Improved bacterial nanocellulose production by co-cultivation

Bacterial cellulose has high degree of crystallinity, high purity, excellent water-binding properties and good shape retention advantages, compared to plant cellulose, and it has many potential applications in various industries. The gluconic acid, a by-product produced during BC production, can decrease the pH of cultivation that leads to low BC yield by Komagataeibacter xylinus. Thus, maintaining the pH of cultivation for BC production was important and urgent task. In this study, the Acinetobacter baylyi ADP1gcd was employed to co-cultivate with K. xylinus, which aimed to well control the pH suitable for BC production by consuming the gluconic acid accumulation during static cultivation. The K. xylinus engineered type (pABCD) and wild type (WT) was proved to be able to produce BC in MA/9 medium. And the pABCD produced 2-fold more BC production than that of WT in MA/9 medium after 5 days. pABCD and WT obtained lower BC productivity in MA/9 medium than that in HS medium. The effect of different concentration glucose addition for growth of pABCD and BC production was also investigated in this study. The highest BC production on 2% glucose addition was around 0.267 g/L produced by pABCD after 5 days cultivation in MA/9 medium, and followed by 5% glucose (0.266 g/L), 1% glucose (0.2 g/L), 3.5% glucose (0.167 g/L) and 0.5% glucose (0.133 g/L). So, the BC productivity of pABCD increased with the increasing of glucose concentration until 2% in MA/9 medium. Moreover, the effect of arabinose (1%) and initial inoculate volume for BC production was studied. The presence of arabinose (1%) was proved to be able to achieve an in-crease of BC biosynthesis in MA/9 medium by inducing overexpression of bcs operon in pABCD strains. It yielded 0.267 g/L BC, which was 2-fold higher than that of arabi-nose absence. And the initial inoculate volume (OD600=0.02 or 0.04) of pABCD has no significant effect on the final BC productivity in MA/9 medium. The maximum concentration of gluconic acid consumed by A. baylyi ADP1gcd was about 80 mM in MA/9 medium. It was demonstrated that A. baylyi ADP1gcd was able to utilize all gluconic acid accumulated in MA/9 medium supplemented with glucose (2%) after 5 days cultivation. Finally, the pH of co-cultivation was maintained at optimized range (5.0-7.0), compared to that of pABCD pure cultivation group (below 4.0). However, the co-cultivation with and without 50 ug/ml chloramphenicol addition, yield approximately 0.267 g/L and 0.1667 g/L BC after 5 days cultivation, respectively, which was much less than that of pABCD pure cultivation group. The A. baylyi ADP1gcd helped in eliminating the gluconic acid and maintaining pH, but the glucose consumption was lower in co-cultivation than in pABCD pure cultivation. This phenomenon is interesting and will be a subject of future study

Seizure outcome after switching antiepileptic drugs: A matched, prospective study.

OBJECTIVE: Outcomes after changing antiepileptic drugs (AEDs) have largely been studied in single cohort series. We recently reported the first study to examine this question in a controlled manner. Here we expand on these results by using a matched, prospective methodology applied to both uncontrolled and well-controlled patients taking any AED. METHODS: We reviewed all outpatient notes over a 9-month period and identified patients with focal epilepsy who were on monotherapy. We classified those who switched AEDs as case patients, with those remaining on the same drug serving as controls. We matched cases with controls for seizure status (seizure-free in the preceding 6 months or not), current AED, and number of failed AEDs. We subsequently assessed outcome 6 months later. RESULTS: Seizure-free patients who switched drug (n = 12) had a 16.7% rate of seizure recurrence at 6 months, compared to 2.8% among controls remaining on the same drug (n = 36, p = 0.11). There was a 37% remission rate among uncontrolled patients who switched drug compared to 55.6% among controls (n = 27 per group, p = 0.18). Uncontrolled patients who had previously tried more than one AED were somewhat less likely to enter remission (p = 0.057). Neither AED mechanism of action nor change in dosage impacted outcome. SIGNIFICANCE: Herein we provide further estimation of the modest risk (~14%) associated with switching AEDs in patients in remission compared to being maintained on the same regimen. Uncontrolled patients were no more likely to enter remission after a drug switch than they were after remaining on the same drug, suggesting that spontaneous changes in disease state, and not drug response, underlie remission in this population

Recognition of Multiomics-Based Molecule-Pattern Biomarker for Precise Prediction, Diagnosis, and Prognostic Assessment in Cancer

