Shallow Subsurface Structure in the Hualien Basin and Relevance to the Damage Pattern and Fault Rupture during the 2018 Hualien Earthquake

The 2018 M[w] 6.4 Hualien earthquake generated a large peak-to-peak velocity of over 2  m/s, with a period of 3 s at the south end of the Milun fault, which resulted in the collapse of five buildings. To investigate the shallow subsurface soil structure and evaluate possible effects on the ground motion and building damage, we performed microtremor measurements in the Hualien basin. Based on the velocity structure jointly inverted from both Rayleigh-wave dispersion curves and microtremor horizontal-to-vertical spectral ratio data, we found that the shallow subsurface structure generally deepens from west to east. Close to the Milun fault, the structure becomes shallower, which is consistent with faulting during the 2018 earthquake and the long-term tectonic displacement. There is no significant variation for the site conditions in the north–south direction that can explain the large peak ground velocity in the south. As a result of the dense measurements in the heavily damaged area, where three high-rise buildings totally collapsed, these locations have the average S-wave velocity of the upper 30 m (AVs₃₀) values and are relatively high compared to the more distant area from the Meilun River. This is somewhat unusual, because lower AVs₃₀ values indicating softer ground conditions are expected close to the river. We did not find any characteristic subsurface soil structure that may contribute to the building collapses. The large 3 s pulse was probably generated by source effects, rather than subsurface soil amplification

PET-Tool: a software suite for comprehensive processing and managing of Paired-End diTag (PET) sequence data

BACKGROUND: We recently developed the Paired End diTag (PET) strategy for efficient characterization of mammalian transcriptomes and genomes. The paired end nature of short PET sequences derived from long DNA fragments raised a new set of bioinformatics challenges, including how to extract PETs from raw sequence reads, and correctly yet efficiently map PETs to reference genome sequences. To accommodate and streamline data analysis of the large volume PET sequences generated from each PET experiment, an automated PET data process pipeline is desirable. RESULTS: We designed an integrated computation program package, PET-Tool, to automatically process PET sequences and map them to the genome sequences. The Tool was implemented as a web-based application composed of four modules: the Extractor module for PET extraction; the Examiner module for analytic evaluation of PET sequence quality; the Mapper module for locating PET sequences in the genome sequences; and the ProjectManager module for data organization. The performance of PET-Tool was evaluated through the analyses of 2.7 million PET sequences. It was demonstrated that PET-Tool is accurate and efficient in extracting PET sequences and removing artifacts from large volume dataset. Using optimized mapping criteria, over 70% of quality PET sequences were mapped specifically to the genome sequences. With a 2.4 GHz LINUX machine, it takes approximately six hours to process one million PETs from extraction to mapping. CONCLUSION: The speed, accuracy, and comprehensiveness have proved that PET-Tool is an important and useful component in PET experiments, and can be extended to accommodate other related analyses of paired-end sequences. The Tool also provides user-friendly functions for data quality check and system for multi-layer data management

Mutation and Lineage Analysis of DNMT3A in BCR-ABL1-negative Chronic Myeloproliferative Neoplasms

SummaryIn addition to the JAK2 V617F mutation, somatic mutation in DNMT3A has been described in BCL-ABL1-negative myeloproliferative neoplasms (MPNs). We have screened for DNMT3A exon 23 mutations in 130 adult Taiwanese patients with chronic phase myeloproliferative neoplasms. Only one somatic DNMT3A R882H mutation was identified in one JAK2 V617F mutation-positive essential thrombocythemia patient (1/91, 1%). Both mutations were detected in the CD34+-, CD19+-, peripheral blood mononuclear cell- and granulocyte-enriched fractions, but were not detected in the CD3+-enriched fraction by lineage analysis. Our findings suggest that DNMT3A mutation is not prevalent in MPNs, and further study is needed to clarify its role in the molecular pathogenesis of myeloproliferative neoplasms

The Dipyridamole Added to Dual Antiplatelet Therapy in Cerebral Infarction After First Acute Myocardial Infarction: A Nationwide, Case-Control Study

