Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases ...significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge.
To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management.
In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM.
We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample.
These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.
Malignant melanoma (MM) is the most aggressive form of skin cancer, with increasing incidence worldwide. To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for ...MM. Our data highlight the potential of metabolomic characterization of cancer stem cell‐ or serum‐derived exosomes using high‐resolution mass spectrometry for the discovery of clinically useful MM biomarkers.
Malignant melanoma (MM) is the most aggressive and life‐threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient‐derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem‐like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high‐resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum‐derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC‐derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic‐based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC‐derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.
Background
To evaluate the importance of larynx compartments in the prognosis of T3‐T4a laryngeal cancer treated with transoral laser microsurgery.
Methods
Two hundred and two consecutive pT3‐T4a ...larynx carcinomas. Pre‐epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease‐specific survival (DSS), and laryngectomy‐free survival (LFS) were evaluated.
Results
The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio HR = 0.289 0.085–0.979) and anterior (HR = 0.278 0.128–0.605) and posterior (HR = 0.269 0.115–0.630) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 1.537–8.495) and posterior (HR = 5.195 2.167–12.455) PGS involvement were independent factors of total laryngectomy. Five‐year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5‐year LFS.
Conclusions
Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.
During the last few years, the numbers of competitors in endurance and ultra-endurance sports modalities have increased significantly. This type of competition is an extreme challenge for athletes. ...Therefore, they have an increased the risk of developing medical and nutritional problems. The aim of the work is to estimate the incidence of nutrition-related adverse outcomes in endurance and ultra-endurance sports, considering the variables that influence them. A critical review was carried out based on the PubMed database, by means of a search strategy based on keywords separated by Boolean connectors. For all the results obtained in a period from 2008 to 2019, a series of inclusion/exclusion criteria was applied to select only the studies that fitted the objective of the present study. Results and discussion: Of the 871 publications identified, 33 met the inclusion criteria. The adverse outcomes found included exercise-associated hyponatremia (EAH), heat stroke by exertion (EHS), gastrointestinal (GI) problems, dehydration, and hypothermia; the provision of misinformation to athletes about nutrient intake and hydration during competition was identified as the main cause. Conclusions: The main adverse outcomes in endurance and ultra-endurance sports modalities are EAH, GI inconveniences, and EHS. These problems can affect the performance and health status of the athlete during and post-competition. Several nutritional guidelines have been suggested that can prevent these adverse outcomes, and it is essential to individualize and adjust the nutritional intake and hydration status according to the characteristics of each competition.
Background
Optimal timing for tracheotomy for critically ill COVID‐19 patients requiring invasive mechanical ventilation (IMV) is not established.
Methods
Multicenter prospective cohort including all ...COVID‐19 patients admitted to intensive care units (ICUs) in 36 hospitals who required tracheotomy during first pandemic wave. With a target emulation trial framework, we studied the causal effects of early (7–10 days) versus late (>10 days) tracheotomy (LT) on time from tracheotomy to weaning, postoperative mortality, and tracheotomy complications.
Results
Of 696 patients, 20.4% received early tracheotomy (ET). ET was associated with faster weaning (hazard ratio HR 95% confidence interval, CI: 1.25 1.00–1.56) without differences in mortality (HR 95% CI: 0.85 0.60–1.21) or complications (adjusted rate ratio 95% CI: 0.56 0.23–1.33).
Conclusions
ET had a similar or lower post‐tracheotomy weaning time than LT, potentially shortening IMV and ICU stays, without changing complication or mortality rates in COVID‐19 patients.
Dispositional Mindfulness (DM) is the awareness of the thoughts and feelings in the present moment. DM in children and adolescents has been related to mechanisms of change in mindfulness-based ...interventions
which have shown significant mediation relationships with mental health outcomes (for instance, lower social anxiety, depression symptoms, or perceived stress). However, the assessment of DM among children and adolescents is being unsatisfactory due cultural biases and/or reliability issues. In this study, we examined the psychometric properties of the Spanish version of the Child and Adolescent Mindfulness Measure (CAMM) in a sample of 687 children and adolescents between 8 and 16 years old. Although the CAMM has been validated in English, Portuguese, Italian, and Catalonian versions, until now no data has been reported in a Spanish context. Results showed that the best CAMM factor structure was constituted by five items from the original version (1, 4, 7, 8, and 9). These items defined dispositional mindfulness. The rest of the items (2, 3, 5, 6, and 10) were eliminated from the Spanish final version. The analyses revealed good reliability and internal consistency for the Spanish version of the CAMM. As we expected, the confirmatory factor analysis showed the unidimensional structure of the CAMM.
