Advanced Diffusion-Weighted Imaging Sequences for Breast MRI: Comprehensive Comparison of Improved Sequences and Ultra-High B-Values to Identify the Optimal Combination

This study investigated the image quality and choice of ultra-high b-value of two DWI breast-MRI research applications. The study cohort comprised 40 patients (20 malignant lesions). In addition to s-DWI with two m-b-values (b50 and b800) and three e-b-values (e-b1500, e-b2000, and e-b2500), z-DWI and IR m-b1500 DWI were applied. z-DWI was acquired with the same measured b-values and e-b-values as the standard sequence. For IR m-b1500 DWI, b50 and b1500 were measured, and e-b2000 and e-b2500 were mathematically extrapolated. Three readers used Likert scales to independently analyze all ultra-high b-values (b1500-b2500) for each DWI with regards to scan preference and image quality. ADC values were measured in all 20 lesions. z-DWI was the most preferred (54%), followed by IR m-b1500 DWI (46%). b1500 was significantly preferred over b2000 for z-DWI and IR m-b1500 DWI (p = 0.001 and p = 0.002, respectively). Lesion detection was not significantly different among sequences or b-values (p = 0.174). There were no significant differences in measured ADC values within lesions between s-DWI (ADC: 0.97 [±0.09] × 10$^{-3}$ mm$^{2}$/s) and z-DWI (ADC: 0.99 [±0.11] × 10$^{-3}$ mm$^{2}$/s; p = 1.000). However, there was a trend toward lower values in IR m-b1500 DWI (ADC: 0.80 [±0.06] × 10$^{-3}$ mm$^{2}$/s) than in s-DWI (p = 0.090) and z-DWI (p = 0.110). Overall, image quality was superior and there were fewer image artifacts when using the advanced sequences (z-DWI + IR m-b1500 DWI) compared with s-DWI. Considering scan preferences, we found that the optimal combination was z-DWI with a calculated b1500, especially regarding examination time

scROSHI: robust supervised hierarchical identification of single cells

Identifying cell types based on expression profiles is a pillar of single cell analysis. Existing machine-learning methods identify predictive features from annotated training data, which are often not available in early-stage studies. This can lead to overfitting and inferior performance when applied to new data. To address these challenges we present scROSHI, which utilizes previously obtained cell type-specific gene lists and does not require training or the existence of annotated data. By respecting the hierarchical nature of cell type relationships and assigning cells consecutively to more specialized identities, excellent prediction performance is achieved. In a benchmark based on publicly available PBMC data sets, scROSHI outperforms competing methods when training data are limited or the diversity between experiments is large

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Euthanasia and palliative care

This chapter focuses on the particular relationship and interconnections between euthanasia and palliative care. Selected key data on assisted dying are presented. Of central importance is the question of how requests for assisted dying should be handled within palliative care, and as part of addressing this question the chapter includes a discussion of the practice in Belgium, where euthanasia is performed within palliative care institutions. Furthermore, the chapter presents the Swiss model, which practises a much clearer separation between assisted dying and both palliative care and clinical medical practice. Statements on assisted dying made by key palliative care organizations are then presented and analysed. The chapter asks whether the palliative care community will be more accepting of euthanasia in the future, following potential new legislation. The concluding remarks consider the current reluctance of doctors to participate, and the pressures they are under to accept a role, in assisted dying

Protection of Erwinia amylovora bacteriophage Y2 from UV-induced damage by natural compounds

Bacteriophages have regained much attention as biocontrol agents against bacterial pathogens. However, with respect to stability, phages are biomolecules and are therefore sensitive to a number of environmental influences. UV-irradiation can readily inactivate phage infectivity, which impedes their potential application in the plant phyllosphere. Therefore, phages for control of Erwinia amylovora, the causative agent of fire blight, need to be protected from UV-damage by adequate measures. We here investigated the protective effect of different light-absorbing substances on phage particles exposed to UV-light. For this, natural extracts from carrot, red pepper, and beetroot were prepared and tested as a natural sunscreen for phage. All compounds were found to significantly increase half-life of UV-irradiated phage particles, due to their high concentration of light absorbing carotenoids and betalaines. Pure astaxanthin, a carotenoid, also offered a significant UV-protection. The extracts themselves did not negatively affect phage viability or infectivity. Altogether, a range of readily available, natural, environmentally-safe and inexpensive substances are suitable as UV-protectants to prevent phage particles from UV-light damage

