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Additional file 1. Figure S1. A map of Greece showing the sampling sites (Amyntaio, Nemea and Crete). Vineyards of Xinomavro, Agiorgitiko and Vidiano cultivars were sampled in Amyntaio, Nemea and Crete regions, respectively. Figure S2. Rarefaction curves for the wood samples analyzed for their fungal (a) and bacterial microbiome (b). Figure S3. Stacked bar plots showing the composition of the fungal community (at the class taxonomic level) in wood samples collected from GTD asymptomatic and symptomatic vines of the cultivars Agiorgitiko (a), Xinomavro (b), Vidiano (c) each located in a distinct viticultural zone in Greece. Figure S4. Fungal ASVs phylogenetically assigned to taxa previously identified as causal agents of GTDs that showed differential abundance in samples collected from symptomatic and asymptomatic vines. Data are presented collectively for all geographic locations/cultivars (a) and for each variety separately (b) Agiorgitiko (c) Xinomavro (d) Vidiano. ASV014: Phaeomoniella chlamydospora, ASV068: Kalmusia variispora, ASV13: Seimatosporium vitis, ASV52: Fomitiporia spp., ASV338: Seimatosporium vitis, ASV005: Phaeomoniella chlamydospora, ASV008: Phaeoacremonium iranianum, ASV75: Neosetophoma spp., ASV159: Neosetophoma spp., ASV074: Diaporthe spp., (Signif. Differences: ���***��� 0.001 ���**��� 0.01 ���*��� 0.05). Figure S5. Stacked bar plots showing the composition of the bacterial community (at the phylum taxonomic level and for the class Proteobacteria) in wood samples collected from GTP asymptomatic and symptomatic vines of the cultivars Agiorgitiko (a), Xinomavro (b), Vidiano (c) each located in a distinct viticultural zone in Greece. Figure S6. Out of bag (OOB) error rates of the Random Forest model parameter states next to the overall model error rates (7.94% shown with the black line) for each one of the 1000 model trees. The confusion matrix is also provided on the plot. Table S1: A list of the wood samples analyzed with all relevant information regarding vine cultivar and viticultural zone, GTD symptoms presence or absence, plant part sampled, vineyard code, plant code and geographic location. Table S2. Primers used for amplicon sequencing analysis. B000X-515f and FI000X-ITS4r are indexed primers used in the second amplification step, which are composed of the sequence of the universal primers 515f (bacteria) and ITS4r (fungi) (bold), the indexes used for samples barcoding (underlined) and a TT (linker) sequence at the 5' end of each primer. Table S3. PCR reagents and thermocycling conditions used for amplicon sequencing analysis. Table S4. PERMANOVA analysis of the fungal and bacterial wood microbiome (Signif. codes: 0.001 ���***��� 0.01 ���**��� 0.05 ���*���). Table S5. ASVs detected in the wood microbiome of the vines studied that are considered as putative pathogens involved in GTDs. Each ASV was phylogenetically assigned to the closest verified taxonomic level (genus or species).

Head and neck cancer (HNC) is a significantly heterogeneous disease and includes ma-lignancies arising from different anatomical sites, such as nasopharyngeal cancer (NPC) and laryn-geal cancer (LC). In the current study, polymorphisms located in angiogenesis‐ and apoptosis‐re-lated genes (VEGFA, FAS, EDNRA and NBS1) were evaluated regarding their clinical significance in HNC patients. In total, 333 HNC patients were enrolled in this study and 34 variants located on the aforementioned genes were genotyped via Sanger sequencing. LC patients, homozygous A for VEGFA rs13207351, had shorter overall survival (OS) as opposed to homozygous G (Hazard ratio (HR) = 2.06, Wald’s p = 0.017) upon adjustment for age, disease stage, and surgery. Following the dominant model, LC patients carrying the A allele had a marginally significantly higher risk for death (HR = 1.72, p = 0.059). NPC patients heterozygous (CT) for FAS rs2234768 had a marginal but significantly higher risk of death compared to those with homozygosity for the T allele (HR = 2.22, p = 0.056). In conclusion, rs13207351 (VEGFA) and rs2234768 (FAS) polymorphisms seem to have prognostic significance in HNC, with VEGFA rs13207351 showing the most promise in this subgroup of LC patients. © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.

Purpose: Gastric cancer is the fifth most common neoplasm worldwide with high rates of mortality. Afatinib, a low molecular, irreversible potent inhibitor of ErbB trans-membrane receptor family, has shown promising results according to preclinical and phase I clinical trial data when combined with chemotherapy. We aimed at evaluating the safety and efficacy of the combination of cisplatin, 5FU with afatinib in molecularly unselected patients with advanced gastric cancer. Methods: Patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma received first line combination therapy of cisplatin, 5FU and afatinib every 21 days, followed by afatinib maintenance monotherapy. The primary endpoint was the Objective Response Rate (ORR); secondary endpoints included Overall Survival (OS), Progression Free Survival (PFS) and the safety profile. Unplanned exploratory analysis of HER2 and tumor mutational profile was performed. Results: Among 55 patients (ITT population) enrolled, 19 (34.5%) achieved an objective tumor response; stable disease was observed in 16 patients (29.1%) and progressive disease in 10 patients (18.2%). The ORR in the per protocol population (PP) was 42.9%. Within a median follow-up of 56 months, the median PFS and OS in the ITT population was 5.0 and 8.7 months, respectively. Seven of the 47 HER2 informative cases carried HER2 positive tumors while TP53, BRCA2 and SMAD4 were the most frequently mutated genes. The most common toxicities were neutrophil count and white blood cell decrease occurring in 56.4% of patients, followed by anemia (50.9%), hyperglycemia (40%), and diarrhea (38.2%). Conclusions: The combination of cisplatin/5FU with afatinib did not surpass the benchmarks of efficacy of the contemporary therapeutic regimens that are being applied for the treatment of patients with advanced gastric cancer. However, the observed efficacy and the improved safety profile support that our administration schedule may be further investigated to overcome toxicity problems when integrating afatinib to cytotoxic chemotherapy. Clinical trial registration: NCT01743365. © 2021 Acta Oncologica Foundation.