Highly divergent satellitomes of two barley species of agronomic importance, Hordeum chilense and H. vulgare.

In this paper, we have performed an in-depth study of the complete set of the satellite DNA (satDNA) families (i.e. the satellitomes) in the genome of two barley species of agronomic value in a breeding framework, H. chilense (H1 and H7 accessions) and H. vulgare (H106 accession), which can be useful tools for studying chromosome associations during meiosis. The study has led to the analysis of a total of 18 satDNA families in H. vulgare, 25 satDNA families in H. chilense (accession H1) and 27 satDNA families in H. chilense (accession H7) that constitute 46 different satDNA families forming 36 homology groups. Our study highlights different important contributions of evolutionary and applied interests. Thus, both barley species show very divergent satDNA profiles, which could be partly explained by the differential effects of domestication versus wildlife. Divergence derives from the differential amplification of different common ancestral satellites and the emergence of new satellites in H. chilense, usually from pre-existing ones but also random sequences. There are also differences between the two H. chilense accessions, which support genetically distinct groups. The fluorescence in situ hybridization (FISH) patterns of some satDNAs yield distinctive genetic markers for the identification of specific H. chilense or H. vulgare chromosomes. Some of the satellites have peculiar structures or are related to transposable elements which provide information about their origin and expansion. Among these, we discuss the existence of different (peri)centromeric satellites that supply this region with some plasticity important for centromere evolution. These peri(centromeric) satDNAs and the set of subtelomeric satDNAs (a total of 38 different families) are analyzed in the framework of breeding as the high diversity found in the subtelomeric regions might support their putative implication in chromosome recognition and pairing during meiosis, a key point in the production of addition/substitution lines and hybrids.

Editorial for the Special Issue "Satellite DNA Genomics".

A significant portion of eukaryotic genomes consists of non-coding repetitive DNA sequences arranged in tandem arrays, known as satellite DNA (satDNA) [...].

Prevalence of Staphylococcus aureus Infections in the Implantation of Orthopedic Devices in a Third-Level Hospital: An Observational Cohort Study.

Using orthopedic devices or prosthetic joints to treat various conditions is expected in a Traumatology and Orthopedics Unit. Recently, the materials used to build these different devices have evolved; however, pathogens can still infect these materials. Additionally, the immune system has limitations when defending against these pathogens, which results in bacterial infections like Staphylococcus aureus, Methicillin-susceptible Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA). A total of 276 patients who attended the Traumatology and Orthopedics Unit of our hospital from 1 June 2018 to 1 June 2019, were included in the present study. Our study analyzed the incidence of S. aureus and other bacterial pathogens in the surgical sites of patients with orthopedic implants, as well as the most used types of implants and implant materials. The specimens obtained from the surgical sites of the patients were cultured in anaerobic and aerobic media for subsequent identification using their phenotypic characteristics. Subsequently, antibiotic susceptibility tests were performed to establish the appropriate treatment. The primary pathogens identified were Staphylococcus aureus (26.4%), followed by Escherichia coli (21.0%) and Staphylococcus epidermidis (15.8%). The most commonly used implants were plates (41.7%), followed by endomedullary nails (20%), Kirschner wires (14.1%), and fixators (10.1%). As for the anatomical regions of the implants, the most frequent sites were the legs, followed by the thighs, wrists, and ankles. The pathogens were more susceptible to ciprofloxacin (95%), clindamycin (89%), and cefotaxime (86%). S. aureus is the primary infectious agent in our hospital, with an incidence of 26.4% after the placement of orthopedic implants. Although its incidence was lower compared to other tertiary hospitals, it is necessary to improve aseptic techniques in such a way as to reduce the incidence of this pathogen further.

The highly dynamic satellitomes of cultivated wheat species.

