Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths.

BACKGROUND: Mesophotic coral communities are increasingly gaining attention for the unique biological diversity they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies on corals have rarely included mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers. RESULTS: Here, we used reduced-representation genome sequencing to conduct a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed deep divergences within the two genera and undescribed diversity across the current taxonomic species. Five of the eight focal species consisted of at least two sympatric and genetically distinct lineages, which were consistently detected across different methods. CONCLUSIONS: The repeated observation of genetically divergent lineages associated with mesophotic depths highlights that there may be many more mesophotic-specialist coral species than currently acknowledged and that an urgent assessment of this largely unstudied biological diversity is warranted.

Pleural effusion in a child with a correctly placed ventricle-peritoneal shunt.

Pleural effusions in children (PE) due to ventricle-peritoneal shunt (VPS) is very rare, with few cases reported. We present a new case of an infant with VPS who had a massive hydrothorax not associated with misplacement or migration of the distal catheter or with ascites. After the evacuation of the PE we managed the patient by adjusting the pressure of the adjustable valve (AV). Sequential thoracic ultrasounds showed a satisfactory outcome. We review the literature thoroughly and describe the possible pathophysiological mechanisms.

Deep Learning-Based Feature Extraction of Acoustic Emission Signals for Monitoring Wear of Grinding Wheels.

Tool wear monitoring is a critical issue in advanced manufacturing systems. In the search for sensing devices that can provide information about the grinding process, Acoustic Emission (AE) appears to be a promising technology. The present paper presents a novel deep learning-based proposal for grinding wheel wear status monitoring using an AE sensor. The most relevant finding is the possibility of efficient feature extraction form frequency plots using CNNs. Feature extraction from FFT plots requires sound domain-expert knowledge, and thus we present a new approach to automated feature extraction using a pre-trained CNN. Using the features extracted for different industrial grinding conditions, t-SNE and PCA clustering algorithms were tested for wheel wear state identification. Results are compared for different industrial grinding conditions. The initial state of the wheel, resulting from the dressing operation, is clearly identified for all the experiments carried out. This is a very important finding, since dressing strongly affects operation performance. When grinding parameters produce acute wear of the wheel, the algorithms show very good clustering performance using the features extracted by the CNN. Performance of both t-SNE and PCA was very much the same, thus confirming the excellent efficiency of the pre-trained CNN for automated feature extraction from FFT plots.

Use of emerging technologies in the extraction of lupeol, α-amyrin and ß-amyrin from sea grape (Coccoloba uvifera L.).

Emerging technologies are being explored to improve extraction yields of phytochemicals or high-value biological compounds. The aim of this study was to evaluate the extraction of lupeol, α-, and ß-amyrin from fruit, leaf and stem of the sea grape tree (Coccoloba uvifera L.) using technologies such as Ultrasound Assisted Extraction (UAE) and High Hydrostatic Pressure Extraction (HHPE). Results were compared to conventional extraction (maceration). Analysis with thin-layer chromatography revealed the presence of lupeol in all studied parts of the tree. Optimal extraction conditions for UAE and HHPE were found; the highest concentration of triterpenes was obtained by UAE after evaluating conventional and non-conventional techniques. Finally, analysis of different tree parts and other vegetable sources showed that the best source of triterpenes was the leaf.

Androgen receptor gene polymorphism influence fat accumulation: A longitudinal study from adolescence to adult age.

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean ± SD: 12.8 ± 3.6 years old at recruitment, and 27.0 ± 4.8 years old at adult age]. Subjects were grouped as CAG short (CAGS ) if harboring repeat lengths ≤ 21, the rest as CAG long (CAGL ); and GGN short (GGNS ) if GGN repeat lengths ≤ 23, or long if > 23 (GGNL ). CAGS and GGNS were associated with lower adiposity than CAGL or GGNL (P < 0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r = 0.34, P = 0.03). At adult age, CAGS men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAGL (P < 0.05). GGNS men also showed lower percentage of body fat (P < 0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age.

Genetic parameters and genotype-environment interactions for skeleton deformities and growth traits at different ages on gilthead seabream (Sparus aurata L.) in four Spanish regions.

