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ARS-CoV-2-specific IgG antibody detection do not differ between cancer patients and healthy subjects.Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.

In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel.

Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divitment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting.

Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting.

This study aimed to investigate the predictors for high data retrieval and the reporting of individual participant data meta-analyses (IPDMAs).

We searched EMBASE, MEDLINE, and the Cochrane Library for articles pertaining to IPDMA from 2011 to 2019. Only IPDMA assessing treatment effects, including randomized controlled trials (RCTs), were included. Adherence to the PRISMA-IPD guideline was checked.

A total of 210 IPDMA covering 18 diseases were sampled; 80 (38.1%) and 123 (58.6%) of the IPDMA retrieved IPD from all and ≥80% RCTs, respectively. Non-Cochrane reviews, IPDMA on nonpharmacological interventions, analyses of smaller numbers of RCTs, and having funding supports were predictors of complete IPD retrieval. Owners of RCTs had an increased probability of obtaining IPD. Only 4.3% described the eligibility criteria covering all the PICO components, 11.0% reported the methods for assessing risk of bias across studies, 11.4% mentioned the IPD integrity, and 9.0% presented detailed results of syntheses.

IPD retrieval and reporting was not satisfactory among the published IPDMA. Encouraging RCT owners to conduct or join in the IPDMA is a potential strategy to maximize the IPD retrieval. IPDMA are suggested to adhere to the PRISMA-IPD guideline during reporting.

