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Effective on-street parking is key to reduce urban traffic and pollution in densely populated cities. Thus, researchers have focused on forecasting future occupancy values depending on factors like time, space, or weather. This approach shows high average performances, but fails in predicting congested scenarios, actually the most critical. This work proposes a data-driven parking level of service (LOS) predictor that outperforms traditional methods, solving its inherent class imbalance issue by means of Random Undersampling Boost classifiers. We trained and validated the LOS classifiers using 13 months of data collected from the smart parking system in the city of Madrid, Spain. Results display average recall values above 0.94 and 0.87 at prediction horizons up to 10 and 60 minutes respectively. We compare these results with traditional regression-based occupancy predictors showing that our classifier clearly outperforms the formers predicting the minority classes, which carry the most significant information for drivers and parking managers. We further analyze the impact on performance of temporal and spatial features, revealing mid-term temporal data as the most relevant forecasting information, and low correlations between parking behaviors in bordering neighborhoods. In the light of these results, we believe that the proposed data-driven parking LOS classification has the potential to open a novel perspective on the parking occupancy forecasting field.

Background and aims Information regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis. Methods and results We recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE). Groups were matched by several CVD risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by ultrasonography. Inflammatory markers included classical variables (leucocytes and high-sensitivity C-reactive protein [hsCRP]) and glycoproteins by nuclear magnetic resonance (1H-NMR) spectroscopy (GlycA, GlycB, GlycF and the height/width [H/W] ratios of GlycA and GlycB). The age of the participants was 44.9 ± 7.8 years, and 20.5% harbored plaque. There were no differences in inflammatory markers among the four study groups. Overall, in multivariate-adjusted models, all 1H-NMR-glycoproteins (except GlycB) were positively associated with IMT measures (IMT of bulb and maximum-IMT of any carotid segment; p Conclusions High 1H-NMR-glycoprotein concentrations have a negative impact on carotid atherosclerosis among women with preeclampsia, regardless of T1D status.

Received 12th May 2021. Accepted 17th May 2021. Published online 28th May 2021. Issue published 1st August 2021.

Online incremental models for recommendation are nowadays pervasive in both the industry and the academia. However, there is not yet a standard evaluation methodology for the algorithms that maintain such models. Moreover, online evaluation methodologies available in the literature generally fall short on the statistical validation of results, since this validation is not trivially applicable to stream-based algorithms. We propose a $k$ k -fold validation framework for the pairwise comparison of recommendation algorithms that learn from user feedback streams, using prequential evaluation. Our proposal enables continuous statistical testing on adaptive-size sliding windows over the outcome of the prequential process, allowing practitioners and researchers to make decisions in real time based on solid statistical evidence. We present a set of experiments to gain insights on the sensitivity and robustness of two statistical tests—McNemar’s and Wilcoxon signed rank—in a streaming data environment. Our results show that besides allowing a real-time, fine-grained online assessment, the online versions of the statistical tests are at least as robust as the batch versions, and definitely more robust than a simple prequential single-fold approach.

Information on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population. Cross-sectional study in 167 consecutive T1D patients without CVD and with at least one of the following: ≥ 40 years, diabetic nephropathy, or ≥ 10 years of T1D duration with another CVD risk factor. The FA profile of erythrocyte membranes was determined by gas chromatography, and the number of carotid plaques (intima-media thickness ≥ 1.5 mm) was assessed by ultrasonography. Regression models were constructed adjusting for classical (age, gender, blood pressure, smoking habit, LDL-cholesterol, body mass index and statins) and T1D-specific risk factors (diabetes duration, HbA1c and chronic complications). A total of 58.7% were men (mean age 48.3 ± 10.3 years, T1D duration 27.2 ± 10.1 years). Sixty-one patients (36.5%) showed carotid plaque. Linoleic acid decreased and all-C18:1trans increased with the number of carotid plaques (none, 1–2, ≥ 3 plaques; p for trend

Background and aims Glycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. Methods and results We selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7–55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p Conclusion In T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

We report the clinical, biochemical and genetic findings from a Spanish boy of Caucasian origin who presented with fever-dependent RALF (recurrent acute liver failure) and osteogenesis imperfecta (OI). Whole-exome sequencing (WES) uncovered two compound heterozygous variants in NBAS (c.[1265 T > C];[1549C > T]:p.[(Leu422Pro)];[(Arg517Cys)]), and a heterozygous variant in P4HB (c.[194A > G];[194=]:p.[(Lys65Arg)];[(Lys65=)]) that was transmitted from the clinically unaffected mother who was mosaic carrier of the variant. Variants in NBAS protein have been associated with ILFS2 (infantile liver failure syndrome-2), SOPH syndrome (short stature, optic nerve atrophy, and Pelger-Huet anomaly syndrome), and multisystem diseases. Several patients showed clinical manifestations affecting the skeletal system, such as osteoporosis, pathologic fractures and OI. Experiments in the patient's fibroblasts demonstrated that mutated NBAS protein is overexpressed and thermally unstable, and reduces the expression of MGP, a regulator of bone homeostasis. Variant in PDI (protein encoded by P4HB) has been associated with CLCRP1 (Cole-Carpenter syndrome-1), a type of severe OI. An increase of COL1A2 protein retention was observed in the patient's fibroblasts. In order to study if the variant in P4HB was involved in the alteration in collagen trafficking, overexpression experiments of PDI were carried out. These experiments showed that overexpression of mutated PDI protein produces an increase in COL1A2 retention. In conclusion, these results corroborate that the variants in NBAS are responsible for the liver phenotype, and demonstrate that the variant in P4HB is involved in the bone phenotype, probably in synergy with NBAS variants.