Cancer is a complex whole-body chronic disease, is involved in multiple causes, multiple processes, and multiple consequences, which are associated with a series of molecular alterations in the different levels of genome, transcriptome, proteome, metabolome, and radiome, with between-molecule mutual interactions. Those molecule-panels are the important resources to recognize the reliable molecular pattern biomarkers for precise prediction, diagnosis, and prognostic assessment in cancer. Pattern recognition is an effective methodology to identify those molecule-panels. The rapid development of computation biology, systems biology, and multiomics is driving the development of pattern recognition to discover reliable molecular pattern biomarkers for cancer treatment. This book chapter addresses the concept of pattern recognition and pattern biomarkers, status of multiomics-based molecular patterns, and future perspective in prediction, diagnosis, and prognostic assessment of a cancer

Research on systemic risk contagion of Chinese financial institutions based on GARCH-VMD-Copula-CoVaR model

With the development of China’s financial market, the risk contagion effect among financial institutions is increasing and becoming more complicated. Few literatures have explored the risk transmission paths of Chinese financial institutions at different frequencies. In order to make up for the gaps in this research field, variable mode decomposition (VMD) technology is introduced in this paper, combined with the Copula-GARCH model to construct the GARCH-VMD-Copula-CoVaR model, which describes the risk contagion paths of major financial institutions in the Chinese financial market at different frequencies (long-term, medium-term and short-term). The research results show that risk dependence and contagion between financial institutions have the characteristics of bidirectionality, asymmetry and time-varying in all frequency studies, and there are differences in different frequencies

Falls and Traumatic Brain Injury in the Elderly on Aspirin or Anticoagulant Therapy

Introduction: Traumatic brain injury (TBI) after a fall in individuals aged 65 and older is a leading cause of morbidity and mortality, but the effect of aspirin and anticoagulant therapy on TBI severity is not fully understood. This study evaluated whether the severity of TBI is associated with use of aspirin or anticoagulant therapy or in combination. Methods: Using retrospective chart review, we identified patients age 65 or older who fell and sustained head trauma that were admitted to Thomas Jefferson University Hospital trauma service from 2017-2018. Based on final diagnosis, patients were classified into three groups of TBI in order of increasing severity: mild TBI, extra-axial hemorrhage, and intra-axial hemorrhage. ANOVA and regression analysis will be used to compare use of aspirin, anticoagulant therapy, both in combination, or neither in the three groups. Results: We hypothesize that patients with more severe head trauma will have increased use of aspirin or anticoagulant therapy or both in combination compared to patients who are on neither aspirin nor anticoagulant therapy. Preliminary results show patients with any diagnosis of TBI were more likely to be on aspirin compared to controls (OR 1.74, p\u3c0.001). Patients with any diagnosis of TBI and anticoagulant therapy had no statistical significant association compared to controls (OR 1.25, p=0.25). Discussion: These findings will guide the understanding of how aspirin and anticoagulant therapy affect severity of TBI. Judicious use of aspirin and anticoagulant therapy in the elderly who are at risk of falling may reduce the incidence of severe TBI

Target of Rapamycin Regulates Photosynthesis and Cell Growth in Auxenochlorella pyrenoidosa

Auxenochlorella pyrenoidosa is an efficient photosynthetic microalga with autotrophic growth and reproduction, which has the advantages of rich nutrition and high protein content. Target of rapamycin (TOR) is a conserved protein kinase in eukaryotes both structurally and functionally, but little is known about the TOR signalling in Auxenochlorella pyrenoidosa. Here, we found a conserved ApTOR protein in Auxenochlorella pyrenoidosa, and the key components of TOR complex 1 (TORC1) were present, while the components RICTOR and SIN1 of the TORC2 were absent in Auxenochlorella pyrenoidosa. Drug sensitivity experiments showed that AZD8055 could effectively inhibit the growth of Auxenochlorella pyrenoidosa, whereas rapamycin, Torin1 and KU0063794 had no obvious effect on the growth of Auxenochlorella pyrenoidosa a. Transcriptome data results indicated that Auxenochlorella pyrenoidosa TOR (ApTOR) regulates various intracellular metabolism and signaling pathways in Auxenochlorella pyrenoidosa. Most genes related to chloroplast development and photosynthesis were significantly down-regulated under ApTOR inhibition by AZD8055. In addition, ApTOR was involved in regulating protein synthesis and catabolism by multiple metabolic pathways in Auxenochlorella pyrenoidosa. Importantly, the inhibition of ApTOR by AZD8055 disrupted the normal carbon and nitrogen metabolism, protein and fatty acid metabolism, and TCA cycle of Auxenochlorella pyrenoidosa cells, thus inhibiting the growth of Auxenochlorella pyrenoidosa. These RNA-seq results indicated that ApTOR plays important roles in photosynthesis, intracellular metabolism and cell growth, and provided some insights into the function of ApTOR in Auxenochlorella pyrenoidosa

