Synthesis, in vitro evaluation, and computational simulations studies of 1,2,3-triazole analogues as DPP-4 inhibitors.

Novel 1,2,3-triazole analogues (S7 ~ S10) were synthesized and evaluated for their inhibitory activity against hDPP-4. All the 1,2,3-triazole analogues exhibited moderate in vitro hDPP-4 inhibitory activities (265 ~ 780 nM). These results are somewhat less potent compared to those of known 1,2,3-triazole analogues (S1 ~ S6, 14 ~ 254 nM). S2 and S3 manifested excellent potency against hDPP-4 with IC50s of 28 and 14 nM, respectively. The role of the 1,2,3-triazole moiety in binding the molecule to the target was investigated using combined 10 1,2,3-triazole analogues (S1 ~ S10). Molecular dynamics (MD) simulations following the aforementioned docking phase were performed to elucidate potential binding modes of sitagliptin's 1,2,3-triazole analogues in hDPP-4, with the use of a cocrystal structure of hDPP-4 with sitagliptin (PDB ID: 1X70). Docking and MD simulations of the complexes of hDPP-4 with sitagliptin, S2 and S3 suggest that Glu205, Glu206, Tyr662, and Tyr666 would be the key amino acid residues for the binding of the molecules with the receptor. Especially, S2 and S3 showed additional strong π-π interaction between Phe357 and 1,2,3-triazole. Same strong π-π interaction is also observed between Phe357 and the 1,2,4-triazole ring of sitagliptin. Furthermore, additional interactions with Tyr547, Cys551, and especially Arg358 would enhance the binding affinity of the compounds for the pocket of the enzyme. In overall, in vitro hDPP-4 inhibitory activities of synthetic 1,2,3-triazole analogues were well matched with results of computational simulations studies.

Synthesis of Halogenated 1,5-Diarylimidazoles and Their Inhibitory Effects on LPS-Induced PGE2 Production in RAW 264.7 Cells.

A series of halogenated 1,5-diarylimidazole compounds were synthesized and their inhibitory effects on LPS-induced PGE2 production in RAW 264.7 cells were evaluated. A wide variety of 2,4-, 4-, and 2-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles were synthesized for SAR study via two different pathways. Overall, 4-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles, regardless of the species of halogen, exhibited very strong inhibitory activities of PGE2 production. Among them, 4-chloro-5-(4-methoxyphenyl)-1-(4-methylsulfonylphenyl)imidazole (3, IC50 3.3 nM ± 2.93), and 4-chloro-5-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)imidazole (13, IC50 5.3 nM ± 0.23) showed the best results.

Analytical evaluation and clinical application of insulin and C-peptide by a whole blood, lateral flow, point of care (POC) assay system.

The analytical performance and clinical application of measuring insulin and connecting peptide (C-peptide) by point of care (POC) assay were evaluated. A POC assay system (SelexOn, Osang Healthcare Inc., Anyang-si, Korea) was evaluated for precision, linearity, limit of blank (LOB), and limit of detection (LOD). Method comparison was performed with the Cobas Elecsys insulin and C-peptide assay (Roche Diagnostics GmbH, Mannheim, Germany) using 215 and 201 patient specimens for insulin and C-peptide, respectively. For clinical application, insulin resistance indices were studied. Homeostasis model assessment (HOMA) 1 and 2, Quantitative insulin sensitivity check index (QUIKI), fasting insulin resistance index (FIRI), and other indices were evaluated. The coefficient of variation (CV) of imprecision for low, medium, and high concentrations was 10.8%1, 15.99%, and 12.05%, respectively, for insulin and 9.21%, 13.51%, and 13.77%, respectively, for C-peptide. The linearity was validated to 839.78 pmol/L for insulin and to 17.30 nmol/L for C-peptide. LOB and LOD were 8.05 and 9.72 pmol/L for insulin and 0.05 and 0.08 nmol/L for C-peptide, respectively. For the method comparison, the regression equation was y = 1.259x - 8.818 (r = 0.957) for insulin and y = 1.163x - 0.088 (r = 0.985) for C-peptide. The ROC value and overall accuracy were as follows: HOMA2 (C-peptide), 0.809, 79.7%; TyG, 0.788, 73.6%; CPR, 0.775, 74.8%; HOMA1, 0.725, 70.3%; QUIKI, 0.720, 70.3%; FIRI, 0.715, 70.1%; McAuley, 0.658, 65.1%; HOMA2 (Insulin), 0.645, 64.7%; Raynaud, 0.611, 61.4%, respectively. The POC assay system for insulin and C-peptide provided reliable results through a rapid and simple test that could be applied to clinical settings.

