Sporadic vascular malformations (VMs) are a large group of disorders of the blood and lymphatic vessels caused by somatic mutations in several genes-mainly regulating the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. We performed a cross-sectional study of 43 patients affected with sporadic VMs, who had received molecular diagnosis by high-depth targeted next-generation sequencing in our center. Clinical and imaging features were correlated with the sequence variants identified in lesional tissues. Six of nine patients with capillary malformation and overgrowth (CMO) carried the recurrent GNAQ somatic mutation p.Arg183Gln, while two had PIK3CA mutations. Unexpectedly, 8 of 11 cases of diffuse CM with overgrowth (DCMO) carried known PIK3CA mutations, and the remaining 3 had pathogenic GNA11 variants. Recurrent PIK3CA mutations were identified in the patients with megalencephaly-CM-polymicrogyria (MCAP), CLOVES, and Klippel-Trenaunay syndrome. Interestingly, PIK3CA somatic mutations were associated with hand/foot anomalies not only in MCAP and CLOVES, but also in CMO and DCMO. Two patients with blue rubber bleb nevus syndrome carried double somatic TEK mutations, two of which were previously undescribed. In addition, a novel sporadic case of Parkes Weber syndrome (PWS) due to an RASA1 mosaic pathogenic variant was described. Finally, a girl with a mild PWS and another diagnosed with CMO carried pathogenic KRAS somatic variants, showing the variability of phenotypic features associated with KRAS mutations. Overall, our findings expand the clinical and molecular spectrum of sporadic VMs, and show the relevance of genetic testing for accurate diagnosis and emerging targeted therapies.

Segmental overgrowth has been widely described in patients with congenital vascular anomalies. However, segmental undergrowth has been poorly characterized, and no large series of patients have been published. We present the clinical and molecular characteristics a cohort of 37 patients with vascular malformations and segmental undergrowth. True undergrowth was only considered when the musculoskeletal system was involved to avoid confusion with other causes of segmental reduction, as in lipodystrophy or the long-term osteopenia seen in patients with Servelle-Martorell syndrome. Deep high-throughput sequencing was performed in tissue samples from 20 patients using a custom panel. We identified three groups: undergrowth associated with (1) venous, (2) capillary-venous, and (3) lymphatic-capillary-venous malformations. Congenital or early childhood onset undergrowth can occur with or without associated overgrowth. Different likely pathogenic or pathogenic variants were detected in 13 of 20 (65%) tissue samples in the PIK3CA, TEK, GNAQ, or GNA11 genes. In conclusion, the eponymous Servelle-Martorell syndrome should not be used as a synonym for undergrowth. Segmental undergrowth should be considered a characteristic associated with vascular malformations. Patients with PIK3CA variants show all different combinations of overgrowth and undergrowth. Thus, the term PROS (PIK3CA-related overgrowth spectrum) does not cover the entire spectrum.

OBJECTIVE: Emerging evidence suggests that cytotoxic therapy may promote drug resistance and metastasis while inhibiting the growth of primary tumors. As yet, however, the underlying mechanisms remain unclear. Here, we aimed to investigate the pro-metastatic effects of adriamycin (ADR) therapy on breast cancer cells and to investigate the mechanisms underlying these effects.
METHODS: Differentially expressed genes between MCF-7 and ADR-resistant MCF-7 breast cancer cells were identified using high-throughput RNA-seq and differential gene expression analyses. In vitro transwell and scratch wound-healing assays, and an in vivo spontaneous metastasis model were used to study the metastatic potential of the breast cancer cells. The relationship between SIRT7 and TEK expression was studied using promoter activity, electrophoretic mobility shift (EMSA), CHIP-qPCR and Co-IP assays.
RESULTS: Using transcriptome sequencing, we identified two key genes (SIRT7 and TEK) that might contribute to the pro-metastatic effect of ADR on breast cancer cells. SIRT7 acted as a negative regulator for TEK by inducing deacetylation of H3K18 at the TEK promoter. Through transcription factor prediction and double fluorescence experiments, we found that EST-1 could bind to the TEK promoter. Knockdown of EST-1 removed the transcriptional inhibition of TEK that was mediated by up-regulation of SIRT7. Co-IP showed that SIRT7 interacts directly with EST-1 in breast cancer cells, indicating that SIRT7 may induce H3K18 deacetylation at the TEK promoter region by directly binding to EST-1. In vitro and in vivo results showed that overexpression of SIRT7 or inhibition of TIE2 significantly reduced ADR-dependent breast cancer cell invasion/metastasis.
CONCLUSIONS: Our findings suggest that ADR therapy may accelerate breast cancer metastasis in a SIRT7/TEK(TIE2) dependent manner.

BACKGROUND: The use of plants in rituals is a little explored corner of biocultural diversity which has developed through time within a complex socio-ecological system. Indeed, rituals are complex interactions between humans and biodiversity shaped by history, culture, and ethnic belonging. Yet, in Western Ukraine, such rituals were forbidden for over 50 years (1939-1991). The current revival of rituals by rural inhabitants is an untapped reservoir of local ecological knowledge. The aim of the present study was to identify the ritual use of wild and cultivated plants in two regions of Western Ukraine, Bukovina and Roztochya, and to compare the findings with historical data. Moreover, we analyzed attitudes toward the ritual use of plants and interactions with the local environment.
METHODS: We conducted 31 in-depth semi-structured interviews among Orthodox Hutsuls of Bukovina and 16 interviews among Greek Catholic rural inhabitants of Roztochya during summer 2018 focusing on the ritual uses of plants.
RESULTS: We documented  28 plant taxa among Bukovinian Hutsuls and 58 plant taxa among inhabitants in Roztochya that were used in 7 religious festivals (of which two were celebrated differently in the two communities). Plants were mainly used in bouquets, but also for decorating churches and houses or in fruit baskets. In both communities, almost 25% of the interviewees could not name the plants they collected for bouquets, but rather referred to \"just beautiful green herbs\" one can get in meadows, forests, and gardens. Comparison with historical data shows a smaller number of taxa currently used (wild taxa have been lost), yet the persistence of 18 taxa used both now and a century ago.
CONCLUSIONS: Contemporary practices concerning the use of plants in Christian rituals in Bukovina and Roztochya can be contextualized in the broader phenomenon of the revitalization of traditional environmental knowledge and practices that have characterized Europe over the past 30 years and in particular Eastern Europe after socialism. The current religious use of plants is to a certain extent the revitalization of historical rituals supported by various internal (knowledge from older generations) and external (church authorities and fashion in the region) drivers. Further research should address changes in regions with longer and more severe prohibition of religious practices and their revival.