Coral Reef Aorta: Literature Review and Analysis of the Published Cases in the Last 20 Years.

BACKGROUND: Coral reef aorta (CRA) is defined by the presence of heavily calcified exophytic plaques that protrude into the aortic lumen. However, the exact causes and development of this condition are still not fully understood. When the aortic branches are affected, it can result in various symptoms. Despite ongoing research, there is currently no established consensus on the best treatment for CRA. This review aims to examine the latest findings regarding the clinical presentation and approach to treating patients with CRA. METHODS: We conducted a systematic electronic search of the literature using the PubMed and Embase databases. Throughout the search, we adhered to the guidelines outlined in the PRISMA framework. From the identified publications, we extracted information pertaining to patients' characteristics, symptoms, and types of treatment from a total of 124 cases reported over the past 20 years. The primary focus of our analysis was to assess the improvement of signs and symptoms, as well as to evaluate any postoperative complications. To achieve this, we performed both descriptive and inferential analyses on the collected data. Additionally, we conducted subgroup analyses based on treatment types and symptoms observed at presentation, presenting the findings in the form of odds ratios (ORs). RESULTS: After removing duplicate articles, we carefully screened the titles of 67 retrieved articles and excluded those that did not align with the purpose of our study. Subsequently, we thoroughly analyzed the remaining 41 articles along with their references, ultimately including 29 studies that were deemed most relevant for our systematic review. We examined a total of 124 cases of patients diagnosed with CRA, comprising 77 (62.1%) females and 48 (38.7%) males, with a mean age of 59 years (range: 37-84). The predominant signs and symptoms observed were intermittent claudication, reported in 57 (46.0%) patients, followed by refractory hypertension in 45 (36.3%) patients, intestinal angina in 28 (22.6%) patients, and renal insufficiency in 15 (12.1%) patients. Among the treated patients, 110 (88.7%) underwent open surgery repair (OSR), 11 (8.9%) received endovascular treatment, and 3 (2.4%) underwent laparoscopy. Postoperatively, a significant number of patients experienced substantial relief or complete resolution of their symptoms, as well as improved control of hypertension and renal function. In the group of patients treated with OSR, the inhospital stay mortality rate was 10.9%, the morbidity rate was 28.2%, and the reintervention rate was 15.5%. The high mortality rate during hospital stays in this group may be associated with such invasive procedures performed on patients who have substantial cardiovascular burden and multiple comorbidities. Conversely, no postoperative complications were reported in the group of patients treated with endovascular procedures or laparoscopic surgery. CONCLUSIONS: While coral reef aorta (CRA) is considered a rare condition, it is crucial for the medical community to remain vigilant about its diagnosis, particularly in patients presenting with symptoms such as intermittent claudication, refractory hypertension, renal impairment, or intestinal angina. Based on the findings of this review, both OSR and endovascular treatment have shown promise as viable therapeutic options. Although endovascular therapies may not always be feasible or may have reduced durability in these calcified bulky lesions, they should be considered in patients with multiple comorbidities, due to the high postoperative mortality rates associated with more invasive approaches. Additionally, these endoluminal procedures have demonstrated good patency rates during the 18-month follow-up period. It is essential to emphasize that the treatment strategy should be determined on a case-by-case basis, involving a multidisciplinary team to tailor it to the specific needs of each individual patient.

Thoracic aortic aneurysms, a single center's 10-years experience and analysis of outcomes.