Mutational and Selective Processes Involved in Evolution during Bacterial Range Expansions

Bacterial populations have been shown to accumulate deleterious mutations during spatial expansions that overall decrease their fitness and ability to grow. However, it is unclear if and how they can respond to selection in face of this mutation load. We examine here if artificial selection can counteract the negative effects of range expansions. We examined the molecular evolution of 20 mutator lines selected for fast expansions (SEL) and compared them to 20 other mutator lines freely expanding without artificial selection (CONTROL). We find that the colony size of all 20 SEL lines have increased relative to the ancestral lines, unlike CONTROL lines, showing that enough beneficial mutations are produced during spatial expansions to counteract the negative effect of expansion load. Importantly, SEL and CONTROL lines have similar numbers of mutations indicating that they evolved for the same number of generations and that increased fitness is not due to a purging of deleterious mutations. We find that loss of function mutations better explain the increased colony size of SEL lines than nonsynonymous mutations or a combination of the two. Interestingly, most loss of function mutations are found in simple sequence repeats (SSRs) located in genes involved in gene regulation and gene expression. We postulate that such potentially reversible mutations could play a major role in the rapid adaptation of bacteria to changing environmental conditions by shutting down expensive genes and adjusting gene expression

Dissection of the mutation accumulation process during bacterial range expansions

Background Recent experimental work has shown that the evolutionary dynamics of bacteria expanding across space can differ dramatically from what we expect under well-mixed conditions. During spatial expansion, deleterious mutations can accumulate due to inefficient selection on the expansion front, potentially interfering with and modifying adaptive evolutionary processes. Results We used whole genome sequencing to follow the genomic evolution of 10 mutator Escherichia coli lines during 39 days ( ~ 1650 generations) of a spatial expansion, which allowed us to gain a temporal perspective on the interaction of adaptive and non-adaptive evolutionary processes during range expansions. We used elastic net regression to infer the positive or negative effects of mutations on colony growth. The colony size, measured after three day of growth, decreased at the end of the experiment in all 10 lines, and mutations accumulated at a nearly constant rate over the whole experiment. We find evidence that beneficial mutations accumulate primarily at an early stage of the experiment, leading to a non-linear change of colony size over time. Indeed, the rate of colony size expansion remains almost constant at the beginning of the experiment and then decreases after ~ 12 days of evolution. We also find that beneficial mutations are enriched in genes encoding transport proteins, and genes coding for the membrane structure, whereas deleterious mutations show no enrichment for any biological process. Conclusions Our experiment shows that beneficial mutations target specific biological functions mostly involved in inter or extra membrane processes, whereas deleterious mutations are randomly distributed over the whole genome. It thus appears that the interaction between genetic drift and the availability or depletion of beneficial mutations determines the change in fitness of bacterial populations during range expansion

Impact of climate change on rainfall over Mumbai using Distribution-based Scaling of Global Climate Model projections

Study region: The study is carried out for Mumbai (18°58′30″ N, 72°49′33″ E). Study focus: Future projections provided by general circulation models (GCMs) suggest the probability of occurrence of intense rainfall will change in the future. However, GCM data generally need to be downscaled and bias-corrected for impact studies. Although the domains covered by Regional Climate Models (RCMs) are increasing, statistical downscaling of GCM results is the main alternative in many regions. We applied a Distribution-based Scaling (DBS) procedure, with 1975–2004 as a reference period, for bias-correcting and downscaling daily rainfall data from nine global climate projections. New hydrological insights for the region: The evaluation in the reference period showed that the scaled data are able to represent various key statistics. All GCMs were unable to accurately reproduce the southwest monsoon season. Using the transient DBS processed projection data, a comprehensive evaluation of key rainfall statistics was performed for three periods: near (2010–2040), intermediate (2041–2070) and distant future (2071–2099). There is an increase in the total accumulated annual rainfall, ranging from 300 to 500 mm in the ensemble. Also, a clear seasonal shift and delayed onset of the monsoon season evolves in the projections, with increasing and decreasing rainfall in September and June, respectively. A trend analysis using Student's t and Mann–Kendall tests was performed for 2010–2099. A significant positive trend was found for four of the GCM projections