Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Chemical strain-relaxation of single-walled carbon nanotubes on plastic substrates for enhanced conductivity

We have demonstrated that the conductivity of single-walled nanotube network films on plastic substrates is enhanced by a simple solvent treatment via chemical welding with aromatic hydrocarbons. The welding effect on the conductivity was confirmed by welding over a surface, the properties of which were controlled by deposition of reduced graphene oxide sheets on the substrate before deposition of the SWCNTs. The correlation between the sheet resistance and the interfacial structure of nanotubes on polyester substrates is further discussed in conjunction with a solvent-induced strain-relaxation of nanotubes and the geometrical change of nanotubes confirmed by atomic force microscopy and Raman spectroscopy after introducing solvents. We observe a clear reversible shift to higher energies in the G-mode band after chemical welding, indicating relaxation of the strain induced by the interface structure at the substrate and network junction.X1145sciescopu

Mucosal malignant melanomas in head and neck surgery: a retrospective study of six patients and review of the literature

INTRODUCTION: Of all malignant processes of the oral mucosa, 0.5% are malignant melanomas. Because of late diagnosis, pattern of growth, close proximity to the bone (particularly in palatinal localizations), and the correlated infiltration, malignant melanomas have a bad prognosis. PATIENTS AND METHODS: In this retrospective study, six cases of patients with oral mucosal malignant melanoma are evaluated, and a critical review of the literature is presented. The female to male proportion was 1:1 with an average age of 60.2 years; all patients were treated between January 1999 and July 2007. A neck dissection was performed on two patients because of clinically positive lymph nodes; one patient received interleukin 2 therapy, and three patients received postoperative radiotherapy. Two male patients died. CONCLUSIONS: We recommend biopsy on every growing lesion, pigmented or nonpigmented, for the required diagnosis and, in cases of malignant melanoma, wide excision as a second step. Neck dissections should be performed in patients with clinically positive lymph nodes. Concerning interleukin 2 therapy, further studies should be performed in order to evaluate a routine application