Search Results (60)

The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but little exists for NSCLC. The objective of this study was to develop a multivariate CT-based radiomics model to a priori predict responses to definitive chemoradiation in patients with lung adenocarcinoma. Methods: Patients diagnosed with locally advanced unresectable lung adenocarcinoma who had undergone chemoradiotherapy followed by at least one dose of maintenance durvalumab were included. The PyRadiomics Python library was used to determine statistical, morphological, and textural features from normalized patient pre-treatment CT images and their wavelet-filtered versions. A nested leave-one-out cross-validation was used for model building and evaluation. Results: Fifty-seven patients formed the study cohort. The clinical stage was IIIA-C in 98% of patients. All but one received 6000–6600 cGy of radiation in 30–33 fractions. All received concurrent platinum-based chemotherapy. Based on RECIST 1.1, 20 (35%) patients were classified as responders (R) to chemoradiation and 37 (65%) patients as non-responders (NR). A three-feature model based on a KNN k = 1 machine learning classifier was found to have the best performance, achieving a recall, specificity, accuracy, balanced accuracy, precision, negative predictive value, F1-score, and area under the curve of 84%, 70%, 80%, 77%, 84%, 70%, 84%, and 0.77, respectively. Conclusions: Our results suggest that a CT-based radiomics model may be able to predict chemoradiation response for lung adenocarcinoma patients with estimated accuracies of 77–84%. Full article

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article

Severe asthma is a subset of difficult-to-treat asthma that requires the verification of inhaler technique, the correction of modifiable risk factors, as well as diagnosis and comorbidity review. When severe asthma is suspected, patients should undergo proper phenotyping (T2-high or T2-low) and be referred to a specialized severe asthma clinic. The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP). The outcomes to evaluate are the reduction in systemic corticosteroid use, the reduction in exacerbations and healthcare use, and improvement in symptoms and lung function. Comorbidities should be carefully considered, and if possible, addressed with the same biologic. Dupilumab, mepolizumab, and omalizumab are also approved for chronic rhinosinusitis with nasal polyps (CRSwNP), the most common asthma comorbidity. There are currently several clinical trials on biologics for severe asthma. Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration. Full article

The occurrence of triplication in the deciduous teeth is rare. However, it can cause several problems in primary dentition, alteration of development, and eruption of permanent successors. Case Presentation: A three-year-old boy presented with an exuberant acute periapical abscess in the left front teeth region of the upper jaw. Examination revealed a presence of a triple tooth involving the central and lateral left primary incisors and a supernumerary tooth. Radiographs showed that the fused teeth had separate roots, pulp chambers and root canals. The implemented treatment was extraction under local anesthesia. After 2 years of observation, surgical exposure of the crowns of the permanent maxillary central incisor was performed. After seven years, the permanent dentition was completed without any sequelae. Discussion: Triple tooth, as observed in this case report, results from the union of three tooth germs, potentially influenced by physical, hereditary, or environmental factors, leading to esthetic and functional issues and increased susceptibility to caries. Treatment is challenging, requiring preventive care, complex endodontic procedures, and, in some cases, extraction with space maintenance to avoid future orthodontic complications. Conclusion: Early diagnosis, an adequate treatment plan and clinical monitoring should be performed, aiming at preventing the possible disturbances. Full article

Triboelectric nanogenerators (TENGs) can convert the mechanical energy of physical activities into electricity. This is particularly useful in sports applications, where physical activity can power devices such as wearables that can provide real-time feedback on athletes’ performance or health. To work, a TENG usually needs tribopositive and tribonegative materials. Currently, the vast majority of TENGs use materials containing perfluoroalkyl and polyfluoroalkyl substances (PFAS) as tribonegative materials. However, these substances pose risks to humans and the environment, which has led the European Union to consider restrictions on these compounds. For this reason, PFAS-free alternatives, such as polydimethylsiloxane (PDMS) and MXenes, need to be better explored to replace PFAS materials while aiming to achieve equal efficiency. This review will explore some of the recent advances that have been developed in the field of PFAS-free TENGs, with an emphasis on sports applications. Full article

