Placing Arrows in Directed Graph Drawings

We consider the problem of placing arrow heads in directed graph drawings without them overlapping other drawn objects. This gives drawings where edge directions can be deduced unambiguously. We show hardness of the problem, present exact and heuristic algorithms, and report on a practical study.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

In and out of Madagascar : dispersal to peripheral islands, insular speciation and diversification of Indian Ocean daisy trees (Psiadia, Asteraceae)

This study was supported by the European Union’s HOTSPOTS Training Network (MEST-2005-020561)Madagascar is surrounded by archipelagos varying widely in origin, age and structure. Although small and geologically young, these archipelagos have accumulated disproportionate numbers of unique lineages in comparison to Madagascar, highlighting the role of waif-dispersal and rapid in situ diversification processes in generating endemic biodiversity. We reconstruct the evolutionary and biogeographical history of the genus Psiadia (Asteraceae), a plant genus with near equal numbers of species in Madagascar and surrounding islands. Analyzing patterns and processes of diversification, we explain species accumulation on peripheral islands and aim to offer new insights on the origin and potential causes for diversification in the Madagascar and Indian Ocean Islands biodiversity hotspot. Our results provide support for an African origin of the group, with strong support for non-monophyly. Colonization of the Mascarenes took place by two evolutionary distinct lineages from Madagascar, via two independent dispersal events, each unique for their spatial and temporal properties. Significant shifts in diversification rate followed regional expansion, resulting in co-occurring and phenotypically convergent species on high-elevation volcanic slopes. Like other endemic island lineages, Psiadia have been highly successful in dispersing to and radiating on isolated oceanic islands, typified by high habitat diversity and dynamic ecosystems fuelled by continued geological activity. Results stress the important biogeographical role for Rodrigues in serving as an outlying stepping stone from which regional colonization took place. We discuss how isolated volcanic islands contribute to regional diversity by generating substantial numbers of endemic species on short temporal scales. Factors pertaining to the mode and tempo of archipelago formation and its geographical isolation strongly govern evolutionary pathways available for species diversification, and the potential for successful diversification of dispersed lineages, therefore, appears highly dependent on the timing of arrival, as habitat and resource properties change dramatically over the course of oceanic island evolution.Publisher PDFPeer reviewe

Castanopsis corallocarpus (Fagaceae), a new species from Royal Belum (Perak) in Peninsular Malaysia

A new species from the Fagaceae family, Castanopsis corallocarpus Tan & Strijk, is described from Royal Belum State Park in Peninsular Malaysia. Here, we provide technical illustrations, colour images and a description of its conservation status and the collecting locality, in addition to a comparative analysis with other species in the region. The solitary nut of C. corallocarpus has a morphologically unique cupule, lined with rows of thick coral-like spines not seen in other Castanopsis species

A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy

Background: Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach. Methods: Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle. These samples underwent gene (GEP) and inflammatory protein expression profiling (IPEP). We explored the predictive potential of exclusively IPEP through Stepwise (Backward) Multivariate Logistic Regression modeling. Additionally, we integrated GEP and IPEP using Bayesian Kernel Regression modeling, aiming to enhance predictive performance. Ultimately, the FOLFIRINOX IPEP (FFX-IPEP) signature was developed. Results: Our findings revealed that proteins exhibited superior predictive accuracy than genes. Consequently, the FFX-IPEP signature consisted of six proteins: AMN, BANK1, IL1RL2, ITGB6, MYO9B, and PRSS8. The signature effectively identified patients transitioning from disease control to progression early during FOLFIRINOX, achieving remarkable predictive accuracy with an AUC of 0.89 in an independent test set. Importantly, the FFX-IPEP signature outperformed the conventional CA19-9 tumor marker. Conclusions: Our six-protein FFX-IPEP signature holds solid potential as a liquid biomarker for the early prediction of PDAC progression during toxic FOLFIRINOX chemotherapy. Further validation in an external cohort is crucial to confirm the utility of the FFX-IPEP signature. Future studies should expand to predict progression under different chemotherapies to enhance the guidance of personalized treatment selection in PDAC.</p

