Abstract Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European ...Dermatology Forum, the European Association of Dermato-Oncology and the European Organisation of Research and Treatment of Cancer was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically using dermoscopy and staging is based upon the AJCC system. CMs are excised with 1–2 cm safety margins. Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours >1 mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies should be considered. BRAF inhibitors like dabrafenib and vemurafenib in combination with the MEK inhibitors trametinib and cobimetinib for BRAF mutated patients should be offered as first or second line treatment. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team (‘Tumour Board’).
Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed ...serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases.
•FAST acquires whole-brain subcellular resolution images with unprecedented speed•FAST is scalable to non-human primate brains and human postmortem brain tissues•FAST renders unbiased group comparisons of the whole-brain high-resolution images
Seiriki et al. developed a very high-speed serial-sectioning imaging system named FAST that allows whole-brain imaging at a spatial resolution to image all brain cells and long-range neuronal projections in experimental animal models and facilitates animal-to-human translational research.
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Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) ...methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development.
Spinal metastases are becoming increasingly common because patients with metastatic disease are living longer. The close proximity of the spinal cord to the vertebral column limits many conventional ...therapeutic options that can otherwise be used to treat cancer. In response to this problem, an innovative multidisciplinary approach has been developed for the management of spinal metastases, leveraging the capabilities of image-guided stereotactic radiosurgery, separation surgery, vertebroplasty, and minimally invasive local ablative approaches. In this Review, we discuss the variables that should be considered during the management of these patients and review the role of each discipline and their respective management options to provide optimal care. This work is synthesised into a practical algorithm to aid clinicians in the management of patients with spinal metastasis.
Minimally invasive thoracic surgery causes significant postoperative pain. Erector spinae plane (ESP) block and serratus anterior plane (SAP) block promise effective thoracic analgesia compared with ...systemically administered opioids, but have never been compared in terms of terms of quality of recovery and overall morbidity after minimally invasive thoracic surgery.
Sixty adult patients undergoing minimally invasive thoracic surgery were randomly assigned to receive either single-shot ESP or SAP block before surgery using levobupivacaine 0.25%, 30 ml. The primary outcome was quality of patient recovery at 24 h, using the Quality of Recovery-15 (QoR-15) scale. Secondary outcomes included area under the curve (AUC) of pain verbal rating scale (VRS) over time, time to first opioid analgesia, postoperative 24 h opioid consumption, in-hospital comprehensive complication index (CCI) score and hospital stay.
The QoR-15 score was higher among ESP patients compared with those in the SAP group, mean (standard deviation): 114 (16) vs 102 (22) (P=0.02). Time (min) to first i.v. opioid analgesia in recovery was 32.6 (20.6) in ESP vs 12.7 (9.5) in SAP (P=0.003). AUC at rest was 92 (31) mm h−1vs 112 (35) in ESP and SAP (P=0.03), respectively, whereas AUC on deep inspiration was 107 mm h−1 (32) vs 129 (32) in ESP and SAP (P=0.01), respectively. VRS pain on movement in ESP and SAP at 24 h was, median (25–75% range): 4 (2–4) vs 5 (3–6) (P=0.04), respectively. Opioid consumption at 24 h postoperatively was 29 (31) vs 39 (34) (P=0.37). Median (25–75%) CCI in ESP and SAP was 1 (0–2) vs 4 (0–26) (P=0.03), whereas hospital stay was 3 (2–6) vs 6 (3–9) days (P=0.17), respectively.
Compared with SAP, ESP provides superior quality of recovery at 24 h, lower morbidity, and better analgesia after minimally invasive thoracic surgery.
NCT 03862612.
Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non-small cell lung cancer (NSCLC). Screening ...has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic.
A guide to large-scale RNA sample preparation Baronti, Lorenzo; Karlsson, Hampus; Marušič, Maja ...
Analytical and bioanalytical chemistry,
05/2018, Letnik:
410, Številka:
14
Journal Article
Recenzirano
Odprti dostop
RNA is becoming more important as an increasing number of functions, both regulatory and enzymatic, are being discovered on a daily basis. As the RNA boom has just begun, most techniques are still in ...development and changes occur frequently. To understand RNA functions, revealing the structure of RNA is of utmost importance, which requires sample preparation. We review the latest methods to produce and purify a variation of RNA molecules for different purposes with the main focus on structural biology and biophysics. We present a guide aimed at identifying the most suitable method for your RNA and your biological question and highlighting the advantages of different methods.
Graphical abstract
In this review we present different methods for large-scale production and purification of RNAs for structural and biophysical studies
Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized ...and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and side effect prediction. The software and benchmark are available at https://github.com/hansaimlim/REMAP.
Hyphenated full-scan MS technology creates large amounts of data. A versatile easy to handle automation tool aiding in the data analysis is very important in handling such a data stream. MetAlign ...softwareas described in this manuscripthandles a broad range of accurate mass and nominal mass GC/MS and LC/MS data. It is capable of automatic format conversions, accurate mass calculations, baseline corrections, peak-picking, saturation and mass-peak artifact filtering, as well as alignment of up to 1000 data sets. A 100 to 1000-fold data reduction is achieved. MetAlign software output is compatible with most multivariate statistics programs.
Abstract
The Genome Database for Rosaceae (GDR, https://www.rosaceae.org) is an integrated web-based community database resource providing access to publicly available genomics, genetics and breeding ...data and data-mining tools to facilitate basic, translational and applied research in Rosaceae. The volume of data in GDR has increased greatly over the last 5 years. The GDR now houses multiple versions of whole genome assembly and annotation data from 14 species, made available by recent advances in sequencing technology. Annotated and searchable reference transcriptomes, RefTrans, combining peer-reviewed published RNA-Seq as well as EST datasets, are newly available for major crop species. Significantly more quantitative trait loci, genetic maps and markers are available in MapViewer, a new visualization tool that better integrates with other pages in GDR. Pathways can be accessed through the new GDR Cyc Pathways databases, and synteny among the newest genome assemblies from eight species can be viewed through the new synteny browser, SynView. Collated single-nucleotide polymorphism diversity data and phenotypic data from publicly available breeding datasets are integrated with other relevant data. Also, the new Breeding Information Management System allows breeders to upload, manage and analyze their private breeding data within the secure GDR server with an option to release data publicly.
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