BACKGROUND AND AIMS: Durum wheat, Triticum turgidum, and bread wheat, Triticum aestivum, are two allopolyploid species of very recent origin that have been subjected to intense selection programs during the thousands of years they have been cultivated. In this paper, we study the durum wheat satellitome and establish a comparative analysis with the previously published bread wheat satellitome. METHODS: We revealed the durum wheat satellitome using the satMiner protocol which is based on consecutive rounds of clustering of Illumina reads by RepeatExplorer2, and estimated abundance and variation for each identified satDNA with RepeatMasker v4.0.5. We have also performed a deep satDNA families characterization including chromosomal location by Fluorescence In Situ Hybridization (FISH) in durum wheat and its comparison with FISH patterns in bread wheat. Basic Local Alignment Search Tool (BLAST®) was used for trailing each satDNA in the assembly of durum wheat genome through NCBI's Genome Data Viewer (GDW) and the genome assemblies of both species were compared. Sequence divergence and consensus turnover rate (CTR) between homologous satDNA families of durum and bread wheat were estimated using MEGA11. KEY RESULTS: This study reveals that in an exceedingly short period, significant qualitative and quantitative changes have occurred in the set of satellite DNAs (satDNAs) of both species, with expansions/contractions of the number of repeats and the loci per satellite, different in each species, and a high rate of sequence change for most of these satellites, in addition to the emergence/loss of satDNAs not shared between the two species analysed. These evolutionary changes in satDNA are common between species but what is truly remarkable and novel about this study is that these processes have taken place in less than the last ~8000 years separating the two species, indicating an accelerated evolution of their satDNAs. CONCLUSIONS: These results, together with the relationship of many of these satellites with transposable elements and the polymorphisms they generate at the level of centromeres and subtelomeric regions of their chromosomes, are analysed and discussed in the context of the evolutionary origin of these species and the selection pressure exerted by man throughout the history of their cultivation.

One-pot, microwave (MW)-assisted production of furfural from almond-, oil-, and wine-derived co-products through biorefinery-based approaches.

This work outlines the first microwave (MW)-assisted protocol for the production of biofuel precursor furfural (FF) from the raw agricultural waste almond hull (AH), olive stone (OS), and the winemaking-derived grape stalk (GS), grape marc (GM) and exhausted grape marc (EGM) through a one-pot synthesis process. To enhance the overall yield, a catalytic process was firstly developed from xylose, major constituent of hemicellulose present in lignocellulosic biomass. This method afforded FF with 100 % selectivity, yielding over 85 % in isolated product when using H2SO4, as opposed to a 37 % yield with AlCl3·6H2O, at 150 °C in only 10 min. For both catalysts, the developed methodology was further validated, proving adaptable and efficient in producing the targeted FF from the aforementioned lignocellulosic raw materials. More specifically, the employment of AlCl3·6H2O resulted in the highest selectivity (up to 89 % from GM) and FF yield (42 % and 39 % molar from OS and AH, respectively), maintaining notable selectivity for the latter (61 and 48 % from AH and OS). At this regard, and considering the environmental factor of sustainability, it is important to point out the role of AlCl3·6H2O in contrast to H2SO4, thus mitigating detrimental substances. This study provides an important management of agricultural waste through sustainable practises for the development of potential bio-based chemicals, aligning with Green Chemistry and process intensification principles.

Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry.

OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.

One-step sputtering of MoSSe metastable phase as thin film and predicted thermodynamic stability by computational methods.

We present the fabrication of a MoS2-xSex thin film from a co-sputtering process using MoS2 and MoSe2 commercial targets with 99.9% purity. The sputtering of the MoS2 and MoSe2 was carried out using a straight and low-cost magnetron radio frequency sputtering recipe to achieve a MoS2-xSex phase with x = 1 and sharp interface formation as confirmed by Raman spectroscopy, time-of-flight secondary ion mass spectroscopy, and cross-sectional scanning electron microscopy. The sulfur and selenium atoms prefer to distribute randomly at the octahedral geometry of molybdenum inside the MoS2-xSex thin film, indicated by a blue shift in the A1g and E1g vibrational modes at 355 cm-1 and 255 cm-1, respectively. This work is complemented by computing the thermodynamic stability of a MoS2-xSex phase whereby density functional theory up to a maximum selenium concentration of 33.33 at.% in both a Janus-like and random distribution. Although the Janus-like and the random structures are in the same metastable state, the Janus-like structure is hindered by an energy barrier below selenium concentrations of 8 at.%. This research highlights the potential of transition metal dichalcogenides in mixed phases and the need for further exploration employing low-energy, large-scale methods to improve the materials' fabrication and target latent applications of such structures.