A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy

Background: Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach. Methods: Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle. These samples underwent gene (GEP) and inflammatory protein expression profiling (IPEP). We explored the predictive potential of exclusively IPEP through Stepwise (Backward) Multivariate Logistic Regression modeling. Additionally, we integrated GEP and IPEP using Bayesian Kernel Regression modeling, aiming to enhance predictive performance. Ultimately, the FOLFIRINOX IPEP (FFX-IPEP) signature was developed. Results: Our findings revealed that proteins exhibited superior predictive accuracy than genes. Consequently, the FFX-IPEP signature consisted of six proteins: AMN, BANK1, IL1RL2, ITGB6, MYO9B, and PRSS8. The signature effectively identified patients transitioning from disease control to progression early during FOLFIRINOX, achieving remarkable predictive accuracy with an AUC of 0.89 in an independent test set. Importantly, the FFX-IPEP signature outperformed the conventional CA19-9 tumor marker. Conclusions: Our six-protein FFX-IPEP signature holds solid potential as a liquid biomarker for the early prediction of PDAC progression during toxic FOLFIRINOX chemotherapy. Further validation in an external cohort is crucial to confirm the utility of the FFX-IPEP signature. Future studies should expand to predict progression under different chemotherapies to enhance the guidance of personalized treatment selection in PDAC.</p

A process evaluation of a worksite vitality intervention among ageing hospital workers

<p>Abstract</p> <p>Background</p> <p>The process evaluation of the Vital@Work intervention was primary aimed at gaining insight into the context, dose delivered, fidelity, reach, dose received, and participants' attitude. Further, the differences between intervention locations were evaluated.</p> <p>Methods</p> <p>Eligible for this study were 730 workers, aged ≥ 45 years, from two academic hospitals. Workers randomised to the intervention group (n = 367) received a 6-months intervention consisting a Vitality Exercise Programme (VEP) combined with three visits to a Personal Vitality Coach (PVC), aimed at goal setting, feedback, and problem solving. The VEP consisted of a guided yoga session, a guided workout session, and aerobic exercising without direct face-to-face instruction, all once a week. Data were collected by means of a questionnaire after the intervention, attendance registration forms (i.e. attendance at guided VEP group sessions), and coaching registration forms (filled in by the PVCs).</p> <p>Results</p> <p>The dose delivered of the yoga and workout sessions were 72.3% and 96.3%. All PVC visits (100%) were offered. The reach for the yoga sessions, workout sessions and PVC visits was 70.6%, 63.8%, and 89.6%, respectively. When taken these three intervention components together, the reach was 52%. This differed between the two locations (59.2% versus 36.8%). The dose received was for the yoga 10.4 sessions/24 weeks and for the workout 11.1 sessions/24 weeks. The attendance rate, defined as the mean percentage of attended group sessions in relation to the total provided group sessions, for the yoga and workout sessions was 51.7% and 44.8%, respectively. For the yoga sessions this rate was different between the two locations (63.2% versus 46.5%). No differences were found between the locations regarding the workout sessions and PVC visits. Workers attended on average 2.7 PVC visits. Overall, workers were satisfied with the intervention components: 7.5 for yoga sessions, 7.8 for workout sessions, and 6.9 for PVC visits.</p> <p>Conclusions</p> <p>The implementation of the intervention was accomplished as planned with respect to the dose delivered. Based on the reach, most workers were willing to attend the guided group sessions and the PVC visits, although there were differences between the locations and between intervention components. Overall, workers were positive about the intervention.</p> <p>Trial registration</p> <p>Trial registration <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1240">NTR1240</a></p

Analyzing Flow Cytometry or Targeted Gene Expression Data Influences Clinical Discoveries—Profiling Blood Samples of Pancreatic Ductal Adenocarcinoma Patients

