A refined picture of the native amine dehydrogenase family revealed by extensive biodiversity screening.

Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.

Contrasting effects of urban trees on air quality: From the aerodynamic effects in streets to impacts of biogenic emissions in cities.

Urban trees are often not considered in air-quality models although they can significantly impact the concentrations of pollutants. Gas and particles can deposit on leaf surfaces, lowering their concentrations, but the tree crown aerodynamic effect is antagonist, limiting the dispersion of pollutants in streets. Furthermore, trees emit Biogenic Volatile Organic Compounds (BVOCs) that react with other compounds to form ozone and secondary organic aerosols. This study aims to quantify the impacts of these three tree effects (dry deposition, aerodynamic effect and BVOC emissions) on air quality from the regional to the street scale over Paris city. Each tree effect is added in the model chain CHIMERE/MUNICH/SSH-aerosol. The tree location and characteristics are determined using the Paris tree inventory, combined with allometric equations. The air-quality simulations are performed over June and July 2022. The results show that the aerodynamic tree effect increases the concentrations of gas and particles emitted in streets, such as NOx (+4.6 % on average in streets with trees and up to +37 % for NO2). This effect increases with the tree Leaf Area Index and it is more important in streets with high traffic, suggesting to limit the planting of trees with large crowns on high-traffic streets. The effect of dry deposition of gas and particles on leaves is very limited, reducing the concentrations of O3 concentrations by -0.6 % on average and at most -2.5 %. Tree biogenic emissions largely increase the isoprene and monoterpene concentrations, bringing the simulated concentrations closer to observations. Over the two-week sensitivity analysis, biogenic emissions induce an increase of O3, organic particles and PM2.5 street concentrations by respectively +1.1, +2.4 and + 0.5 % on average over all streets. This concentration increase may reach locally +3.5, +12.3 and + 2.9 % respectively for O3, organic particles and PM2.5, suggesting to prefer the plantation of low-emitting VOC species in cities.

Plasma 16:0 ceramide as a marker of cardiovascular risk estimated by carotid intima-media thickness in people with type 2 diabetes.

AIM: New tools are required to better assess cardiovascular risk in individuals with type 2 diabetes mellitus (T2DM). Plasma ceramides emerge as promising candidates, given their substantial influence on the pathogenesis of both T2DM and atherosclerosis. The current study aimed to investigate whether plasma ceramides in patients with T2DM are a predictive factor for carotid intima-media thickness (CIMT), a well-established noninvasive marker for atherosclerosis that predicts adverse cardiovascular outcomes. METHODS: A lipidomic analysis was carried out on the circulating ceramides of a large cohort consisting of 246 patients with T2DM who underwent a high-resolution real-time B ultrasonography to measure CIMT. RESULTS: Both plasma 16:0 ceramide and the 16:0/24:0 ceramide ratio were positively associated with CIMT, even after adjustment for traditional cardiovascular risk factors [standardized ß ± standard error: 0.168 ± 0.072 (P = 0.020) and 0.180 ± 0.068 (P = 0.009), respectively]. Similar independent associations were found with respect to the prediction of CIMT ≥ 0.80 mm [ß = 8.07 ± 3.90 (P = 0.038) and 16.5 ± 7.0 (P = 0.019), respectively]. The goodness-of-fit for multivariate models in predicting CIMT was 5.7 and 7.6 times higher when plasma 16:0 ceramide or the 16:0/24:0 ceramide ratio were included in combination with traditional cardiovascular risk factors (P = 0.020 and 0.015, respectively). This reached a 3.1 and 10.0-fold increase regarding the ability to predict CIMT ≥ 0.80 mm (P = 0.039 and 0.008, respectively). CONCLUSIONS: Our findings suggest that 16:0 ceramide and the 16:0/24:0 ceramide ratio may serve as plasma biomarkers to improve cardiovascular risk assessment in individuals with T2DM.

Collaborative and privacy-enhancing workflows on a clinical data warehouse: an example developing natural language processing pipelines to detect medical conditions.