Flavonoids interfere with NLRP3 inflammasome activation.

NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome is a component of innate immunity, and is responsible for producing mature IL-1ß and -18. Several flavonoids were found to affect inflammasome pathway, but the mechanism of action is still obscure. To elucidate the effects on NLRP3 inflammasome pathway and to determine the structure-activity relationships, NLRP3 inflammasome in differentiated THP-1 cells was activated via treatment with monosodium urate (MSU) crystals. Levels of mature IL-1ß, NLRP3 inflammasome components and apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC) oligomerization were investigated and the mechanisms of action were also elucidated. Among the 56 flavonoids initially tested, only flavone, 2',4'-dihhydroxyflavone, 3',4'-dichloroflavone, 4',5,7-trihydroxyflavone (apigenin), 3,4',5,7-tetrahydroxyflavone (kaempferol) and 3,3',4',5,7-pentahydroxyflavone (quercetin) significantly inhibited IL-1ß production at 10 µM. Apigenin, kaempferol and 3',4'-dichloroflavone inhibited ASC oligomerization without affecting the ASC level in cell lysates. Apigenin also inhibited absent in melanoma 2 (AIM2) inflammasome-related pathway, but not NLR family CARD domain-containing protein 4 (NLRC4) inflammasome activation. The action of apigenin on NLRP3 inflammasome activation is mediated partly via inhibition of phosphorylation of spleen tyrosine kinase/protein tyrosine kinase 2 (Syk/Pyk2) pathway. Furthermore, orally administered apigenin (100 mg/kg) strongly reduced the number of neutrophils and monocytes in MSU-induced peritonitis in mice. The present study, for the first time, demonstrated the structure-activity profiles of flavonoids in NLRP3 inflammasome activation and mechanisms of cellular action. Certain flavonoids including apigenin are expected to ameliorate the inflammatory symptoms in autoinflammatory diseases associated with NLRP3 inflammasome activation.

Synthesis and biological evaluation of pyrimidine derivatives with diverse azabicyclic ether/amine as novel GPR119 agonist.

A class of novel pyrimidine derivatives bearing diverse conformationally restricted azabicyclic ether/amine were designed, synthesized and evaluated for their GPR119 agonist activities against type 2 diabetes. Most compounds exhibited superior hEC50 values to endogenous lipid oleoylethanolamide (OEA). Analogs with 2-fluoro substitution in the aryl ring showed more potent GPR119 activation than those without fluorine. Especially compound 27m synthesized from endo-azabicyclic alcohol was observed to have the best EC50 value (1.2nM) and quite good agonistic activity (112.2% max) as a full agonist.

Novel 5-nitropyrimidine derivatives bearing endo-azabicyclic alcohols/amines as potent GPR119 agonists.

A series of GPR119 agonists based on a 5-nitropyrimidine scaffold bearing endo-azabicyclic substituents were synthesized and evaluated for their GPR119 agonistic activities. Most compounds exhibited much stronger EC50 values than that of oleoylethanolamide (OEA). Among them, derivatives from endo-azabicyclic alcohols displayed more potent GPR119 agonistic activities than compounds with endo-azabicyclic amines. Especially the optimized compounds (6, 7, 8, 12, 17) were shown to have potent biological activities and were identified as full agonists. Isopropyl carbamate compound 8 synthesized from endo-azabicyclic alcohol was observed to have the best EC50 value (0.6nM). Generally 2-fluoro substitution of the aryl group at the C4 position of 5-nitropyrimidine scaffold resulted in the increase of biological activity.

Evaluation of a novel point-of-care test kit, ABSOGEN™ PCT, in semi-quantitative measurement of procalcitonin in whole blood.