Botulism is a life-threatening presynaptic disorder of the neuromuscular transmission produced by the neurotoxin elaborated by the botulinum neurotoxin-producing clostridia. We describe the management of a case series of 14 patients, members of 5 different families that were exposed to home-canned tuna and developed symptoms compatible with a mild clinical presentation of foodborne botulism. The electrophysiological study of the index case represented a reliable diagnostic test as it demonstrated a slight presynaptic dysfunction of the neuromuscular junction. Definite diagnosis was later confirmed by microbiological tests. Out of 14, only 3 patients presenting with a shorter period from symptom onset and with signs of multiple cranial neuropathies received botulinum antitoxin. All the patients remained stable and recovered progressively. Treatment with antitoxin may not be necessary in patients with late-presenting disease and mild and stable clinical picture.

This work presents an identification procedure of flexural behavior of toenail plates in twenty subjects with no history of feet or nails injury as of in-vivo measurements. In particular, four different mechanical models are considered to describe such properties, ranging from the pure elastic to viscoelastic, the latter from the classical and fractional points of view. The quality of the adjustment of each model is examined by a group of performance indices. Experimental data show that the best identification is achieved by the fractional order viscoelastic model for all subjects. These novel results in modeling flexural behavior of toenails are consistent with the published literature suggesting that viscoelastic materials may be successfully modeled with derivatives of fractional order. This could contribute, together with additional variables, to help health professionals, and more especially podiatrists, to have reliable and quantitative measures of the nail flexural behavior susceptible of treatment or for prevention, i.e., for clinical purposes.

It is a well-known fact that the 1989 Exxon Valdez disaster caused the escort towing of laden tankers in many coastal areas of the world to become compulsory. In order to implement a new type of escort towing, specially designed to be employed in very adverse weather conditions, considerable changes in the hull form of escort tugs had to be made to improve their stability and performance. Since traditional winch and ropes technologies were only effective in calm waters, tugs had to be fitted with new devices. These improvements allowed the remodeled tugs to counterbalance the strong forces generated by the maneuvers in open waters. The aim of this paper is to perform a comprehensive literature review of the new high-performance automatic dynamic winches. Furthermore, a thorough analysis of the best available technologies regarding towline, essential to properly exploit the new winches, will be carried out. Through this review, the way in which the escort towing industry has faced this technological challenge is shown.

Articular hyaline cartilage injuries can occur as a result of either traumatic of progressive degeneration. When the articular cartilage in a joint is damaged, it can cause joint pain and dysfunction, predisposing patients for the development of early-onset osteoarthritis. There are many restoration procedures available to treat these injuries, such as bone marrow−stimulation techniques, osteoarticular auto/allograft transplants, and autologous chondrocyte implantation. Each of these techniques has its own limitations, which led researchers to explore new regenerative and repair techniques to produce normal hyaline cartilage. The purpose of this Technical Note is to describe in detail the particulated autologous chondral−platelet-rich plasma matrix implantation (PACI) technique that could be used as a single-stage cartilage restoration procedure for treatment of full-thickness cartilage and osteochondral defects., Technique Video Video 1 Description of the particulated autologous chondral−platelet-rich plasma matrix implantation (PACI) technique.

Aims Endurance training improves aerobic fitness and cardiac function in individuals with heart failure. However, the underlying mechanisms are not well characterized. Exercise training could therefore act as a tool to discover novel targets for heart failure treatment. We aimed to associate changes in Ca2+ handling and electrophysiology with micro-RNA (miRNA) profile in exercise trained heart failure rats to establish which miRNAs induce heart failure-like effects in Ca2+ handling and electrophysiology. Methods and results Post-myocardial infarction (MI) heart failure was induced in Sprague Dawley rats. Rats with MI were randomized to sedentary control (sed), moderate (mod)- or high-intensity (high) endurance training for 8 weeks. Exercise training improved cardiac function, Ca2+ handling and electrophysiology including reduced susceptibility to arrhythmia in an exercise intensity-dependent manner where high intensity gave a larger effect. Fifty-five miRNAs were significantly regulated (up or down) in MI-sed, of which 18 and 3 were changed towards Sham-sed in MI-high and MI-mod, respectively. Thereafter we experimentally altered expression of these “exercise-miRNAs” individually in human induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CM) in the same direction as they were changed in MI. Of the “exercise-miRNAs”, miR-214-3p prolonged AP duration, whereas miR-140 and miR-208a shortened AP duration. miR-497-5p prolonged Ca2+ release whereas miR-214-3p and miR-31a-5p prolonged Ca2+ decay. Conclusion Using exercise training as a tool, we discovered that miR-214-3p, miR-497-5p, miR-31a-5p contribute to heart-failure like behaviour in Ca2+ handling and electrophysiology and could be potential treatment targets.

Osteochondral fractures of the knee represent a challenging entity to manage since there are many different surgical techniques for cartilage repair or other salvage procedures. In terms of cartilage repair, several hardware devices can be used, and many of them could imply a second-stage surgery for hardware removal. The purpose of this article is to describe in detail a one-stage osteochondral fracture repair technique with knotless anchors and interconnected crossing suture sliding loops for the knee. This technique is a one-stage open or arthroscopic procedure with an unlimited number of loops configurations with no particular need for a second surgery for hardware removal, no knot damage, and without the use of bone tunnels. It can be used in different cartilage anatomic locations, such as femoral condyles, trochlea, patella, or other joints.