Evolution of ancient satellite DNAs in extant alligators and caimans (Crocodylia, Reptilia).

BACKGROUND: Crocodilians are one of the oldest extant vertebrate lineages, exhibiting a combination of evolutionary success and morphological resilience that has persisted throughout the history of life on Earth. This ability to endure over such a long geological time span is of great evolutionary importance. Here, we have utilized the combination of genomic and chromosomal data to identify and compare the full catalogs of satellite DNA families (satDNAs, i.e., the satellitomes) of 5 out of the 8 extant Alligatoridae species. As crocodilian genomes reveal ancestral patterns of evolution, by employing this multispecies data collection, we can investigate and assess how satDNA families evolve over time. RESULTS: Alligators and caimans displayed a small number of satDNA families, ranging from 3 to 13 satDNAs in A. sinensis and C. latirostris, respectively. Together with little variation both within and between species it highlighted long-term conservation of satDNA elements throughout evolution. Furthermore, we traced the origin of the ancestral forms of all satDNAs belonging to the common ancestor of Caimaninae and Alligatorinae. Fluorescence in situ experiments showed distinct hybridization patterns for identical orthologous satDNAs, indicating their dynamic genomic placement. CONCLUSIONS: Alligators and caimans possess one of the smallest satDNA libraries ever reported, comprising only four sets of satDNAs that are shared by all species. Besides, our findings indicated limited intraspecific variation in satellite DNA, suggesting that the majority of new satellite sequences likely evolved from pre-existing ones.

Bread wheat satellitome: a complex scenario in a huge genome.

In bread wheat (Triticum aestivum L.), chromosome associations during meiosis are extremely regulated and initiate at the telomeres and subtelomeres, which are enriched in satellite DNA (satDNA). We present the study and characterization of the bread wheat satellitome to shed light on the molecular organization of wheat subtelomeres. Our results revealed that the 2.53% of bread wheat genome is composed by satDNA and subtelomeres are particularly enriched in such DNA sequences. Thirty-four satellite DNA (21 for the first time in this work) have been identified, analyzed and cytogenetically validated. Many of the satDNAs were specifically found at particular subtelomeric chromosome regions revealing the asymmetry in subtelomere organisation among the wheat subgenomes, which might play a role in proper homologous recognition and pairing during meiosis. An integrated physical map of the wheat satellitome was also constructed. To the best of our knowledge, our results show that the combination of both cytogenetics and genome research allowed the first comprehensive analysis of the wheat satellitome, shedding light on the complex wheat genome organization, especially on the polymorphic nature of subtelomeres and their putative implication in chromosome recognition and pairing during meiosis.

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Ecological implications of stomatal density and stomatal index in the adult stage of Mimosa L. (Leguminosae, Caesalpinioideae).

Differences in stomatal density (SD) and stomatal index (SI) are associated with the conditions of the environment in which they are distributed. Mimosa species are important elements in different plant communities, yet knowledge of the ecological implications of its stomatal characteristics is scarce. For this reason, SD and SI were determined in seven Mimosa species from different environments in this study. Five individuals per species were selected, and a sample of leaflets was obtained from each. Fifteen mature leaflets per individual were then extracted and observed by optical microscopy. SD, SI, epidermal cell density (ECD), and guard cell length (GCL) values were obtained. Differences between species were analyzed through a balanced analysis of variance test, and the correspondence between the stomatal characteristics and 21 climate variables was determined by canonical correspondence analysis. The species differed in all evaluated characteristics. It should be noted that only M. affinis showed differences between the leaflet surfaces. Both DE and ECD were negatively associated with altitude and solar radiation and positively with temperature and precipitation. SI was explained by temperature and seasonality of precipitation, and GCL by temperature oscillation and seasonality of precipitation. The results suggest that the stomatal characteristics of the leaflets confer resistance in the species to alterations in environmental conditions.