IPD retrieval and reporting was not satisfactory among the published IPDMA. Encouraging RCT owners to conduct or join in the IPDMA is a potential strategy to maximize the IPD retrieval. IPDMA are suggested to adhere to the PRISMA-IPD guideline during reporting.The aim of this study is to clarify absorption mechanisms after oral administration of ritonavir (RTV) from different types of lipid-based formulations (LBFs) with particular emphasis on the effect of lipid digestion and drug permeation/re-dissolution on the oral absorption. Four LBFs were prepared; three contained either long-chain (LC) or medium-chain (MC) lipids [lipid formulation classification system (LFCS) Type II-LC, Type IIIA-MC, and Type IIIB-MC] and the fourth contained only surfactant and co-solvent (Type IV). The solubility of RTV in those LBFs was determined and drug subsequently loaded at 85% w/w of the saturated solubility in the formulations. Then, each LBF containing drug was added into a model rat intestinal fluid at approximately 2.5% w/v for evaluation using an in vitro digestion model. In vitro digestion study showed the ability of Type II-LC and Type IIIA-MC to support continued solubilization of RTV, and moderate supersaturation was observed in Type IIIA-MC. In contrast, RTV partly precdetailed absorption mechanisms from LBFs with different compositions. Our findings may be useful for selecting appropriate excipients to design optimal LBFs for poorly water-soluble drugs.Toll-like receptors (TLRs) are important pattern recognition receptors (PRRs) of innate immune system, playing crucial roles in immune defense against pathogens. TLR18, a member of TLR1 family, is fish-specific TLR and involves in the immune response against bacterial infection. Currently, the structural biology of fish TLR18 is poorly elaborated. In this study, the structure and ligand binding of TLR18 (smTLR18) of soiny mullet (Liza haematocheila), an economically valuable aquaculture mugilid species, were analyzed. The extracellular domain (ECD) of smTLR18 formed an open-loop horseshoe-shaped structure with the concave surfaces made up of 19 parallel β-strands (LRR1-LRR19), lacking Z-loop that seen in human TLR9. The intracellular Toll/interleukin (IL)-1 (TIR) domain contained a central 4-parallel β-sheet (βA-βD) surrounded by 5 α-helices (αA-αE). Molecular docking analysis revealed that both ECD domain and TIR domain of smTLR18 could form homodimers. For the ECD homodimer, the main residues involved in dimer formation were located from LRR10 to LRR14. For the TIR homodimer, the residues involved in dimer formation were located in BB loop, αB helix, αC helix and DD loop. Ligand binding analyses revealed that peptidoglycans (PGNs) and lipopolysaccharides (LPS), two main bacterial pathogen-associated molecular patterns (PAMPs), were the potential ligands of smTLR18. The van der Waals and Coulombic interactions contributed to the interactions between smTLR18 and PGNs, while only van der Waals dominated the interactions between smTLR18 and LPS. #link# The residues involved in ligands binding were located from LRR9 to LRR13. Our results provided the structural bases for elucidate the ligand binding of fish TLR18.The tick Amblyomma testudinarium Koch, 1844 (Acari Ixodidae) is known as a vector of several pathogens such as Rickettsia tamurae and severe fever with thrombocytopenia syndrome (SFTS) virus. This tick species is present in many Asian countries, including Japan, where its distribution is limited to the warm areas of Kanto region and the southwestern region. The present study reports the recovery of a partially engorged A. testudinarium from a wild brown bear captured in Shari town, Hokkaido. In addition to morphological identification, the specimen was genetically characterized by the complete mitochondrial genome sequencing. The results showed that the length of the obtained mitogenome is 14,835 bp that encodes 13 protein-coding, two ribosomal RNA (rRNA) (12S and 16S), and 22 transfer RNA genes with two non-coding control regions. The phylogenetic analysis indicated that our sample clustered with A. testudinarium from Nara, Japan, but separated from A. testudinarium from China. Although the introduction of the tick through livestock transportation cannot be ruled out, the detection of A. testudinarium in Hokkaido prefecture, which is separated from the main island where A. testudinarium is present in the south, may suggest the introduction by migratory birds. This study provides important insights on the distribution and host range of A. testudinarium. This will be useful for the future taxonomic analysis of ticks based on the complete mitogenome sequencing. To our knowledge, this is the northernmost detection point of the tropical tick A. testudinarium.The comprehensive modeling and hierarchical positioning of a new concept in an ontology heavily relies on its set of proper subsumption relationships (IS-As) to other concepts. Identifying a concept's IS-A relationships is a laborious task requiring curators to have both domain knowledge and terminology skills. In this work, we propose a method to automatically predict the presence of IS-A relationships between a new concept and pre-existing concepts based on the language representation model BERT. This method converts the neighborhood network of a concept into "sentences" and harnesses BERT's Next Sentence Prediction (NSP) capability of predicting the adjacency of two sentences. To augment our method's performance, we refined the training data by employing an ontology summarization technique. We trained our model with the two largest hierarchies of the SNOMED CT 2017 July release and applied it to predicting the parents of new concepts added in the SNOMED CT 2018 January release. The results showed that our method achieved an average F1 score of 0.88, and the average Recall score improves slightly from 0.94 to 0.96 by using the ontology summarization technique.Cyanobacteria are often reported as abundant components of the sponge microbiome; however their diversity below the phylum level is still underestimated. Aiming to broaden our knowledge of sponge-cyanobacteria association, we isolated cyanobacterial strains from Aegean Sea sponges in previous research, which revealed high degree of novel cyanobacterial diversity. Herein, EPZ004777 concentration aim to further characterize sponge-associated cyanobacteria and re-evaluate their classification based on an extensive polyphasic approach, i.e. a combination of molecular, morphological and ecological data. This approach resulted in the description of five new genera (Rhodoploca, Cymatolege, Metis, Aegeococcus, and Thalassoporum) and seven new species (R. sivonenia, C. link2 spiroidea, C. isodiametrica, M. fasciculata, A. anagnostidisi, A. thureti, T. komareki) inside the order Synechococcales, and a new pleurocapsalean species (Xenococcus spongiosum). X. link3 spongiosum is a baeocyte-producing species that shares some morphological features with other Xenococcus species, but has distinct phylogenetic and ecological identity. Rhodoploca, Cymatolege, Metis and Thalassoporum are novel well supported linages of filamentous cyanobacteria that possess distinct characters compared to their sister taxa. Aegeococcus is a novel monophyletic linage of Synechococcus-like cyanobacteria exhibiting a unique ecology, as sponge-dweller. The considerable number of novel taxa characterized in this study highlights the importance of employing polyphasic culture-dependent approaches in order to reveal the true cyanobacterial diversity associated with sponges.