Developmental stage on day-5 and fragmentation rate on day-3 can influence the implantation potential of top-quality blastocysts in IVF cycles with single embryo transfer

Background  

In IVF-ICSI cycles with single embryo transfer (SET), embryo selection for transfer is of crucial importance. The present study aimed to define which embryo parameters might be related to the implantation potential of advanced blastocysts.     

Inhibition of c‐MET increases the antitumour activity of PARP inhibitors in gastric cancer models

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer‐related death worldwide. Activation of c‐MET increases tumour cell survival through the initiation of the DNA damage repair pathway. PARP is an essential key in the DNA damage repair pathway. The primary role of PARP is to detect and initiate an immediate cellular response to single‐strand DNA breaks. Tumours suppressor genes such as BRCA1/2 are closely associated with the DNA repair pathway. In BRCA1/2 mutations or deficiency status, cells are more likely to develop additional genetic alterations and chromosomal instability and can lead to cancer. In this study, we investigate the role of c‐MET and PARP inhibition in a gastric cancer model. We exploited functional in vitro and in vivo experiments to assess the antitumour potential of co‐inhibition of c‐MET (SU11274) and PARP (NU1025). This leads to a reduction of gastric cancer cells viability, especially after knockdown of BRCA1/2 through apoptosis and induction of γ‐Η2ΑΧ. Moreover, in AGS xenograft models, the combinatorial treatment of NU1025 plus SU11274 reduced tumour growth and triggers apoptosis. Collectively, our data may represent a new therapeutic approach for GC thought co‐inhibition of c‐MET and PARP, especially for patients with BRCA1/2 deficiency tumours.     

Spatiotemporal patterns of marine mammal distribution in coastal waters of Galicia, NW Spain

The spatial and seasonal distribution of cetaceans and possible links with environmental conditions were studied at the Galician continental shelf. Data were collected between February–August 2001 and June–September 2003 during opportunistic surveys onboard fishing boats. Seven species of cetaceans were identified from 250 sightings of 6,846 individuals. The common dolphin (Delphinus delphis) was by far the most frequently sighted and the most widely distributed species. Spatiotemporal trends in cetacean distribution and abundance, and their relationships with environmental parameters (sea depth, SST and chlorophyll-a) were quantified using generalised additive models (GAMs). Results for all cetaceans were essentially the same as for common dolphins alone. Modelling results indicated that the number of common dolphin sightings per unit effort was higher further south. The number of individual common dolphins seen per sighting of this species (i.e. group size) was however higher in the north and west of the study area, higher later in the year and higher in 2001 than in 2003. In contrast, the number of common dolphin calves seen (per sighting of this species) was higher in the south. Models including environmental variables indicated larger common dolphin group sizes in deeper waters and at higher chlorophyll concentrations (i.e. in more productive areas). There was also a positive relationship between survey effort and group size, which is probably an artefact of the tendency of the survey platforms (fishing boats) to spend most time in areas of high fish abundance. Numbers of common dolphin calves per sighting were found to be higher in shallower waters. The results are consistent with common dolphins foraging mainly in deeper waters of the Galician continental shelf, while more southern inshore waters may represent a nursery area.     

Light interception and radiation use efficiency of okra and normal leaf cotton isolines

Okra-leaf cotton (Gossypium hirsutum L.) types have been reputed to produce equal or higher amounts of lint yield than normal-leaf types, while intercepting less or similar amounts of radiation. In this field study, okra- and normal-leaf cotton isolines were compared for their efficiency to produce dry matter utilizing intercepted radiation. At three weeks after first flower, the two leaf-shape isolines produced similar amounts of dry matter, with the okra-leaf type partitioning a larger fraction to fruiting organs. However, at the end of the season no differences in lint yield, yield components and fiber-quality properties were recorded between the two isolines. Fractional light interception throughout the period of the study was greater for the normal-leaf type compared to the okra-leaf type. The okra-leaf isoline utilized intercepted radiation more efficiently to produce dry matter. Values of radiation use efficiency were estimated at 1.897 and 2.636 g MJ⁻¹ of intercepted photosynthetically active radiation for the normal- and okra-leaf types, respectively. Growth chamber studies revealed similar single leaf carbon exchange rates, therefore radiation use efficiency differences between the leaf shape isolines could be attributed to light interception characteristics.     

Prediction of high-grade vesicoureteral reflux after pediatric urinary tract infection: external validation study of procalcitonin-based decision rule

Background

Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility.

Study Design

A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated.

Results

The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41–52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50–76), leading to a difference of 20% (95%CI, 17–36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one.

Conclusions

The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted.     

Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.     