INTRODUCTION: Thoracic aortic aneurysms (TAAs) are an increasingly prevalent pathology with significant associated morbidity and mortality. Thoracic endovascular aortic repair (TEVAR) is the primary line of treatment. The purpose of this study was to analyse a single center's experience in the treatment of TAAs and identify possible risk factors for worse outcomes. METHODS: A retrospective review of our institutional database was done to identify all patients treated for TAAs in a 10-year period, from 1 January 2012 to 31 December 2022. Data were extracted from patients' medical records. Primary outcome was all-cause mortality and secondary outcomes were procedure related morbidity (vascular access complications, medullary ischaemia, stroke, endoleaks, migration, aneurysm sac enlargement >5 mm) and need for reintervention at 1-, 6- and 12-month follow-up. A descriptive and inferential analysis of the data was performed. Statistical analyses were conducted using the IBM Statistical Package for Social Sciences (SPSS) software. RESULTS: We identified 34 patients treated for TAAs in this period. Mean age was 68 years [47-87] and 79.4% of patients were male. Mean aneurysm diameter was 63 mm [35-100], 55.9% fusiform and 44.1% saccular. The majority (91.2%) were located at the descending thoracic aorta and 3 (8.8%) of them extended to the aortic arch. The most common aetiology was degenerative in 22 patients (64.7%), followed by aortic dissection in 8 patients (23.5%). Elective surgery was performed in 19 (61.3%) patients and 12 (38.7%) had urgent repair. TEVAR was the treatment of choice in 24 (77.4%) patients, and the remaining 7 (22.6%) were treated with hybrid surgery. Mean length of hospital stay was 10 days [2-80] (6 days for elective repair versus 16 days for urgent repair, p = .016). Follow-up period ranged from 1 month to 10 years. At 1 year follow-up, all-cause mortality was 15%, morbidity was 30% (with 6 (22%) patients having a type Ia endoleak) and need for reintervention was 22%. Aneurysm diameter was a significant risk factor for procedure related morbidity (median diameter of 73.5 mm versus 56.0 mm in patients with no morbidity; p = .027). The presence of type Ia endoleak was significantly associated with higher reintervention rates (p = .001), but not with higher mortality rates (p = .515). Age, female sex, aetiology and urgent repair weren't associated with any significant differences in the outcomes. CONCLUSIONS: TEVAR proved to be effective in the treatment of TAAs, with good outcomes at short and mid-term follow-up. TAAs should be diagnosed earlier and be promptly treated when meeting criteria to prevent worse outcomes.

Characterising people with focal drug-resistant epilepsy: A retrospective cohort study.

OBJECTIVES: To describe the demographics, clinical characteristics, drug treatment outcomes, healthcare resource utilization, and injuries among people with focal drug-resistant epilepsy (F-DRE) analysed separately for six European countries. METHODS: We used electronic medical record data from six European (Belgium, Spain, Italy, France, UK and Germany) primary care/specialist care databases to identify antiseizure medication (ASM) treatment-naïve people (aged ≥ 18 years at F-DRE diagnosis). They were followed from their epilepsy diagnosis until death, the date of last record available, or study end. We used descriptive analyses to characterise the F-DRE cohort, and results were reported by country. RESULTS: One-thousand-seventy individuals with F-DRE were included (mean age 52.5 years; 55.4 % female). The median follow-up time from the first diagnosis to the end of the follow-up was 95.5 months across all countries. The frequency of F-DRE diagnosis in 2021 ranged from 8.8 % in Italy to 18.2 % in Germany. Psychiatric disorders were the most common comorbidity across all countries. Frequently reported psychiatric disorders were depression (26.7 %) and anxiety (11.8 %). The median time from epilepsy diagnosis to the first ASM failure ranged from 5.9 (4.2-10.2) months in France to 12.6 (5.8-20.4) months in Spain. Levetiracetam and lamotrigine were the most commonly used ASM monotherapies in all countries. Consultation with a general practitioner is sought more frequently after F-DRE diagnosis than after epilepsy diagnosis, except in the UK. SIGNIFICANCE: No one ASM is optimal for all people with F-DRE, and the risks and benefits of the ASM must be considered. Comorbidities must be an integral part of the management strategy and drive the choice of drugs.

Best Medical Treatment in Patients with Asymptomatic Carotid Stenosis: Myth or Reality?

BACKGROUND: Approximately 1.4 million strokes/year causing about 1.1 million deaths annually occur in Europe and 10%-15% of those strokes are result of thromboembolism from a previously significant asymptomatic carotid stenosis (ACS). Medical treatment has improved considerably in the last 15 years; however, its success depends on patient compliance. The aim of our study was to evaluate, in patients with ACS, the implementation and patient adherence to best medical treatment (BMT). Additionally, we sought to determine the "real-world" incidence of cerebrovascular/coronary events in a cohort of nonoperated ACS patients and weighing this risk against surgical complications in patients with ACS undergoing surgical treatment at our Department. METHODS: Patients with ACS ≥ 60% identified by a carotid ultrasound performed at our Department were retrospectively evaluated. Patients selected to BMT were excluded if the follow-up period was inferior to 2 years, as well as patients lost in follow-up, with missing clinical information and submitted to carotid stenting. Patients' data collection was supported by hospital reporting system and data were introduced into a database created for the purpose. Statistical analysis was performed using SPSS-25 software. RESULTS: After exclusion criteria were applied, the last 120 consecutive patients (60 with ACS submitted do carotid endarterectomy and 60 with ACS under BMT) were retrospectively evaluated. Twenty one patients had ipsilateral events for more than 6 months. Most patients had hypertension (n = 107; 89%), dyslipidemia (n = 101; 84%), 40% had diabetes, 33% diagnosed coronary disease, 32% were overweight or obese, and 17% were current smokers. Blood pressure control, normal weight, statin with/without ezetimibe association, and antiaggregant therapy were only achieved in 33 patients and only 5 had additionally low-density lipoprotein levels < 70 mg/dL, hemoglobin A1c < 7%, and were nonsmokers. Of the 60 patients assigned to medical treatment, 3 (5%) had a stroke at 2 years of follow-up, which was fatal in 1 patient. Among patients submitted to carotid endarterectomy, perioperative stroke was documented in 3% of the patients, none of them disabling or fatal. CONCLUSIONS: Although some recent studies report a risk of ipsilateral stroke of only 0.34% per year in patients with ACS ≥ 50% under BMT therapy in our everyday practice strict compliance to medical treatment fails in most patients. In consequence, we think that a "one-size-fits-all" guideline policy may not be appropriate for all patients and the management of specific ACS patients may need to be individualized.

Enhancing Health Benefits through Chlorophylls and Chlorophyll-Rich Agro-Food: A Comprehensive Review.

Chlorophylls play a crucial role in photosynthesis and are abundantly found in green fruits and vegetables that form an integral part of our diet. Although limited, existing studies suggest that these photosynthetic pigments and their derivatives possess therapeutic properties. These bioactive molecules exhibit a wide range of beneficial effects, including antioxidant, antimutagenic, antigenotoxic, anti-cancer, and anti-obesogenic activities. However, it is unfortunate that leafy materials and fruit peels often go to waste in the food supply chain, contributing to the prevailing issue of food waste in modern societies. Nevertheless, these overlooked materials contain valuable bioactive compounds, including chlorophylls, which offer significant health benefits. Consequently, exploring the potential of these discarded resources, such as utilizing them as functional food ingredients, aligns with the principles of a circular economy and presents exciting opportunities for exploitation.

Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study.

BACKGROUND: First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer. METHODS: We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment. FINDINGS: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group. INTERPRETATION: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population. FUNDING: Merck Sharp & Dohme.

Maximizing mRNA vaccine production with Bayesian optimization.

Messenger RNA (mRNA) vaccines are a new alternative to conventional vaccines with a prominent role in infectious disease control. These vaccines are produced in in vitro transcription (IVT) reactions, catalyzed by RNA polymerase in cascade reactions. To ensure an efficient and cost-effective manufacturing process, essential for a large-scale production and effective vaccine supply chain, the IVT reaction needs to be optimized. IVT is a complex reaction that contains a large number of variables that can affect its outcome. Traditional optimization methods rely on classic Design of Experiments methods, which are time-consuming and can present human bias or based on simplified assumptions. In this contribution, we propose the use of Machine Learning approaches to perform a data-driven optimization of an mRNA IVT reaction. A Bayesian optimization method and model interpretability techniques were used to automate experiment design, providing a feedback loop. IVT reaction conditions were found under 60 optimization runs that produced 12 g · L-1 in solely 2 h. The results obtained outperform published industry standards and data reported in literature in terms of both achievable reaction yield and reduction of production time. Furthermore, this shows the potential of Bayesian optimization as a cost-effective optimization tool within (bio)chemical applications.

Extracorporeal sheath shunt technique in trauma: A different vascular shunt in civilian trauma.

