| 1. |
- Agriesti, Serio Angelo Maria, et al.
(författare)
-
Roadworks warning-closure of a lane, the Impact of C-ITS messages
- 2020
-
Ingår i: Infrastructures. - : MDPI AG. - 2412-3811. ; 5:3
-
Tidskriftsartikel (refereegranskat)abstract
- By now, it is widely acknowledged among stakeholders and academia that infrastructures will have to be composed both by a physical component and a digital one. The deployment of technologies exploiting dedicated short-range communications is viewed as the most cost-effective solution to face the foreseen growth of mobility. Still, little has been done to define the best implementation logic of DSRC. Aim of this paper is to frame the possible impacts arising by the implementation of a cooperative intelligent transport system (C-ITS)-use case: roadworks warning.closure of a lane, and, in order to achieve this result, microsimulations are exploited. The results are intended to support both road operators and car-makers in defining the best operational logics and the possible benefits achievable by presenting the cooperative message at a certain distance for certain market penetrations. Moreover, if the C-ITS message actually entails benefits or simply disrupts the upstream traffic should be assessed in advance, before implementing the system. The obtained results show that the risk of disruption and of reduction in traffic efficiency arises at lower market penetration levels. Nevertheless, a consistent trend in delay reduction is recorded upstream the roadworks, the highest reduction being equal to 8.66%. Moreover, the average speed at the roadworks entrance on the closing lane increases by a difference equal to around 10 km/h, while the average time in the queue at the highest market penetration reduces by 60 s on the open lane and 25 s on the closing one. These presented results reflect the way the traffic shifts from the slow to the fast lane thanks to the C-ITS system and effectively frames both the potentialities and the risks of the system.
|
|
| 2. |
- Bonfiglio, Silvia, et al.
(författare)
-
BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib
- 2023
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:12, s. 2794-2806
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet need. Though Bruton tyrosine kinase (BTK) and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL on ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2. BTK hotspot mutations were validated by droplet digital polymerase chain reaction (ddPCR) (0.1% sensitivity). By integrating NGS and ddPCR results, 32 of 49 relapsing cases (65%) carried at least 1 hotspot BTK and/or PLCG2 mutation(s); in 6 of 32, BTK mutations were only detected by ddPCR (variant allele frequency [VAF] 0.1% to 1.2%). BTK/PLCG2 mutations were also identified in 6 of 49 responding patients (12%; 5/6 VAF <10%), of whom 2 progressed later. Among the relapsing patients, the BTK-mutated (BTKmut) group was enriched for EGR2 mutations, whereas BTK-wildtype (BTKwt) cases more frequently displayed BIRC3 and NFKBIE mutations. Using an extended capture-based panel, only BRAF and IKZF3 mutations showed a predominance in relapsing cases, who were enriched for del(8p) (n = 11; 3 BTKwt). Finally, no difference in TP53 mutation burden was observed between BTKmut and BTKwt relapsing cases, and ibrutinib treatment did not favor selection of TP53-aberrant clones. In conclusion, we show that BTK/PLCG2 mutations were absent in a substantial fraction (35%) of a real-world cohort failing ibrutinib, and propose additional mechanisms contributing to resistance.
|
|
| 3. |
- Wirbel, Jakob, et al.
(författare)
-
Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
- 2019
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:4, s. 679-689
-
Tidskriftsartikel (refereegranskat)abstract
- Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10 −5 ). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
|
|
