Newly developed post-operative atrial fibrillation is associated with an increased risk of late recurrence of atrial fibrillation in patients who underwent open heart surgery: Long-term follow up

Background: Herein is sought to determine whether the occurrence of post-operative atrial fibrillation (POAF) increases the risk of late recurrence of atrial fibrillation (AF) in patients undergoing open heart surgery (OHS). Methods: This study included 938 patients (56.7 ± 13.1 years old, 550 males) with no history of AF who underwent OHS. All patients were monitored continuously for development of POAF after surgery until the time of hospital discharge and received clinical follow up with serial evaluation of rhythm status. Results: Among the total population, POAF occurred in 207 (22.1%) patients and late AF in 88 (9.4%) patients during the mean follow up period of 78.1 ± 39.1 months. Development of late AF oc¬curred more frequently in patients with POAF than in those without [29.0% (60/207) vs. 3.8% (28/731), p < 0.01]. Higher septal E/e’ ratio (HR 1.04, 95% CI 1.00–1.08, p = 0.04) was an independent predic¬tor of late occurrence of AF and an episode of POAF (HR 27.12, 95% CI 8.46–86.96, p < 0.01) was the most powerful predictor. Conclusions: POAF is significantly associated with an increased risk of late AF recurrence during long-term follow up. Careful concern regarding late recurrence of AF with serial evaluation of rhythm status is required in patients with POAF

Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family

BACKGROUND: The genetic heterogeneity of sensorineural hearing loss is a major hurdle to the efficient discovery of disease-causing genes. We designed a multiphasic analysis of copy number variation (CNV), linkage, and single nucleotide variation (SNV) of whole exome sequencing (WES) data for the efficient discovery of mutations causing nonsyndromic hearing loss (NSHL). RESULTS: From WES data, we identified five distinct CNV loci from a NSHL family, but they were not co-segregated among patients. Linkage analysis based on SNVs identified six candidate loci (logarithm of odds [LOD] >1.5). We selected 15 SNVs that co-segregated with NSHL in the family, which were located in six linkage candidate loci. Finally, the novel variant p.M305T in ACTG1 (DFNA20/26) was selected as a disease-causing variant. CONCLUSIONS: Here, we present a multiphasic CNV, linkage, and SNV analysis of WES data for the identification of a candidate mutation causing NSHL. Our stepwise, multiphasic approach enabled us to expedite the discovery of disease-causing variants from a large number of patient variants

Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer

Tumor heterogeneity influences the clinical outcome of patients with cancer, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six patients with lung cancer using whole-exome sequencing and RNA sequencing. Although somatic single-nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomic location of the tumors. Four of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer. Cancer Res; 76(22); 6568-76. ©2016 AACR

Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients.

Targeted deep sequencing across broad genomic regions has been used to detect circulating tumor DNA (ctDNA) in pancreatic ductal adenocarcinoma (PDAC) patients. However, since most PDACs harbor a mutation in KRAS, sequencing of broad regions needs to be systemically compared to analyzing only KRAS mutations for PDAC. Using capture-based targeted deep sequencing, we detected somatic tumor mutations in 17 fine needle aspiration biopsy and 69 longitudinal cell-free DNA (cfDNA) samples from 17 PDAC patients. KRAS mutations were detected in 10 out of 17 pretreatment patient plasma samples. Next, interrogation of genetic alterations in matched primary tumor samples detected ctDNA in 12 of 17 pretreatment plasma samples and cfDNA sequencing across the 83 target genes identified ctDNA in 15 of 17 cases (88.2% sensitivity). This improved sensitivity of ctDNA detection resulted in enhanced tumor burden monitoring when we analyzed longitudinal plasma samples. We found that cfDNA sequencing detected the lowest mutant allelic fractions and number of variants when complete response or partial response to chemotherapy was achieved. We demonstrated that ctDNA levels measured by targeted deep sequencing sensitively indicate the presence of cancer and correlate well with clinical responses to therapy and disease progression in PDAC patients

Influence of terahertz waves on the fiber direction of CFRP composite laminates

The importance of Carbon-fiber reinforced plastics (CFRP) are widely utilized due to more high performance in engineering structures. It was well known that a nondestructive technique would be very beneficial. A new terahertz radiation has been recognized for their importance in technological applications. Recently, T-ray (terahertz ray) advances of technology and instrumentation has provided a probing field on the electromagnetic spectrum. The THz-TDS can be considered as a useful tool using general non-conducting materials; however it is quite limited to conducting materials. In order to solve various material properties, the index of refraction (n) and the absorption coefficient (α) are derived in reflective and transmission configuration using the terahertz time domain spectroscopy. However, the T-ray is limited in order to penetrate a conducting material to some degree. Here, the T-ray would not go through easily the CFRP composite laminates since carbon fibers are electrically conducting while the epoxy matrix is not. So, investigation of terahertz time domain spectroscopy (THz TDS) was made and reflection and transmission configurations were studied for a 48-ply thermoplastic PPS (poly-phenylene sulfide)-based CFRP solid laminate. It is found that the electrical conductivity of CFRP composites depends on the direction of unidirectional fibers. Also, the T-ray could penetrate a CFRP composite laminate a few ply based on the E-filed (Electrical field) of carbon fibers. The terahertz scanning images were made at the angles ranged from 0° to 180° with respect to the nominal fiber axis. So, the images were mapped out based on the electrical field (E-field) direction in the CFRP solid laminates. Also, using two-dimensional spatial Fourier transform, interface C-scan images were transformed into quantitatively angular distribution plots to show the fiber orientation information therein and to predict the orientation of the ply

Pathological hypersexuality induced by dopamine replacement therapy in a patient with progressive supranuclear palsy

To the Editor: The pathogenesis of pathological hypersexuality is still in controversy. To our knowledge, this is the first report of pathological hypersexuality induced by two different dopamine receptor agonists in a single patient with progressive supranuclear palsy. In this case, dopamine D2 receptor agonism, perhaps specifically D3 receptor subclass agonism, might have played a key role in the development of pathological hypersexuality induced by dopamine replacement therapy

Exploiting Binary Abstractions in Deciphering Gene Interactions

We consider computationally reconstructing gene regulatory networks on top of the binary abstraction of gene expression state information. Unlike previous Boolean network approaches, the proposed method does not handle noisy gene expression values directly. Instead, two-valued "hidden state" information is derived from gene expression profiles using a robust statistical technique, and a gene interaction network is inferred from this hidden state information. In particular, we exploit Espresso, a well-known 2-level Boolean logic optimizer in order to determine the core network structure. The resulting gene interaction networks can be viewed as dynamic Bayesian networks, which have key advantages over more conventional Bayesian networks in terms of biological phenomena that can be represented. The authors tested the proposed method with a time-course gene expression data set from microarray experiments on anti-cancer drugs doxorubicin and paclitaxel. A gene interaction network was produced by our method, and the identified genes were validated with a public annotation database. The experimental studies we conducted suggest that the proposed method inspired by engineering systems can be a very effective tool to decipher complex gene interactions in living system

Myotonic Dystrophy Type 1 Presenting as Male Infertility

Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia and azoospermia, and increased follicle-stimulating hormone levels. We describe a rare case of DM1 presenting as infertility in a 29-year-old man