Background and Purpose: No previous study has compared the impact of dipyridamole-based triple antiplatelet therapy on secondary stroke prevention and long-term outcomes to that of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI) and previous stroke. This study aimed to evaluate the impact of dipyridamole added to DAPT on stroke prevention and long-term outcomes in patients with cerebral infarction after first AMI.Methods: This nationwide, case-control study included 75,789 patients with cerebral infarction after first AMI. A 1:4 propensity score matching ratio was adopted based on multiple variables. Finally, the data of 4,468 patients included in the DAPT group and 1,117 patients included in the Dipyridamole-DAPT group were analyzed. Primary outcome was overall survival. Secondary outcomes were cumulative event rate of recurrent MI or stroke, and cumulative intracerebral hemorrhage (ICH) and gastrointestinal bleeding rate.Results: Long-term survival rate was comparable between the two groups (log-rank P = 0.1117), regardless of sex analyses. However, after first year, DAPT subgroup revealed better survival over DAPT-dipyridamole subgroup (log-rank P = 0.0188). In age subgroup analysis, a lower survival rate was detected in younger patients from the Dipyridamole-DAPT group after first year (log-rank P = 0.0151), but no survival difference for older patients. No benefit of Dipyridamole-DAPT was detected for patients after AMI, regardless of the myocardial infarction type. DAPT was superior to Dipyridamole-DAPT in patients who underwent percutaneous coronary intervention (PCI) (log-rank P = 0.0153) and ST elevation myocardial infarction after first year (log-rank P = 0.0019). Dipyridamole-DAPT did not reduce cumulative event rate of recurrent MI or stroke in patients after AMI. Moreover, Dipyridamole-DAPT increased the cumulative ICH rate (log-rank P = 0.0026), but did not affect the cumulative event rate of gastrointestinal bleeding. In Cox analysis, dipyridamole did not improve long-term survival.Conclusions: This nationwide study showed that Dipyridamole-DAPT, compared with DAPT, did not improve long-term survival in patients with stroke after AMI, and was related to poor outcomes after 1 year. Dipyridamole-DAPT did not reduce recurrent rate of MI or stroke, but increased the ICH rate without impacting the incidence of gastrointestinal bleeding

Genetic Knock-Down of Hdac3 Does Not Modify Disease-Related Phenotypes in a Mouse Model of Huntington's Disease

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expansion of a CAG/polyglutamine repeat for which there are no disease modifying treatments. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression and has been recapitulated across multiple HD models. Altered histone acetylation has been proposed to underlie this transcriptional dysregulation and histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA), have been shown to improve polyglutamine-dependent phenotypes in numerous HD models. However potent pan-HDAC inhibitors such as SAHA display toxic side-effects. To better understand the mechanism underlying this potential therapeutic benefit and to dissociate the beneficial and toxic effects of SAHA, we set out to identify the specific HDAC(s) involved in this process. For this purpose, we are exploring the effect of the genetic reduction of specific HDACs on HD-related phenotypes in the R6/2 mouse model of HD. The study presented here focuses on HDAC3, which, as a class I HDAC, is one of the preferred targets of SAHA and is directly involved in histone deacetylation. To evaluate a potential benefit of Hdac3 genetic reduction in R6/2, we generated a mouse carrying a critical deletion in the Hdac3 gene. We confirmed that the complete knock-out of Hdac3 is embryonic lethal. To test the effects of HDAC3 inhibition, we used Hdac3+/− heterozygotes to reduce nuclear HDAC3 levels in R6/2 mice. We found that Hdac3 knock-down does not ameliorate physiological or behavioural phenotypes and has no effect on molecular changes including dysregulated transcripts. We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD

Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

<p>Abstract</p> <p>Background</p> <p>Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET) approach to investigate the melanoma transcriptome and characterize the global pathway aberrations.</p> <p>Methods</p> <p>GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo). Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes.</p> <p>Results</p> <p>Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg⁺⁺, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain region(s) of the pathway. Expression levels of c-<it>Myc </it>and <it>Trp53 </it>were also higher in melanoma. Moreover, transcriptional variants resulted from alternative transcription start sites or alternative polyadenylation sites were found in <it>Ras </it>and genes encoding adhesion or cytoskeleton proteins such as integrin, β-catenin, α-catenin, and actin.</p> <p>Conclusion</p> <p>The highly correlated results unmistakably point to a systematic downregulation of mitochondrial activities, which we hypothesize aims to downgrade the mitochondria-mediated apoptosis and the dependency of cancer cells on angiogenesis. Our results also demonstrate the advantage of using the PET approach in conjunction with KEGG database for systematic pathway analysis.</p

The open abdomen in trauma and non-trauma patients : WSES guidelines

Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a "planned second-look" laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented.Peer reviewe