Made available in DSpace on 2021-06-25T10:35:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 In predictive maintenance, vibration signal analyses are frequently used to diagnose reducer failures because these analyses contain information about the conditions of the mechanical components. Reducer vibration signals are very noisy and the signal-to-noise ratio is so low that extracting information from the signal components is complex, especially in practical situations. Therefore, signal processing techniques are used to solve this problem and facilitate the retrieval of information. In this work, the adopted technique included noise-canceling technique, synchronous temporal mean (TSA), and continuous Morlet wavelet transform (CWT), designed to extract resources and diagnose local gear damage. These techniques are used in measured signals in an experimental workbench consisting of the gear pair coupled to a motor and a generator. The experiment was monitored according to the conditions of a gear pair throughout its useful life. The continuous wavelet transforms accurately identified faults in the gear teeth, and it was possible to detect in which tooth the fault was occurring. Ppg in Mechanical Engineering Dem FEIS/UNESP Department of Mechanical Engineering Dem FEIS/UNESP Department of Mathematics Mat FEIS/UNESP Department of Biofuels Araçatuba Technology College Fatec Ppg in Mechanical Engineering Dem FEIS/UNESP Department of Mechanical Engineering Dem FEIS/UNESP Department of Mathematics Mat FEIS/UNESP

The meniscus is an essential structure for the knee functioning and survival. Meniscectomy is the most common surgical procedure in orthopaedic surgery. Following total or subtotal meniscectomy, meniscal allograft transplantation (MAT) should be considered in symptomatic active young patients. Several MAT techniques have been described in the literature as an attempt to restore normal knee kinematics and potentially decrease the risk of developing knee osteoarthritis. The purpose of this article is to describe in detail an efficient and reproducible all-arthroscopic MAT technique with bone plugs and preloaded sutures.

With a lot of uncertainty, unclear, and frequently changing management protocols, COVID-19 has significantly impacted the orthopaedic surgical practice during this pandemic crisis. Surgeons around the world needed closed introspection, contemplation, and prospective consensual recommendations for safe surgical practice and prevention of viral contamination. One hundred orthopaedic surgeons from 50 countries were sent a Google online form with a questionnaire explicating protocols for admission, surgeries, discharge, follow-up, relevant information affecting their surgical practices, difficulties faced, and many more important issues that happened during and after the lockdown. Ten surgeons critically construed and interpreted the data to form rationale guidelines and recommendations. Of the total, hand and microsurgery surgeons (52%), trauma surgeons (32%), joint replacement surgeons (20%), and arthroscopy surgeons (14%) actively participated in the survey. Surgeons from national public health care/government college hospitals (44%) and private/semiprivate practitioners (54%) were involved in the study. Countries had lockdown started as early as January 3, 2020 with the implementation of partial or complete lifting of lockdown in few countries while writing this article. Surgeons (58%) did not stop their surgical practice or clinics but preferred only emergency cases during the lockdown. Most of the surgeons (49%) had three-fourths reduction in their total patients turn-up and the remaining cases were managed by conservative (54%) methods. There was a 50 to 75% reduction in the number of surgeries. Surgeons did perform emergency procedures without COVID-19 tests but preferred reverse transcription polymerase chain reaction (RT-PCR; 77%) and computed tomography (CT) scan chest (12%) tests for all elective surgical cases. Open fracture and emergency procedures (60%) and distal radius (55%) fractures were the most commonly performed surgeries. Surgeons preferred full personal protection equipment kits (69%) with a respirator (N95/FFP3), but in the case of unavailability, they used surgical masks and normal gowns. Regional/local anesthesia (70%) remained their choice for surgery to prevent the aerosolized risk of contaminations. Essential surgical follow-up with limited persons and visits was encouraged by 70% of the surgeons, whereas teleconsultation and telerehabilitation by 30% of the surgeons. Despite the protective equipment, one-third of the surgeons were afraid of getting infected and 56% feared of infecting their near and dear ones. Orthopaedic surgeons in private practice did face 50 to 75% financial loss and have to furlough 25% staff and 50% paramedical persons. Orthopaedics meetings were cancelled, and virtual meetings have become the preferred mode of sharing the knowledge and experiences avoiding human contacts. Staying at home, reading, and writing manuscripts became more interesting and an interesting lifestyle change is seen among the surgeons. Unanimously and without any doubt all accepted the fact that COVID-19 pandemic has reached an unprecedented level where personal hygiene, hand washing, social distancing, and safe surgical practices are the viable antidotes, and they have all slowly integrated these practices into their lives. Strict adherence to local authority recommendations and guidelines, uniform and standardized norms for admission, inpatient, and discharge, mandatory RT-PCR tests before surgery and in selective cases with CT scan chest, optimizing and regularizing the surgeries, avoiding and delaying nonemergency surgeries and follow-up protocols, use of teleconsultations cautiously, and working in close association with the World Health Organization and national health care systems will provide a conducive and safe working environment for orthopaedic surgeons and their fraternity and also will prevent the resurgence of COVID-19.

This randomized clinical trial evaluated the efficacy of five different adhesive systems in the restoration of occlusal cavities after one year of function. Two etch-and-rinse (Optibond™FL, Prime&Bond®NT™) and three self-etch (Clearfil™SE Bond, Xeno®III, Xeno®V+) adhesive systems were evaluated on 159 occlusal restorations, incrementally filled with a microhybrid composite resin. Restorations were assessed using the FDI criteria at baseline, 6 months and 1 year. Statistical analysis was performed with Friedman-test and Kruskal-Wallis test (p

espanolEstamos ante las patologias que con mayor frecuencia afronta el cirujano general. Aunque habitualmente se tratan de forma programada en regimen de cirugia mayor ambulatoria, su presentacion en urgencias no es infrecuente, transformandose en una patologia grave con una tasa de mortalidad reconocida. El diagnostico es, basicamente, clinico y exploratorio y es, por tanto, necesario que la comunidad medica este familiarizada con sus formas de presentacion. La evolucion de las tecnicas quirurgicas nos ha llevado a hacerlas menos agresivas y mas eficientes, generalizandose el empleo de mallas en su tratamiento. La ubicacion de las protesis y la composicion de las mallas tambien han mejorado, realizandose tecnicas mas eficientes con mallas mas resistentes y mas biocompatibles. EnglishAll of them are the most frequent pathologies for general surgeons. Usually the intervention is scheduled as ambulatory major surgery; nevertheless, it is not uncommon the presentation of hernias in emergency department as a severe pathology with a recognized mortality rate. Being its diagnosis clinical and exploratory, the knowledge of its forms of presentation is required. Surgical techniques have evolved and nowadays are less aggressive and more efficient; the use of meshes is becoming more widespread. Moreover, prosthesis placement and mesh composition have also been improved, so more efficient techniques are performed with more resistant and biocompatible meshes.