Background: Platinum-based chemotherapy (PBC) followed by avelumab maintenance is a treatment option for patients with advanced urothelial carcinoma (aUC) patients. However, the optimal treatment sequencing in the era of antibody–drug conjugates (ADCs) is yet to be determined. Recent studies suggest that the timing of immune checkpoint inhibitor (ICI) administration may impact patient outcomes, with a potential benefit from morning infusions. Methods: This retrospective study included 105 patients with aUC treated with avelumab in Portugal and intended to assess the safety and clinical outcomes (progression-free survival (PFS), overall survival (OS), and overall response rate (ORR)) and evaluate the impact of treatment timing (morning vs. afternoon) on patient outcomes. Results: The median follow-up from the start of avelumab was 17.7 months, the median PFS (mPFS) was 9.8 months (95% CI 4.9–14.7), and the median OS (mOS) was 39.5 months (95% CI 13.2–65.7). Immune-related adverse events (irAEs) were reported in 65.8% of patients, with 6.7% experiencing G3 irAEs. Among those who received a subsequent-line ADC upon disease progression (43%), the mOS from the start of avelumab was 23.1 months (95% CI 9.2–37.0). Multivariate analysis showed significant improvement in mOS with morning avelumab infusions (HR 0.35, 95% CI: 0.12–0.97, p = 0.042) and a trend towards improved mPFS (HR 0.43, 95% CI: 0.179–1.02, p = 0.055). Conclusions: This study confirms the clinical efficacy and safety of avelumab, showing improved outcomes over JAVELIN Bladder 100 and suggesting that morning infusions may offer a survival benefit in this context. Further research is needed to optimize treatment sequencing and explore the impact of infusion timing in ICI strategies. Full article

Inherited retinal diseases (IRDs) are genetic disorders affecting photoreceptors and the retinal pigment epithelium, leading to progressive vision loss. Retinitis pigmentosa (RP), the most common IRD, manifests as night blindness, peripheral vision loss, and eventually central vision decline. RP is genetically diverse and can be categorized into non-syndromic and syndromic. Advanced imaging technologies such as fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) facilitate diagnosing and managing these conditions. The integration of artificial intelligence in analyzing retinal images has shown promise in identifying genes associated with RP. This study used a dataset from Portuguese public hospitals, comprising 2798 FAF images labeled for syndromic and non-syndromic RP across 66 genes. Three pre-trained models, Inception-v3, ResNet-50, and VGG-19, were used to classify these images, obtaining an accuracy of over 80% in the training data and 54%, 56%, and 54% in the test data for all models. Data preprocessing included class balancing and boosting to address variability in gene representation. Model performance was evaluated using some main metrics. The findings demonstrate the effectiveness of deep learning in automatically classifying retinal images for different RP-associated genes, marking a significant advancement in the diagnostic capabilities of artificial intelligence and advanced imaging techniques in IRD. Full article

Vaccination is an effective, cost-efficient method to preventing disease outbreaks. However, vaccine procedures can induce adverse reactions due to stress, increasing plasma cortisol in the short term. In this context, tryptophan may prove to be fundamental as it has been demonstrated to have various desirable neuroendocrine attributes in different fish species. Therefore, this study aimed to evaluate both short-term (3 days) and long-term (21 days) effects of dietary tryptophan supplementation on European seabass juveniles’ (26.23 ± 7.22 g) response to vaccination and disease resistance to Tenacibaculum maritimum. The short-term tryptophan-fed fish exhibited increased hepatic superoxide dismutase and plasma cortisol levels, along with the downregulation of immune-related genes. Despite these changes, disease resistance was unaffected. When fish were later dip vaccinated, tryptophan prevented the stress-induced plasma cortisol increase and upregulated the gene expression of igm, suggesting tryptophan’s role in enhancing vaccination efficiency by counteracting stress-associated effects. In the long term, the lowest supplementation dose counteracted vaccine-mediated reduced gene expression, and fish fed this diet showed a more modest molecular response. Overall, the findings suggest a complex interplay between tryptophan supplementation, immune responses, and vaccine efficiency in fish. Further research is necessary to clarify how tryptophan could consistently improve vaccine efficiency in aquaculture. Full article

Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease’s natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing–remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research. Full article

Background/Objectives: Diabetic retinopathy (DR) is a common diabetes complication that can lead to blindness through vision-threatening complications like clinically significant macular edema and proliferative retinopathy. Identifying eyes at risk of progression using non-invasive methods could help develop targeted therapies to halt diabetic retinal disease progression. Methods: A set of 82 imaging and systemic features was used to characterize the progression of nonproliferative diabetic retinopathy (NPDR). These features include baseline measurements (static features) and those capturing the temporal dynamic behavior of these static features within one year (dynamic features). Interpretable models were trained to distinguish between eyes with Early Treatment Diabetic Retinopathy Study (ETDRS) level 35 and eyes with ETDRS levels 43–47. The data used in this research were collected from 109 diabetic type 2 patients (67.26 ± 2.70 years; diabetes duration 19.6 ± 7.26 years) and acquired over 2 years. Results: The characterization of the data indicates that NPDR progresses from an initial stage of hypoperfusion to a hyperperfusion response. The performance of the classification model using static features achieved an area under the curve (AUC) of the receiver operating characteristics equal to 0.84 ± 0.07, while the model using both static and dynamic features achieved an AUC of 0.91 ± 0.05. Conclusion: NPDR progresses through an initial hypoperfusion stage followed by a hyperperfusion response. Characterizing and automatically identifying this disease progression stage is valuable and necessary. The results indicate that achieving this goal is feasible, paving the way for the improved evaluation of progression risk and the development of better-targeted therapies to prevent vision-threatening complications. Full article

Atrial wall thickness (AWT) is a significant factor in understanding the pathological physiological substrate of atrial fibrillation, with a potentially substantial impact on the outcomes of catheter ablation procedures. Precise measurements of the AWT may provide valuable insights for categorising patients with AF and planning targeted interventions. Objectives: The purpose of this study was to evaluate the characteristics of the left atrium (LA) using non-invasive multidetector computed tomography (MDCT) scans and subsequent three-dimensional (3D) image post-processing using novel software designed to calculate atrial thickness dimensions and mass. Methods: We retrospectively analysed 128 consecutive patients (33.6% females; mean age 55.6 ± 11.2 years) referred for AF ablation (37 with persistent AF and 91 with paroxysmal AF) who underwent preprocedural MDCT. The images were post-processed and analysed using the ADAS software (Galgo Medical), automatically calculating the LA volume and regional wall thickness. In addition, the software employed a regional semi-automatic LA parcellation feature that divided the atrial wall into 12 segments, generating atrial wall thickness (AWT) maps per segment for each patient. Results: This study demonstrated considerable variability in the average thickness of LA walls, with the anterior segments being the thickest across the cohort. Distinct sex-specific differences were observed, with males exhibiting greater anterior and septal wall thickness than females. No significant associations were identified between the average AWT and body mass index, LA volume, or sphericity. Survival analysis conducted over 24 months revealed a meaningful relationship between mean anterior wall thickness and recurrence-free survival, with increased thickness associated with a lower likelihood of AF-free survival. No such relationship was observed for the indexed LA volume. Conclusions: The variability in AWT and its association with recurrence-free survival following AF ablation suggest that AWT should be considered when stratifying patients for AF management and ablation strategies. These findings underscore the need for personalised treatment approaches and further research on the interplay of the structural properties of the left atrium as factors that can serve as important prognostic markers in AF treatment. Full article

Energy poverty (EP) is a crucial socio-economic problem in current society, as it deprives people of a basic standard of living and quality of life. In general, EP is linked to various factors, but it is primarily associated with high energy costs, low household income, and inefficient building structures. Due to the recent energy crisis in Europe, the importance of these factors has escalated. Bearing in mind the above remarks, the REVERTER EU-funded LIFE project will develop and test nine roadmaps in four European countries (Brezovo—Bulgaria; Athens Urban area—Greece; Riga—Latvia; and Coimbra—Portugal) to alleviate EP by addressing the poor energy efficiency of dwellings. To directly observe real-life scenarios in designated pilot regions, questionnaire surveys were conducted, involving approximately 300 households in each pilot area. This paper presents and evaluates the outcomes of the survey conducted in the central region of Portugal. The findings allow for a deeper comprehension of the factors that impact energy poverty in Portugal, spanning socio-economic aspects, housing characteristics, mechanical systems, energy expenses, and behaviors, as well as the awareness of available support initiatives. Drawing from the survey’s insights, novel strategies are suggested to alleviate energy poverty, with a primary emphasis on crafting tailored, efficient policies that address the genuine requirements of households and individuals. Full article