Trait‐based life strategies,ecological niches,and niche overlap in the nekton of the data‐poor Mediterranean Sea

Biological traits can determine species ecological niches and define species responses to environmental variation. Species have a specific functional position in the biological community, resulting in interactions like interspecific competition. In this study, we used biological traits in order to define the life strategies of 205 nektonic species of the Mediterranean Sea. Furthermore, traits related to resource use were analyzed to determine the level of trait and niche overlap and their relationship to life strategies. Focusing on habitats of importance (Posidonia beds, coralligène formations, and lagoons), we investigated strategies and niches of the species present there. Finally, we examined the life strategy of Lessepsian species and investigated the niche overlap between them and indigenous species. Archetypal analysis indicated the existence of three life histories corresponding to strategies already documented for fish (equilibrium, periodic, and opportunistic), with some species also placed in intermediate positions. Niche overlap was evaluated by multiple correspondence analysis and the generation of a single distance metric between all species pairs. This identified species occupying relatively empty (underexploited) ecological niches, like the Lessepsian species Siganus luridus and S. rivulatus, a finding that can also be associated with their establishment in the Mediterranean. Most Lessepsian species were associated with the opportunistic life history strategy, again an important aspect related to their establishment. Also, we documented that most species occurring in important habitats have a relatively high overlap of niches. No significant differences were found in the life strategies across Mediterranean habitats; however, variation in niche overlap and traits related to habitat use was detected. The findings can be useful to determine theoretical competition between species and to identify empty ecological niches. Fisheries science can also benefit from comprehending the dynamics of competing stocks or predict the responses of data‐poor stocks to anthropogenic stressors from known examples of species with shared life strategies.     

The SPECIES and ORGANISMS Resources for Fast and Accurate Identification of Taxonomic Names in Text

The exponential growth of the biomedical literature is making the need for efficient, accurate text-mining tools increasingly clear. The identification of named biological entities in text is a central and difficult task. We have developed an efficient algorithm and implementation of a dictionary-based approach to named entity recognition, which we here use to identify names of species and other taxa in text. The tool, SPECIES, is more than an order of magnitude faster and as accurate as existing tools. The precision and recall was assessed both on an existing gold-standard corpus and on a new corpus of 800 abstracts, which were manually annotated after the development of the tool. The corpus comprises abstracts from journals selected to represent many taxonomic groups, which gives insights into which types of organism names are hard to detect and which are easy. Finally, we have tagged organism names in the entire Medline database and developed a web resource, ORGANISMS, that makes the results accessible to the broad community of biologists. The SPECIES software is open source and can be downloaded from http://species.jensenlab.org along with dictionary files and the manually annotated gold-standard corpus. The ORGANISMS web resource can be found at http://organisms.jensenlab.org.     

Clinical course and seizure outcome of idiopathic childhood epilepsy: determinants of early and long-term prognosis

Background

Idiopathic epilepsies and epileptic syndromes predominate childhood and adolescence epilepsy. The aim of the present study was to investigate the clinical course and outcome of idiopathic childhood epilepsy and identify variables determining both early and long-term prognosis.

Methods

We followed 303 children with newly diagnosed idiopathic epilepsy aged 1–14 years old, both prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of follow-up, as well as at the end of the study period for all patients. Based on the data collected, patients were classified in four patterns of clinical course: “excellent”, “improving”, “relapsing” and “poor”. Variables defined at intake and after the initial year of treatment were analyzed for their prognostic relevance towards the clinical course and outcome of the patients.

Results

The mean age at seizure onset was 6,7 years and the mean duration of follow-up was 8,3 years (range 2,0-22,0,SD 4,24). During the initial year of treatment, 70,3% of patients were seizure-free. The course of epilepsy was “excellent” in 53,1% of the subjects, “improving” in 22,8%, “relapsing” in 22,1% whereas only 6 children with idiopathic epilepsy (2%) had a “poor” clinical course exhibiting drug-resistance. After multivariate analysis, variables predictive of a poor initial response to therapy were early seizure onset, multiple seizure types and history of status epilepticus. At the end of follow-up, early response to treatment was of significant positive predictive value, while the presence of multiple seizure types and the history of migraine had a negative impact on prognosis.

Conclusions

In the vast majority of children, the long-term prognosis of idiopathic epilepsy is favorable. More than half of the patients attain seizure freedom immediately and their clinical course is considered “excellent”. About one fifth exhibit either an improving or a fluctuating course. Early seizure onset, multiple seizure types and status epilepticus are predictive of an initial poor response to treatment in children with idiopathic epilepsy. Initial non-response to treatment, multiple seizure types and history of migraine are determinants of a less favorable final outcome after long-term follow-up.