One of the most important problems of fish aquaculture is the high incidence of fish deformities, which are mainly skeletal. In this study, genetic parameters on gilthead seabream (Sparus aurata L.) for skeleton deformities at different ages (179, 269, 389, 539 and 689 days) and their correlations with growth traits were estimated, as were as their genotype × environment interactions (G × E) at harvesting age. A total of 4093 offspring from the mass spawning of three industrial broodstocks belonging to the PROGENSA(®) breeding programme were mixed and on-grown by different production systems in four Spanish regions: Canary Islands (tanks and cage), Andalusia (estuary), Catalonia (cage) and Murcia (cage). Parental assignment was inferred using the standardized SMsa1 microsatellite multiplex PCR. From three broodstocks, 139 breeders contributed to the spawn and a total of 297 full-sibling families (52 paternal and 53 maternal half-sibling families) were represented. Heritabilities at different ages were medium for growth traits (0.16-0.48) and vertebral deformities (0.16-0.41), and low for any type of deformity (0.07-0.26), head deformities (0.00-0.05) and lack of operculum (0.06-0.11). The genetic correlations between growth and deformity traits were medium and positive, suggesting that to avoid increasing deformities they should be taken into account in breeding programmes when growth is selected. The G × E interactions among the different facilities were weak for length and deformity and strong for growth rate during this period. These results highlight the potential for the gilthead seabream industry to reduce the prevalence of deformities by genetic improvement tools.

Inhibition of quorum-sensing-dependent virulence factors and biofilm formation of clinical and environmental Pseudomonas aeruginosa strains by ZnO nanoparticles.

UNLABELLED: Quorum quenching decreases Pseudomonas aeruginosa virulence factors and biofilm formation, alleviating infections in animal models. Nevertheless, it is usually performed in laboratory strains such as PAO1 and PA14, and studies involving clinical or environmental isolates are scarce. In this work, the effects of ZnO nanoparticles, a potent quorum and virulence quencher for the PAO1 strain, were tested in six clinical strains from cystic fibrosis patients, a furanone C-30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C-30 resistant mutant and four environmental isolates. ZnO nanoparticles effectively decreased elastase, pyocyanin, and biofilm formation for most of the strains; regardless their origin or their resistance against the canonical quorum quencher C-30 or the novel antimicrobial gallium. The data indicate ZnO nanoparticles may have a broad spectrum for the quorum quenching of relevant strains and that may be an alternative to treat Ps. aeruginosa recalcitrant infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Virulence inhibition by quorum quenchers in Pseudomonas aeruginosa is usually tested in laboratory strains and studies of their effects in relevant clinical and environmental strains are scarce. This study is significant as the effects of ZnO nanoparticles in QS-dependent virulence factor production were tested in six clinical strains from cystic fibrosis patients, a C-30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C-30 resistant mutant, and four environmental isolates. ZnO nanoparticles decreased elastase, pyocyanin, and biofilms for most of the strains; indicating they have broad spectrum and may be an alternative to treat Ps. aeruginosa infections.

Coincidence of Tracheobronchomegaly (Mounier-Kuhn Syndrome) and Juvenile Idiopathic Arthritis.

Mounier-Kuhn syndrome (MKS) or tracheobronchomegaly includes clinical and radiographic findings of tracheobronchial dilatation and recurrent respiratory infections. MKS is a very rare pathology, especially in the paediatric age group which makes it a diagnostic challenge. A 4-year-old girl suffered from dyspnea, recurrent respiratory infections and joint pain. Chest radiography detected peribronchial reinforcement and CT-scan revealed extended tracheal dilatation and bronchiectasis. In addition to MKS our patient was diagnosed with juvenile idiopathic arthritis (JIA) and scleroderma. MKS can be caused by congenital disorder or acquired aetiology. Several connective tissue diseases have been associated with MKS but no cases of JIA or scleroderma are described previously. Our case illustrates that patients who suffer from recurrent respiratory infections with unsatisfactory evolution and unspecific chest X-ray alteration, MKS always has to be considered in the differential diagnosis particularly in patients who suffer from connective tissue diseases.

Analysis of stroke care resources in Spain in 2012: have we benefitted from the Spanish Health System's stroke care strategy?

