Ide-cel or standard regimens in relapsed and refractory multiple myeloma

BACKGROUND: Survival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma. METHODS: In this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150×10 RESULTS: A total of 386 patients underwent randomization: 254 to ide-cel and 132 to a standard regimen. A total of 66% of the patients had triple-class-refractory disease, and 95% had daratumumab-refractory disease. At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the ide-cel group, as compared with 4.4 months in the standard-regimen group (hazard ratio for disease progression or death, 0.49; 95% confidence interval, 0.38 to 0.65; P\u3c0.001). A response occurred in 71% of the patients in the ide-cel group and in 42% of those in the standard-regimen group (P\u3c0.001); a complete response occurred in 39% and 5%, respectively. Data on overall survival were immature. Adverse events of grade 3 or 4 occurred in 93% of the patients in the ide-cel group and in 75% of those in the standard-regimen group. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88%, with 5% having an event of grade 3 or higher, and investigator-identified neurotoxic effects occurred in 15%, with 3% having an event of grade 3 or higher. CONCLUSIONS: Ide-cel therapy significantly prolonged progression-free survival and improved response as compared with standard regimens in patients with triple-class-exposed relapsed and refractory multiple myeloma who had received two to four regimens previously. The toxicity of ide-cel was consistent with previous reports. (Funded by 2seventy bio and Celgene, a Bristol-Myers Squibb company; KarMMa-3 ClinicalTrials.gov number, NCT03651128.)

Comparing Supervised Machine Learning Strategies and Linguistic Features to Search for Very Negative Opinions

In this paper, we examine the performance of several classifiers in the process of searching for very negative opinions. More precisely, we do an empirical study that analyzes the influence of three types of linguistic features (n-grams, word embeddings, and polarity lexicons) and their combinations when they are used to feed different supervised machine learning classifiers: Naive Bayes (NB), Decision Tree (DT), and Support Vector Machine (SVM). The experiments we have carried out show that SVM clearly outperforms NB and DT in all datasets by taking into account all features individually as well as their combinationsThis research was funded by project TelePares (MINECO, ref:FFI2014-51978-C2-1-R), and the Consellería de Cultura, Educación e Ordenación Universitaria (accreditation 2016-2019, ED431G/08) and the European Regional Development Fund (ERDF)S

A lexicon based method to search for extreme opinions

Studies in sentiment analysis and opinion mining have been focused on many aspects related to opinions, namely polarity classification by making use of positive, negative or neutral values. However, most studies have overlooked the identification of extreme opinions (most negative and most positive opinions) in spite of their vast significance in many applications. We use an unsupervised approach to search for extreme opinions, which is based on the automatic construction of a new lexicon containing the most negative and most positive wordsS

A computational study of two promising tweezers

A DFT study was carried out to explore the properties of two nonplanar π-conjugated systems that share dibenzo[a,e]-cyclooctatetraene (DBCOT) as a fundamental element. These systems were presented as molecules with potential use as tweezers and in optoelectronic applications due to their expected nonlinear optical effects. Structure optimizations, TD-DFT calculations, molecular orbitals and topological analysis were performed for C 36 N 2 H 18 O 4 and C 26 H 18 structures, formed by one and two 1,3,5,7- cyclooctatetraene rings, respectively, with and without the Na cation. This alkali cation was used as a model to investigate the potential of these molecules as tweezers. The results show a V-shaped structure as a minimum in the ground state for both molecules. This angular structure can trap the Na cation very effectively, especially for one of the cases. In addition, the present analysis opens new studies to explore the use of these systems as tweezers of other cations, anions or aromatic molecules that may exhibit π-stacking. The analysis of the molecular orbitals involved in the main electronic transitions allows us to propose that these systems will have interesting optical properties.Xunta de Galicia | Ref. GRC2019/24Universidade de Vigo/CISU

Is the reduced growth of the halophyte Suaeda maritima under hypoxia due to toxicity of iron or manganese?

For most plants, submergence in water is a rare occurrence, but for plants that grow on salt marshes flooding with seawater may be a twice-daily event. This is the case for plants of the halophyte Suaeda maritima, growing at low elevations on salt marshes. These plants are, however, smaller than those growing at higher elevations, where flooding is less frequent and the soil is better drained. We investigated whether the reduced growth brought about by flooding with saline water was a consequence of toxicity of manganese or iron. Seedlings of S. maritima were grown both in a sold medium (a mixture of salt-marsh mud and sand) that was either submerged twice a day or continuously flooded with half-strength seawater and in a hydroponic solution where the oxygen concentration was adjusted by bubbling with nitrogen or air. Hypoxia, reduced the growth of plants in both solid and liquid media and resuted in increases in manganese and iron in the shoots and roots. Experiments in culture solution showed that elevated levels of manganese were unlikely to be toxic, but that iron did reach toxic concentrations in flooded plants

Centralization and directional preference: an updated systematic review with synthesis of previous evidence

Background: Centralization and directional preference are common management and prognostic factors in spinal symptoms. Objective: To update the previous systematic review. Design: Systematic review to synthesis multiple aspects of centralization and directional preference. Method: Contemporary search was made of multiple databases using relevant search terms. Abstracts and titles were filtered by two authors; relevant articles were independently reviewed by two authors for content, data extraction, and quality. Results: Forty-three additional relevant articles were found. The quality of the studies, using PEDro for randomized controlled trials, was moderate or high in six out of ten RCTs; moderate or high in six out of 12 cohort studies. Prevalence of centralization was 40%, the same as the previous review. Directional preference prevalence was only 26%, much lower than the previous review; but neither clinical response was recorded in about a third of patients. Centralization and directional preference were confirmed as key positive prognostic factors, certainly in patients with low back pain, but limited evidence for patients with neck pain. There was no evidence that these might be important treatment effect modifiers. One study evaluated reliability, and found generally poor levels, despite training. Conclusions: Centralization and directional preference are worthwhile indicators of prognosis, and should be routinely examined for even in patients with chronic low back pain. But they do not occur in all patients with spinal problems, and there was no evidence that they were treatment effect modifiers

Ameloblastic neoplasia spectrum : a cross-sectional study of MMPS expression and proliferative activity

Objective. To compare the proliferation and the expression of matrix metalloproteinases (MMPs; MMP-2 and MMP-9) in solid and unicystic ameloblastomas with ameloblastic carcinomas. Study Design.Five cases of ameloblastic carcinoma (AC), 18 cases of solid ameloblastoma (SA), and seven of unicystic ameloblastoma (UA) were selected. The immunohistochemical expression of MMPs was assessed by the percentage of positive tumor cells and stained stroma. The mean argyrophilic nucleolar organizer region (AgNOR) and the percentage of cells with more than one AgNOR per nucleus were evaluated. Results. Statistically significant higher mean AgNOR was observed in AC than in SA and UA. MMP-2 was expressed similarly in tumor and stroma among groups. MMP-9 was higher in the stroma of SA than that of UA (P = .0484). Conclusions. The cell proliferation was related to the greater aggressiveness of AC. High expression of MMP-2 and MMP-9 in all lesions highlighted the importance of these enzymes in the biology of ameloblastic tumors

Stage‐structured population systems with temporally periodic delay

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115917/1/mma3424_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115917/2/mma3424.pd

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics