Chemokine-like Orion is involved in the transformation of glial cells into phagocytes in different developmental neuronal remodeling paradigms.

During animal development, neurons often form exuberant or inappropriate axons and dendrites at early stages, followed by the refinement of neuronal circuits at late stages. Neural circuit refinement leads to the production of neuronal debris in the form of neuronal cell corpses, fragmented axons and dendrites, and pruned synapses requiring disposal. Glial cells act as predominant phagocytes during neuronal remodeling and degeneration, and crucial signaling pathways between neurons and glia are necessary for the execution of phagocytosis. Chemokine-like mushroom body neuron-secreted Orion is essential for astrocyte infiltration into the γ axon bundle leading to γ axon pruning. Here, we show a role of Orion in debris engulfment and phagocytosis in Drosophila. Interestingly, Orion is involved in the overall transformation of astrocytes into phagocytes. In addition, analysis of several neuronal paradigms demonstrates the role of Orion in eliminating both peptidergic vCrz+ and PDF-Tri neurons via additional phagocytic glial cells like cortex and/or ensheathing glia. Our results suggest that Orion is essential for phagocytic activation of astrocytes, cortex and ensheathing glia, and point to Orion as a trigger of glial infiltration, engulfment and phagocytosis.

The Drosophila chemokine-like Orion bridges phosphatidylserine and Draper in phagocytosis of neurons.

Phagocytic clearance of degenerating neurons is triggered by "eat-me" signals exposed on the neuronal surface. The conserved neuronal eat-me signal phosphatidylserine (PS) and the engulfment receptor Draper (Drpr) mediate phagocytosis of degenerating neurons in Drosophila. However, how PS is recognized by Drpr-expressing phagocytes in vivo remains poorly understood. Using multiple models of dendrite degeneration, we show that the Drosophila chemokine-like protein Orion can bind to PS and is responsible for detecting PS exposure on neurons; it is supplied cell-non-autonomously to coat PS-exposing dendrites and to mediate interactions between PS and Drpr, thus enabling phagocytosis. As a result, the accumulation of Orion on neurons and on phagocytes produces opposite outcomes by potentiating and suppressing phagocytosis, respectively. Moreover, the Orion dosage is a key determinant of the sensitivity of phagocytes to PS exposed on neurons. Lastly, mutagenesis analyses show that the sequence motifs shared between Orion and human immunomodulatory proteins are important for Orion function. Thus, our results uncover a missing link in PS-mediated phagocytosis in Drosophila and imply conserved mechanisms of phagocytosis of neurons.

Major Concepts in Treatment with Bempedoic Acid and Inclisiran that Clinicians Need To Know.

PURPOSE OF REVIEW: There have been recent developments of novel therapeutic agents for lipid lowering. This article reviews treatment concepts for two of the newest lipid-lowering medications. RECENT FINDINGS: Bempedoic acid inhibits adenosine citrate lyase, decreasing intracellular lipogenesis. This oral medication is a prodrug and requires activation by enzymes present in hepatocytes but absent in the skeletal muscle. Clinical trials demonstrated additive benefit with statin therapy, and it was well tolerated in statin-intolerant populations. Inclisiran uses RNA interference to prevent translation of PCSK9 mRNA. Due to its stability, it can be given as an injection every 6 months and produces consistent, durable, and potent cholesterol lowering. Bempedoic acid and inclisiran represent new avenues of treatment for the prevention and treatment of cardiovascular disease. This will allow for more comprehensive care by addressing challenges with medication adherence, such as adverse effects to prior medications as well as ease of dosing.

Comparison of clockwise and counterclockwise right atrial flutter using high-resolution mapping and automated velocity measurements.

