Recent technical developments have enabled the transcriptomes of hundreds of cells to be assayed in an unbiased manner, opening up the possibility that new subpopulations of cells can be found. ...However, the effects of potential confounding factors, such as the cell cycle, on the heterogeneity of gene expression and therefore on the ability to robustly identify subpopulations remain unclear. We present and validate a computational approach that uses latent variable models to account for such hidden factors. We show that our single-cell latent variable model (scLVM) allows the identification of otherwise undetectable subpopulations of cells that correspond to different stages during the differentiation of naive T cells into T helper 2 cells. Our approach can be used not only to identify cellular subpopulations but also to tease apart different sources of gene expression heterogeneity in single-cell transcriptomes.
Epigenome modulation potentially provides a mechanism for organisms to adapt, within and between generations. However, neither the extent to which this occurs, nor the mechanisms involved are known. ...Here we investigate DNA methylation variation in Swedish Arabidopsis thaliana accessions grown at two different temperatures. Environmental effects were limited to transposons, where CHH methylation was found to increase with temperature. Genome-wide association studies (GWAS) revealed that the extensive CHH methylation variation was strongly associated with genetic variants in both cis and trans, including a major trans-association close to the DNA methyltransferase CMT2. Unlike CHH methylation, CpG gene body methylation (GBM) was not affected by growth temperature, but was instead correlated with the latitude of origin. Accessions from colder regions had higher levels of GBM for a significant fraction of the genome, and this was associated with increased transcription for the genes affected. GWAS revealed that this effect was largely due to trans-acting loci, many of which showed evidence of local adaptation.
Sea turtle by-catch data in the Mediterranean were reviewed and analysed with fishing effort. The results indicate over 132 000 captures per year, with probably over 44 000 incidental deaths per ...year, while many others are killed intentionally. Small vessels using set net, demersal longline or pelagic longline represent most of the Mediterranean fleet and likely cause more incidental or intentional deaths than large vessels typically using bottom trawl or pelagic longline. When interactions, mortality, intentional killing, size (a proxy for reproductive value) and turtle populations are considered, results indicate that Mediterranean green (Chelonia mydas) and loggerhead turtles (Caretta caretta) are more affected (i) by fishing gears such as bottom trawlers, demersal longlines and set nets, (ii) by small-scale fisheries, and (iii) by fishing in the eastern basin. Although small-scale fisheries should be the priority target, available measures are easier to implement on the fewer large vessels. Moreover, these measures are few, and they are not implemented yet, while others should still be tested for the Mediterranean fisheries. Thus, measures for reducing captures or mortality through changing gear-specific characteristics may help, but probably a more holistic conservation strategy aimed to an ecosystem-based fishery management for a sustainable fishing would be the only solution for the long-term survival of Mediterranean Sea turtle populations and their habitats. Small-scale fisheries should manage marine resources, including turtles, in a responsible and sustainable way. Turtles may not only benefit from but can also help this process if their non-consumptive value is fully recognized.
The homing journeys of nine loggerhead turtles translocated from their nesting beach to offshore release sites, were reconstructed through Argos and GPS telemetry while their water-related ...orientation was simultaneously recorded at high temporal resolution by multi-sensor data loggers featuring a three-axis magnetic sensor. All turtles managed to return to the nesting beach area, although with indirect routes encompassing an initial straight leg not precisely oriented towards home, and a successive homebound segment carried out along the coast. Logger data revealed that, after an initial period of disorientation, turtles were able to precisely maintain a consistent direction for several hours while moving in the open sea, even during night-time. Their water-related headings were in accordance with the orientation of the resulting route, showing little or no effect of current drift. This study reveals a biphasic homing strategy of displaced turtles involving an initial orientation weakly related to home and a successive shift to coastal navigation, which is in line with the modern conceptual framework of animal migratory navigation as deriving from sequential mechanisms acting at different spatial scales.
The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the ...review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents.
Objective
To evaluate the accuracy of a new electronic nose to recognize prostate cancer in urine samples.
Methods
A blind, prospective study on consecutive patients was designed. Overall, 174 ...subjects were included in the study: 88 (50.6%) in prostate cancer group, and 86 (49.4%) in control group. Electronic nose performance for prostate cancer was assessed using sensitivity and specificity. The diagnostic accuracy of electronic nose was reported as area under the receiver operating characteristic curve.