OBJECTIVE: To develop and validate a natural language processing (NLP) pipeline that detects 18 conditions in French clinical notes, including 16 comorbidities of the Charlson index, while exploring a collaborative and privacy-enhancing workflow. MATERIALS AND METHODS: The detection pipeline relied both on rule-based and machine learning algorithms, respectively, for named entity recognition and entity qualification, respectively. We used a large language model pre-trained on millions of clinical notes along with annotated clinical notes in the context of 3 cohort studies related to oncology, cardiology, and rheumatology. The overall workflow was conceived to foster collaboration between studies while respecting the privacy constraints of the data warehouse. We estimated the added values of the advanced technologies and of the collaborative setting. RESULTS: The pipeline reached macro-averaged F1-score positive predictive value, sensitivity, and specificity of 95.7 (95%CI 94.5-96.3), 95.4 (95%CI 94.0-96.3), 96.0 (95%CI 94.0-96.7), and 99.2 (95%CI 99.0-99.4), respectively. F1-scores were superior to those observed using alternative technologies or non-collaborative settings. The models were shared through a secured registry. CONCLUSIONS: We demonstrated that a community of investigators working on a common clinical data warehouse could efficiently and securely collaborate to develop, validate and use sensitive artificial intelligence models. In particular, we provided an efficient and robust NLP pipeline that detects conditions mentioned in clinical notes.

Natural language processing of multi-hospital electronic health records for public health surveillance of suicidality.

There is an urgent need to monitor the mental health of large populations, especially during crises such as the COVID-19 pandemic, to timely identify the most at-risk subgroups and to design targeted prevention campaigns. We therefore developed and validated surveillance indicators related to suicidality: the monthly number of hospitalisations caused by suicide attempts and the prevalence among them of five known risks factors. They were automatically computed analysing the electronic health records of fifteen university hospitals of the Paris area, France, using natural language processing algorithms based on artificial intelligence. We evaluated the relevance of these indicators conducting a retrospective cohort study. Considering 2,911,920 records contained in a common data warehouse, we tested for changes after the pandemic outbreak in the slope of the monthly number of suicide attempts by conducting an interrupted time-series analysis. We segmented the assessment time in two sub-periods: before (August 1, 2017, to February 29, 2020) and during (March 1, 2020, to June 31, 2022) the COVID-19 pandemic. We detected 14,023 hospitalisations caused by suicide attempts. Their monthly number accelerated after the COVID-19 outbreak with an estimated trend variation reaching 3.7 (95%CI 2.1-5.3), mainly driven by an increase among girls aged 8-17 (trend variation 1.8, 95%CI 1.2-2.5). After the pandemic outbreak, acts of domestic, physical and sexual violence were more often reported (prevalence ratios: 1.3, 95%CI 1.16-1.48; 1.3, 95%CI 1.10-1.64 and 1.7, 95%CI 1.48-1.98), fewer patients died (p = 0.007) and stays were shorter (p < 0.001). Our study demonstrates that textual clinical data collected in multiple hospitals can be jointly analysed to compute timely indicators describing mental health conditions of populations. Our findings also highlight the need to better take into account the violence imposed on women, especially at early ages and in the aftermath of the COVID-19 pandemic.

No effect of liraglutide on high density lipoprotein apolipoprotein AI kinetics in patients with type 2 diabetes.

AIM: The catabolism of high density lipoprotein (HDL) apolipoprotein AI (apoAI) is accelerated in patients with type 2 diabetes (T2D), related to hypertriglyceridemia, insulin resistance and low plasma adiponectin levels. Since liraglutide is likely to partly correct these abnormalities, we hypothesized that it might have a beneficial effect on HDL apoAI kinetics in patients with T2D. METHODS: An in vivo kinetic study of HDL apoAI was performed in 10 patients with T2D before and after 6 months of treatment with 1.2 mg/day of liraglutide, using a bolus of l-[1-13C]leucine followed by a 16-hour constant infusion. RESULTS: Liraglutide reduced BMI (34.9 ± 4.7 vs 36.6 ± 4.9 kg/m2, P = 0.012), HbA1c (7.1 ± 1.1 vs 9.6 ± 2.6%, P = 0.003), HOMA-IR (5.5 ± 1.9 vs 11.6 ± 11.2, P = 0.003), fasting triglycerides (1.76 ± 0.37 vs 2.48 ± 0.69 mmol/l, P < 0.001) and triglycerides during kinetics (2.34 ± 0.81 vs 2.66 ± 0.65 mmol/l, P = 0.053). Plasma HDL cholesterol and adiponectin concentrations were unchanged (respectively 0.97 ± 0.26 vs 0.97 ± 0.19 mmol/l, P = 1; 3169 ± 1561 vs 2618 ± 1651 µg/l, P = 0.160), similar to triglyceride content in HDL (5.13 ± 1.73 vs 5.39 ± 1.07%, P = 0.386). Liraglutide modified neither HDL apoAI fractional catabolic rate (0.35 ± 0.11 vs 0.38 ± 0.11 pool/day, P = 0.375), nor its production rate (0.44 ± 0.13 vs 0.49 ± 0.15 g/l/day, P = 0.375), nor its plasma concentration (1.26 ± 0.19 vs 1.29 ± 0.14 g/l, P = 0.386). CONCLUSION: Six months of treatment with 1.2 mg/day of liraglutide had no effect on the kinetics of HDL apoAI in patients with T2D. The lack of decrease in triglyceride content in HDL related to an only moderate decrease in triglyceridemia, probably greatly explains these results. Insufficient improvement of insulin sensitivity and adiponectinemia may also be implied.

Variability of ambient air ammonia in urban Europe (Finland, France, Italy, Spain, and the UK).

This study addressed the scarcity of NH3 measurements in urban Europe and the diverse monitoring protocols, hindering direct data comparison. Sixty-nine datasets from Finland, France, Italy, Spain, and the UK across various site types, including industrial (IND, 8), traffic (TR, 12), urban (UB, 22), suburban (SUB, 12), and regional background (RB, 15), are analyzed to this study. Among these, 26 sites provided 5, or more, years of data for time series analysis. Despite varied protocols, necessitating future harmonization, the average NH3 concentration across sites reached 8.0 ± 8.9 µg/m3. Excluding farming/agricultural hotspots (FAHs), IND and TR sites had the highest concentrations (4.7 ± 3.2 and 4.5 ± 1.0 µg/m3), followed by UB, SUB, and RB sites (3.3 ± 1.5, 2.7 ± 1.3, and 1.0 ± 0.3 µg/m3, respectively) indicating that industrial, traffic, and other urban sources were primary contributors to NH3 outside FAH regions. When referring exclusively to the FAHs, concentrations ranged from 10.0 ± 2.3 to 15.6 ± 17.2 µg/m3, with the highest concentrations being reached in RB sites close to the farming and agricultural sources, and that, on average for FAHs there is a decreasing NH3 concentration gradient towards the city. Time trends showed that over half of the sites (18/26) observed statistically significant trends. Approximately 50 % of UB and TR sites showed a decreasing trend, while 30 % an increasing one. Meta-analysis revealed a small insignificant decreasing trend for non-FAH RB sites. In FAHs, there was a significant upward trend at a rate of 3.51[0.45,6.57]%/yr. Seasonal patterns of NH3 concentrations varied, with urban areas experiencing fluctuations influenced by surrounding emissions, particularly in FAHs. Diel variation showed differing patterns at urban monitoring sites, all with higher daytime concentrations, but with variations in peak times depending on major emission sources and meteorological patterns. These results offer valuable insights into the spatio-temporal patterns of gas-phase NH3 concentrations in urban Europe, contributing to future efforts in benchmarking NH3 pollution control in urban areas.

Inter-annual trends of ultrafine particles in urban Europe.