BACKGROUND: Only few studies have been performed that explore the electrophysiological differences between clockwise (CW) and counterclockwise (CCW) right atrial (RA) cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) using the high-resolution Rhythmia mapping system. OBJECTIVES: We sought to compare CW and CCW CTI-dependent AFL in pure right AFL patients (pts) using the ultra-high-definition (ultra-HD) Rhythmia mapping system and we mathematically developed a cartography model based on automatic velocity RA measurements to identify electrophysiological AFL specificities. METHODS AND RESULTS: Thirty-three pts were recruited. The mean age was 71 ± 13 years old. The sinus venosus (SV) block line was present in 32/33 of cases (97%) and no significant difference was found between CCW and CW CTI AFL (100% vs. 91%; p = .7). No line was localized in the region of the crista terminalis (CT). A superior gap was present in the posterior line in 14/31 (45.2%) but this was similarly present in CCW AFL, when compared to CW AFL (10/22 [45.5%] vs. 4/10 [40%]; p = .9). When present, the extension of the posterior line of block was observed in 18/31 pts (58%) without significant differences between CCW and CW CI AFL (12/22 [54.5%] vs. 6/10 [60%]; p = .9) The Eustachian ridge line of block was similarly present in both groups (82% [18/22] vs. 45.5% [5/11]; p = .2). The absence of the Eustachian ridge line of block led to significantly slowed velocity in this area (28 ± 10 cm/s; n = 8), and the velocities were similarly altered between both groups (26 ± 10 [4/22] vs. 29.8 ± 11 cm/s [4/11]; p = .6). We created mathematical, three-dimensional RA reconstruction-velocity model measurements. In each block localization, when the block line was absent, velocity was significantly slowed (≤20 cm/s). A systematic slowdown in conduction velocity was observed at the entrance and exit of the CTI in 100% of cases. This alteration to the conduction entrance was localized at the lateral side of the CTI for the CCW AFL and at the septal side of the CTI for CW AFL. The exit-conduction alteration was localized at the CTI septal side for the CCW AFL and at the CTI lateral side for the CW AFL. CONCLUSION: The ultra-HD Rhythmia mapping system confirmed the absence of significant electrophysiological differences between CCW and CW AFL. The mechanistic posterior SV and Eustachian ridge block lines were confirmed in each arrhythmia. A systematic slowing down at the entrance and exit of the CTI was demonstrated in both CCW and CW AFL, but in reverse positions.

Modal Propellant Gauging: High-resolution and non-invasive gauging of both settled and unsettled liquids in reduced gravity.

The modal response of a liquid-filled tank to external acoustic excitation can be used to infer with high resolution the mass of contained liquid, the mass flow rate of liquids into and out of the tank, and changes in tank pressure. Both contained liquid mass and internal ullage pressure affect the modal response of the tank walls through fluid mass-loading of the tank walls and pressure-induced wall stiffening, respectively. Modal Propellant Gauging refers to the technology that exploits these shifts in modal frequencies to infer the mass of propellant in a tank. MPG is a non-invasive gauging technology that has demonstrated gauging resolutions of 1% for settled propellants and 2-3% for unsettled, sloshing propellants. Extensive parabolic flight testing of the MPG system on model tanks has been conducted to validate the technology in reduced gravity. MPG testing on a qualification tank for the Orion Program's European Service Module has also been conducted and is reported here. Finite element modeling of the Orion ESM ″upper" tank is discussed and compared with measurement data. Three computational approaches to mass determination, Peak Tracking, Point Sensor, and Spectral Density methods, are described here. Use cases are defined and analyzed in the context of the Orion ESM Qualification tank data, and an implementation scheme for continuous mass gauging on the Orion ESM is discussed.

Antimicrobial resistance, virulence potential and genomic epidemiology of global genomes of the rare Salmonella enterica serovar Orion.

AIMS: Our aim is to characterize through whole-genome sequencing (WGS) the antimicrobial resistance (AMR) and heavy metal tolerance (HMT) genes content, plasmid presence, virulence potential and genomic diversity of the rare non-typhoid Salmonella enterica serovar Orion (S. Orion) from 19 countries of the African, American, Eastern Mediterranean, European, Southeastern Asia and Western Pacific regions. METHODS AND RESULTS: Totally 324 S. Orion genomes were screened for AMR, HMT and virulence genes, plasmids and Salmonella Pathogenicity Islands (SPIs). Genomic diversity was investigated using Multi-Locus Sequence Typing (MLST) and core-genome MLST (cgMLST). Efflux pump encoding genes mdsA and mdsB were present in all genomes analysed, while quinolone chromosomal point mutations and aminoglycoside, beta-lactam, colistin, lincosamide, macrolide, phenicol, sulphonamide, trimethoprim, tetracycline and disinfectant resistance genes were found in 0.3%-5.9%. A total of 17 genomes (5.2%) from Canada, the United Kingdom, the USA and Tanzania showed a potential multi-drug resistance profile. Gold tolerance genes golS and golT were detected in all genomes analysed, while arsenic, copper, mercury, silver and tellurium tolerance genes were found in 0.3%-35.5%. Col(MGD2) was the most frequently detected plasmid, in 15.4% of the genomes. Virulence genes related to adherence, macrophage induction, magnesium uptake, regulation, serum resistance, stress adaptation, type III secretion systems and six SPIs (1, 2, 3, 4, 5, 9, 12, 13, 14 and C63PI) were detected. ST639 was assigned to 89.2% of the S. Orion genomes, while cgMLST showed core-genome STs and clusters of strains specific by countries. CONCLUSION: The high virulence factor frequencies, the genomic similarity among some non-clinical and clinical strains circulating worldwide and the presence of a strain carrying a resistance gene against a last resource antimicrobial like colistin, highlight the potential risk of S. Orion strains for public health and food safety and reinforce the importance to not underestimate the potential hazard of rare non-typhoid Salmonella serovars.