Results
The electronic nose in the study population reached a sensitivity 85.2% (95% confidence interval 76.1–91.9; 13 false negatives out of 88), a specificity 79.1% (95% confidence interval 69.0–87.1; 18 false positives out of 86). The accuracy of the electronic nose represented as area under the receiver operating characteristic curve 0.821 (95% confidence interval 0.764–0.879).
Conclusions
The diagnostic accuracy of electronic nose for recognizing prostate cancer in urine samples is high, promising and susceptible to supplemental improvement. Additionally, further studies will be necessary to design a clinical trial to validate electronic nose application in diagnostic prostate cancer nomograms.
The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We ...distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed (“prostatic cancer”, “albumin”, “globulin”, “albumin to globulin ratio”) following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430−0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259−0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.
Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate ...cancer (PC) patients. The incidence of PVs in homologous recombination repair (HRR) genes among men with metastatic PC varied between 11% and 33%, which was significantly higher than that in non-metastatic PC, and
mutations were more frequent when compared to other DDR genes. The determination of the somatic or germline PVs of
was able to define a tailored therapy using PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) progression after first-line therapy, with significant improvements in the radiologic progression-free survival (rPFS) and overall survival (OS) rates. We propose testing all metastatic PC patients for somatic and germline HRR mutations. Somatic determination on the primary site or on historic paraffin preparations with a temporal distance of no longer than 5 years should be preferred over metastatic site biopsies. The prognostic use of DDR PVs will also be used in selected high-risk cases with non-metastatic stages to better arrange controls and therapeutic primary options. We anticipate that the use of poly-ADP-ribose polymerase (PARP) inhibitors in hormone-sensitive prostate cancer (HSPC) and in combination with androgen receptor signaling inhibitors (ARSI) will be new strategies.
Knowledge about migratory routes and highly frequented areas is a priority for sea turtle conservation, but the movement patterns of juveniles frequenting the Adriatic have not been investigated yet, ...although juveniles represent the bulk of populations. We tracked by satellite six juvenile and one adult female loggerhead from the north Adriatic. The results indicated that loggerhead juveniles (1) can either show a residential behaviour remaining in the Adriatic throughout the year or perform seasonal migrations to other areas, (2) can remain even in the coldest, northernmost area during winter, (3) can frequent relatively small foraging areas, (4) mostly frequent the eastern part of the Adriatic, and (5) follow preferred migratory routes along the western and eastern Adriatic coasts. The movements of the adult turtle also revealed (6) a behavioural polymorphism in Mediterranean adults, which included a lack of area fidelity and connection between distant neritic foraging grounds.
Abstract Context Repeat transurethral resection (reTUR) is advocated as a fundamental step towards complete clearance and appropriate staging of T1 bladder cancer tumors. Objective To assess the ...impact of reTUR in T1 bladder cancer via a systematic review of the literature and meta-analysis of available data sets. Evidence acquisition After definition of the population and of the outcome, a systematic search of English language articles in the literature from 1980 to 2016 was performed. The pooled prevalence of residual tumor and of upstaging at reTUR were assessed and computed using a random effects model to take into account heterogeneity showed by I2 and Cochran's Q values. A sensitivity analysis was conducted to exclude excessive influence by a single study. Evidence synthesis Among the papers identified, 29 were selected. A total of 3566 and 2556 cases formed the study population for assessment of the prevalence of residual tumor and upstaging, respectively. The corresponding numbers for the subgroup with detrusor muscle involvement at the initial TUR were 1565 and 1187. The pooled prevalence was 0.56 (95% confidence interval CI 0.48–0.63) for residual tumor and 0.1 (95% CI 0.06–0.14) for upstaging to T2 at reTUR. The corresponding rates for the detrusor muscle subgroup were 0.47 (95% CI 0.33–0.62) and 0.1 (95% CI 0.06–0.14). The sensitivity analysis excluded an excessive influence of each of the studies examined. Conclusions Pooled prevalence rates for residual tumor (∼50%) and upstaging to invasive disease (10%) at reTUR in T1 cases were high, and were stable among studies in different decades and for cases with detrusor muscle involvement at the initial TUR. Therefore, reTUR remains a fundamental procedure. Patient summary Repeat transurethral resection after a diagnosis of stage T1 bladder cancer is recommended given the high risk of misallocation to the proper treatment.
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