We report the case of a Caucasian Spanish origin female who showed severe psychomotor developmental delay, hypotonia, strabismus, epilepsy, short stature, and poor verbal language development. Brain magnetic resonance imaging scans showed thickened corpus callosum, cortical malformations, and dilated and abnormal configuration of the lateral ventricles without hydrocephalus. Whole-exome sequence uncovered a de novo variant in the microtubule associated serine/threonine kinase 1 gene (MAST1; NM_014975.3:c.1565G>A:p.(Gly522Glu)) that encodes for the MAST1. Only 12 patients have been identified worldwide with 10 different variants in this gene: six patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; two patients with microcephaly and cerebellar hypoplasia; two patients with autism, one patient with diplegia, and one patient with microcephaly and dysmorphism. Our patient shows a new phenotypic subtype defined by mega-corpus-callosum syndrome with cortical malformations without cerebellar hypoplasia. In conclusion, our data expand the phenotypic spectrum associated to MAST1 gene variants.

Purpose Although preeclampsia (PE) is a well-established cardiovascular risk factor (CVRF) in the general population, its role in type 1 diabetes (T1D) has been scarcely studied. We assessed the association between PE and preclinical atherosclerosis in T1D. Methods We recruited 112 women without cardiovascular disease and last pregnancy ≥5 years before: (1) T1D and previous PE (T1D+/PE+; n = 28); (2) T1D without preeclampsia (T1D+/PE–; n = 28); (3) previous PE without T1D (T1D–/PE+; n = 28); and (4) controls (without T1D or PE; T1D–/PE–; n = 28). Groups were matched by age, several CVRFs, and diabetes duration and retinopathy (in T1D participants). Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥ 1.5 mm) were assessed by standardized ultrasonography protocol. Results Mean age of the participants was 44.9 ± 7.8 years (14.3% hypertension and 21.4% active smokers). Groups including T1D (T1D+/PE+ and T1D+/PE–) more frequently presented hypertension and statin treatment (23.2% vs 5.4% and 37.5% vs 8.9%; respectively; P < 0.01), without differences in other CVRFs. Carotid plaques were observed in 20.5%. In multivariate models adjusted for age, CVRF, and statins, both T1D and PE showed a similar impact on the presence of plaque, with odds ratios (95% confidence interval), 5.45 (1.36–21.9) and 4.24 (1.04–17.3), respectively. Both entities showed an additive effect when combined, both in common carotid-IMT (T1D+/PE– or T1D–/PE+, β = 0.198; T1D+/PE+, β = 0.297) and in the presence of plaque (8.53 [1.07–68.2] and 28.1 [2.67–296.4], respectively). Conclusions Previous PE was independently associated with preclinical atherosclerosis in T1D. Further studies are needed to ascertain its usefulness for stratifying risk in T1D women.

Background: The identification of biomarkers for the early diagnosis of Parkinson’s Disease (PD) might improve treatment and avoid complications. However, the search of such biomarkers is a real challenge. The main reason for this is that finding samples for that purpose is not an easy task. In this work, we propose a set of reliable samples for the identification of biomarkers for the early diagnosis of PD. In fact, the original source of these samples can be searched for similar purposes when dealing with other diseases.Materials and methods: Case-control study included 12 plasma samples of subjects that subsequently developed PD and 21 plasma samples of matched healthy controls from the Spanish EPIC-Navarra cohort, part of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study. All the case samples were provided by healthy volunteers who were followed up for a mean of 15.9 (± 4.1) years and developed PD disease later on. Therefore, these sample are ideal for the search of early biomarkers of PD. We used an analytical multiplatform based on liquid chromatography and tandem mass spectrometry in order to find significant differences in the amounts of previously reported metabolites that are altered when the disease has been established and diagnosed. Results: Out of all 40 analytes that were studied, seven significant metabolites were observed. Benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol and quinolinic acid were significantly changed in subjects that developed PD. These metabolites are closely related to mitochondrial dysfunction, the oxidative stress and the mechanisms of energy production, which might indicate that these mechanisms are already affected before disease onset.Conclusions: We propose the samples from the EPIC study as reliable and priceless samples for the search of early biomarkers of PD, although many other diseases can be also studied as long as the information stored about the participants recorded such details. As a proof of concept, we showed that these samples were useful for the study of metabolites that may be altered before the participants developed PD. This might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.

Background: Although cardiovascular disease (CVD) remains the leading cause of mortality in type 1 diabetes (T1D), the use of cardioprotective drugs is scarce. We aimed to evaluate the impact of carotid ultrasonography (US) on the improvement in cardiovascular risk factors (CVRFs) in T1D.Methods: T1D patients without CVD meeting criteria for lipid treatment according to guidelines (age ≥40 years, nephropathy and/or ≥10 years of diabetes duration with ≥1 additional CVRFs) were included. The carotid-US group (US-G) underwent a standardized US protocol and CVRF assessment; recommendations were made according to subclinical atherosclerosis status. The control group (CG) followed usual clinical practice. Changes in CVRFs, specially statin use and LDL-cholesterol levels, at one year were analysed.Results: A total of 318 patients were included (51.3% female, mean age of 49.1 years and 25.5 years of diabetes duration): 211 in the US-G and 107 in the CG. Participants in the US-G had a higher baseline LDL-cholesterol than controls (114 vs. 102 mg/dL; pConclusions: Carotid-US is independently associated with an intensification of lipid-lowering therapy in a high-risk T1D population.