BACKGROUND/OBJECTIVE: Temporary intravascular shunts are widely used in military surgery, representing a bridging until definitive vascular reconstruction. In civilian practice, shunts are mainly used as damage control and as a temporary measure until orthopaedic fixation. The objective of this report is to illustrate a new approach to the temporary restoration of perfusion during open management of extremity arterial injury. METHODS: The authors present a technique that uses sheaths introducers, instead of commercial or purpose-built shunts, which can be used through surgical or percutaneous approaches. Three clinical cases are presented where this technique was performed.Results/Conclusion: In the presented cases, this technique reduced time of shunt construction by avoiding artery surgical approach. This technique can facilitate the creation of an intravascular shunt among other than vascular surgeons.

Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice.

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world's leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1-positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.

The impact of the COVID-19 pandemic on the short-term survival of patients with cancer in Northern Portugal.

The COVID-19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID-19 on the short-term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO-Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score-adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow-up to 31 October, there were 154 (11.8%) deaths observed before COVID-19 and 131 (17.2%) after COVID-19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20-1.91) and 1.10 (0.86-1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14-4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14-13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96-3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46-0.83). The higher overall short-term mortality observed during the COVID-19 pandemic largely reflects the effects of the epidemic on the case-mix of patients being diagnosed with cancer.

Malformations and mortality in zebrafish early stages associated with elevated caspase activity after 24 h exposure to MS-222.

Tricaine methanesulfonate (MS-222) is a commonly used anaesthetic agent for immobilization of aquatic species. However, delayed development and malformations have been observed in 24 hpf (hours post-fertilization) zebrafish embryos after long-term immobilization. Still, no comprehensive study has been described regarding zebrafish exposure to MS-222 during the first hours of development, which are one of the most sensitive life stages to toxicants. Therefore, this research aimed to assess the toxicity of a 24 h exposure to MS-222 on zebrafish embryonic development. Based on the MS-222 LC50, early blastula stage embryos (~2 hpf) were exposed to 0, 12.5, 25 and 50 mg L-1 for 24 h and then allowed to develop up to 144 hpf. The chromatographic analysis showed that this anaesthetic agent bioaccumulates in 26 hpf zebrafish larvae in a concentration-dependent manner. In addition, increased mortalities and skeletal abnormalities were observed at 144 hpf, namely in the highest tested concentration. Yet, no craniofacial anomalies were observed either by alcian blue or calcein staining methods. Independently of the tested concentration, decreased speed and distance travelled were perceived in 144 hpf larvae. At the biochemical level, decreased in vivo reactive oxygen species (ROS) generation and apoptosis was observed. Additionally, catalase activity was increased at 26 hpf while results of mRNA expression showed a decreased gclc transcript content at the same time-point. Overall, data obtained highlight the toxicological risk of MS-222 and support ROS-mediated cell death signalling changes through the elevation of catalase activity as an adaptative or protective response.

Small cell lung cancer treatment and survival in Portugal: A retrospective analysis from the I-O Optimise initiative.

OBJECTIVE: We aim to describe treatment patterns and overall survival (OS) among a Portuguese cohort of patients with small cell lung cancer (SCLC). METHODS: This study utilised a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with SCLC at IPO-Porto between January 2012 and June 2017, with follow-up to December 2017, were included. Patients were stratified into subgroups with limited disease (LD) or extensive disease (ED). Treatment analyses were performed from 2015 onwards. RESULTS: Overall, 227 patients diagnosed with SCLC (37 LD; 190 ED) were analysed. Median OS (interquartile range [IQR]) was 15.0 months (3.8-39.3) for LD-SCLC and 5.0 months (1.7-10.3) for ED-SCLC. Among 19 patients diagnosed with LD-SCLC from 2015 onwards, 12 (63.2%) received initial treatment with systemic anticancer therapy (SACT) ± radiotherapy; 6 (31.6%) received best supportive care (BSC). Among 89 patients with ED-SCLC, 57 (68.5%) received SACT ± palliative radiotherapy; 28 (31.5%) received BSC. For patients receiving platinum doublet chemotherapy (±radiotherapy), median OS (IQR) was not reached for LD-SCLC and 5.4 months (2.3-10.9) for ED-SCLC. CONCLUSION: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for patients diagnosed with SCLC, particularly those with ED, and highlights a need for more effective therapies.

Phenological and productive characteristics of blackberry genotypes grown in an organic production system.

