: right 53.1 +/- 10.42 degrees, left 53.8 +/- 10.03 degrees). Likewise, the BA in the age group >= 40 years (males: right 14.4 +/- 6.62 degrees, left 13.1 +/- 7.14 degrees; females: right 17.0 +/- 9.02 degrees, left 16.9 +/- 8.72 degrees). The latter proved to be statistically significant in the t test for independent samples, assuming variance equivalence on the right, with P =0.009, and with rejection of the variant equivalence on the left, with P = 0.002. The right and left HCI and BA joint values showed highly significant linear dependence at P = 40 years with assumed variance equality than in the age group < 40 years (P = 0.002 right, P = 0.003 left). The groups relating to the Helkimo index (HI) did not differ significantly in all function-specific parameters. If it is assumed that there is no significant influence on the occlusion if the HCI values differ by 7 to 8 degrees from the average value, only approximately one third of all cases (35.1%) were characterized by a purely average value setting in the articulator. In 41.7% of cases, one joint value was situated outside the average value range; in 23.2% of the cases both values were outside the average value range. Without a measurement of the condylar path inclination, however, it is impossible to decide to what extent the HCI deviates from the average value, and which joint side is larger or smaller than the other and to what extent. These results suggest that in extensive and complex cases, the articulator should be adjusted according to individual, function-specific joint values