COVID-19 has dramatically struck each section of our society: health, economy, employment, and mobility. This work presents a data-driven characterization of the impact of COVID-19 pandemic on public and private mobility in a mid-size city in Spain (Fuenlabrada). Our analysis used real data collected from the public transport smart card system and a Bluetooth traffic monitoring network, from February to September 2020, thus covering relevant phases of the pandemic. Our results show that, at the peak of the pandemic, public and private mobility dramatically decreased to 95% and 86% of their pre-COVID-19 values, after which the latter experienced a faster recovery. In addition, our analysis of daily patterns evidenced a clear change in the behavior of users towards mobility during the different phases of the pandemic. Based on these findings, we developed short-term predictors of future public transport demand to provide operators and mobility managers with accurate information to optimize their service and avoid crowded areas. Our prediction model achieved a high performance for pre- and post-state-of-alarm phases. Consequently, this work contributes to enlarging the knowledge about the impact of pandemic on mobility, providing a deep analysis about how it affected each transport mode in a mid-size city.

Bladder cancer (BC) ranks as the sixth most prevalent cancer in the world, with a steady rise in its incidence and prevalence, and is accompanied by a high morbidity and mortality. BC is a complex disease with several molecular and pathological pathways, thus reflecting different behaviors depending on the clinical staging of the tumor and molecular type. Diagnosis and monitoring of BC is mainly performed by invasive tests, namely periodic cystoscopies; this procedure, although a reliable method, is highly uncomfortable for the patient and it is not exempt of comorbidities. Currently, there is no formal indication for the use of molecular biomarkers in clinical practice, even though there are several tests available. There is an imperative need for a clinical non-invasive testing for early detection, disease monitoring, and treatment response in BC. In this review, we aim to assess and compare different tests based on molecular biomarkers and evaluate their potential role as new molecules for bladder cancer diagnosis, follow-up, and treatment response monitoring. This research was funded by FCT ("Portuguese Foundation for Science and Technology") through a PhD grant to R.B. (SFRH/BD/111321/2015). Further funding was obtained from the project "Advancing cancer research: from basic knowledge to application" NORTE-01-0145-FEDER-000029: "Projetos Estruturados de I & D & I," funded by Norte 2020 - Programa Operacional Regional do Norte. This article is also a result of the project PTDC/MED-ONC/31438/2017 (The Other Faces of Telomerase: Looking beyond Tumor Immortalization), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), COMPETE 2020?Operacional Programme for Competitiveness and Internationalisation (POCI) and by Portuguese funds through FCT. The APC was funded by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalisation?COMPETE 2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM.

BACKGROUND: Neuropathic symptoms are commonly reported in Parkinson's disease (PD), but robust data on the epidemiology of such symptoms are lacking. The present study sought to investigate the prevalence and determinants of peripheral sensory neuropathic symptoms (PSNS) in idiopathic PD (IPD) and ascertain the effects of such symptoms on the patients' quality of life (QoL). METHODS: Patients with IPD and age-matched and gender-matched controls were screened for neuropathic symptoms using the Michigan Neuropathy Screening Instrument. The impact of neuropathic symptoms on QoL was investigated using the 36-Item Short Form Survey. RESULTS: Fifty-two patients and 52 age-matched and gender-matched controls were recruited. PSNS were reported more frequently in patients with IPD than in the control subjects (57.7 versus 28.8%, p = 0.003). No significant relationships were found between PD-related clinical characteristics (i.e. disease severity and duration, duration of exposure to levodopa) and the presence of PSNS. Significant correlations were found between the number of PSNS and physical functioning (Spearman's Rho - 0.351), even after adjusting for age, gender and Hoehn and Yahr score. CONCLUSION: Our results support the notion of a greater prevalence of PSNS in IPD patients as compared to the general population, which, at least in part, may be secondary to large and/or small fibre peripheral neuropathy. This warrants further investigation in larger studies that include detailed neurophysiological assessments. 118 3 445 450

Background The alteration of microRNA (miRNA) processing is a driver event in several tumors including thyroid cancer (TC). Upon the discovery of DICER mutations affecting the miRNA biogenesis in TC, other genes encoding proteins with similar functions have been studied. The DiGeorge Critical Region 8 (DGCR8) gene holds a critical role in miRNA biogenesis as a microprocessor complex component. Previous studies identified a hotspot DGCR8 mutation - the variant c.1552G > A (p.E518K) that alters canonical miRNA production. As miRNAs are necessary to accurately establish thyroid follicles and hormone synthesis, the deregulation of their expression are common in TC. The goal of this study was to characterize the variant p.E518K of DGCR8 in thyroid lesions and evaluate its expression. Methods 242 samples of 214 patients with tumor or tumor-like lesions of thyroid were evaluated by direct sequencing for the presence of c.1552 G > A (p.E518K). Formalin-fixed paraffin embedded (FFPE) sections of these lesions were studied for DGCR8 immunoexpression. When frozen tissue was available, DGCR8 mRNA expression was analyzed by quantitative PCR (qPCR). Results The presence of the variant c.1552G > A (p.E518K) was a rare event in our series. Only 1 case was found mutated, and it corresponded to a poorly differentiated thyroid carcinoma (PDTC). Unexpectedly, mRNA DGCR8 expression and DGCR8 expression shown an aberrant expression in PDTC cases which could lead to a miRNA downregulation. Conclusions The results obtained so far point that DGCR8 may have a role in thyroid carcinogenesis. Although mutations are rare, aberrant expression affecting miRNA expression seems to be a common event.

