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Our study consists in aligning the interface terminology of the Bordeaux university hospital (TLAB) to the Logical Observation Identifiers Names and Codes (LOINC). The objective was to facilitate the shared and integrated use of biological results with other health information systems.
We used an innovative approach based on a decomposition and re-composition of LOINC concepts according to the transversal relations that may be described between LOINC concepts and their definitional attributes. TLAB entities were first anchored to LOINC attributes and then aligned to LOINC concepts through the appropriate combination of definitional attributes. Finally, using laboratory results of the Bordeaux data-warehouse, an instance-based filtering process has been applied.
We found a small overlap between the tokens constituting the labels of TLAB and LOINC. However, the TLAB entities have been easily aligned to LOINC attributes. Thus, 99.8% of TLAB entities have been related to a LOINC analyte and 61.0% to a LOINC system. A total of 55.4% of used TLAB entities in the hospital data-warehouse have been mapped to LOINC concepts. We performed a manual evaluation of all 1-1 mappings between TLAB entities and LOINC concepts and obtained a precision of 0.59.
We aligned TLAB and LOINC with reasonable performances, given the poor quality of TLAB labels. In terms of interoperability, the alignment of interface terminologies with LOINC could be improved through a more formal LOINC structure. This would allow queries on LOINC attributes rather than on LOINC concepts only.
We aligned TLAB and LOINC with reasonable performances, given the poor quality of TLAB labels. In terms of interoperability, the alignment of interface terminologies with LOINC could be improved through a more formal LOINC structure. This would allow queries on LOINC attributes rather than on LOINC concepts only.Chimeric antigen receptor (CAR) T cells are highly successful in the treatment of hematologic malignancies. We recently generated affinity-optimized CD38CAR T cells, which effectively eliminate multiple myeloma (MM) cells with little or no toxicities against nonmalignant hematopoietic cells. The lack of universal donors and long manufacturing times however limit the broad application of CAR T cell therapies. Natural killer (NK) cells generated from third party individuals may represent a viable source of "off the shelf" CAR-based products, as they are not associated with graft-versus-host disease unlike allogeneic T cells. We therefore explored the preclinical anti-MM efficacy and potential toxicity of the CD38CAR NK concept by expressing affinity-optimized CD38CARs in KHYG-1 cells, an immortal NK cell line with excellent expansion properties. KHYG-1 cells retrovirally transduced with the affinity-optimized CD38CARs expanded vigorously and mediated effective CD38-dependent cytotoxicity towards CD38high MM cell lines as well as primary MM cells ex vivo. Importantly, the intermediate affinity CD38CAR transduced KHYG-1 cells spared CD38neg or CD38int nonmalignant hematopoietic cells, indicating an optimal tumor nontumor discrimination. Irradiated, short living CD38CAR KHYG-1 cells also showed significant anti-MM effects in a xenograft model with a humanized bone marrow-like niche. Finally, CD38CAR KHYG-1 cells effectively eliminated primary MM cells derived from patients who are refractory to CD38 antibody daratumumab. Taken together, the results of this proof-of-principle study demonstrate the potential value of engineering affinity-optimized CD38CARs in NK cells to establish effective anti-MM effects, with an excellent safety profile, even in patients who failed to response to most advanced registered myeloma therapies, such as daratumumab.Mutations in the calreticulin (CALR) gene are seen in about 30% of essential thrombocythemia and primary myelofibrosis patients. To address the contribution of the human CALR mutants to the pathogenesis of myeloproliferative neoplasms (MPNs) in an endogenous context, we modeled the CALRdel52 and CALRins5 mutants by induced pluripotent stem cell (iPSC) technology using CD34+ progenitors from 4 patients. We describe here the generation of several clones of iPSC carrying heterozygous CALRdel52 or CALRins5 mutations. We showed that CALRdel52 induces a stronger increase in progenitors than CALRins5 and that both CALRdel52 and CALRins5 mutants favor an expansion of the megakaryocytic lineage. Moreover, we found that both CALRdel52 and CALRins5 mutants rendered colony forming unit-megakaryocyte (CFU-MK) independent from thrombopoietin (TPO), and promoted a mild constitutive activation level of signal transducer and activator of transcription 3 in megakaryocytes. Unexpectedly, a mild increase in the sensitivity of colony forming unit-granulocyte (CFU-G) to granulocyte-colony stimulating factor was also observed in iPSC CALRdel52 and CALRins5 compared with control iPSC. Moreover, CALRdel52-induced megakaryocytic spontaneous growth is more dependent on Janus kinase 2/phosphoinositide 3-kinase/extracellular signal-regulated kinase than TPO-mediated growth and opens a therapeutic window for treatments in CALR-mutated MPN. selleck chemicals The iPSC models described here represent an interesting platform for testing newly developed inhibitors. Altogether, this study shows that CALR-mutated iPSC recapitulate MPN phenotypes in vitro and may be used for drug screening.Background Microbial water quality serves to indicate health risks associated with the consumption of contaminated water. Nevertheless, little is known about the microbiological characteristics of water in Lake Bunyonyi. This study was therefore undertaken to examine the spatial and temporal variations of faecal indicator bacteria (FIB) in relation to physicochemical parameters in Lake Bunyonyi. Result The FIB concentration was consistently measured during sampling months and correlated with each other showing the presumed human faecal pollution in the lake. The highest concentration values for E. coli (64.7 ± 47.3 CFU/100 mL) and enterococci (24.6 ± 32.4 CFU/100 mL were obtained in the station close to the Mugyera trading centre. On a temporal basis, the maximum values were recorded during the rainy season in October 2019 (70.7 ± 56.5 CFU/100 mL for E. coli and 38.44 ± 31.8 CFU/100 mL for enterococci. FIB did not differ significantly among the study stations (p > 0.05) but showed significant temporal variations among the months (p less then 0.
My Website: https://www.selleckchem.com/products/linderalactone.html
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