INTRODUCTION: The Spanish Health System's stroke care strategy (EISNS) is a consensus statement that was drawn up by various government bodies and scientific societies with the aim of improving quality throughout the care process and ensuring equality among regions. Our objective is to analyse existing healthcare resources and establish whether they have met EISNS targets. MATERIAL AND METHODS: The survey on available resources was conducted by a committee of neurologists representing each of Spain's regions; the same committee also conducted the survey of 2008. The items included were the number of stroke units (SU), their resources (monitoring, neurologists on call 24h/7d, nurse ratio, protocols), SU bed ratio/100,000 inhabitants, diagnostic resources (cardiac and cerebral arterial ultrasound, advanced neuroimaging), performing iv thrombolysis, neurovascular interventional radiology (neuro VIR), surgery for malignant middle cerebral artery (MCA) infarctions and telemedicine availability. RESULTS: We included data from 136 hospitals and found 45 Stroke Units distributed unequally among regions. The ratio of SU beds to residents ranged from 1/74,000 to 1/1,037,000 inhabitants; only the regions of Cantabria and Navarre met the target. Neurologists performed 3,237 intravenous thrombolysis procedures in 83 hospitals; thrombolysis procedures compared to the total of ischaemic strokes yielded percentages ranging from 0.3 to 33.7%. Hospitals without SUs showed varying levels of available resources. Neuro VIR is performed in every region except La Rioja, and VIR is only available on a 24h/7 d basis in 17 cities. Surgery for malignant MCA infarction is performed in 46 hospitals, and 5 have telemedicine. CONCLUSION: Stroke care has improved in terms of numbers of participating hospitals, the increased use of intravenous thrombolysis and endovascular procedures, and surgery for malignant MCA infarction. Implementation of SUs and telemedicine remain insufficient. The availability of diagnostic resources is good in most SUs and irregular in other hospitals. Regional governments should strive to ensure better care and territorial equality, which would achieve the EISNS objectives.

Combined application of high pressure and ultrasound in fig paste: effect on bioactive and volatile compounds.

The combined impact of high-hydrostatic pressure (HHP) and ultrasound (US) on the cyanidin-3-O-rutinoside (C3R), quercetin-3-O-rutinoside (Q3R), and volatile compounds from fig (Ficus carica) paste was investigated. The HHP increased the content of C3R and Q3R, from 70 to 133 mg/kg fw and 31 to 44 mg/kg fw, respectively. The combination of HHP and US further enhanced the extraction of these bioactive compounds. Specifically, processing fig paste with US for 5 min at 40 °C yielded approximately 250 mg of C3R/kg fw and 45 mg of Q3R/kg fw, after 20 min. More than 25 volatile compounds were identified, with benzaldehyde being the predominant compound, accounting > 75%. Trace amounts of hydroxymethylfurfural (< 0.36 mg/100 g fw) were detected in HHP-processed fig paste. The application of HHP at mild temperatures and short time, combined with US, effectively promotes the content of bioactive compounds present in fig paste without adversely affecting the fruit's volatile compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01410-1.

Isoinertial and isokinetic sprints: muscle signalling.

To determine if the muscle signalling response to a 30 s all-out sprint exercise is modulated by the exercise mode and the endocrine response, 27 healthy volunteers were divided in 2 groups that performed isokinetic (10 men and 5 women) and isoinertial (7 men and 5 women) Wingate tests. Blood samples and vastus lateralis muscle biopsies were taken before, immediately after, 30 and 120 min after the sprints. Groups were comparable in age, height, body weight, percentage of body fat, peak power per kg of lower extremities lean mass (Pmax) and muscle fibre types. However, the isoinertial group achieved a 25% greater mean power (Pmean). Sprint exercise elicited marked increases in the musculus vastus lateralis AMPKα, ACCß, STAT3, STAT5 and ERK1/2 phosphorylation (all P<0.05). The AMPKα, STAT3, and ERK1/2 phosphorylation responses were more marked after the isoinertial than isokinetic test (interaction: P<0.01). The differences in muscle signalling could not be accounted for by differences in Pmax, although Pmean could explain part of the difference in AMPKα phosphorylation. The leptin, insulin, glucose, GH, IL-6, and lactate response were similar in both groups. In conclusion, the muscle signalling response to sprint exercise differs between isoinertial and isokinetic sprints.

Comparative study of anthocyanin and volatile compounds content of four varieties of Mexican roselle (Hibiscus sabdariffa L.) by multivariable analysis.

Anthocyanins are a group of water-soluble pigments that provide red, purple or blue color to the leaves, flowers, and fruits. In addition, benefits have been attributed to hypertension and cardiovascular diseases. This study compared the content of total anthocyanins and volatile compounds in aqueous and ethanolic extracts of four varieties of Mexican roselle, with different levels of pigmentation. The multivariable analysis of categorical data demonstrated that ethanol was the best solvent for the extraction of both anthocyanins and volatile compounds. The concentration of anthocyanin in pigmented varieties ranged from 17.3 to 32.2 mg of cyanidin 3-glucoside/g dry weight, while volatile compounds analysis showed that geraniol was the main compound in extracts from the four varieties. The principal component analysis (PCA) allowed description of results with 77.38% of variance establishing a clear grouping for each variety in addition to similarities among some of these varieties. These results were validated by the confusion matrix obtained in the classification by the factorial discriminate analysis (FDA); it can be useful for roselle varieties classification. Small differences in anthocyanin and volatile compounds content could be detected, and it may be of interest for the food industry in order to classify a new individual into one of several groups using different variables at once.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Spatial and temporal patterns of genetic variation in the widespread antitropical deep-sea coral Paragorgia arborea.

Numerous deep-sea species have apparent widespread and discontinuous distributions. Many of these are important foundation species, structuring hard-bottom benthic ecosystems. Theoretically, differences in the genetic composition of their populations vary geographically and with depth. Previous studies have examined the genetic diversity of some of these taxa in a regional context, suggesting that genetic differentiation does not occur at scales of discrete features such as seamounts or canyons, but at larger scales (e.g. ocean basins). However, to date, few studies have evaluated such diversity throughout the known distribution of a putative deep-sea species. We utilized sequences from seven mitochondrial gene regions and nuclear genetic variants of the deep-sea coral Paragorgia arborea in a phylogeographic context to examine the global patterns of genetic variation and their possible correlation with the spatial variables of geographic position and depth. We also examined the compatibility of this morphospecies with the genealogical-phylospecies concept by examining specimens collected worldwide. We show that the morphospecies P. arborea can be defined as a genealogical-phylospecies, in contrast to the hypothesis that P. arborea represents a cryptic species complex. Genetic variation is correlated with geographic location at the basin-scale level, but not with depth. Additionally, we present a phylogeographic hypothesis in which P. arborea originates from the North Pacific, followed by colonization of the Southern Hemisphere prior to migration to the North Atlantic. This hypothesis is consistent with the latest ocean circulation model for the Miocene.

Centring ability and apical transportation after overinstrumentation with ProTaper Universal and ProFile Vortex instruments.

AIM: To evaluate morphological changes to the major foramen after overinstrumentation with ProTaper Universal and ProFile Vortex Ni-Ti rotary instruments. METHODOLOGY: Twenty-eight mesiobuccal canals of maxillary and mandibular first molars were divided into two groups of 14 canals each. The root canals were prepared with ProTaper Universal or ProFile Vortex instruments. ProTaper and Vortex instruments were used until the file tip protruded 1 mm beyond the working length (0.5 mm beyond the major foramen). The major foramen was photographed before and after overinstrumentation with each file of the two systems used. The images were superimposed and evaluated using Adobe Photoshop. The parameters evaluated were canal transportation, centring ability and shape of the major foramen. Transportation and centring ability were calculated in two directions: the direction of maximum curvature (MC) and a direction vertical to the maximum curvature (VC). Measurements of canal transportation and centring ability were analysed by anova followed by post hoc least significance difference (LSD) multiple comparisons. RESULTS: No significant differences were observed amongst the different instruments with respect to centring ability in either direction (P > 0.05). The F3 ProTaper Universal instrument was associated with a higher mean values for transportation in the direction of MC (P < 0.05) than the S1, S2 and F1 ProTaper Universal instruments and the size 15, 0.06 taper, size 20, 0.06 taper, and size 25, 0.06 taper ProFile Vortex instruments. The size 30, 0.06 taper ProFile Vortex instrument had a larger mean value for transportation in the direction of MC (P < 0.05) than the S1 ProTaper Universal and size 15, 0.06 taper ProFile Vortex instruments. The S1, S2, F1, F2 and F3 ProTaper Universal files and the size 15, 0.06 taper, size 20, 0.06 taper, size 25, 0.06 taper, and size 30, 0.06 taper ProFile Vortex files produced an oval foramen in 71%, 71%, 85%, 85%, 71%, 71%, 85%, 85% and 89% of the cases, respectively. CONCLUSIONS: In most samples, the ProTaper Universal and ProFile Vortex files produced transportation of the major foramen and created an oval-shaped major foramen after overinstrumentation.