BACKGROUND: In response to inflammation, procalcitonin plasma concentrations increase more rapidly than other acute-phase reactants and higher values are associated with severe disease. Procalcitonin measurements assist in determining whether antibiotic therapy should be used. point-of-care testing (POCT) is performed for early decision making about additional testing or therapy. The ABSOGEN™ PCT (Bumyoungbio, Inc., Suwon, Korea) is a rapid novel semi-quantitative immunochromatographic PCT assay that analyses whole blood samples. We compared the patient quantitative test results to ABSOGEN™ PCT test results. METHODS: Whole blood was loaded onto an ABSOGEN™ PCT cartridge and incubated for 10 minutes. The color intensity of the band of the cartridge was measured using an accompanying device and with the naked eye. The results were graded as negative (<0.1 ng/mL), low (0.1 to <1.0 ng/mL), middle (1.0-2.0 ng/mL), and high (>2.0 ng/mL). A total of 158 specimens with procalcitonin levels measured from 0 to 18.96 ng/mL were used for comparison study. RESULTS: The concordance rate between ABSOGEN™ PCT using the reader and quantitative assay, between ABSOGEN™ PCT using naked eyes and quantitative assay, and between ABSOGEN™ PCT using the reader and naked eyes for the same category was 83.5% (P=.040), 78.5% (P<.001), and 82.3% (P=.001), respectively. The concordance rates for the ±1 categories were all 100%. CONCLUSION: ABSOGEN™ PCT is an accurate assay. It is easy to use, simple, fast, portable. The assay has potential value in clinical applications, especially in emergency care.

Synthesis and Structure Revision of Dimeric Tadalafil Analogue Adulterants in Dietary Supplements.

A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products. During the course of this synthesis, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was proven to be the reagent of choice for amide coupling to produce these dimeric tadalafil analogues. Moreover, the trans-isomer structures tentatively assigned for the isolated dimeric tadalafil analogues (bisprehomotadalafil and bisprecyclopentyltadalafil) found in dietary supplements are now revised to cis-isomer structures.

Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11ß-Hydroxycurvularin.

The first total synthesis and structure revision of (-)-11ß-hydroxycurvularin (1b), a macrolide possessing a ß-hydroxyketone moiety, were accomplished. The ß-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

Evaluation of the Performance of Two Point-of-Care Analyzers for Total Cholesterol, Triglyceride, and High-Density Lipoprotein Cholesterol Analysis.

BACKGROUND: In this study, we evaluated the analytic performance of two POCT devices and compared the results with a central laboratory method. METHODS: A total of 100 patients were enrolled in this study. LipidPro (Infopia, USA) and LandMark (Infopia, Korea), were used for measuring total cholesterol (TC), triglyceride (TG), and high density lipoprotein cholesterol (HDL-C). Imprecision and linearity were assessed and the results of two POCT analyzers were compared with a central laboratory method. RESULTS: Imprecision of LipidPro met the National Cholesterol Education Program (NCEP) criteria (mean % CV: TC 2.8%, TG 3.9%, and HDL-C 4.0%). LandMark met the National Cholesterol Education Program (NCEP) imprecision criteria for TC and TG, but not HDL-C (mean % CV: 2.7%, 3.5%, and 4.7%, respectively). Both analyzers showed excellent linearity for TC, TG, and HDL-C in test ranges. Total errors of TC, TG, and HDL-C measured by LipidPro were 6.1%, 8.7%, and 8.1%, respectively, and met the NCEP goals. The total errors of TG and HDL-C measured by LandMark met the NCEP goals; however, the total error of TC analysis did not meet the NCEP goals (total error; TC 11.1%, TG 11.2%, and HDL-C 9.6%). CONCLUSIONS: LipidPro and LandMark are simple and rapid tests that provide a reliable alternative to conventional laboratory methods. The LipidPro device showed a slightly better analytical performance than LandMark based on the NCEP goals.

Analytical Performance Evaluation of Infopia Element™ Auto-coding Blood Glucose Monitoring System for Self-Monitoring of Blood Glucose.

