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Motivation: We introduce SMapper, a novel web and software tool for visualizing spatial prevalence data of all types including those suffering from incomplete geographic coverage and insufficient sample sizes. We demonstrate the benefits of our tool in overcoming interpretational issues with existing tools caused by such data limitations. We exemplify the use of SMapper by applications to human genotype and phenotype data relevant in an epidemiological, anthropological and forensic context. Availability and implementation: A web implementation is available at https://rhodos.ccg.uni-koeln.de/smapper/. A stand-alone version, released under the GNU General Public License version 3 as published by the Free Software Foundation, is available from https://rhodos.ccg.uni-koeln.de/smapper/software-download.php as a Singularity container (https://docs.sylabs.io/guides/latest/user-guide/index.html) and a native Linux Python installation.
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Introduction: Lung cancer has been one of the most prevalent cancers worldwide in recent decades. According to the findings of the KEYNOTE-407 (2018) study on patients with stage IV squamous cell lung cancer, the combination of pembrolizumab and chemotherapy in the first-line treatment prolongs overall survival compared with chemotherapy alone. This study aimed to evaluate the efficacy and side effects of treating patients with stage IV non-small cell lung cancer with pembrolizumab in combination with platinum-based doublet chemotherapy. Methods: A retrospective multicenter study on 46 patients at four hospitals in Vietnam between June 2018 and August 2022. Patients received first-line treatment with a protocol of pembrolizumab in combination with platinum-based doublet chemotherapy (pemetrexed plus carboplatin or paclitaxel plus carboplatin). The study's primary endpoints were progression-free survival and safety. The secondary endpoint was overall survival. Results: The median progression-free survival was 11.0 months (95% CI, 7.4-14.7 months). The median overall survival was 23.1 months (95% CI, 18.4-27.8 months). The survival rate of patients after 1 and 2 years was 82.3% and 43.3%, respectively. The most common side effects were anemia and elevated liver enzymes, but they were primarily mild or moderate severity. Progression-free survival did not depend on cancer type based on histology (p = 0.13). The progression-free survival was independent of programmed death ligand-1 expression levels < 50% or ≥ 50% (p = 0.68). Conclusion: Treatment of stage IV non-small cell lung cancer without EGFR and ALK gene mutations with the immunotherapy protocol of pembrolizumab in combination with platinum-based doublet chemotherapy resulted in favorable outcomes without any new safety concerns. A larger sample size and longer follow-up in the future are necessary to yield more complete results.
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Despite numerous studies on various surface modifications on titanium and its alloys, it remains unclear what kind of titanium-based surface modifications are capable of controlling cell activity. This study aimed to understand the mechanism at the cellular and molecular levels and investigate the in vitro response of osteoblastic MC3T3-E1 cultured on the Ti-6Al-4V surface modified by plasma electrolytic oxidation (PEO) treatment. A Ti-6Al-4V surface was prepared by PEO at 180, 280, and 380 V for 3 or 10 min in an electrolyte containing Ca2+/Pi ions. Our results showed that PEO-treated Ti-6Al-4V-Ca2+/Pi surfaces enhanced the cell attachment and differentiation of MC3T3-E1 compared to the untreated Ti-6Al-4V control but did not affect cytotoxicity as shown by cell proliferation and cell death. Interestingly, on the Ti-6Al-4V-Ca2+/Pi surface treated by PEO at 280 V for 3 or 10 min, MC3T3-E1 showed a higher initial adhesion and mineralization. In addition, the alkaline phosphatase (ALP) activity significantly increased in MC3T3-E1 on the PEO-treated Ti-6Al-4V-Ca2+/Pi (280 V for 3 or 10 min). In RNA-seq analysis, the expression of dentin matrix protein 1 (DMP1), sortilin 1 (Sort1), signal-induced proliferation-associated 1 like 2 (SIPA1L2), and interferon-induced transmembrane protein 5 (IFITM5) was induced during the osteogenic differentiation of MC3T3-E1 on the PEO-treated Ti-6Al-4V-Ca2+/Pi. DMP1 and IFITM5 silencing decreased the expression of bone differentiation-related mRNAs and proteins and ALP activity in MC3T3-E1. These results suggest that the PEO-treated Ti-6Al-4V-Ca2+/Pi surface induces osteoblast differentiation by regulating the expression of DMP1 and IFITM5. Therefore, surface microstructure modification through PEO coatings with Ca2+/Pi ions could be used as a valuable method to improve biocompatibility properties of titanium alloys.