Blackberry is a species which has high potential to grow in an organic production system. However, there is scarce information on the behavior of cultivars and selections of this species conducted in an ecologically based system, a fact that makes it difficult to recommend cultivars for this production system. This study aimed to evaluate and characterize the phenology and productive aspects of six blackberry genotypes grown in an organic system, in Pelotas, Rio Grande do Sul (RS) state, Brazil. Evaluation of the following variables was carried out in the three first production cycles (2015-2016, 2016-2017 and 2017-2018): phenology, number of fruits.pl-¹, mean fruit yield.pl-¹, yield (kg.ha-¹), mean fruit mass (g) and soluble solid content (° Brix). Regarding phenology, genotype Black 112 was later than the others whereas Black 178 was the most precocious one. In the last year under evaluation, genotypes yielded around 10 ton.ha-¹, except Black 128 selection, which yielded approximately 6,767 ton.ha-¹. Genotypes Black 178, Black 112 and Black 145 and both cultivars BRS Xingu and Tupy exhibited potential to grow in an organic production system.

Optimizing classical risk scores to predict complications in head and neck surgery: a new approach.

PURPOSE: To validate tools to identify patients at risk for perioperative complications to implement prehabilitation programmes in head and neck surgery (H&N). METHODS: Retrospective cohort including 128 patients submitted to H&N, with postoperative Intermediate Care Unit admittance. The accuracy of the risk calculators ASA, P-POSSUM, ACS-NSQIP and ARISCAT to predict postoperative complications and mortality was assessed. A multivariable analysis was subsequently performed to create a new risk prediction model for serious postoperative complications in our institution. RESULTS: Our 30-day morbidity and mortality were 45.3% and 0.8%, respectively. The ACS-NSQIP failed to predict complications and had an acceptable discrimination ability for predicting death. The discrimination ability of ARISCAT for predicting respiratory complications was acceptable. ASA and P-POSSUM were poor predictors for mortality and morbidity. Our new prediction model included ACS-NSQIP and ARISCAT (area under the curve 0.750, 95% confidence intervals: 0.63-0.87). CONCLUSION: Despite the insufficient value of these risk calculators when analysed individually, we designed a risk tool combining them which better predicts the risk of serious complications.

Towards a Modular On-Premise Approach for Data Sharing.

The growing demand for everyday data insights drives the pursuit of more sophisticated infrastructures and artificial intelligence algorithms. When combined with the growing number of interconnected devices, this originates concerns about scalability and privacy. The main problem is that devices can detect the environment and generate large volumes of possibly identifiable data. Public cloud-based technologies have been proposed as a solution, due to their high availability and low entry costs. However, there are growing concerns regarding data privacy, especially with the introduction of the new General Data Protection Regulation, due to the inherent lack of control caused by using off-premise computational resources on which public cloud belongs. Users have no control over the data uploaded to such services as the cloud, which increases the uncontrolled distribution of information to third parties. This work aims to provide a modular approach that uses cloud-of-clouds to store persistent data and reduce upfront costs while allowing information to remain private and under users' control. In addition to storage, this work also extends focus on usability modules that enable data sharing. Any user can securely share and analyze/compute the uploaded data using private computing without revealing private data. This private computation can be training machine learning (ML) models. To achieve this, we use a combination of state-of-the-art technologies, such as MultiParty Computation (MPC) and K-anonymization to produce a complete system with intrinsic privacy properties.

Provisioning, Authentication and Secure Communications for IoT Devices on FIWARE.

The increasing pervasiveness of the Internet of Things is resulting in a steady increase of cyberattacks in all of its facets. One of the most predominant attack vectors is related to its identity management, as it grants the ability to impersonate and circumvent current trust mechanisms. Given that identity is paramount to every security mechanism, such as authentication and access control, any vulnerable identity management mechanism undermines any attempt to build secure systems. While digital certificates are one of the most prevalent ways to establish identity and perform authentication, their provision at scale remains open. This provisioning process is usually an arduous task that encompasses device configuration, including identity and key provisioning. Human configuration errors are often the source of many security and privacy issues, so this task should be semi-autonomous to minimize erroneous configurations during this process. In this paper, we propose an identity management (IdM) and authentication method called YubiAuthIoT. The overall provisioning has an average runtime of 1137.8 ms ±65.11+δ. We integrate this method with the FIWARE platform, as a way to provision and authenticate IoT devices.

