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AbstractThe formation of the Cluster of Differentiation 47 (CD47, PDB code: 2JJT)/signal regulatory protein α (SIRPα) complex is very important as it protects healthy cells from immune clearance while promoting macrophage phagocytosis for tumour elimination. Although several antibodies have been developed for cancer therapy, new function-blocking aptamers are still under development. This study aims to design the aptamer AptCD47, which can block the formation of the CD47/SIRPα complex. This study employs the MARTINI coarse-grained (CG) force field and the stochastic tunnelling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method to identify the most stable AptCD47/CD47 complexes. Coarse-grained molecular dynamics (CGMD) simulations were used to obtain root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analyses. The results demonstrate that the formation of AptCD47/CD47 complexes renders the CD47 structure more stable than the single CD47 molecule in a water environment. The minimum energy pathway (MEP) obtained by the nudged elastic band (NEB) method indicates that the binding processes of 5′-ATTCAATTCC-3′ and 5′-AGTGCAATCT-3′ to CD47 are barrierless, which is much lower than the binding barrier of SIRPα to CD47 of about 14.23 kcal/mol. Therefore, these two AptCD47/CD47 complexes can create a high spatial binding barrier for SIRPα, preventing the formation of a stable CD47/SIRPα complex. The proposed numerical process with the MARTINI CG force field can be used to design CD47 aptamers that efficiently block SIRPα from binding to CD47.Communicated by Ramaswamy H. Sarma

TERTgene promoter mutations are known in multiple cancer types. Other TERTalterations remain poorly characterized. Sequencing data from 30,773 tumors analyzed by a hybridization capture next-generation sequencing assay (Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets) were analyzed for the presence of TERTalterations. Promoter rearrangements (500 bases upstream of the transcriptional start site), hypermethylation (n= 57), and gene expression (n= 155) were evaluated for a subset of cases. Mutually exclusive and recurrent promoter mutations were identified at three hot spots upstream of the transcriptional start site in 11.3% of cases (−124: 74%; −146: 24%; and −138: <2%). Mutually exclusive amplification events were identified in another 2.3% of cases, whereas mutually exclusive rearrangements proximal to the TERTgene were seen in 24 cases. The highest incidence of TERTpromoter mutations was seen in cutaneous melanoma (82%), whereas amplification events significantly outnumbered promoter mutations in well-differentiated/dedifferentiated liposarcoma (14.1% versus 2.4%) and adrenocortical carcinoma (13.6% versus 4.5%). Gene expression analysis suggests that the highest levels of gene expression are seen in cases with amplifications and rearrangements. Hypermethylation events upstream of the TERTcoding sequence were not mutually exclusive with known pathogenic alterations. Studies aimed at defining the prevalence and prognostic impact of TERTalterations should incorporate other pathogenic TERTalterations as these may impact telomerase function.

Hepatic angiosarcoma (HAS) is rare but often fatal. A review of literature in 1979 found that only 3 of the 70 patients lived for more than 2 years, but the survival might have been improved over the years. We conducted a retrospective study and reviewed the medical records of patients who visited a teaching hospital in Taiwan from January 2000 to August 2010 and had pathological proof of HAS. In addition, we conducted a review of literature and compared those who survived for 2 years or more to those who did not. Of the 3503 patients with primary liver cancer we identified, 9 had HAS, of whom 3 (33.3) survived for 2 years or more. One survived for 24 months without surgical resection, and the other two received surgery with postoperative chemotherapy and were still alive 32 and 37 months later, respectively. Through reviewing literature, we identified 3 more patients in Taiwan who had survived for 2 years or more. One survived for 42 months without surgical resection, the other two received segmentectomy with postoperative chemotherapy or radiotherapy. We also identified 8 such cases outside Taiwan, including 1 who received chemotherapy without surgery and survived for 53 months. None of the differences in the clinical characteristics between those who had and had not survived for 2 years or more reached statistical significance. In conclusion, we believe the combination of surgery and adjuvant chemotherapy may be able to achieve long-term survival in some HAS patients nowadays, and it is even possible to achieve fair survival using chemotherapy alone.

Approximately two-thirds of the patients with severe sepsis or septic shock are first encountered in the emergency departments (EDs) of western countries, in which bacteremia is present in about 50% of patients with severe sepsis. The situation of bacteremia presenting to the EDs in Taiwan is not well documented. The objective of this study was to examine the epidemiology and microbiology of bacteremia in adult patients who visited the ED of a medical center in southern Taiwan.

This paper presents a general multiple-base (GMB) data embedding algorithm to conceal a serial secret bit stream equivalent to an M -ary secret digit in a pixel-cluster consisting of n pixels, where M is automatically determined by the initial input ( n, F ) given by the end user. Through the change of two parameters, n and M , the proposed algorithm offers a multiple-purpose message embedding style to produce a high quality embedded image or provide a large embedding payload. Inspired by a single base (SB) data embedding approach, this study first introduces a multiple-base (MB) scheme which adopts an n -tuple optimal base vector ( OBV ) to conceal a secret M -ary digit with minimal pixel distortion, where M is the product of all vector components in the OBV . This study extends the MB scheme to develop the GMB algorithm, which supports a serial secret bit stream as a secret message. Four binary to M -ary conversion schemes are introduced, allowing the GMB algorithm to carry an extra secret bit per pixel-cluster, offering a larger payload without increasing the pixel distortion caused by data embedding. The proposed algorithm is analyzed, and mathematical expressions are derived so that prior to a real message embedding, it is possible to predict the expected payloads and the corresponding image quality. Finally, we extend the GMB algorithm to support content-adaptive data embedding. To the best of the authors' knowledge, the proposed algorithm is the first multiple-purpose data embedding technique, providing greater flexibility and offering large payloads or high image quality. Experimental results demonstrate that the proposed scheme outperforms current state-of-the-art competitors. [ABSTRACT FROM AUTHOR]