Epidemiology of patients with dizziness over a 3-year period, requiring utilization of the emergency medical serviced system: A pre- and post-COVID pandemic comparative study using the population-based ORION registry.

OBJECTIVE: We aimed to identify the proportion of each medical condition or disease contributing to dizziness and their disposition in the Emergency Department (ED). METHODS: This retrospective, descriptive study examined data from the Osaka Emergency Information Research Intelligent Operation Network system in Japan for the period from January 1, 2018 to December 31, 2020. The inclusion criteria were patients with presumptive ICD-10 codes including "dizziness" or "vertigo". Patient demographics were compared using the χ2 test and Kruskal-Wallis test. Logistic regression analysis was performed to calculate disposition from ED (emergency admission or discharge) over the 3-year study period. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate analyses. RESULTS: During the 3-year study period, a total of 1,346,457 patients (462,773 in 2018, 468,697 in 2019, and 414,987 in 2020; P < 0.001), including 53,190 patients with dizziness (18,396 in 2018, 18,649 in 2019, and 16,145 in 2020; P = 0.058), were identified as having been transported to hospitals by ambulance in Osaka Prefecture. Dizziness and giddiness (R42) was the most common form of dizziness, in 27,075 cases (9,570 in 2018, 9,613 in 2019, and 7,892 in 2020; P < 0.001; Gender composition showed 10,483 males and 16,592 females.) Vestibular Neuronitis (H81.2) showed significant increase in 2020 compared to the two preceding years (91 in 2018, 119 in 2019, and 130 in 2020, P = 0.003; including 174 males and 167 females, respectively). Of the 53,190 patients with dizziness, 11,862 (22.3%; 4,323 males, 7,539 females) were admitted to hospital. The odds ratio (OR) for emergency admission for dizziness in 2020 during the COVID-19 pandemic was 0.98 (95% confidence interval (CI), 0.93- 1.03) with reference to 2018. CONCLUSION: Patients with dizziness accounted approximately 4% of ED transportations, with about 20% requiring hospital admission, irrespective of the COVID-19 pandemic. Vestibular neuronitis was significantly increased in 2020.

Single-center experience of ultra-high-density mapping guided catheter ablation of focal atrial tachycardia.

INTRODUCTION: Catheter ablation is the treatment of choice for recurrent focal atrial tachycardia (FAT) as medical therapy is limited. Routinely, a three-dimensional mapping system is used. Whether or not optimized signal detection does improve ablation success rates has not yet been investigated. This retrospective cohort study compared ablation procedures using an ultra-high-density mapping system (UHDM, Rhythmia, Boston Scientific) with improved signal detection and automatic annotation with procedures using a conventional electroanatomic mapping system (CEAM, Biosense Webster, CARTO). METHODS: All patients undergoing ablation for FAT using UHDM or CEAM from April 2015 to August 2018 were included. Endpoints comprised procedural parameters, acute success as well as freedom from arrhythmia 12 months after ablation. RESULTS: A total of 70 patients underwent ablation (48 with UHDM, 22 with CEAM). No significant differences were noted for parameters like procedural and radiation duration, area dose, and RF applications. Acute success was significantly higher in the UHDM cohort (89.6% vs. 68.2%, p = .03). Nevertheless, arrhythmia freedom 12 months after ablation was almost identical (56.8% vs. 60%, p = .87), as more patients with acute success of ablation presented with a relapse during follow-up (35.0 vs. 7.7%, p = .05). CONCLUSION: Acute success rate of FAT ablation might be improved by UHDM, without an adverse effect on procedural parameters. Nevertheless, further research is needed to understand the underlying mechanism for increased recurrence rates after acute successful ablation.