Electroluminescence (EL) is an innovative technology in the lighting area. EL devices’ main structure consists of a phosphor layer sandwiched between two electrodes. In this work, several alternating-current EL devices were developed by applying a set of sequential layers with combinations of in-house prepared inks and a commercially available ink as the phosphor layer. A flexible polyester textile substrate was functionalized with the inks by spray coating, after knife coating an interfacial layer directly on the surface. A thorough study was carried out on the phosphor layer composition to optimize the EL device performance, more precisely, illuminance intensity and illuminance homogeneity. The developed phosphor layer was composed of zinc sulfide doped with copper (between 30.0 and 38.1 wt%) and diluted by using a diluent at different concentrations (from 28.0 to 35.5 wt%). The best peak illuminance intensity of 61 lux was obtained when the phosphor ink presented a 35.4% ZnS:Cu ratio and was diluted with 33.0% diluent. This study aimed to determine the best formulation of the phosphor layer, which can be highly useful for further developments of EL devices, taking into account different applications in the market. Full article

Leishmania infantum, a zoonotic vector-born parasite, is endemic in the Mediterranean region, presenting mostly as visceral (VL), but also as cutaneous (CL) and mucosal leishmaniasis (ML). This study aimed to describe the epidemiological and clinical aspects of the CL and ML cases diagnosed in mainland Portugal between 2010 and 2020. Collaboration was requested from every hospital of the Portuguese National Health System. Cases were screened through a search of diagnostic discharge codes or positive laboratory results for Leishmania infection. Simultaneously, a comprehensive literature search was performed. Descriptive statistics and hypothesis testing were performed using IBM^® SPSS^® Statistics. A total of 43 CL and 7 ML cases were identified, with a predominance of autochthonous cases (86%). In CL, immunosuppressed individuals constituted a significant proportion of patients (48%), and in this group, disseminated CL (22%) and simultaneous VL (54%) were common. In autochthonous cases, lesions, mostly papules/nodules (62%), were frequently observed on the head (48%). The approach to treatment was very heterogeneous. ML cases were all autochthonous, were diagnosed primarily in older immunosuppressed individuals, and were generally treated with liposomal amphotericin B. The findings suggest a need for enhanced surveillance and reporting, clinical awareness, and diagnostic capacity of these forms of leishmaniasis to mitigate underdiagnosis and improve patient outcomes. A holistic One Health approach is advocated to address the multifaceted challenges posed by leishmaniases in Portugal and beyond. Full article

Postmenopausal abnormal uterine bleeding is a common clinical problem addressed in gynaecological practice and should prompt clinical investigation due to the significant prevalence of malignant and premalignant lesions of the endometrium in this age group. Nevertheless, other causes should be considered, since its diagnostic and therapeutic management may differ considerably. Here, we present a case of a colouterine fistula due to chronic diverticulitis presenting with postmenopausal abnormal uterine bleeding. This is an infrequent occurrence and is caused by the rupture of a diverticular abscess into the uterine wall, resulting in an inflammatory adhesion of the colon and uterus, with necrosis and subsequent fistula formation. The clinical presentation is variable and may include abdominal pain, gastrointestinal tract symptoms, vaginal discharge, and abnormal uterine bleeding. The laboratory and imaging techniques may be not completely conclusive and definitive diagnosis can be made intraoperatively. There are different treatment options, with en bloc resection and primary anastomosis being used most often, allowing complete treatment. The prognosis for a colouterine fistula secondary to diverticulitis is excellent after surgery. This case highlights the importance of clinical suspicion of an unusual cause of uterine bleeding and an effective and multidisciplinary approach that allowed complete surgical treatment and patient recovery. Full article