Abstract With the advent of the cloud computing model allowing a shared access to massive computing facilities, a surging demand emerges for the protection of the intellectual property tied to the ...programs executed on these uncontrolled systems. If novel paradigm as confidential computing aims at protecting the data manipulated during the execution, obfuscating techniques (in particular at the source code level) remain a popular solution to conceal the purpose of a program or its logic without altering its functionality, thus preventing reverse-engineering on the program even with the help of computing resources. The many advantages of code obfuscation, together with its low cost, makes it a popular technique. This paper proposes a novel methodology for source code obfuscation that can be used together with other traditional obfuscation techniques, making the code more robust against reverse engineering attacks. Three program complexity metrics are used to define three different single-objective combinatorial optimization versions of the problem, which are solved and analysed. Additionally, three multi-objective problems are defined, those considering each of the selected metrics together with the program execution time, in order to avoid strong obfuscations penalizing the performance. The goal of the defined problems is to find sequences of LLVM optimizations that lead to highly obfuscated versions of the original code. These transformations are applied to the back-end pseudo-assembly code (i.e., LLVM Intermediate Representation), thus avoiding any further optimizations by the compiler. Classical genetic algorithms (GAs) are used to solve the studied problems, namely a basic cellular GA for the single-objective problems and the popular NSGA-II for the multi-objective ones. The promising results show the potential of the proposed technique.
Introduction
Metronomic chemotherapy combined with bevacizumab has proved to be effective in various tumour types. The aim of this study is to review our experience in recurrent ovarian carcinomas ...treated with low-dose cyclophosphamide and bevacizumab.
Materials and methods
Retrospective analysis of pre-treated ovarian cancer patients, i.e., ≥2 previous chemotherapy regimens who received treatment with oral cyclophosphamide 50 mg/day and bevacizumab 10 mg/kg IV every two weeks. Patients with a performance status 0–2 were included. The endpoints were response rates, progression-free disease and safety profile.
Results
Nine patients with advanced, measurable ovarian cancer were included. Of these, 8 were platinum-resistant and had received prior regimens with gemcitabine (88%), topotecan (77%) and liposomal doxorubicin (66%). There was a mean of 5 previous lines of chemotherapy, range 2–7. Applying RECIST criteria, the efficacy data were as follows: objective response (OR) 44%; 4/9 (CR 2/9 and PR 2/9), SD 2/9 and DP 3/9. At 6 months, 33% of patients were progression free. Response lasted for 12.5 months in three patients treated for 12 months; a further two patients who were re-treated achieved complete response. Mean time to progression was 5.5 months (95% CI 4.5–5.5). No severe adverse effects were reported. Only one patient had to delay several cycles due to G3 haematuria. Other toxicities observed include G3 abdominal pain (1 case); G2 mucositis and G2 dyspnoea in one patient.
Conclusions
Combined bevacizumab and metronomic oral cyclophosphamide is a safe and effective regimen for heavily pre-treated ovarian cancer patients. Further research is needed on predictive factors to screen for those patients who will benefit from anti-angiogenic therapy.
Species interactions can propagate disturbances across space via direct and indirect effects, potentially connecting species at a global scale. However, ecological and biogeographic boundaries may ...mitigate this spread by demarcating the limits of ecological networks. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among plant-frugivore networks, while accounting for background spatial and elevational gradients and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1496 plant and 1004 bird species) distributed across 67 ecoregions, 11 biomes, and 6 continents. We show that dissimilarities in species and interaction composition, but not network structure, are greater across ecoregion and biome boundaries and along different levels of human disturbance. Our findings indicate that biogeographic boundaries delineate the world's biodiversity of interactions and likely contribute to mitigating the propagation of disturbances at large spatial scales.
Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease.
The authors sought to assess the performance of ...coronary IVL in calcified coronary lesions in a real-life, all comers, setting.
The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events MACE). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients.
A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients P = 0.073).
Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study Registry of Coronary Lithotripsy in Spain; NCT04298307).
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