BACKGROUND: Element™ Auto-coding Blood Glucose Monitoring System (BGMS; Infopia Co., Ltd., Anyang-si, Korea) was developed for self-monitoring of blood glucose (SMBG). METHODS: Precision, linearity, and interference were tested. Eighty-four capillary blood samples measured by Element™ BGMS were compared with central laboratory method (CLM) results in venous serum. Accuracy was evaluated using ISO 15197:2013 criteria. RESULTS: Coefficients of variation (CVs; mean) were 2.4% (44.2 mg/dl), 3.7% (100.6 mg/dl), and 2.1% (259.8 mg/dl). Linearity was shown at concentrations 39.25-456.25 mg/l (y = 0.989 + 0.984x, SE = 17.63). Up to 15 mg/dl of galactose, ascorbic acid, and acetaminophen, interference > 10.4% was not observed. Element™ BGMS glucose was higher than CLM levels by 3.2 mg/dl (at 200 mg/dl) to 8.2 mg/dl (at 100 mg/dl). The minimum specification for bias (3.3%) was met at 140 and 200 mg/l glucose. In the Clarke and consensus error grids, 100% of specimens were within zone A and B. For Element™ BGMS values, 92.9% (78/84) to 94.0% (79/84) were within a 15 mg/dl (< 100 mg/dl) or 15% (> 100 mg/dl) of the average CLM value. CONCLUSION: Element™ BGMS was considered an appropriate SMBG for home use; however, the positive bias at low-to-mid glucose levels requires further improvement.

Stereoselective construction of 2,6-cis-disubstituted tetrahydropyrans via intramolecular amide enolate alkylation: total synthesis of (-)-centrolobine.

A highly stereoselective construction of 2,6-cis-disubstituted tetrahydropyrans was achieved by using an intramolecular amide enolate alkylation with KHMDS. The efficiency and practicality of this methodology was successfully demonstrated in the total synthesis of (-)-centrolobine (1).

Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FREND™ PSA Plus.

BACKGROUND: We evaluated the analytical performance of a new one-step rapid quantitative sandwich immunoassay for total prostate-specific antigen (tPSA), the FREND™ PSA Plus (FREND PSA) (NanoEnTek Inc., Seoul, Korea). METHODS: The imprecision, linearity, hook effect, detection limit (LoD), and interference were evaluated and trueness verification and matrix validation were performed. For method comparison, 79 patient specimens were analyzed with FREND PSA and two comparative tPSA assays (Architect® total PSA and cobas® total PSA assay). RESULTS: Total CVs of the imprecision for low (0.208 ng/mL), medium (4.051 ng/mL), and high PSA levels (5.469 ng/mL) were 15.9%, 6.4%, and 9.1%, respectively. Linearity was observed from 1.01 to 19.15 ng/mL and the hook phenomenon was absent up to 171.48 ng/mL. The LoD was 0.094 ng/mL. The regression equations between FREND (y) and Architect or cobas were as follows: y=0.0133+1.054x (r=0.973), y=-0.2144+1.066x (r=0.977), respectively. Differences between FREND PSA and the comparative methods at a medical decision level of 4.0 ng/mL were less than the optimum specification bias (9.3%). The percentage biases from the trueness verification and interference test were less than the desirable specifications for bias (18.7%). The plasma tPSA level measured with lithium heparin or K2EDTA was comparable to that in the serum. CONCLUSIONS: The FREND PSA provided reliable analytical performance and test results in comparison to two widely used tPSA assays. It is a simple and rapid test for tPSA and can be applied in point-of-care testing.

Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800 (Beckman Coulter).