Dataset of experimental measurements for the Orion beam structure.

This data article comprises experimental data to investigate the nonlinear dynamic behavior of the Orion beam structure, which consists of two duraluminum beams assembled by bolted joints. To retain contact on a small area between both beams, this new lap-joint configuration proposes contact patches at each bolt connection. The Orion beam suggests an assembly configuration that associates bolts dedicated to 'static' functions and to those to perform 'damping' functions. This ensures a significant increase in the structural damping without degrading the structural stiffness. Experiments have been performed on the laboratory ple Vibration and Acoustic, located at FEMTO-ST Institute, CNRS/UFC/ENSMM/UTBM, Department of Applied Mechanics, 24 chemin de lEpitaphe, 25000 Besanon, France. This data aim to provide the geometrical step and all the experimental measurements performed on our lap-joint for several excitation amplitudes and tightening torques, as far as possible and with the degree of uncertainties of the measurements. By doing so, we intend to provide experimental data, as precise and reliable as possible, which are required to progress on the numerical modelling of the dry friction damping in assembly structures. This Data in Brief article is an additional research item alongside the following paper published in the Mechanical Systems and Signal Processing journal: R. O. Teloli, P. Butaud, G. Chevallier and S. da Silva, Good practices for designing and experimental testing of dynamically excited jointed structures: the Orion beam.

The genome sequence of the grey wolf, Canis lupus Linnaeus 1758.

We present a genome assembly from an individual male Canis lupus orion (the grey wolf, subspecies: Greenland wolf; Chordata; Mammalia; Carnivora; Canidae). The genome sequence is 2,447 megabases in span. The majority of the assembly (98.91%) is scaffolded into 40 chromosomal pseudomolecules, with the X and Y sex chromosomes assembled.

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Presbyopic Glaucoma Patients in a Randomized Phase 2b Clinical Trial.

PURPOSE: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population. PATIENTS AND METHODS: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia. RESULTS: Use of 1% PMOS did not lead to a statistically significant decrease in diurnal IOP compared to placebo (P = 0.89) but trended toward a greater decrease in patients with lower IOP baselines. PMOS produced a statistically significant mean 20% PD reduction under both photopic and mesopic conditions that was sustained for 36 hours post-dosing. A statistically significant number of patients with PMOS compared to placebo demonstrated ≥1 line of improvement in photopic DCNVA at day 8 (P = 0.0018), day 15 (P = 0.0072), and day 16 (P = 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo. CONCLUSION: Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.

Population Genetic Structure and Demography of the Critically Endangered Chequered Blue Butterfly (Scolitantides orion) in a Highly Isolated Part of Its Distribution Range.

Scolitantides orion is a butterfly species threatened in many European countries. In Poland, it survived in a single highly isolated area (Vistula River valley), which is an example of the dramatic decline in the population number. We studied the two largest remaining populations inhabiting opposite banks of the river. Mark-release-recapture studies showed that both populations were small, and they fluctuated in numbers, but adult individuals were twice as numerous on the western site. Genetic analyses were carried out using a mitochondrial (COI, ND5) and nuclear markers (Wgl, EF-1α, and microsatellite loci). We found out that genetic variation was low at both sites but higher in the smaller eastern population. This pattern is likely to be better explained by past distribution, when the butterfly, as a continental species used to be much more widespread in the east. However, the genetic differentiation between populations was low. This could suggest that the existing gene flow is facilitated by dominant regional wind direction, which may also contribute to a better genetic condition of the western population. Finally, a comparison of the obtained COI sequences with others available enabled us to reveal the phylogeographic pattern of the S. orion from different localities within its range.

Novel emerging therapies in atherosclerosis targeting lipid metabolism.

INTRODUCTION: Recent years have brought significant developments in lipid and atherosclerosis research. Although statins are a cornerstone in hyperlipidemia management, new non-statin therapies have had an impact. The reduction of low-density lipoprotein cholesterol (LDL-C) further translates into the lowering of cardiovascular mortality. Additionally, lipid research has progressed beyond LDL-C reduction and this has brought triglyceride (TG) and other apoprotein-B containing lipids into focus. AREAS COVERED: Inclisiran and pemafibrate, with expected approval soon, come under the spotlight. We discuss other therapeutics such as lomitapide, mipomersen, volanesorsen, and evinacumab and newly approved non-statin-based therapies such as ezetimibe, icosapent ethyl (IPE), and bempedoic acid. EXPERT OPINION: New options now exist for the prevention of atherosclerosis in patients that are not optimized on statin therapy. Multiple guidelines endorse ezetimibe, PCSK9 inhibitors, bempedoic, and IPE as add-on therapy. Recently approved bempedoic acid/ezetimibe combination might gain popularity among clinicians. Inclisiran and pemafibrate show promise in the reduction of LDL-C and TG, respectively, and results are pending in cardiovascular outcome trials. Combination strategies could improve outcomes, but the challenge will be balancing cost and selecting the correct patient population for each treatment modality to maximize benefit with the fewest medications.

[Experience feedback committees (CREX) in French radiotherapy departments in 2019]. / Comités de retour d'expérience (CREX) dans les centres de radiothérapie français en 2019.

Ten years after the beginning of CREX in radiotherapy departments we wanted to know about users' feeling. We sent a survey to 168 centers in the whole country and a hundred of them answer. The time, top management's involvement and professionals' training seem to be the key success factors. Systemic analysis methods and mainly the Orion© one are not identified as an issue. The main challenge for the next years will be the effectiveness check of actions.

Initial single centre experience with the novel Rhythmia© high density mapping system in an all comer collective of 400 electrophysiological patients.

BACKGROUND: A novel, automatically annotating ultra-high density mapping system (Rhythmia©, Boston Scientific) collects a high number and quality of electrograms (EGMs). So far, data on general use in the electrophysiological laboratory are sparse. METHODS: We retrospectively analyzed all our ablations using Rhythmia and recorded patient clinical data, procedural parameters, and mapping parameters including the count of EGMs, mapping time, and mapping volume. Where appropriate, procedural parameters were compared over time to assess a learning curve. RESULTS: 400 patients underwent ablation of atrial fibrillation (n = 202), typical (n = 16) or atypical atrial flutter (n = 49), VT (n = 48), PVC (n = 35), accessory pathways (n = 14), AVNRT (n = 4), and focal atrial tachycardia (n = 32). System use was feasible, as no procedure had to be stopped for technical reasons and no ablation had to be withheld because of mapping failure, and safe, with an overall complication rate of 2.25%. Initial restrictions in manoeuvrability of the mapping catheter were overcome rapidly, as indicated by a significant decrease of fluoroscopy time (20 vs. 14 min, p = 0.02), use of contrast agent (50 vs. 40 ml; p < 0.01), and (not significant) lower procedure times (194 vs. 170 min; p = 0.12; comparing the first with the last third of patients undergoing pulmonary vein isolation only procedure). Ablation of complex left atrial, focal and ventricular tachycardias benefited from the reliable automatic annotation of a high number of EGMs. CONCLUSION: The use of the Rhythmia is feasible and safe. Initial restrictions in manoeuvrability of the Orion mapping catheter were overcome rapidly. The procedures that benefit the most from ultra-high density mapping are complex left atrial tachycardias, focal tachycardias, and ventricular tachycardias.

Nosocomial outbreaks caused by Acinetobacter baumannii and Pseudomonas aeruginosa: Results of a systematic review.

BACKGROUND: Large outbreaks of infection by Acinetobacter baumannii and Pseudomonas aeruginosa have been reported. This research compares characteristics of such outbreaks. OBJECTIVES: Determination of risk factors for the occurrence and appropriate infection control measures. DATA SOURCES: The Outbreak Database, PubMed, and reference lists of identified articles were used. Key words included nosocomial and (outbreak or epidemic) and (aeruginosa or baumannii). STUDY ELIGIBILITY CRITERIA: Articles were included if they describe distinct outbreak(s) caused by A baumannii or P aeruginosa and were published between 2000 and 2015. There were no further restrictions with respect to language or type of article. RESULTS: One hundred fifty outbreaks by A baumannii and 131 outbreaks by P aeruginosa were included, including multidrug-resistant strains in 113 Acinetobacter and 49 Pseudomonas outbreaks. Acinetobacter outbreaks were mainly reported from intensive care units, after use of antibiotics, during mechanical ventilation, and presented with a mortality rate of 47% compared with 23% by Pseudomonas. Resistance did not alter mortality by either species. Most infection control measures were implemented or enforced more often in Acinetobacter outbreaks. CONCLUSIONS: These findings should support staff in infection control departments and on wards if an outbreak is suspected. Better adherence to the Outbreak Reports and Intervention Studies of Nosocomial Infection guidelines in outbreak reporting is necessary. A precise definition of multidrug resistance for Acinetobacter and Pseudomonas is lacking.