Ultrafine particles (UFP, those with diameters ≤ 100 nm), have been reported to potentially penetrate deeply into the respiratory system, translocate through the alveoli, and affect various organs, potentially correlating with increased mortality. The aim of this study is to assess long-term trends (5-11 years) in mostly urban UFP concentrations based on measurements of particle number size distributions (PNSD). Additionally, concentrations of other pollutants and meteorological variables were evaluated to support the interpretations. PNSD datasets from 12 urban background (UB), 5 traffic (TR), 3 suburban background (SUB) and 1 regional background (RB) sites in 15 European cities and 1 in the USA were evaluated. The non-parametric Theil-Sen's method was used to detect monotonic trends. Meta-analyses were carried out to assess the overall trends and those for different environments. The results showed significant decreases in NO, NO2, BC, CO, and particle concentrations in the Aitken (25-100 nm) and the Accumulation (100-800 nm) modes, suggesting a positive impact of the implementation of EURO 5/V and 6/VI vehicle standards on European air quality. The growing use of Diesel Particle Filters (DPFs) might also have clearly reduced exhaust emissions of BC, PM, and the Aitken and Accumulation mode particles. However, as reported by prior studies, there remains an issue of poor control of Nucleation mode particles (smaller than 25 nm), which are not fully reduced with current DPFs, without emission controls for semi-volatile organic compounds, and might have different origins than road traffic. Thus, contrasting trends for Nucleation mode particles were obtained across the cities studied. This mode also affected the UFP and total PNC trends because of the high proportion of Nucleation mode particles in both concentration ranges. It was also found that the urban temperature increasing trends might have also influenced those of PNC, Nucleation and Aitken modes.

Recommendations for reporting equivalent black carbon (eBC) mass concentrations based on long-term pan-European in-situ observations.

A reliable determination of equivalent black carbon (eBC) mass concentrations derived from filter absorption photometers (FAPs) measurements depends on the appropriate quantification of the mass absorption cross-section (MAC) for converting the absorption coefficient (babs) to eBC. This study investigates the spatial-temporal variability of the MAC obtained from simultaneous elemental carbon (EC) and babs measurements performed at 22 sites. We compared different methodologies for retrieving eBC integrating different options for calculating MAC including: locally derived, median value calculated from 22 sites, and site-specific rolling MAC. The eBC concentrations that underwent correction using these methods were identified as LeBC (local MAC), MeBC (median MAC), and ReBC (Rolling MAC) respectively. Pronounced differences (up to more than 50 %) were observed between eBC as directly provided by FAPs (NeBC; Nominal instrumental MAC) and ReBC due to the differences observed between the experimental and nominal MAC values. The median MAC was 7.8 ± 3.4 m2 g-1 from 12 aethalometers at 880 nm, and 10.6 ± 4.7 m2 g-1 from 10 MAAPs at 637 nm. The experimental MAC showed significant site and seasonal dependencies, with heterogeneous patterns between summer and winter in different regions. In addition, long-term trend analysis revealed statistically significant (s.s.) decreasing trends in EC. Interestingly, we showed that the corresponding corrected eBC trends are not independent of the way eBC is calculated due to the variability of MAC. NeBC and EC decreasing trends were consistent at sites with no significant trend in experimental MAC. Conversely, where MAC showed s.s. trend, the NeBC and EC trends were not consistent while ReBC concentration followed the same pattern as EC. These results underscore the importance of accounting for MAC variations when deriving eBC measurements from FAPs and emphasize the necessity of incorporating EC observations to constrain the uncertainty associated with eBC.

Bioplastic degradation and assimilation processes by a novel bacterium isolated from the marine plastisphere.

Biosourced and biodegradable plastics offer a promising solution to reduce environmental impacts of plastics for specific applications. Here, we report a novel bacterium named Alteromonas plasticoclasticus MED1 isolated from the marine plastisphere that forms biofilms on foils of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Experiments of degradation halo, plastic matrix weight loss, bacterial oxygen consumption and heterotrophic biosynthetic activity showed that the bacterial isolate MED1 is able to degrade PHBV and to use it as carbon and energy source. The likely entire metabolic pathway specifically expressed by this bacterium grown on PHBV matrices was shown by further genomic and transcriptomic analysis. In addition to a gene coding for a probable secreted depolymerase, a gene cluster was located that encodes characteristic enzymes involved in the complete depolymerization of PHBV, the transport of oligomers, and in the conversion of the monomers into intermediates of central carbon metabolism. The transcriptomic experiments showed the activation of the glyoxylate shunt during PHBV degradation, setting the isocitrate dehydrogenase activity as regulated branching point of the carbon flow entering the tricarboxylic acid cycle. Our study also shows the potential of exploring the natural plastisphere to discover new bacteria with promising metabolic capabilities.

Screening and management of metabolic complications of mTOR inhibitors in real-life settings.

