Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study

INTRODUCTION: Systemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU). METHODS: From January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis. RESULTS: A total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death. CONCLUSION: The mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU

Omics approach for generating a high-yield CHO cell line producing monoclonal antibodies

Chinese hamster ovary (CHO) cells are extensively used for the industrial manufacture of therapeutic antibodies. Generating high producing cell lines for secretory protein production requires knowing the bottleneck in the cellular machinery for protein expression. Integration site of gene of interest (GOI) is one of the important factors that influence the protein productivity. Even though screening of cells randomly integrated GOI can select high producing cells, the selected cell might not stable due to the chromosome instability. Here, we would like to look for host integration sites where GOI is high yield and stable by screening a single copy integration system. We developed several methods to identify integration sites including PCR based, whole genome sequencing based, and a platform to integrate a single copy of GOI into host genome. By determining the integration sites of the high producing clones, we can elucidate the major high yield sites for target gene expression. We have also employed the genome-editing tool, TALEN and CRISPR/cas9 to specifically integrate the vector with an antibody gene into two integration sites of CHO genome. Our data showed, IS1 and IS2 integration sites can be actively edited and specifically integrated an antibody expression vector of 15kb by either TALEN or CRISPR/Cas9. We successfully established site specifically integrated cell pools and expanded the FACS-sorted single cell into a cell line. Each single cell derived cell lines was confirmed by junction-PCR and sequence analysis. Furthermore, these single cells derived CHO cell lines are shown to express antibody gene with high titer. With the combination of omics knowledge and toolbox, including CHO genomics, transcriptomics and CHO specific microarray, GOI can be stably and highly produced

Transcriptome analysis of Dnmt3l knock-out mice derived multipotent mesenchymal stem/stromal cells during osteogenic differentiation

Multipotent mesenchymal stem/stromal cells (MSCs) exhibit great potential for cell-based therapy. Proper epigenomic signatures in MSCs are important for the maintenance and the subsequent differentiation potential. The DNA methyltransferase 3-like (DNMT3L) that was mainly expressed in the embryonic stem (ES) cells and the developing germ cells plays an important role in shaping the epigenetic landscape. Here, we report the reduced colony forming ability and impaire

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Association of <it>SELE</it> genotypes/haplotypes with sE-selectin levels in Taiwanese individuals: interactive effect of MMP9 level

Abstract Background E-selectin is implicated in various inflammatory processes and related disorders. We aimed to investigate the role of SELE-gene genotypes/haplotypes on plasma levels of MMP9 and sE-selectin in Taiwanese individuals. Methods Five hundred twenty individuals were enrolled. Seven tagging SELE single nucleotide polymorphisms were analyzed. Results SELE genotypes were found associated with MMP9 and sE-selectin levels. Multivariate analysis identified that the most significant genetic polymorphism (rs5368 genotype) was independently associated with MMP9 levels (P P = 0.0490). One SELE SNP, (rs3917406, P = 0.031) was associated with sE-selectin levels after adjusting for MMP9 and sICAM1 levels. Subgroup and interaction analysis revealed association of SELE SNP rs10800469 with sE-selectin levels only in the highest quartile of MMP9 level (P = 0.002, interaction P = 0.023). Haplotype analysis showed one haplotype (AAAAAGC) borderline associated with sE-selectin level (P = 0.0511). Conclusion SELE genotypes/haplotypes are independently associated with MMP9 and E-selectin levels in Taiwanese individuals. The associations of SELE genotypes/haplotypes with sE-selectin levels are affected by MMP9 levels.</p

Development and evaluations of the broadband ocean bottom seismometer (Yardbird-BB OBS) in Taiwan

Abstract This study focuses on developing and evaluating the broadband ocean bottom seismometer (Yardbird-BB OBS) in Taiwan. The Yardbird-BB OBS is a crucial instrument for recording seismic signals in deep-sea environments. Rigorous testing ensures optimal performance and data recording capabilities. Following assembly, the Yardbird-BB OBS undergoes a 3–6 month deployment test in the deep sea, capturing seismic signals worldwide. Data from 2016 and 2017 deployments in the Okinawa Trough analyze significant seismic events, including a magnitude 7.8 earthquake in New Zealand and a magnitude 6.3 earthquake from a North Korean nuclear test. Waveform analysis, focusing on tele-seismic events and waveform quality, assesses the OBS’s performance, highlighting successful automatic leveling adjustment. These high-quality recordings benefit research, aiding the study of plate tectonics, crustal age estimation, seafloor ambient noise determination, and earthquake location accuracy improvement. The study also details methods for verifying instrumental self-noise, dynamic range, digitization sensitivity, linearity error, clock drift, and data logger power consumption. Calibration procedures and evaluation methods provide insights into Yardbird-BB OBS performance characteristics, contributing to its understanding and enhancement for effective long-term underwater data recording and valuable scientific research

Resistance Analysis and Characterization of a Thiazole Analogue, BP008, as a Potent Hepatitis C Virus NS5A Inhibitor

Hepatitis C virus (HCV) is a global health problem, affecting approximately 3% of the world's population. The standard treatment for HCV infection is often poorly tolerated and ineffective. Therefore, the development of novel or more effective treatment strategies to treat chronic HCV infection is urgently needed. In this report, BP008, a potent small-molecule inhibitor of HCV replication, was developed from a class of compounds with thiazol core structures by means of utilizing a cell-based HCV replicon system. The compound reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC50) and selective index value of 4.1 ± 0.7 nM and >12,195, respectively. Sequencing analyses of several individual clones derived from BP008-resistant RNAs purified from cells harboring HCV1b replicon revealed that amino acid substitutions mainly within the N-terminal region (domain I) of NS5A were associated with decreased inhibitor susceptibility. Q24L, P58S, and Y93H are the key substitutions for resistance selection; F149L and V153M play the compensatory role in the replication and drug resistance processes. Moreover, BP008 displayed synergistic effects with alpha interferon (IFN-α), NS3 protease inhibitor, and NS5B polymerase inhibitor, as well as good oral bioavailability in SD rats and favorable exposure in rat liver. In summary, our results pointed to an effective small-molecule inhibitor, BP008, that potentially targets HCV NS5A. BP008 can be considered a part of a more effective therapeutic strategy for HCV in the future