Psychophysiological assessment and correction of spatial disorientation during simulated Orion spacecraft re-entry.

The National Aeronautics and Space Administration (NASA) has identified a potential risk of spatial disorientation, motion sickness, and degraded performance to astronauts during re-entry and landing of the proposed Orion crew vehicle. The purpose of this study was to determine if a physiological training procedure, Autogenic-Feedback Training Exercise (AFTE), can mitigate these adverse effects. Fourteen men and six women were assigned to two groups (AFTE, no-treatment Control) matched for motion sickness susceptibility and gender. All subjects received a standard rotating chair test to determine motion sickness susceptibility; three training sessions on a manual performance task; and four exposures in the rotating chair (Orion tests) simulating angular accelerations of the crew vehicle during re-entry. AFTE subjects received 2 h of training before Orion tests 2, 3, and 4. Motion sickness symptoms, task performance, and physiological measures were recorded on all subjects. Results showed that the AFTE group had significantly lower symptom scores when compared to Controls on test 2 (p = .05), test 3 (p = .03), and test 4 (p = .02). Although there were no significant group differences on task performance, trends showed that AFTE subjects were less impaired than Controls. Heart rate change scores (20 rpm minus baseline) of AFTE subjects indicated significantly less reactivity on Test 4 compared to Test 1 (10.09 versus 16.59, p = .02), while Controls did not change significantly across tests. Results of this study indicate that AFTE may be an effective countermeasure for mitigating spatial disorientation and motion sickness in astronauts.

Clustering the Orion B giant molecular cloud based on its molecular emission.

CONTEXT: Previous attempts at segmenting molecular line maps of molecular clouds have focused on using position-position-velocity data cubes of a single molecular line to separate the spatial components of the cloud. In contrast, wide field spectral imaging over a large spectral bandwidth in the (sub)mm domain now allows one to combine multiple molecular tracers to understand the different physical and chemical phases that constitute giant molecular clouds (GMCs). AIMS: We aim at using multiple tracers (sensitive to different physical processes and conditions) to segment a molecular cloud into physically/chemically similar regions (rather than spatially connected components), thus disentangling the different physical/chemical phases present in the cloud. METHODS: We use a machine learning clustering method, namely the Meanshift algorithm, to cluster pixels with similar molecular emission, ignoring spatial information. Clusters are defined around each maximum of the multidimensional Probability Density Function (PDF) of the line integrated intensities. Simple radiative transfer models were used to interpret the astrophysical information uncovered by the clustering analysis. RESULTS: A clustering analysis based only on the J = 1 - 0 lines of three isotopologues of CO proves suffcient to reveal distinct density/column density regimes (nH ~ 100 cm-3, ~ 500 cm-3, and > 1000 cm-3), closely related to the usual definitions of diffuse, translucent and high-column-density regions. Adding two UV-sensitive tracers, the J = 1 - 0 line of HCO+ and the N = 1 - 0 line of CN, allows us to distinguish two clearly distinct chemical regimes, characteristic of UV-illuminated and UV-shielded gas. The UV-illuminated regime shows overbright HCO+ and CN emission, which we relate to a photochemical enrichment effect. We also find a tail of high CN/HCO+ intensity ratio in UV-illuminated regions. Finer distinctions in density classes (nH ~ 7 × 103 cm-3 ~ 4 × 104 cm-3) for the densest regions are also identified, likely related to the higher critical density of the CN and HCO+ (1 - 0) lines. These distinctions are only possible because the high-density regions are spatially resolved. CONCLUSIONS: Molecules are versatile tracers of GMCs because their line intensities bear the signature of the physics and chemistry at play in the gas. The association of simultaneous multi-line, wide-field mapping and powerful machine learning methods such as the Meanshift clustering algorithm reveals how to decode the complex information available in these molecular tracers.