INTRODUCTION: Inhibitors of mTOR (mTORi) are frequently used as anticancer treatment. They were responsible for metabolic side-effects in phase 3 studies, which provided only an incomplete picture of these metabolic complications. The aim of our study was therefore to evaluate, in a real-life setting, outcomes for patients with dyslipidemia or diabetes under mTORi, and the incidence and management of metabolic abnormalities occurring under mTORi in the absence of known metabolic history. METHODS: This single-center retrospective study included all 177 patients receiving everolimus in the Cancer Center of Dijon, France, between May 2015 and November 2018. RESULTS: Diabetes was diagnosed in 15 patients (9%), with an estimated mean time to onset of 160±173 days. Antidiabetic treatment was introduced in 41% of these patients. After mTORi discontinuation, diabetes persisted in 60% of patients in whom it had been diagnosed. Dyslipidemia was diagnosed in 22 patients (14%): 55% with hypercholesterolemia and 45% with hypertriglyceridemia. 18% were placed on lipid-lowering therapy. While all patients were screened for hyperglycemia and monitored for known diabetes, only 42% of patients without dyslipidemia were screened for lipids, and only 8% of patients with known dyslipidemia were monitored for lipids. CONCLUSION: Our study is one of the few to look at metabolic complications secondary to mTORi in a real-life situation. The incidence of diabetes was high, but the use of antidiabetic treatment was variable. Normalization of glucose homeostasis after mTORi discontinuation is possible, particularly in patients who have not been placed on antidiabetic therapy. Screening for dyslipidemia was clearly inadequate in our study, making the data on this point more difficult to interpret. It appears that adherence to guidelines needs to be improved to optimize the management of patients treated with mTORi.

Plasma ceramides are associated with MRI-based liver fat content but not with noninvasive scores of liver fibrosis in patients with type 2 diabetes.

BACKGROUND: There is growing evidence that ceramides play a significant role in the onset and progression of non-alcoholic fatty liver disease (NAFLD), a highly prevalent condition in patients with type 2 diabetes associated with hepatic and cardiovascular events. However, the relationship between plasma ceramide levels and NAFLD severity in type 2 diabetes remains unclear. The main purpose of the present study was to investigate whether circulating levels of ceramides in patients with type 2 diabetes are associated with liver steatosis assessed by the highly accurate magnetic resonance imaging proton density fat fraction (MRI-PDFF). The secondary objective was to assess the relationship between plasma ceramides and noninvasive scores of liver fibrosis. METHODS: In this cross-sectional single-center study, plasma concentrations of 7 ceramides were measured by liquid chromatography-mass spectrometry in 255 patients with type 2 diabetes (GEPSAD cohort). Liver fat content was assessed by MRI-PDFF, and noninvasive scores of liver fibrosis (i.e. Fibrosis-4 index, NAFLD Fibrosis Score, FibroTest® and Fibrotic NASH Index) were calculated. A validation cohort of 80 patients with type 2 diabetes was also studied (LIRA-NAFLD cohort). RESULTS: Liver steatosis, defined as a liver fat content > 5.56%, was found in 62.4 and 82.5% of individuals with type 2 diabetes in the GEPSAD and LIRA-NAFLD cohorts, respectively. In GEPSAD, MRI-PDFF-measured liver fat content was positively associated with plasma levels of total ceramides (r = 0.232, p = 0.0002), and 18:0, 20:0, 22:0 and 24:0 ceramides in univariate analysis (p ≤ 0.0003 for all). In multivariate analysis, liver fat content remained significantly associated with total ceramides (p = 0.001), 18:0 (p = 0.006), 22:0 (p = 0.0009) and 24:0 ceramides (p = 0.0001) in GEPSAD, independently of age, diabetes duration, body mass index and dyslipidemia. Overall, similar relationship between plasma ceramides and liver fat content was observed in the LIRA-NAFLD validation cohort. No significant association was found between plasma ceramides and noninvasive scores of fibrosis after adjustment for age in both cohorts. CONCLUSIONS: Plasma ceramide levels are associated with liver steatosis in patients with type 2 diabetes, independently of traditional risk factors for NAFLD. The independent association between plasma ceramides and liver steatosis adds new insights regarding the relationship between ceramides and NAFLD in type 2 diabetes.

