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237 mg/cm2·h-1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient's need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.While intrinsic molecular subtypes provide important biological classification of breast cancer, the subtype assignment of individuals is influenced by assay technology and study cohort composition. We sought to develop a platform-independent absolute single-sample subtype classifier based on a minimal number of genes. Pairwise ratios for subtype-specific differentially expressed genes from un-normalized expression data from 432 breast cancer (BC) samples of The Cancer Genome Atlas (TCGA) were used as inputs for machine learning. The subtype classifier with the fewest number of genes and maximal classification power was selected during cross-validation. The final model was evaluated on 5816 samples from 10 independent studies profiled with four different assay platforms. Upon cross-validation within the TCGA cohort, a random forest classifier (MiniABS) with 11 genes achieved the best accuracy of 88.2%. Applying MiniABS to five validation sets of RNA-seq and microarray data showed an average accuracy of 85.15% (vs. 77.72% for Absolute Intrinsic Molecular Subtype (AIMS)). Only MiniABS could be applied to five low-throughput datasets, showing an average accuracy of 87.93%. The MiniABS can absolutely subtype BC using the raw expression levels of only 11 genes, regardless of assay platform, with higher accuracy than existing methods.Social distancing plays a leading role in controlling the spread of coronavirus. However, prolonged lockdown can lead to negative consequences in terms of mental health. The goal of the research is to examine the relationship between anxiety and general psychosomatic functioning during the COVID-19 pandemic; the impact of psychological flexibility and mindfulness is also considered. Variables were measured with self-report questionnaires and symptom checklists. The sample included 170 people (M = 27.79, SD = 8.16). Pearson's correlation, stepwise regression, and path analysis were conducted. The results showed a significant positive relationship between state anxiety and somatic and psychological responses to the pandemic. Path analysis revealed that mindfulness had a direct negative impact on and decreased the level of state anxiety (b = -0.22, p = 0.002), whereas psychological flexibility influenced the variable indirectly (b = 0.23, p = 0.002) by enhancing psychosomatic functioning (b = -0.64, p less then 0.001). Psychological flexibility and mindfulness may mediate the development of mental disorders and facilitate achieving overall wellbeing. The study points to the usefulness of mindfulness practice as a form of self-help with anxiety symptoms; this is crucial during the pandemic because contact with clients is restricted.In December 2019, Spain considered for the first time the presence of radon to the Technical Building Code (Basic Document HS 6 Radon Exposure Protection), although it only mentions minimum presences and the need for ventilation. INCB39110 This research shows that in buried structures or in places with little ventilation, even in soils with a low probability of granite, a high content of radon gas can be found. The city of Alicante has been used as a measurement location for different architectural sites; here, the level of 100 Bq/m3 is the first threshold where the gas must be monitored, and the level of 300 Bq/m3 is the maximum threshold above which corrective ventilation measures must be taken. The research conducted during the years 2015 and 2016 shows that it is necessary to account for also the areas considered to be "low presence of radon gas" to achieve healthy constructions. The renewal of air in the different places will be tested for the presence of radon, i.e., the greater the accumulation is, the less ventpresence of radon gas in nongranite soils as long as the conditions for its accumulation are present.Dyskerin is a nucleolar protein involved in the small nucleolar RNA (snoRNA)-guided pseudouridylation of specific uridines on ribosomal RNA (rRNA), and in the stabilization of the telomerase RNA component (hTR). Loss of function mutations in DKC1 causes X-linked dyskeratosis congenita, which is characterized by a failure of proliferating tissues and increased susceptibility to cancer. However, several tumors show dyskerin overexpression. We observed that patients with primary breast cancers with high dyskerin levels are more frequently characterized by shorter survival rates and positive lymph node status than those with tumors with a lower dyskerin expression. To functionally characterize the effects of high dyskerin expression, we generated stably overexpressing DKC1 models finding that increased dyskerin levels conferred a more aggressive cellular phenotype in untransformed immortalized MCF10A cells. Contextually, DKC1 overexpression led to an upregulation of some snoRNAs, including SNORA67 and a significantly increased U1445 modification on 18S rRNA, the known target of SNORA67.