Spreading of pollutants from alkaline mine drainage. Rodalquilar mining district (SE Spain).

In the Rodalquilar mining district of SE Spain, a total of 46 soil samples that were between 0 and 20 cm in depth were taken from the tailings dump, stream sediments, and surfaces that were presumably were unaffected by mining. In each soil sample, organic carbon content, pH, particle size distribution and total and soluble trace element content were analysed. Pollutants were scattered by runoff from two source areas: tailings from Au mining (Sn, Sb, As and Se) and wastes from Pb mining (Pb, Cu and Zn). Sn, Pb, and Sb were spread mostly in the solid phase of the runoff, while Cu, Zn, As and Se were spread in both the solid and soluble phases of the runoff. The pollutants with the highest soluble concentrations were As and Se, which were scattered at greater distances from the source. Some evidence suggests that tailings from Au mining could also be scattered by wind, but no farther than 1500 m from the source.

[NEMS: a new predictor of mortality in the critical patient?]. / NEMS: ¿nuevo predictor de mortalidad en el paciente crítico?

Numerical scales are commonly used in intensive care units to predict hospital mortality and to assess the therapeutic effort and care that critically ill patients require. The aim of this work was to study whether the NEMS value can be used as a predictor of mortality, comparing it with the APACHE II. A prospective study in a 24 intensive care unit beds was conducted. The APACHE II and NEMS values were stratified into three levels. Demographic data and the first 24 hours values of APACHE II and NEMS scales were collected. A total of 1257 patients were included, 16.4% of whom died. 69.6% were surgical; median stay was 2 days (1-4). Median age was 66 years (50-77), 59.3% were men. The median APACHE II and NEMS for the living and the dead in the subsequent course was 10 (6-20) versus 22.5 (17.25 to 29) (p <0.001) and 24 (18-29) versus 34 (25 to 39.7) (p<0.001) respectively. The correlation between both scales was rho=0.457 (p<0.01). Logistic regression controlled for age, sex and APACHE II showed an OR of 3.1 (95% CI: 1.5-6.6) only for high NEMS, compared to the lowest level. According to the results NEMS should not be used as a predictor of mortality, although the risk of death increases by three times with high NEMS.

[Mechanical restraint: its use in intensive cares]. / Contención mecánica: su uso en cuidados intensivos.

OBJECTIVE: To analyze the impact of the use of mechanical restraint (MR) or physical restraints in a Critical Care unit and to evaluate the procedure. BASIC PROCEDURES: A descriptive, prospective study. INCLUSION CRITERIA: patients who required MR from March to June 2010. VARIABLES: demographic, clinical presentation, indications, techniques and devices. A statistical analysis with mean, standard deviation and percentages using the program SPSS 14.0. RESULTS: A total of 85 cases were studied: 65.9% male, mean age 64.19 (±17.9), NEMS 29.3 (±8.2). Incidence of MR: 15.6%. Main indication for MR: Risk of serious disruption of treatment processes (80%). Decision nurse (94.1%). Urgent action: (85.9%). Registration procedure: 57.6%. Information to the family: 9.4%. Previous actions: verbal containment (100%), pharmacological (48.2%). CONCLUSIONS: There is a relevant incidence of MR. The principal reason is that of avoiding interruption of the therapeutic process. The nurse makes the initial decision. Necessary information/training of professionals for legal and ethical repercussions is needed.

[Bibliometric analysis of the thematic evolution in fibromyalgia and biomechanics (1985-2021)]. / Análisis bibliométrico de la evolución temática en fibromialgia y biomecánica (1985-2021).

The main objective of the study is to analyse the scientific evolution of the research field of fibromyalgia and biomechanics. A search was carried out in Web of Science, from 1985 to 2021. With those results, a bibliometric map of keywords was created with VOSviewer. On top of that, scientific mapping and performance analysis were also conducted using SciMAT. A total of 233 articles from around the world were analysed, highlighting the production of the USA and Spain. The results show great diversity in topics with 54 different topics and 33 keywords. Although most of the topics found are not widely developed except the topics of physical activity and symptomatology. In conclusion, the study of fibromyalgia and biomechanics has generally grown over time.

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background: The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting. Methods: This is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the "on-treatment" principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators. Results: Among 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96-2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43-0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52-0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60-0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction. Conclusion: Among all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations. CREA-ARIAM Andalucía: (ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).