TrisOxine abiotic siderophores for technetium complexation: radiolabeling and biodistribution studies.

BACKGROUND: Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit. First, the radiolabeling of O-TRENOX and O-TRENSOX with 99mTc was investigated. Different parameters such as the quantity of chelating agent, type of reducing agent, pH and temperature of the reaction mixture were adjusted in order to find the best radiolabeling conditions. Then an assessment of the partition coefficient by measuring the distribution of each radiosynthesized complex between octanol and phosphate-buffered saline was realized. The complex's charge was evaluated on three different celluloses (neutral, negatively charged P81 and positively charged DE81), and finally in vivo studies with biodistribution and SPECT imaging of [99mTc]Tc-O-TRENOX and [99mTc]Tc-O-TRENSOX were performed. RESULTS: The radiolabeling studies showed a rapid and efficient complexation of 99mTc with both chelating agents. Using tin pyrophosphate as the reducing agent and a minimum of 100 nmol of ligand, we obtained the [99mTc]Tc-O-TRENOX complex with a radiochemical purity of more than 98% and the [99mTc]Tc-O-TRENSOX complex with one above 97% at room temperature within 5 min. [99mTc]Tc-O-TRENOX complex was lipophilic and neutral, leading to a hepatobiliary elimination in mice. On the contrary, the [99mTc]Tc-O-TRENSOX complex was found to be hydrophilic and negatively charged. This was confirmed by a predominantly renal elimination in mice. CONCLUSIONS: These encouraging results allow us to consider the O-TRENOX/99mTc and O-TRENSOX/99mTc complexes as serious candidates for SPECT imaging chelators. This study should be continued by conjugating these tris-oxine ligands to peptides or antibodies and comparing them with the other bifunctional agents used with Tc.

Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. METHODS: The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. RESULTS: In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1ß, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. CONCLUSION: Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. TRIAL REGISTRATION: The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).

Impact of a Tripartite Collaboration between Oncologist, Pharmacist and Diabetologist in the Management of Patients with Diabetes Starting Chemotherapy: The ONCODIAB Trial.

BACKGROUND: Diabetes negatively impacts cancer prognosis. The objective of this work was to evaluate a tripartite oncologist-pharmacist-diabetologist collaboration in the management of patients with diabetes starting chemotherapy. PATIENTS AND METHODS: The prospective ONCODIAB study (NCT04315857) included 102 adults with diabetes starting chemotherapy by whom a continuous glucose monitoring device was worn for fourteen days from the first day of the first and second chemotherapy cycles. The primary outcome was to assess pharmacist and diabetologist interventions. The secondary outcome was to evaluate the impact of the ONCODIAB follow-up on individualized patient glycemic targets at 6 months. RESULTS: A total of 191 (2 per patient) were made either by clinical pharmacists (n = 95) or diabetologists (n = 96) during the first two chemotherapy cycles. The anatomic therapeutic chemical drug classes most frequently involved in pharmacist interventions were cardiovascular system (23%), alimentary tract and metabolism (22%), and anti-infectives for systemic use (14%). Diabetologists modified the antidiabetic treatment in 58 (62%) of patients: dose reduction (34%), drug discontinuation (28%), drug addition (24%), and dose increase (15%). Glycated hemoglobin decreased from 7.6 ± 1.7% at baseline to 7.1 ± 1.1% at 6 months (p = 0.02). Compared to individualized targets, HbA1c was higher, in the interval, or lower in 29%, 44%, and 27% of patients at baseline vs. in 8%, 70%, and 22% of patients at 6 months, respectively (p < 10-3). CONCLUSIONS: In our study, a close collaboration between oncologists, pharmacists, and diabetologists helped by continuous glucose monitoring led to overall medication optimization and better glycemic control in patients with diabetes starting chemotherapy.

Thermodynamical framework for effective mitigation of high aerosol loading in the Indo-Gangetic Plain during winter.