The purpose of this study was to evaluate specifically the relationship between glycated haemoglobin (HbA1c) levels and retinal optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in type 1 Diabetes Mellitus (DM). A total of 478 type 1 DM patients and 115 controls were included in a prospective OCTA trial (ClinicalTrials.gov NCT03422965). Subgroup analysis was performed for controls, no diabetic retinopathy (DM-no DR) and DR patients (DM-DR), and HbA1c levels. OCT and OCTA measurements were compared with HbA1c levels (current and previous 5 years). DM-no DR patients with HbA1c levels &gt, 7.5% showed lower VD than DM-DR and controls (20.16 vs. 20.22 vs. 20.71, p &lt, 0.05), and showed a significant correlation between HbA1c levels and FAZc (p = 0.04), after adjusting for age, gender, signal strength index, axial length, and DM disease duration. DM-DR patients with HbA1c &gt, 7.5% presented greater CRT than DM-no DR and controls (270.8 vs. 260 vs. 251.1, p &lt, 0.05) and showed a significant correlation between HbA1c and CRT (p = 0.03). In conclusion, greater levels of HbA1c are associated with OCTA changes in DM-no DR patients, and with structural OCT changes in DM-DR patients. The combination of OCTA and OCT measurements and HbA1c levels may be helpful to identify patients at risk of progression to greater stages of the diabetic microvascular disease.

Introduction and objectives: Obesity represents a major global public health problem. Its etiology is multifactorial and includes poor dietary habits, such as hypercaloric and hyperlipidic diets (HFDs), physical inactivity, and genetic factors. Regular exercise is, per se, a tool for the treatment and prevention of obesity, and recent studies suggest that the beneficial effects of exercise can be potentiated by the fasting state, thus potentially promoting additional effects. Despite the significant number of studies showing results that corroborate such hypothesis, very few have evaluated the effects of fasted-state exercise in overweight/obese populations. Therefore, the aim of this study was to evaluate the subacute effects (12 h after conclusion) of a single moderate-intensity exercise bout, performed in either a fed or an 8 h fasted state, on serum profile, substrate-content and heat shock pathway–related muscle protein immunocontent in obese male rats. Methods: Male Wistar rats received a modified high-fat diet for 12 weeks to induce obesity and insulin resistance. The animals were allocated to four groups: fed rest (FER), fed exercise (FEE), fasted rest (FAR) and fasted exercise (FAE). The exercise protocol was a 30 min session on a treadmill, with an intensity of 60% of VO2max. The duration of the fasting period was 8 h prior to the exercise session. After a 12 h recovery, the animals were killed and metabolic parameters of blood, liver, heart, gastrocnemius and soleus muscles were evaluated, as well as SIRT1 and HSP70 immunocontent in the muscles. Results: HFD induced obesity and insulin resistance. Soleus glycogen concentration decreased in the fasted groups and hepatic glycogen decreased in the fed exercise group. The combination of exercise and fasting promoted a decreased concentration of serum total cholesterol and triglycerides. In the heart, combination fasting plus exercise was able to decrease triglycerides to control levels. In the soleus muscle, both fasting and fasting plus exercise were able to decrease triglyceride concentrations. In addition, heat shock protein 70 and sirtuin 1 immunocontent increased after exercise in the gastrocnemius and soleus muscles. Conclusions: An acute bout of moderate intensity aerobic exercise, when realized in fasting, may induce, in obese rats with metabolic dysfunctions, beneficial adaptations to their health, such as better biochemical and molecular adaptations that last for at least 12 h. Considering the fact that overweight/obese populations present an increased risk of cardiovascular events/diseases, significant reductions in such plasma markers of lipid metabolism are an important achievement for these populations.

Purpose: To report visual, clinical and radiological outcomes of three patients with fibromuscular dysplasia (FMD) that presented different ocular ischemic events, supported by different multimodal imaging. Methods: A retrospective study including patients who attended a tertiary referral hospital from July 2016 to June 2019 referring acute visual loss and later diagnosed of FMD. Ophthalmological examination included best corrected visual acuity (BCVA), biomicroscopy, fundoscopy, fluorescein angiography (FA), and macular and retinal nerve fiber layer spectral domain optic coherence tomography (SD-OCT). Patients were admitted by the Neurology service, completing the study with blood and cerebrospinal fluid (CSF) test, serology and cultures, cerebral magnetic resonance angiography (angioMRI), and arteriography. Results: Three patients were included; one male and second females. All referred unilateral acute visual loss, with BCVA of counting fingers or hand-motion. Relative afferent pupilar defect was present in all patients. Two patients associated neurological focal signs and one had chronic hypertension. Fundoscopy revealed hemorrhages and exudates in all patients, and the typical sign of “string-of-beads” in one. FA showed dye filling delay and macular and peripheral hypofluorescence. SD-OCT revealed acute and chronic retinal ischemic signs. Blood and CSF tests, serologies and cultures resulted negative. All presented cerebral vascular involvement, objectified in the cerebral angioMRI or arteriography. Conclusions: FMD should be considered in cases with unilateral sudden visual loss associated to neurological focal deficits in young patients. The typical “string-of-beads” image is rare in small arteries such as the retinal vasculature. When suspected, a complete ophthalmological examination and cerebral vascular imaging is essential to confirm the diagnosis.

As we have seen as a consequence of the COVID-19 global pandemic, our scientific-technological society requires a transformation of knowledge in a global, digital and virtual manner. In light of this, and to improve the public health skills of professionals working to promote health education, one of the current priorities is to train pre-service teachers on how to search for health-related scientific knowledge relating to bio-health through digital literacy in health. The objectives of this study were to determine the level of eHealth literacy, scientific knowledge in health and confidence on the part of students, analyzing the degree of improvement following a teaching intervention with students of the Bachelor’s Degree of Education of the University of Extremadura. A quasi-experimental longitudinal study was carried out with pre-test and post-test groups and a mixed data analysis. It involved the application of an active cooperative methodology with tutoring using the jigsaw technique, with the use of four quality digital browsers to enhance scientific rigor. The results show that the initial level of eHealth literacy and confidence was problematic. Following the intervention with the cooperative methodology, both these levels and the level of scientific knowledge in health reached an excellent level. In conclusion, this suggests that university training programs need to be implemented to improve digital and scientific skills in health education as they are currently insufficient. It has been demonstrated that a cooperative active methodology improved these levels and accordingly its use in active and digital higher education should be promoted.