Sudden Hearing Loss: WRS Importance and Timing of Medical Intervention

Objective: The aim of this study was to evaluate recovery in hearing acuity of idiopathic sudden sensorineural hearing loss (ISSNHL) based on timing of onset to determine how late is too late to medically intervene. Study Design: A retrospective chart review was conducted in patients previously treated for primary complaint of sudden hearing loss (HL). Participants meeting inclusion criteria were analyzed based on timing of onset to service date, age, gender, associated ear, associated symptoms as well as recovery in pure tone average (PTA) and recovery in word recognition scores (WRS). Setting: All patients seeking treatment for SSNHL were seen in a hospital/medical setting by otolaryngologists/otologists. Methods: Utilizing the hospital’s medical record system, an initial sample of 696 participants treated for ISSNHL from 2016-2019 was collected. Of the 696 participants, 161 met the inclusion criteria and were analyzed. Results: Timing of symptoms onset to treatment initiation as well as recovery detail were statistically significant in recovery anticipation. Conclusion: Pure tone average (PTA) and word recognition score (WRS) recovery two variables analyzed as part of hearing recovery based on symptom onset to treatment initiation. Of the recovered participants, 14.9% and 42.2% experienced with BothRecovery or EitherReocvery respectively. Recovery detail, especially WRS recovery, is a key variable which should be analyzed when anticipating recovery of symptoms. WRS recovery was also identified in participants who sought treatment after 42 days of onset, suggesting recovery is possible beyond clinical guidelines set by the American Academy of Otolaryngology-Head and Neck Surgery (AAO).https://jdc.jefferson.edu/ariaposters/1002/thumbnail.jp

Research progress on biochar-based material adsorption and removal of ibuprofen

Ibuprofen, commonly used for pain relief, inflammation, and to reduce high fever, etc., is a widely available over-the-counter drug. In recent years, due to the excessive use of ibuprofen, its presence in the aquatic environments has shown a significant increasing trend, raising concerns about potential risks to environmental safety, which attracted people’s close attention. Notably, biochar, known as an environmentally friendly functional material, had been widely studied and applied for the removal of ibuprofen in water environments. According to current reports, the adsorption capacity value of biochar for IBP is between 9.69–309 mg/g, and the adsorption mechanism mainly includes π-π stacking, hydrogen bonding, pore filling, etc. In response to this research hotspot, this study reviewed the most recent research progress on the adsorption of ibuprofen using biochar-based materials, including the modified preparation process of biochar and the adsorption mechanism of IBP on various modified biochar surfaces. Additionally, potential challenges and future development directions for the practical applications of biochar were discussed and proposed

DRIVE: Dockerfile Rule Mining and Violation Detection

A Dockerfile defines a set of instructions to build Docker images, which can then be instantiated to support containerized applications. Recent studies have revealed a considerable amount of quality issues with Dockerfiles. In this paper, we propose a novel approach DRIVE (Dockerfiles Rule mIning and Violation dEtection) to mine implicit rules and detect potential violations of such rules in Dockerfiles. DRIVE firstly parses Dockerfiles and transforms them to an intermediate representation. It then leverages an efficient sequential pattern mining algorithm to extract potential patterns. With heuristic-based reduction and moderate human intervention, potential rules are identified, which can then be utilized to detect potential violations of Dockerfiles. DRIVE identifies 34 semantic rules and 19 syntactic rules including 9 new semantic rules which have not been reported elsewhere. Extensive experiments on real-world Dockerfiles demonstrate the efficacy of our approach

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.

Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy. Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity of subjects as joint primary outcomes. Results: All patients receiving Ad5-GUCY2C-PADRE completed the study and none developed adverse events greater than grade 1. Antibody responses to GUCY2C were detected in 10% of patients, while 40% exhibited GUCY2C-specific T-cell responses. GUCY2C-specific responses were exclusively CD8+ cytotoxic T cells, mimicking pre-clinical studies in mice in which GUCY2C-specific CD4+ T cells are eliminated by self-tolerance, while CD8+ T cells escape tolerance and mediate antitumor immunity. Moreover, pre-existing neutralizing antibodies (NAbs) to the Ad5 vector were associated with poor vaccine-induced responses, suggesting that Ad5 NAbs oppose GUCY2C immune responses to the vaccine in patients and supported by mouse studies. Conclusions: Split tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector. TRIAL REGISTRATION: This trial (NCT01972737) was registered at ClinicalTrials.gov on October 30th, 2013. https://clinicaltrials.gov/ct2/show/NCT01972737