Peripheral arterial disease in hemodialysis patients 10 years later.

BACKGROUND AND OBJECTIVE: Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported. MATERIAL AND METHODS: Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale. RESULTS: Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64 ±â€¯16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20-57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD 52.38% (11/21) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with: an elevated index of Charlson (3.9±2.1 vs. 7.7 ±â€¯3.5; P = 0.001),being male (19 vs. 2; P = 0.001), diabetic (no: 7; yes: 15; P = 0.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P = 0.001), 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. Univariate analysis showed that age, C reactive protein, albumin, and number of surgical interventions, but not PAD, were associated with mortality. In the multivariate analysis adjusted for other factors, only C reactive protein was related to overall survival Exp ß: 2.17; P = 0.011; CI (1.19-3.97). Regarding cardiovascular mortality, in the multivariate Cox analysis, only PAD was related to mortality of cardiovascular origin Exp ß: 1.73; P = 0.006; CI (1.17-2.56). CONCLUSIONS: A significant number of patients on hemodialysis develop PAD requiring peripheral vascular surgery. PAD was not associated with overall mortality in our cohort, but it did show an association with cardiovascular mortality. Prospective studies with a larger sample size are necessary. New surgical treatments and Follow-up by vascular surgeons could improve the severity of PAD and the long-term prognosis.

A Delphi consensus on the management of Spanish patients with osteoporosis at high risk of fracture: OSARIDELPHI study.

The OSARIDELPHI study evaluated the level of agreement between specialists in osteoporosis regarding the management of patients with high-risk fractures in Spain. The results provide expert-based recommendations for prevention, diagnosis, and treatment related to fracture risk. Therefore, the study facilitates clinical decision-making for managing this patient's profile. PURPOSE: To evaluate the level of agreement between specialists in osteoporosis regarding the management of patients with high-risk fractures in Spain. METHODS: A two-round Delphi study was performed using an online survey. In round 1, panel members rated their level of agreement with assessments on a 9-point Likert scale. Item selection was based on acceptance by ≥ 66.6% of panel experts and the agreement of the scientific committee. In round 2, the same panelists evaluated non-consensus items in round 1. RESULTS: A total of 80 panelists participated in round 1; of these, 78 completed the round 2 survey. In round 1, 122 items from 4 dimensions (definition of fracture risk: 11 items, prevention and diagnosis: 38 items, choice of treatment: 24 items, and treatment-associated quality of life: 49 items) were evaluated. The consensus was reached for 90 items (73.8%). Panelists agreed that categorizing high risk, very high risk, or imminent risk determines secondary prevention actions (97.5%). Experts agreed that treatment with bone-forming drugs should be considered in case of a very high risk of fracture, and a sequential change to antiresorptive drugs should be made after 1-2 years (97.5%). Panelists also recommended corrective action plans for non-adherent patients to improve adherence (97.5%). A total of 131 items were finally accepted after round 2. CONCLUSION: This Delphi study provides expert-based recommendations on clinical decision-making for managing patients with osteoporosis at high risk of fracture.

Management of Specific Clinical Profiles in Axial Spondyloarthritis: An Expert's Document Based on a Systematic Literature Review and Extended Delphi Process.

INTRODUCTION: The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. METHODS: Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). RESULTS: Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. CONCLUSIONS: These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.

Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate.