The Indo-Gangetic Plain (IGP) experiences severe air pollution every winter, with ammonium chloride and ammonium nitrate as the major inorganic fractions of fine aerosols. Many past attempts to tackle air pollution in the IGP were inadequate, as they targeted a subset of the primary pollutants in an environment where the majority of the particulate matter burden is secondary in nature. Here, we provide new mechanistic insight into aerosol mitigation by integrating the ISORROPIA-II thermodynamical model with high-resolution simultaneous measurements of precursor gases and aerosols. A mathematical framework is explored to investigate the complex interaction between hydrochloric acid (HCl), nitrogen oxides (NOx), ammonia (NH3), and aerosol liquid water content (ALWC). Aerosol acidity (pH) and ALWC emerge as governing factors that modulate the gas-to-particle phase partitioning and mass loading of fine aerosols. Six "sensitivity regimes" were defined, where PM1 and PM2.5 fall in the "HCl and HNO3 sensitive regime", emphasizing that HCl and HNO3 reductions would be the most effective pathway for aerosol mitigation in the IGP, which is ammonia-rich during winter. This study provides evidence that precursor abatement for aerosol mitigation should not be based on their descending mass concentrations but instead on their sensitivity to high aerosol loading.

The variability of mass concentrations and source apportionment analysis of equivalent black carbon across urban Europe.

This study analyzed the variability of equivalent black carbon (eBC) mass concentrations and their sources in urban Europe to provide insights into the use of eBC as an advanced air quality (AQ) parameter for AQ standards. This study compiled eBC mass concentration datasets covering the period between 2006 and 2022 from 50 measurement stations, including 23 urban background (UB), 18 traffic (TR), 7 suburban (SUB), and 2 regional background (RB) sites. The results highlighted the need for the harmonization of eBC measurements to allow for direct comparisons between eBC mass concentrations measured across urban Europe. The eBC mass concentrations exhibited a decreasing trend as follows: TR > UB > SUB > RB. Furthermore, a clear decreasing trend in eBC concentrations was observed in the UB sites moving from Southern to Northern Europe. The eBC mass concentrations exhibited significant spatiotemporal heterogeneity, including marked differences in eBC mass concentration and variable contributions of pollution sources to bulk eBC between different cities. Seasonal patterns in eBC concentrations were also evident, with higher winter concentrations observed in a large proportion of cities, especially at UB and SUB sites. The contribution of eBC from fossil fuel combustion, mostly traffic (eBCT) was higher than that of residential and commercial sources (eBCRC) in all European sites studied. Nevertheless, eBCRC still had a substantial contribution to total eBC mass concentrations at a majority of the sites. eBC trend analysis revealed decreasing trends for eBCT over the last decade, while eBCRC remained relatively constant or even increased slightly in some cities.

Ambient air particulate total lung deposited surface area (LDSA) levels in urban Europe.

This study aims to picture the phenomenology of urban ambient total lung deposited surface area (LDSA) (including head/throat (HA), tracheobronchial (TB), and alveolar (ALV) regions) based on multiple path particle dosimetry (MPPD) model during 2017-2019 period collected from urban background (UB, n = 15), traffic (TR, n = 6), suburban background (SUB, n = 4), and regional background (RB, n = 1) monitoring sites in Europe (25) and USA (1). Briefly, the spatial-temporal distribution characteristics of the deposition of LDSA, including diel, weekly, and seasonal patterns, were analyzed. Then, the relationship between LDSA and other air quality metrics at each monitoring site was investigated. The result showed that the peak concentrations of LDSA at UB and TR sites are commonly observed in the morning (06:00-8:00 UTC) and late evening (19:00-22:00 UTC), coinciding with traffic rush hours, biomass burning, and atmospheric stagnation periods. The only LDSA night-time peaks are observed on weekends. Due to the variability of emission sources and meteorology, the seasonal variability of the LDSA concentration revealed significant differences (p = 0.01) between the four seasons at all monitoring sites. Meanwhile, the correlations of LDSA with other pollutant metrics suggested that Aitken and accumulation mode particles play a significant role in the total LDSA concentration. The results also indicated that the main proportion of total LDSA is attributed to the ALV fraction (50 %), followed by the TB (34 %) and HA (16 %). Overall, this study provides valuable information of LDSA as a predictor in epidemiological studies and for the first time presenting total LDSA in a variety of European urban environments.