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Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)-tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.

BACKGROUND:Cell-free circulating DNA (cfDNA) is becoming a useful biopsy for noninvasive diagnosis of diseases. Microbial sequences in plasma cfDNA may provide important information to improve prognosis and treatment. We have developed a stringent method to identify microbial species via microbial cfDNA in the blood plasma of early-onset breast cancer (EOBC) patients and healthy females. Empirically, microbe-originated sequence reads were identified by mapping non-human PE reads in cfDNA libraries to microbial databases. Those mapped concordantly to unique microbial species were assembled into contigs, which were subsequently aligned to the same databases. Microbial species uniquely aligned were identified and compared across all individuals on MCRPM (Microbial CfDNA Reads Per Million quality PE reads) basis. RESULTS:The predominant microbial cfDNAs in all plasma samples examined are originated from bacteria and these bacteria were limited to only a few genera. Among those, Acinetobacter johnsonii XBB1 and low levels of Mycobacterium spp. were commonly found in all healthy females, but also present in an EOBC patient. Compared to those in healthy counterparts, bacterial species in EOBC patients are more diverse and more likely to present at high levels. Among these three EOBC patients tested, a patient who has record high titer (2,724 MCRPM) of Pseudomonas mendocina together with 8.82 MCRPM of Pannonibacter phragmitetus has passed away; another patient infected by multiple Sphingomonas species remains alive; while the third patient who has similar microbial species (Acinetobacter johnsonii XBB1) commonly seen in normal controls is having a normal life. CONCLUSIONS:Our preliminary data on the profiles of microbial cfDNA sequences suggested that it may have some prognostic value in cancer patients. Validation in larger number of patients is warranted.

Body fluid DNA sequencing is a powerful noninvasive approach for the diagnosis of genetic defects, infectious agents and diseases. The success relies on the quantity and quality of the DNA samples. However, numerous clinical samples are either at low quantity or of poor quality due to various reasons. To overcome these problems, we have developed T oligo-primed polymerase chain reaction (TOP-PCR) for full-length nonselective amplification of minute quantity of DNA fragments. TOP-PCR adopts homogeneous "half adaptor" (HA), generated by annealing P oligo (carrying a phosphate group at the 5' end) and T oligo (carrying a T-tail at the 3' end), for efficient ligation to target DNA and subsequent PCR amplification primed by the T oligo alone. Using DNA samples from body fluids, we demonstrate that TOP-PCR recovers minute DNA fragments and maintains the DNA size profile, while enhancing the major molecular populations. Our results also showed that TOP-PCR is a superior method for detecting apoptosis and outperforms the method adopted by Illumina for DNA amplification.

The mitochondrial genome (mitogenome) Rhagastis binoculata (Matsumura, 1909), an endemic moth species in Taiwan, was sequenced and analyzed. The complete circular mitogenome of R. binoculata is 15,303 bp and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an AT-rich control region. The mitogenome has an overall nucleotide composition of 41.2% A, 11.9% C, 7.5% G, and 39.4% T, with an AT content of 80.6%. Of the protein-coding genes (PCGs), 12 start with ATG, ATT, and ATC, and COX1 starts with a "CGA" codon. All of the stop codons are "TAA, TAG, or T". Our phylogenetic analysis of 21 species of Sphingidae insects suggests that R. binoculata is clustered with Rhagastis mongoliana, which belongs to the subfamily Macroglossinae. [ABSTRACT FROM AUTHOR]

Producing an animation requires extensive labor, time, and money. Experienced directors and screenwriters are required to design scenes using standard props and actors in position. This study structurally analyzes the script and defines scenes, characters, positions, dialogue, etc., according to their dramatic attributes. These are entered into a model developed by this research, called "animated behavior by understanding the script module" (ABUSM), which implements a design for scenes, props, and role-related databases, producing a corresponding picture. Then, through mutual correspondence between attributes, data mining theories calculate a module for each character and its interactions related to other characters. Finally, these modules are rendered into animation. This demonstrates the relationships between behaviors through an animation demonstration system. Our research results will help nonprofessional theater animation designers, providing a reference for designing and modifying scripts through animated presentation until they are satisfactorily developed. This reduces the cost, time, and labor in recording a drama or producing an animation and can serve as a reference or training for nonprofessional screenwriters and script designers.