Introduction: While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential. Methods: In an effort to develop an immunogen with the capacity to induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions of SARS-CoV-2 structural proteins associated with long-term immunity, termed CoV2-BMEP. Here we describe the characterization, immunogenicity and efficacy of CoV2-BMEP using two delivery platforms: nucleic acid DNA and attenuated modified vaccinia virus Ankara (MVA). Results: In cultured cells, both vectors produced a main protein of about 37 kDa as well as heterogeneous proteins with size ranging between 25-37 kDa. In C57BL/6 mice, both homologous and heterologous prime/boost combination of vectors induced the activation of SARS-CoV-2-specific CD4 and CD8 T cell responses, with a more balanced CD8+ T cell response detected in lungs. The homologous MVA/MVA immunization regimen elicited the highest specific CD8+ T cell responses in spleen and detectable binding antibodies (bAbs) to S and N antigens of SARS-CoV-2. In SARS-CoV-2 susceptible k18-hACE2 Tg mice, two doses of MVA-CoV2-BMEP elicited S- and N-specific bAbs as well as cross-neutralizing antibodies against different variants of concern (VoC). After SARS-CoV-2 challenge, all animals in the control unvaccinated group succumbed to the infection while vaccinated animals with high titers of neutralizing antibodies were fully protected against mortality, correlating with a reduction of virus infection in the lungs and inhibition of the cytokine storm. Discussion: These findings revealed a novel immunogen with the capacity to control SARS-CoV-2 infection, using a broader antigen presentation mechanism than the approved vaccines based solely on the S antigen.

Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry.

PURPOSE: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. METHODS: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1-3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). RESULTS: A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003-10 (210), and GEICAM-2006-10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. CONCLUSIONS: This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. TRIAL REGISTRATION: ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.

Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk.

Succinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p < 0.05). However, regression analysis did not detect any significant correlation between most metabolite concentrations and infarct size, extent of edema or other cardiac magnetic resonance (CMR) variables. In conclusion, spontaneous reperfusion in TIMI 2 patients associates with enhanced succinate levels in peripheral blood, suggesting that succinate release increases overtime following reperfusion. However, early plasma levels of succinate and other metabolites obtained from peripheral blood does not correlate with the degree of irreversible injury or area at risk in STEMI patients, and cannot be considered as predictors of CMR variables.Trial registration: Registered at www.clinicaltrials.gov (NCT02404376) on 31/03/2015. EudraCT number: 2015-001000-58.

Microwave radiation-assisted synthesis of levulinic acid from microcrystalline cellulose: Application to a melon rind residue.

The circular economy considers waste to be a new raw material for the development of value-added products. In this context, agroindustrial lignocellulosic waste represents an outstanding source of new materials and platform chemicals, such as levulinic acid (LA). Herein we study the microwave (MW)-assisted acidic conversion of microcrystalline cellulose (MCC) into LA. The influence of acidic catalysts, inorganic salt addition and ball-milling pre-treatment of MCC on LA yield was assessed. Depolymerization and disruption of cellulose was monitored by FTIR, TGA and SEM, whereas the products formed were analyzed by HPLC and NMR spectroscopy. The parameters that afforded the highest LA yield (48 %, 100 % selectivity) were: ball-milling pre-treatment of MCC for 16 min at 600 rpm, followed by MW-assisted thermochemical treatment for 20 min at 190 °C, aqueous p-toluenesulfonic acid (p-TSA) 0.25 M as catalyst and saturation with KBr. These optimal conditions were further applied to a lignocellulosic feedstock, namely melon rind, to afford a 51 % yield of LA. These results corroborate the suitability of this method to obtain LA from agroindustrial wastes, in line with a circular economy-based approach.

The Piezoresponse in WO3 Thin Films Due to N2-Filled Nanovoids Enrichment by Atom Probe Tomography.

Tungsten trioxide (WO3) is a versatile n-type semiconductor with outstanding chromogenic properties highly used to fabricate sensors and electrochromic devices. We present a comprehensive experimental study related to piezoresponse with piezoelectric coefficient d33 = 35 pmV-1 on WO3 thin films ~200 nm deposited using RF-sputtering onto alumina (Al2O3) substrate with post-deposit annealing treatment of 400 °C in a 3% H2/N2-forming gas environment. X-ray diffraction (XRD) confirms a mixture of orthorhombic and tetragonal phases of WO3 with domains with different polarization orientations and hysteresis behavior as observed by piezoresponse force microscopy (PFM). Furthermore, using atom probe tomography (APT), the microstructure reveals the formation of N2-filled nanovoids that acts as strain centers producing a local deformation of the WO3 lattice into a non-centrosymmetric structure, which is related to piezoresponse observations.