Academic literature on the topic 'Imido functionality'

Background Immune-mediated inflammatory diseases (IMIDs) are systemic conditions associated with a high social and health impact. New treatments have changed the prognosis of IMIDs and have increased patient autonomy in disease management. Mobile apps have enormous potential to improve health outcomes in patients with IMIDs. Although a large number of IMID apps are available, the app market is not regulated, and functionality and reliability remain uncertain. Objective Our aims are to review available apps for patients with IMIDs or caregivers and to describe the main characteristics and functionalities of these apps. Methods We performed an observational, cross-sectional, descriptive study of all apps for patients with IMIDs. Between April 5 and 14, 2021, we conducted a search of the App Store (iOS) and Play Store (Android) platforms. We used the names of the different IMIDs as search terms. The inclusion criteria were as follows: content related to IMIDs, English or Spanish language, and user population consisting of patients and health care consumers, including family and caregivers. The variables analyzed were as follows: app name, type of IMID, platform (Android or iOS), country of origin, language, category of the app, cost, date of the last update, size, downloads, author affiliation, and functionalities. Results We identified 713 apps in the initial search, and 243 apps met the criteria and were analyzed. Of these, 37% (n=90) were on Android, 27.2% (n=66) on iOS, and 35.8% (n=87) on both platforms. The most frequent categories were health and well-being/fitness apps (n=188, 48.5%) and medicine (n=82, 37.9%). A total of 211 (82.3%) apps were free. The mean time between the date of the analysis and the date of the most recent update was 18.5 (SD 19.3) months. Health care professionals were involved in the development of 100 (41.1%) apps. We found differences between Android and iOS in the mean time since the last update (16.2, SD 14.7 months vs 30.3, SD 25.7 months) and free apps (85.6% vs 75.8%; respectively). The functionalities were as follows: general information about lifestyles, nutrition, or exercises (n=135, 55.6%); specific information about the disease or treatment (n=102, 42%); recording of symptoms or adverse events (n=51, 21%); agenda/calendar (n=44, 18.1%); reminder medication (n=41, 16.9%); and recording of patient-reported outcomes (n=41, 16.9%). A total of 147 (60.5%) apps had more than one functionality. Conclusions IMID-related apps are heterogeneous in terms of functionality and reliability. Apps may be a useful complement to IMID care, especially inpatient education (their most frequent functionality). However, more than half of the IMID apps had not been developed by health care professionals or updated in the last year.

The synthesis and structural characterisation of novel imino cyclophanes incorporating various spacer units is described. All the imino cyclophanes exhibit comparable antibacterial activity against Gram positive (Bacillus subtillus, Staphylococcus aureus) and Gram negative (Escherchia coli, Klebsiella pneumonia) bacterial strains. The imino cyclophanes also exhibit good antifungal activity against human pathogenic fungus, Candida albicans.

A range of thermoplastic polyimides has been synthesized and used to modify a DGEBA-DDS epoxy thermoset. The influence of polyimide end-group functionality and particle size has been examined. Increases in fracture toughness of up to three times that of the neat resin have been achieved, together with no loss of modulus. Thermal capability is little affected across the range of modifying polyimides. The influence of copoly(imide–imide)s has also been studied. Morphological examination has revealed a range of structures in the blends, including some which are unusual. A particulate toughening mechanism is proposed for one high fracture toughness system.

This iodine-catalysed expedient process furnished functionally-rich pyrazoles regioselectively in ethanol under aerobic conditions. The cascade reaction for the pyrazole formation proceeds through enamine–imino diaza-Nazarov 4π-electrocyclization.

Functionally-rich pyrazoles in a cascade reaction from in situ generated hydrazones and acetophenones under aerobic conditions were synthesized through novel enamine–imino diaza-Nazarov 4π-electrocyclization which is supported by DFT calculations.

Optically active tertiary aminonaphthol ligands were obtained by a new, convenient procedure and were found to catalyze the enantioselective alkenyl and phenyl transfer to aldehydes in high yields and excellent enantiomeric excesses (ee's). The catalytic asymmetric introduction of alkynyl functionality to α-amino acid derivatives was realized by the direct addition of terminal alkynes to α-imino ester in the presence of chiral copper(I) complex under mild reaction conditions.

