Glycerol is a valuable byproduct in biodiesel production by transesterification, soap manufacturing by saponification as well as hydrolysis reaction. The purity of glycerol obtained is low due to the ...presence of impurities such as remaining catalyst, water, soaps, salts and esters formed during the reaction. Purification of glycerol as well as the conversion of glycerol into valuable products has attained growing interest in recent years due to the dramatic growth of the biodiesel industry. This paper reviews different methods of producing crude glycerol as the major by-product. Purification of glycerol was reported as well as value-added products produced from glycerol.
Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later ...line of treatment for patients with mTNBC.
Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1–positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival.
All enrolled patients (N = 170) were women, 61.8% had PD-L1–positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7–9.9) in the total and 5.7% (2.4–12.2) in the PD-L1–positive populations. Disease control rate (95% CI) was 7.6% (4.4–12.7) and 9.5% (5.1–16.8), respectively. Median duration of response was not reached in the total (range, 1.2+–21.5+) and in the PD-L1–positive (range, 6.3–21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9–2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6–11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs.
Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile.
ClinicalTrials.gov, NCT02447003
Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II ...KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC.
Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival.
All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9–31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9–34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0–2.2), and median overall survival was 18.0 months (95% CI 12.9–23.0).
Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC.
ClinicalTrials.gov, NCT02447003.
Genera of phytopathogenic fungi: GOPHY 1 Marin-Felix, Y.; Groenewald, J.Z.; Cai, L. ...
Studies in mycology,
March 2017, 20170301, 2017-Mar, 2017-03-01, Volume:
86, Issue:
1
Journal Article
Peer reviewed
Open access
Genera of Phytopathogenic Fungi (GOPHY) is introduced as a new series of publications in order to provide a stable platform for the taxonomy of phytopathogenic fungi. This first paper focuses on 21 ...genera of phytopathogenic fungi: Bipolaris, Boeremia, Calonectria, Ceratocystis, Cladosporium, Colletotrichum, Coniella, Curvularia, Monilinia, Neofabraea, Neofusicoccum, Pilidium, Pleiochaeta, Plenodomus, Protostegia, Pseudopyricularia, Puccinia, Saccharata, Thyrostroma, Venturia and Wilsonomyces. For each genus, a morphological description and information about its pathology, distribution, hosts and disease symptoms are provided. In addition, this information is linked to primary and secondary DNA barcodes of the presently accepted species, and relevant literature. Moreover, several novelties are introduced, i.e. new genera, species and combinations, and neo-, lecto- and epitypes designated to provide a stable taxonomy. This first paper includes one new genus, 26 new species, ten new combinations, and four typifications of older names.
Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a ...riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.
Summary
Background
Plasma and other body fluids contain membranous extracellular vesicles (EVs), which are considered to derive from activated or apoptotic cells. EVs participate in physiological and ...pathological processes and have potential applications in diagnostics or therapeutics. Knowledge on EVs is, however, limited, mainly due to their sub‐micrometer size and to intrinsic limitations in methods applied for their characterization.
Objectives
Our aim was to provide a comprehensive description of EVs from plasma of healthy subjects.
Methods
Cryo‐transmission electron microscopy combined with receptor‐specific gold labeling was used to reveal the morphology, size and phenotype of EVs. An original approach based on sedimentation on electron microscopy grids was developed for enumerating EVs. A correlation was performed between conventional flow cytometry and electron microscopy results.
Results
We show that platelet‐free plasma samples contain spherical EVs, 30 nm to 1 μm in diameter, tubular EVs, 1–5 μm long, and membrane fragments, 1–8 μm large. We show that only a minority of EVs expose the procoagulant lipid phosphatidylserine, in contrast to the classical theory of EV formation. In addition, the concentrations of the main EV sub‐populations are determined after sedimentation on EM grids. Finally, we show that conventional flow cytometry, the main method of EV characterization, detects only about 1% of them.
Conclusion
This study brings novel insights on EVs from normal plasma and provides a reference for further studies of EVs in disease situations.
Heterochromatin spreading, the expansion of repressive chromatin structure from sequence-specific nucleation sites, is critical for stable gene silencing. Spreading re-establishes gene-poor ...constitutive heterochromatin across cell cycles but can also invade gene-rich euchromatin de novo to steer cell fate decisions. How chromatin context (i.e. euchromatic, heterochromatic) or different nucleation pathways influence heterochromatin spreading remains poorly understood. Previously, we developed a single-cell sensor in fission yeast that can separately record heterochromatic gene silencing at nucleation sequences and distal sites. Here we couple our quantitative assay to a genetic screen to identify genes encoding nuclear factors linked to the regulation of heterochromatin nucleation and the distal spreading of gene silencing. We find that mechanisms underlying gene silencing distal to a nucleation site differ by chromatin context. For example, Clr6 histone deacetylase complexes containing the Fkh2 transcription factor are specifically required for heterochromatin spreading at constitutive sites. Fkh2 recruits Clr6 to nucleation-distal chromatin sites in such contexts. In addition, we find that a number of chromatin remodeling complexes antagonize nucleation-distal gene silencing. Our results separate the regulation of heterochromatic gene silencing at nucleation versus distal sites and show that it is controlled by context-dependent mechanisms. The results of our genetic analysis constitute a broad community resource that will support further analysis of the mechanisms underlying the spread of epigenetic silencing along chromatin.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) ...was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.
Background
Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) have better prognosis and treatment response compared to HPV‐negative OPSCC. This study aims to ...noninvasively predict HPV status of OPSCC using clinical and/or radiological variables.
Methods
Seventy‐seven magnetic resonance radiomic features were extracted from T1‐weighted postcontrast images of the primary tumor of 153 patients. Logistic regression models were created to predict HPV status, determined with immunohistochemistry, based on clinical variables, radiomic features, and its combination. Model performance was evaluated using area under the curve (AUC).
Results
Model performance showed AUCs of 0.794, 0.764, and 0.871 for the clinical, radiomic, and combined models, respectively. Smoking, higher T‐classification (T3 and T4), larger, less round, and heterogeneous tumors were associated with HPV‐negative tumors.
Conclusion
Models based on clinical variables and/or radiomic tumor features can predict HPV status in OPSCC patients with good performance and can be considered when HPV testing is not available.
Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still ...heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse.
The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort.
Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS hazard ratio (HR) 5.1; P < 0.0001. The median OS of high- and low-risk groups were 10.2 95% confidence interval (CI) of 6.5 and 13.2 months and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings.
These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.
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