Introduction:Monitoring the therapeutic response of pancreatic ductal adenocarcinoma (PDAC) patients is crucial to determine treatment strategies. Several studies have examined the effectiveness of FOLFIRINOX as a first-line treatment in patients with locally advanced pancreatic cancer, but little attention has been paid to the immunologic alterations in peripheral blood caused by this chemotherapy regimen. Furthermore, the influence of the measurement type (e.g., flow cytometry and targeted gene expression) on the clinical discoveries is unknown. Therefore, we aimed to scrutinize the influence of using flow cytometry or targeted immune gene expression to study the immunological changes in blood samples of PDAC patients who were treated with a single-cycle FOLFIRINOX combined with lipegfilgrastim (FFX-Lipeg). Material and Methods: Whole-blood samples from 44 PDAC patients were collected at two time points: before the first FOLFIRINOX cycle and 14 days after the first cycle. EDTA blood tubes were used for multiplex flow cytometry analyses to quantify 18 immune cell populations and for complete blood count tests as the standard clinical routine. The flow cytometry data were analyzed with FlowJo software. In addition, Tempus blood tubes were used to isolate RNA and measure 1230 immune-related genes using NanoString Technology®. Data quality control, normalization, and analysis were performed using nSolver™ software and the Advanced Analysis module. Results: FFX-Lipeg treatment increased the number of neutrophils and monocytes, as shown by flow cytometry and complete blood count in concordance with elevated gene expression measured via targeted gene expression profiling analysis. Interestingly, flow cytometry analysis showed an increase in the number of B and T cells after treatment, while targeted gene expression analysis showed a decrease in B and T cell-specific gene expression. Conclusions: Targeted gene expression complements flow cytometry analysis to provide a comprehensive understanding of the effects of FFX-Lipeg. Flow cytometry and targeted gene expression showed increases in neutrophils and monocytes after FFX-Lipeg. The number of lymphocytes is increased after treatment; nevertheless, their cell-specific gene expression levels are downregulated. This highlights that different techniques influence clinical discoveries. Therefore, it is important to carefully select the measurement technique used to study the effect of a treatment.</p

Chromosome‐level reference genome of the soursop (Annona muricata) : a new resource for Magnoliid research and tropical pomology

The flowering plant family Annonaceae includes important commercially grown tropical crops, but development of promising species is hindered by a lack of genomic resources to build breeding programs. Annonaceae are part of the magnoliids, an ancient lineage of angiosperms for which evolutionary relationships with other major clades remain unclear. To provide resources to breeders and evolutionary researchers, we report a chromosome-level genome assembly of the soursop (Annona muricata). We assembled the genome using 444.32 Gb of DNA sequences (676x sequencing depth) from PacBio and Illumina short-reads, in combination with 10x Genomics and Bionano data (v1). A total of 949 scaffolds were assembled to a final size of 656.77 Mb, with a scaffold N50 of 3.43 Mb (v1), and then further improved to seven pseudo-chromosomes using Hi-C sequencing data (v2; scaffold N50: 93.2 Mb, total size in chromosomes: 639.6 Mb). Heterozygosity was very low (0.06%), while repeat sequences accounted for 54.87% of the genome, and 23,375 protein-coding genes with an average of 4.79 exons per gene were annotated using de novo, RNA-seq and homology-based approaches. Reconstruction of the historical population size showed a slow continuous contraction, probably related to Cenozoic climate changes. The soursop is the first genome assembled in Annonaceae, supporting further studies of floral evolution in magnoliids, providing an essential resource for delineating relationships of ancient angiosperm lineages. Both genome-assisted improvement and conservation efforts will be strengthened by the availability of the soursop genome. As a community resource, this assembly will further strengthen the role of Annonaceae as model species for research on the ecology, evolution and domestication potential of tropical species in pomology and agroforestry