BACKGROUND: In the Retic channel of DxH 800 (Beckman Coulter), the red blood cells (RBCs) resistant to hemoglobin clearing are counted as unghosted cells (UGCs). The aim of this study was to evaluate that the UGC is a surrogate marker for both the detection and counting of target cells. METHODS: In total, 1181 samples including 22 from iron deficiency anemia (IDA) patients, 95 from jaundice, 2 from sickle cell anemia, 3 from thalassemia, 1 cord blood, and 269 from normal controls were analyzed. Slides were prepared from all samples except normal controls and target cells were counted for correlation analysis of target cell counts to UGCs. RESULTS: The normal control samples showed 0.01% (0%-0.01%) UGCs, and the reference range was set at ≤0.02%. The IDA samples showed 0.015% (0.01%-0.03%) UGC count and 0.05% (0%-0.2%) target cell count. The jaundice samples showed 0.98% (0.1%-5.36%) UGC count, and 1.4% (0.1%-7.0%) target cell count. The two sickle cell anemia samples showed 0.41% and 3.74% UGC counts and 0.4% and 11.5% target cell counts. A cord blood sample showed 0.01% UGCs and 0% target cells. The three thalassemia samples showed 0.01%, 1.99%, and 7.82% UGC counts and 0%, 1.4%, and 15.5% target cell counts. The samples showing poikilocytosis other than target cells showed normal UGC count (≤0.02%). The positive predictive value of UGCs was 58.2% (124/213) and the negative predictive value was 96.8% (674/696). The UGC counts were well correlated to the manual target cell counts (r=0.944, p=0.000). CONCLUSIONS: This study demonstrates for the first time in the literature that a hematological parameter obtained automatically every time a reticulocyte counting is performed can be used to both screen for the presence of target cells and reliably quantify them.

LEGO plot for simultaneous application of multiple quality requirements during trueness verification of quantitative laboratory tests.

BACKGROUND: We developed a two-dimensional plot for viewing trueness that takes into account potential shift and variable quality requirements to verify trueness using certified reference material (CRM). METHODS: Glucose, total cholesterol (TC), and creatinine levels were determined by two kinds of assay in two levels of a CRM. Available quality requirements were collected, codified, and sorted in an ascending order in the plot's header row. Centering on the mean of measured values from CRM, the "mean ± US CLIA '88 allowable total error" was located in the header of the leftmost and rightmost columns. Twenty points were created in intervening columns as potential shifts. Uncertainties were calculated according to regression between certified values and uncertainties of CRM, and positioned in the corresponding columns. Cells were assigned different colors where column and row intersected based on comparison of the 95% confidence interval of the percentage bias with each quality requirement. RESULTS: A glucose assay failed to meet the highest quality criteria, for which shift of +0.13-0.14 mmol/l was required. A TC assay met the quality requirement and a shift of ±0.03 mmol/l was tolerable. A creatinine assay also met the quality requirement but any shift was not tolerable. CONCLUSION: The plot provides a systematic view of the trueness of quantitative laboratory tests.

The analytical performance evaluation of Freelite™ Human Kappa Free and Human Lambda Free on the SPAPLUS™ immunoturbidimetric analyzer.

BACKGROUND: SPAPLUS™ is a turbidimetric immunoassay analyzer for detection of excess free light chain (FLC) antigens in serum. Here, we evaluated the analytical performance of Freelite™ Human Kappa Free and Lambda Free on a SPAPLUS™ instrument. METHODS: We evaluated the precision, linearity, sample carryover, and drift of the SPAPLUS™ instrument and compared it with Hitachi 7600 and BN™ II instruments. We evaluated the detection of antigen excess for 12 specimens from patients with monoclonal gammopathy. RESULTS: The coefficients of variations of κFLC and λFLC were below 5.0%. Linearity was shown in the range of 9.68-152.25 mg/l for κFLC and 4.96-171.09 mg/l for λFLC, and no drift was observed. The κFLC sample carryover was statistically significant, but much smaller than the optimum allowable bias. Agreement rates with the two comparative methods were 87.1, 87.1, and 97.1% or higher for κFLC, λFLC, and the κ/λ ratio, respectively. Antigen excess signals were observed for all 12 antigen excess specimens. CONCLUSIONS: The Freelite™ on the SPAPLUS™ exhibited appropriate precision, linearity, and relative comparability to the reagents on the other instruments. It was good at detecting specimens that had previously demonstrated the hook effect due to antigen excess.

Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal dysplasia: a case report.

