Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients.

BackgroundTopoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well.Summary of methodsWe analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well.ResultsOverexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer.ConclusionOur data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation

Asymptomatic Coronary Artery Disease in Adults with Familial Hypercholesterolemia and use of Coronary Artery Imaging as a Screening Tool

Background: Heterozygous Familial Hypercholesterolemia (heFH) is an autosomal dominant disorder caused by a defect in a low-density lipoprotein (LDL) receptor gene and results in drastically elevated serum LDL levels. These patients have a decreased life expectancy secondary to sudden death and myocardial infarction. The clinical course of heFH patients is variable and not directly related to serum LDL levels. Recent studies have also shown that many heFH patients with coronary artery disease (CAD) present asymptomatically. Computed tomography coronary angiography (CTCA) is one means of detecting subclinical CAD. However, CTCA screening has yet to be proven to improve outcomes in those with asymptomatic CAD, but outcomes of heFH patients have yet to be studied specifically. The purpose of this systematic review is to compile research that compares asymptomatic heFH populations with healthy adults, and determine if CTCA could be warranted in asymptomatic heFH patients. Method: A search of Medline-OVID, Web of Science, and CINAHL with Full Text was conducted using key words: CT angiography/angiography/coronary angiography, familial hypercholesterolemia and asymptomatic/subclinical. Studies were reviewed and included based on relevant criteria. Those relevant articles were assessed using the GRADE system for quality. Results: Three observational studies met inclusion criteria and were included in this systematic review. All three studies showed a significant increase in the number of heFH participants with subclinical CAD as seen on CTCA, with almost one quarter of heFH patients demonstrating severe vessel occlusion. Conclusion: These studies indicate the heFH patient are more likely to have subclinical coronary atherosclerosis. In order to justify the use of CTCA in asymptomatic heFH patients, further research looking at outcomes of heFH patients diagnosed with early CAD is needed. While CTCA does have the ability to detect which heFH patients have CAD, whether or not this information, when applied to treatment strategies, can reduce risk of CAD and mortality has yet to be determined

A Trip Back Home: Resistance to Herbivores of Native and Non-Native Plant Populations of Datura stramonium

When colonizing new ranges, plant populations may benefit from the absence of the checks imposed by the enemies, herbivores, and pathogens that regulated their numbers in their original range. Therefore, rates of plant damage or infestation by natural enemies are expected to be lower in the new range. Exposing both non-native and native plant populations in the native range, where native herbivores are present, can be used to test whether resistance mechanisms have diverged between populations. Datura stramonium is native to the Americas but widely distributed in Spain, where populations show lower herbivore damage than populations in the native range. We established experiments in two localities in the native range (Mexico), exposing two native and two non-native D. stramonium populations to natural herbivores. Plant performance differed between the localities, as did the abundance of the main specialist herbivore, Lema daturaphila. In Teotihuacan, where L. daturaphila is common, native plants had significantly more adult beetles and herbivore damage than non-native plants. The degree of infestation by the specialist seed predator Trichobaris soror differed among populations and between sites, but the native Ticuman population always had the lowest level of infestation. The Ticuman population also had the highest concentration of the alkaloid scopolamine. Scopolamine was negatively related to the number of eggs deposited by L. daturaphila in Teotihuacan. There was among-family variation in herbivore damage (resistance), alkaloid content (scopolamine), and infestation by L. daturaphila and T. soror, indicating genetic variation and potential for further evolution. Although native and non-native D. stramonium populations have not yet diverged in plant resistance/constitutive defense, the differences between ranges (and the two experimental sites) in the type and abundance of herbivores suggest that further research is needed on the role of resource availability and adaptive plasticity, specialized metabolites (induced, constitutive), and the relationship between genealogical origin and plant defense in both ranges

Inter-annual variation in the abundance of specialist herbivores determines plant resistance in Datura stramonium

The expression of plant resistance traits against arthropod herbivores often comes with costs to other essential plant functions such as growth and fitness. These trade-offs are shaped by the allocation of limited resources. However, plants might also possess the capability to allocate resources to both resistance and growth, thereby ensuring their survival when under herbivore attacks. Additionally, the extent of damage caused by herbivores could vary across different years or seasons, subsequently impacting plant performance. In this study, we aimed to investigate how the annual variations in herbivore abundance and damage levels affect plant performance. We generated F-2 progeny through a cross between two populations of the annual herb Datura stramonium (Solanaceae). These populations are known to have differing levels of chemical defense and herbivory. These F-2 plants were cultivated in a common natural environment for two consecutive years (2017 and 2018). Our findings reveal that plants with higher resistance, attained higher seed production but this trend was evident only during 2018. This relationship coincided with a five-fold increase in the abundance of Lema daturaphila (Chrysomelidae) larvae in 2018. Indeed, the plants experienced a 13-fold increase in damage during this second year of study. Furthermore, our results indicated that there was no trade-off between resistance, growth, and fitness in either of the 2 years. In contrast, during 2018, when plants faced stronger herbivore pressure, they allocated all available nutritional resources to enhance both resistance and growth. Our study highlights how the selection for plant resistance is dependent upon the inter-annual variation in herbivore abundance

An Invitation to Hypercomplex Phase Retrieval: Theory and Applications

Hypercomplex signal processing (HSP) provides state-of-the-art tools to handle multidimensional signals by harnessing intrinsic correlation of the signal dimensions through Clifford algebra. Recently, the hypercomplex representation of the phase retrieval (PR) problem, wherein a complex-valued signal is estimated through its intensity-only projections, has attracted significant interest. The hypercomplex PR (HPR) arises in many optical imaging and computational sensing applications that usually comprise quaternion and octonion-valued signals. Analogous to the traditional PR, measurements in HPR may involve complex, hypercomplex, Fourier, and other sensing matrices. This set of problems opens opportunities for developing novel HSP tools and algorithms. This article provides a synopsis of the emerging areas and applications of HPR with a focus on optical imaging.Comment: 10 pages, 4 figures, 2 table

Beurling-Selberg Extremization for Dual-Blind Deconvolution Recovery in Joint Radar-Communications

Recent interest in integrated sensing and communications has led to the design of novel signal processing techniques to recover information from an overlaid radar-communications signal. Here, we focus on a spectral coexistence scenario, wherein the channels and transmit signals of both radar and communications systems are unknown to the common receiver. In this dual-blind deconvolution (DBD) problem, the receiver admits a multi-carrier wireless communications signal that is overlaid with the radar signal reflected off multiple targets. The communications and radar channels are represented by continuous-valued range-times or delays corresponding to multiple transmission paths and targets, respectively. Prior works addressed recovery of unknown channels and signals in this ill-posed DBD problem through atomic norm minimization but contingent on individual minimum separation conditions for radar and communications channels. In this paper, we provide an optimal joint separation condition using extremal functions from the Beurling-Selberg interpolation theory. Thereafter, we formulate DBD as a low-rank modified Hankel matrix retrieval and solve it via nuclear norm minimization. We estimate the unknown target and communications parameters from the recovered low-rank matrix using multiple signal classification (MUSIC) method. We show that the joint separation condition also guarantees that the underlying Vandermonde matrix for MUSIC is well-conditioned. Numerical experiments validate our theoretical findings.Comment: 5 pages, 3 figure