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients’ skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP’s role in normal and diseased skeletal muscle homeostasis.

Aims To evaluate the impact of a prepregnancy care (PPC) programme, beyond HbA1c, on hypoglycaemia awareness and glycaemic variability (GV). Methods Prospective pilot study. We selected women with Type 1 diabetes who initiated a PPC programme with normal hypoglycaemia awareness (n = 24). Hypoglycaemia awareness, hypoglycaemic events and GV derived from masked-continuous glucose monitoring were evaluated in the first visit and within 2 weeks after pregnancy confirmation. Results The duration was 16.5 ± 13.0 months. HbA1c significantly decreased (−0.8 ± 0.7; p Conclusions A PPC programme improved HbA1c as well as GV with no significant impact on hypoglycaemia awareness. Moreover, GV could help to identify women less likely to achieve glycaemic targets. Larger studies are needed to confirm these results.

Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. Methods: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal. Methods: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal. This study was industry-sponsored by the pharmaceutical company Ipsen Portugal. João Vinagre (CEECIND/00201/2017) and Paula Soares receive funding from the Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020; Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia)/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and the project “Advancing Cancer Research: From Basic Knowledge to Application” (NORTE-01-0145-FEDER-000029); and “Projetos Estruturados de I&D&I,” funded by Norte 2020—Programa Operacional Regional do Norte. Further funding was from the European Regional Development Fund (ERDF) through the Operational Program for Competitiveness and Internationalization (COMPETE 2020) and Portuguese national funds via FCT (Fundação para a Ciência e a Tecnologia), under the project “POCI-01-0145-FEDER-016390: CANCEL STEM.” Maria João Bugalho and João Vinagre were funded by the Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo through the Study Group for Neuroendocrine Tumours. info:eu-repo/semantics/publishedVersion

Factors influencing fallopian tube occlusion in women with a lower genital tract infection remain incompletely elucidated. We evaluated whether a polymorphism in the mannose-binding lectin (MBL) gene at codon 54 influences the occurrence of fallopian tube blockage in relation to exposure to Chlamydia trachomatis. In a case–control study at The Hospital das Clinicas, University of Sao Paulo, Brazil, 75 women with hysterosalpingography-documented tubal occlusion and 75 women with patent fallopian tubes were analyzed for detection of single-nucleotide polymorphism in codon 54 of the MBL gene and for IgG anti-C. trachomatis antibodies in their sera. Both groups were matched for age, race, and sexual variables. Prior exposure to C. trachomatis, as evidenced by the presence of IgG antibodies, was comparable in both groups. Detection of the polymorphic MBL allele was more prevalent in women with blocked tubes (p

We report the clinical, biochemical and genetic findings from a Spanish girl of Caucasian origin who presented with macrocephaly, dysmorphic facial features, developmental delay, hypotonia, combined oxidative phosphorylation (OxPhos) deficiency, epilepsy and anti-phospholipid antibodies (aPL). Whole-exome sequencing (WES) uncovered a heterozygous variant in the MTOR gene (NM_004958.3: c.7235A>T: p.(Asp2412Val)) that encodes for the Serine/threonine-protein kinase mTOR. The substrates phosphorylation experiments demonstrated that this variant exerts its effect by gain-of-function (GOF) and autosomal dominant mechanism. GOF variants in this protein have been associated with Smith-Kingsmore syndrome (SKS), a rare autosomal dominant disorder characterized by intellectual disability, macrocephaly, seizure, developmental delay and dysmorphic facial features. Furthermore, the mTOR pathway has been demonstrated previously to be involved in many types of endothelium injuries including the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by the production of aPL with recurrent vascular thrombosis. Therefore, our patient is the first one with an mTOR variant and diagnosed with SKS and APS. In conclusion, our data expand both the genetic and phenotypic spectrum associated with MTOR gene variants.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self‐renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher‐risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh/TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer., What's new? Telomerase reverse transcriptase (TERT) activation is central to cancer cell immortalization. It acts, however, through relatively unknown mechanisms. In urothelial bladder cancer (UBC) in particular, TERT activation can occur in the presence or absence of mutation, raising questions about alternative activation mechanisms. Our study shows that hypermethylation of the TERT promoter (THOR) plays a key part in UBC, being a dynamic and progressive process, with hypermethylation levels increasing with bladder cancer severity. Moreover, both hypermethylation and TERT promoter mutation contributed to increased telomerase expression. The findings provide insight into telomere biology in UBC and may be applicable to other tumors.

Although widely used, the majority of current music recommender systems still focus on recommendations’ accuracy, userpreferences and isolated item characteristics, without evaluating other important factors, like the joint item selections and the recommendation moment. However, when it comes to playlist recommendations, additional dimensions, as well as the notion of user experience and perception, should be taken into account to improve recommendations’ quality. In this work, HybA, a hybrid recommender system for automatic playlist continuation, that combines Latent Dirichlet Allocation and Case-Based Reasoning, is proposed. This system aims to address “similar concepts” rather than similar users. More than generating a playlist based on user requirements, like automatic playlist generation methods, HybA identifies the semantic characteristics of a started playlist and reuses the most similar past ones, to recommend relevant playlist continuations. In addition, support to beyond accuracy dimensions, like increased coherence or diverse items’ discovery, is provided. To overcome the semantic gap between music descriptions and user preferences, identify playlist structures and capture songs’ similarity, a graph model is used. Experiments on real datasets have shown that the proposed algorithm is able to outperform other state of the art techniques, in terms of accuracy, while balancing between diversity and coherence. This work has been partially supported by the Catalan Agency for Management of University and Research Grants (AGAUR) (2017 SGR 574), by the European Regional Development Fund (ERDF), through the Incentive System to Research and Technological development, within the Portugal2020 Competitiveness and Internationalization Operational Program –COMPETE 2020– (POCI-01-0145-FEDER006961), and by the Portuguese Foundation for Science and Technology (FCT) (UID/EEA/50014/2013).