On Conditional Tsallis Entropy.

There is no generally accepted definition for conditional Tsallis entropy. The standard definition of (unconditional) Tsallis entropy depends on a parameter α that converges to the Shannon entropy as α approaches 1. In this paper, we describe three proposed definitions of conditional Tsallis entropy suggested in the literature-their properties are studied and their values, as a function of α, are compared. We also consider another natural proposal for conditional Tsallis entropy and compare it with the existing ones. Lastly, we present an online tool to compute the four conditional Tsallis entropies, given the probability distributions and the value of the parameter α.

The Entropy Universe.

About 160 years ago, the concept of entropy was introduced in thermodynamics by Rudolf Clausius. Since then, it has been continually extended, interpreted, and applied by researchers in many scientific fields, such as general physics, information theory, chaos theory, data mining, and mathematical linguistics. This paper presents The Entropy Universe, which aims to review the many variants of entropies applied to time-series. The purpose is to answer research questions such as: How did each entropy emerge? What is the mathematical definition of each variant of entropy? How are entropies related to each other? What are the most applied scientific fields for each entropy? We describe in-depth the relationship between the most applied entropies in time-series for different scientific fields, establishing bases for researchers to properly choose the variant of entropy most suitable for their data. The number of citations over the past sixteen years of each paper proposing a new entropy was also accessed. The Shannon/differential, the Tsallis, the sample, the permutation, and the approximate entropies were the most cited ones. Based on the ten research areas with the most significant number of records obtained in the Web of Science and Scopus, the areas in which the entropies are more applied are computer science, physics, mathematics, and engineering. The universe of entropies is growing each day, either due to the introducing new variants either due to novel applications. Knowing each entropy's strengths and of limitations is essential to ensure the proper improvement of this research field.

Birth seasonality of childhood central nervous system tumors: Analysis of primary data from 16 Southern-Eastern European population-based registries.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys <5 years born during summer seemed to be at a lower risk of embryonal tumors (IRR: 0.73, 95% CI: 0.54-0.99). A clustering of astrocytomas was also found among girls (0-14 years) born during spring (IRR: 1.23, 95% CI: 1.03-1.46). Although the present exploratory results are by no means definitive, they provide some indications for age-, gender- and histology-related seasonal variations of CNS tumors. Expansion of registration and linkage with cytogenetic reports could refine if birth seasonality is causally associated with CNS tumors and shed light into the complex pathophysiology of this lethal disease.

Digital imaging-assisted quantification of H3K27me3 immunoexpression in luminal A/B-like, HER2-negative, invasive breast cancer predicts patient survival and risk of recurrence.

BACKGROUND: Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis. We assessed H3K27me3 immunoexpression with digital imaging software assistance, in a cohort of luminal-like BC patients with long-term follow-up time and evaluated its association with clinically relevant endpoints and its clinical usefulness. METHODS: H3K27me3 immunoexpression was assessed, by means of digital-imaging system, in archival tissue samples of 160 luminal A/B-like HER2-negative invasive BC, stages I-III. Survival analysis was performed using Kaplan-Meier and Cox regression. Cases were categorized as 'low' or 'high' expression based on cut-off defined by receiver operating characteristic (ROC) curve analysis. RESULTS: The patient cohort showed a median age of 61-years, with a median follow-up time of 11.7 years. Low H3K27me3 expression (below 85% cut-off) was significantly associated with recurrence, both in univariable (HR = 1.99, 95%CI 1.066-3.724) and multivariable analysis when adjusting for grade and age (HR = 1.89, 95%CI 1.004-3.559). A trend for higher risk of death in low H3K27me3 expression BC was observed (p = 0.069), reaching statistical significance in younger patients (p = 0.021). CONCLUSIONS: H3K27me3 immunoexpression assessed by digital imaging scoring software is an independent prognosis biomarker in luminal-like BC patients and may assist in more individualized adjuvant treatment decisions, thus potentially reducing recurrences after curative-intent treatment, while sparing unnecessary toxicity.