Abstract Background: IMiDs cytotoxicity in MM cells is mediated through their binding to CRBN within the cullin ring (CRL4) ligase. This binding triggers the ubiquitylation and proteasomal degradation of IKZF1/3. CRBN thalidmomide binding domain (TBD) was mapped to its C-terminus and the crystal structure of the CRBN-IMiDs bound complex identified several aa within exons 10 and 11 as essential for the IMiDs glutarimide ring binding to CRBN. Several groups including ours have reported that loss of CRBN is associated with resistance to IMiDs, however this does not appear to be the sole mechanism of resistance in primary MM cells. Furthermore, and while CRBN mutants (Y384A and W386A) are defective for IMiDs binding, acquisition of CRBN mutation is a rare event in MM patients suggesting alternative mechanisms of resistance. Thirteen splice variants of CRBN are reported (ensembl.org), however to date it is unclear whether these isoforms are expressed as proteins and their contribution to IMiDs resistance is yet to be defined. Methods and Results: In this study we investigated whether expression of full length CRBN (FL-CRBN) relative to its variants lacking the TBD and particularly the splice variant CRBN-005 (ENST00000424814) lacking exon 10, contribute to IMiDs resistance. RNA-seq analysis was performed on CD138 sorted cells in 15 paired patients samples obtained sequentially prior to lenalidomide treatment initiation and after development of resistance. Transcriptome sequence data was generated by RNA-seq with a minimum of 70x106 reads per sample. Filtered Fastq files were processed with the splice aligner TopHat against hg19. Of interest, splice isoforms of CRBN including isoforms lacking exon 10 and to a lesser extent exon 8 were identified in nearly all patients, albeit with at variable frequency. Splicing almost universally involved the full length of exon 10 including aa W382 and H378 that are now recognized to bind the 2 carbonyls residues on the IMiDs glutarimide ring and hence required for IMiDs binding to CRBN. Of note, mutation analysis of these 30 samples using the GATK RNAseq pipeline did not identify any mutations within CRBN exons 10 or 11. Furthermore, exome sequencing of CD138 cells from 10 additional lenalidomide resistant patients did not identify any CRBN SNVs or indels confirming the rarity of this event. In order to assess the contribution of FL-CRBN transcript and/or its splice variant (CRBN-005) to IMiDs sensitivity, we first confirmed by qRT-PCR (n=26, amplicons with 2 sets of primers overlapping exons 8-9 and exons 10-11) that low pre-treatment CRBN levels was significantly associated with shorter PFS (p=0.008) to lenalidomide. We next compared FL-CRBN (probe spanning exons 10-11) and CRBN-005 (Taqman probe spanning exons 9-11 junction) mRNA expression (qRT-PCR) in paired samples (n=21 patients - 42 pairs) collected immediately pre-treatment and at the time of progression post-lenalidomide. In 9/21 (42.8%), a significant reduction (2-ΔΔCT < 0.75) in the FL-CRBN amplicon levels was observed between the paired pre- and post-treatment samples. The ratio of spliced CRBN-005 to full length CRBN (CRBN-005 / FL-CRBN) was significantly higher (1.3 to 54 fold) at the time of relapse in 11/21 (52.3%), including 5 patients where CRBN-FL transcript levels were unchanged. Lastly, to confirm whether CRBN-005 expresses a stable protein and to evaluate its role in IMiDs resistance, we cloned spliced CRBN-005 isoform (Δ10-CRBN) or full length CRBN (WT-CRBN) into pcDNA3 plasmid and transfected them in HEK293T cells. The Δ10-CRBN and WT-CRBN plasmids expressed a ~ 45 and 51 kDa proteins respectively that were detectable by western blotting with CRBN65 antibody (Celgene). Functionally, we co-transfected HEK293T cells with a lentiviral plasmid expressing Aiolos and the Δ10-CRBN or WT-CRBN plasmids. While treatment of WT-CRBN expressing cells with lenalidomide resulted in full loss of Aiolos, the expression of Δ10-CRBN significantly mitigated this effect. Conclusions: Study of the transcriptome of paired pre- and post-IMIDs in myeloma primary cells confirms the expression of CRBN-005 splice isoform lacking the IMiDs binding domain and reveals its enrichment in a subset of IMiDs resistance patients. Functionally we have demonstrated a novel mechanism of IMiDs resistance where the spliced isoform CRBN-005 acts as a dominant negative blocking IMiDs binding the CRL4 E3 ligase. Disclosures Bahlis: Celgene: Honoraria, Research Funding.