Resumen La situacion actual de la pandemia por SARS-CoV-2 tiene paralizada la cirugia no urgente y/u oncologica en muchos hospitales de nuestro pais con lo que esto conlleva para la salud de los ciudadanos que estan pendientes de una intervencion quirurgica. La cirugia mayor ambulatoria puede abarcar en su cartera de servicios mas del 85% de los procedimientos quirurgicos que se realizan en un servicio de cirugia y se presenta como una alternativa factible y segura en el momento actual ya que no requiere camas de ingreso y disminuye claramente el riesgo de infeccion. Ademas, es la herramienta que deberia generalizarse para solucionar la acumulacion de pacientes en lista de espera que la pandemia esta generando, por lo que parece oportuno que desde la seccion de Cirugia Mayor Ambulatoria de la Asociacion Espanola de Cirujanos se presente una serie de recomendaciones para la implementacion de la misma en estas circunstancias excepcionales que nos toca vivir.

Aims The reduction in androgens serum concentration is a physiological condition that accompanies age advancement but can also occur because of prostate cancer and gender affirming treatment or pathological conditions such as functional hypogonadism. However, androgen deficiency is related to a higher risk of developing metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Considering that glucagon-like peptide 1 (GLP1) analogs are increasingly used in the treatment of T2DM, we investigated if liraglutide could also attenuate the metabolic changes caused by orchiectomy in rats. Main methods Wistar rats were orchiectomized (ORC), and subdivided in four groups: sham saline, sham liraglutide, ORC saline, and ORC liraglutide. After sixty days, metabolic parameters were evaluated in blood, muscle, liver, brown (BAT) and white adipose tissue (WAT) visceral depots. Glucose utilization, oxidation, and conversion to lipids by de novo lipogenesis, and basal and adrenaline-stimulated lipolysis were evaluated in BAT and WAT depots. Key findings Orchiectomy increased triglyceridemia, BAT and rtWAT weight, and lipolysis and reduced glucose utilization. Liraglutide treatment reversed these effects. Significance These results indicate that liraglutide improves triglyceridemia and glucose metabolism in WAT depots, which suggests that it may be a promising therapeutic strategy to handle disruptions in energy metabolism caused by androgen deficiency.

O Mecanismo de Desenvolvimento Limpo (MDL) é um instrumento de flexibilização apresentado no Protocolo de Quioto para projetos de redução de emissão de Gases do Efeito Estufa. Este artigo tem por objetivo estudar o uso e a viabilidade de projetos MDL em sistemas fotovoltaicos. Utilizou-se a metodologia do MDL adequada para geração de energia renovável conectada à rede, calculou-se as reduções de emissões de CO2 e as Reduções Certificadas de Emissões (RCEs) a fim de determinar a geração fotovoltaica necessária para obter projetos de MDL viáveis. A aplicação do projeto de MDL apresenta viabilidade econômica ao projeto de geração fotovoltaica mesmo não apresentando uma diferença significativa em termos econômicos considerado os indicadores econômicos calculados sem o MDL. A menor Rentabilidade obtida sem e com a aplicação do MDL foi, respectivamente, 243% e 102%, considerando o período total de vida útil do projeto fotovoltaico de 25 anos. Pode-se considerar que esses resultados apresentariam uma diferença mais significativa em gerações superiores ao apresentado neste estudo.

This review addresses the impact of molecular alterations on the diagnosis and prognosis of differentiated thyroid carcinoma (DTC), including papillary, follicular, and well-differentiated carcinoma NOS, as well as oncocytic neoplasms. The molecular characterization of DTC is based upon the well-established dichotomy of BRAF-like and RAS-like designations, together with a remaining third group, less homogeneous, composed of non-BRAF-/non-RAS-like tumors. The role of BRAF V600E mutation in risk stratification is discussed in the clinico-pathological context, namely, staging and invasive features of classic papillary thyroid carcinoma (PTC) and histopathological variants carrying an excellent prognosis (microPTC) or a guarded prognosis, including the aggressive variants tall cell and hobnail cell PTCs. In follicular patterned tumors, namely, follicular thyroid carcinoma (FTC), with or without oncocytic features, the most prevalent molecular alteration are RAS mutations that do not carry prognostic significance. The only genetic alteration that has been proven to play a role in risk stratification of PTC and FTC is TERT promoter (TERTp) mutation.

In the past decade, we have witnessed the widespread adoption of Deep Neural Networks (DNNs) in several Machine Learning tasks. However, in many critical domains, such as healthcare, finance, or law enforcement, transparency is crucial. In particular, the lack of ability to conform with prior knowledge greatly affects the trustworthiness of predictive models. This paper contributes to the trustworthiness of DNNs by promoting monotonicity. We develop a multi-layer learning architecture that handles a subset of features in a dataset that, according to prior knowledge, have a monotonic relation with the response variable. We use two alternative approaches: (i) imposing constraints on the model’s parameters, and (ii) applying an additional component to the loss function that penalises non-monotonic gradients. Our method is evaluated on classification and regression tasks using two datasets. Our model is able to conform to known monotonic relations, improving trustworthiness in decision making, while simultaneously maintaining small and controllable degradation in predictive ability.