BACKGROUND: Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature, early-onset osteoarthritis mainly involving the hip and knee joints, and abnormally small and/or irregular epiphyses. Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six genes are associated with the phenotype of multiple epiphyseal dysplasia. CASE PRESENTATION: A 12-year-old Korean boy presented with intermittent knee pain. His height was 144.6 cm (20th percentile) and family history was notable for early-onset osteoarthritis in his father. The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel c.104G>A substitution in exon 2 of COL9A3, resulting in p.Gly35Asp in the proband and his father. In silico analyses predicted the p.Gly35Asp amino acid change to be detelerious, and molecular dynamics simulation demonstrated a major structural change in the heterotrimeric collagen IX. CONCLUSION: So far, three COL9A3 mutations, have been reported. These three mutations are located at the splice donor or acceptor site of COL9A3 and cause skipping of exon 3, resulting in the deletion of 12 aminoacids in the COL3 domain of COL9A3. In contrast, the novel missense mutation identified in this two-generation family with multiple epiphyseal dysplasia is a missense mutation affecting the Gly residue of the Pro-Pro-Gly repeat sequence in the COL3 domain of collage IX, with accompanying major structural change of the collagen peptide.

Involvement of the anterior insula and frontal operculum during wh-question comprehension of wh-in-situ Korean language.

In this research, we employed functional magnetic resonance imaging (fMRI) to examine the neurological basis for understanding wh-questions in wh-in-situ languages such as Korean, where wh-elements maintain their original positions instead of moving explicitly within the sentence. Our hypothesis centered on the role of the salience and attention network in comprehending wh-questions in wh-in-situ languages, such as the discernment of wh-elements, the demarcation between interrogative types, and the allocation of cognitive resources towards essential constituents vis-à-vis subordinate elements in order to capture the speaker's communicative intent. We explored subject and object wh-questions and scrambled wh-questions, contrasting them with yes/no questions in Korean. Increased activation was observed in the left anterior insula and bilateral frontal operculum, irrespective of the wh-position or scrambling of wh-element. These results suggest the interaction between the salience and attentional system and the syntactic linguistic system, particularly the left anterior insula and bilateral frontal operculum, in comprehending wh-questions in wh-in-situ languages.

Laboratory Preparation for Digital Medicine in Healthcare 4.0: An Investigation Into the Awareness and Applications of Big Data and Artificial Intelligence.

Background: Healthcare 4.0. refers to the integration of advanced technologies, such as artificial intelligence (AI) and big data analysis, into the healthcare sector. Recognizing the impact of Healthcare 4.0 technologies in laboratory medicine (LM), we seek to assess the overall awareness and implementation of Healthcare 4.0 among members of the Korean Society for Laboratory Medicine (KSLM). Methods: A web-based survey was conducted using an anonymous questionnaire. The survey comprised 36 questions covering demographic information (seven questions), big data (10 questions), and AI (19 questions). Results: In total, 182 (17.9%) of 1,017 KSLM members participated in the survey. Thirty-two percent of respondents considered AI to be the most important technology in LM in the era of Healthcare 4.0, closely followed by 31% who favored big data. Approximately 80% of respondents were familiar with big data but had not conducted research using it, and 71% were willing to participate in future big data research conducted by the KSLM. Respondents viewed AI as the most valuable tool in molecular genetics within various divisions. More than half of the respondents were open to the notion of using AI as assistance rather than a complete replacement for their roles. Conclusions: This survey highlighted KSLM members' awareness of the potential applications and implications of big data and AI. We emphasize the complexity of AI integration in healthcare, citing technical and ethical challenges leading to diverse opinions on its impact on employment and training. This highlights the need for a holistic approach to adopting new technologies.

A piece of the action: modulation of sensory-motor regions by action idioms and metaphors.

The idea that the conceptual system draws on sensory and motor systems has received considerable experimental support in recent years. Whether the tight coupling between sensory-motor and conceptual systems is modulated by factors such as context or task demands is a matter of controversy. Here, we tested the context sensitivity of this coupling by using action verbs in three different types of sentences in an fMRI study: literal action, apt but non-idiomatic action metaphors, and action idioms. Abstract sentences served as a baseline. The result showed involvement of sensory-motor areas for literal and metaphoric action sentences, but not for idiomatic ones. A trend of increasing sensory-motor activation from abstract to idiomatic to metaphoric to literal sentences was seen. These results support a gradual abstraction process whereby the reliance on sensory-motor systems is reduced as the abstractness of meaning as well as conventionalization is increased, highlighting the context sensitive nature of semantic processing.