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Nonsense mutations create premature termination codons (PTCs), activating the nonsense-mediated mRNA decay (NMD) pathway to degrade most PTC-containing mRNAs. The undegraded mRNA is translated, but translation terminates at the PTC, leading to no production of the full-length protein. This work presents targeted PTC pseudouridylation, an approach for nonsense suppression in human cells. Specifically, an artificial box H/ACA guide RNA designed to target the mRNA PTC can suppress both NMD and premature translation termination in various sequence contexts. Targeted pseudouridylation exhibits a level of suppression comparable with that of aminoglycoside antibiotic treatments. When targeted pseudouridylation is combined with antibiotic treatment, a much higher level of suppression is observed. Transfection of a disease model cell line (carrying a chromosomal PTC) with a designer guide RNA gene targeting the PTC also leads to nonsense suppression. Thus, targeted pseudouridylation is an RNA-directed gene-specific approach that suppresses NMD and concurrently promotes PTC readthrough.
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Codón sin Sentido , Biosíntesis de Proteínas , Humanos , Codón sin Sentido/genética , Degradación de ARNm Mediada por Codón sin Sentido , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
RNA-guided pseudouridylation, a widespread post-transcriptional RNA modification, has recently gained recognition for its role in cellular processes such as pre-mRNA splicing and the modulation of premature termination codon (PTC) readthrough. This review provides insights into its mechanisms, functions, and potential therapeutic applications. It examines the mechanisms governing RNA-guided pseudouridylation, emphasizing the roles of guide RNAs and pseudouridine synthases in catalyzing uridine-to-pseudouridine conversion. A key focus is the impact of RNA-guided pseudouridylation of U2 small nuclear RNA on pre-mRNA splicing, encompassing its influence on branch site recognition and spliceosome assembly. Additionally, the review discusses the emerging role of RNA-guided pseudouridylation in regulating PTC readthrough, impacting translation termination and genetic disorders. Finally, it explores the therapeutic potential of pseudouridine modifications, offering insights into potential treatments for genetic diseases and cancer and the development of mRNA vaccine.
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Seudouridina , Precursores del ARN , Seudouridina/genética , Seudouridina/metabolismo , Precursores del ARN/metabolismo , ARN Guía de Sistemas CRISPR-Cas , ARN/metabolismo , Procesamiento Postranscripcional del ARN , Biosíntesis de ProteínasRESUMEN
Medical education was greatly affected by the COVID-19 pandemic, and remote teaching through lectures and classes through videoconferencing was heavily used. However, the need to use cameras led to scopophobia, which is the fear of being watched, which can lead to psychological symptoms. Despite the relevance and prevalence of depression and the increase in the use of cameras for learning, research evaluating the impact of scopophobia on students' mental health is surprisingly scarce. Hence, to fill up this gap, a cross-sectional study was carried out in medical schools in Brazil. To assess the presence of depressed mood, the Patient Health Questionnaire-9 (PHQ-9) was applied. We used logistic regression models to verify the associations. The overall prevalence of positive PHQ9 found in our study was 62%. By studying the factors associated with a high risk of scopophobia, we could identify that the PHQ was statistically associated with scopophobia (odds ratio 2.43 (confidence interval 1.11-5.26), adjusted p value = .0269). Also, a lower family income, a higher number of household inhabitants, and female gender were associated. These results suggest that scopophobia is associated with depression, leading us to believe that interventions to mitigate this risk in students are opportune, especially if targeted at lower-income students.
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Estudiantes de Medicina , Humanos , Femenino , Estudiantes de Medicina/psicología , Depresión/epidemiología , Brasil/epidemiología , Estudios Transversales , PandemiasRESUMEN
This study aimed to analyze the diet and trophic niche breadth of an insectivorous bat very common in an urban environment in southern Brazil. To analyze the feeding habit of Molossus rufus, it was necessary to collect fecal samples in urban colonies in the city of Maringá, State of Paraná. Samplings occurred from November 2018 to September 2019, including rainy and dry seasons. The fragments found in the samples were identified up to the level of order or family whenever possible. Percentage of volume and frequency of occurrence, Feeding Index (IAi%), PERMANOVA, and trophic niche breadth were used. Thus, a total of 140 samples were obtained, 92 for the rainy season and 48 for the dry season. In terms of percentage of volume, the diet consisted mainly of Hymenoptera (46.9%) in the rainy season and Coleoptera (39.2%) in the dry season. The results for standardized trophic niche breadth were Ba = 0.36 for the rainy season and Ba = 0.37 in the dry season, indicating a low food diversity. In conclusion, there was a food preference on the part of M. rufus according to the season evaluated, with Hymenoptera and Coleoptera being the most relevant dietary items.
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Quirópteros , Escarabajos , Animales , Estaciones del Año , Dieta , Preferencias Alimentarias , Heces , BrasilRESUMEN
The control of weeds in agriculture is mainly conducted with the use of synthetic herbicides. However, environmental and human health concerns and increased resistance of weeds to existing herbicides have increased the pressure on researchers to find new active ingredients for weed control which present low toxicity to non-target organisms, are environmentally safe, and can be applied at low concentrations. It is herein described the synthesis of glycerol-fluorinated triazole derivatives and evaluation of their phytotoxic and cytogenotoxic activities. Starting from glycerol, ten fluorinated triazole derivatives were prepared in four steps. The assessment of them on Lactuca sativa revealed that they present effects on phytotoxic and cytogenotoxic parameters with different degrees of efficiency. The compounds 4a, 4b, 4d, 4e, 4i, and 4j have pre-emergent inhibition behavior, while all the investigated compounds showed post emergent effect. Mechanism of action as clastogenic, aneugenic, and epigenetic were observed in the lettuce root meristematic cells, with alterations as stick chromosome, bridge, delay, c-metaphase, and loss. It is believed that glycerol-fluorinated triazole derivatives possess a scaffold that can be explored towards the development of new chemicals for the control of weed species.
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Alcaloides , Herbicidas , Humanos , Glicerol/toxicidad , Alcoholes de Triosa , Triazoles/toxicidad , Meristema , Alcaloides/farmacología , Herbicidas/toxicidad , Herbicidas/química , Malezas , LactucaRESUMEN
BACKGROUND: Scopophobia can be described in the medical field as the fear of being watched or stared at. Despite the relevance of scopophobia in remote learning scenarios, which have always existed and have been largely expanded during the pandemic in medical education, studies on this topic are exceedingly rare worldwide. Hence, to fill up this gap, a cross-sectional study of medical students was developed to assess the association of scopophobia with the prevalence of online learning fatigue. METHODS: A cross-sectional, quantitative, analytical study was carried out in Medical Schools of Brazil. To assess the risk of scopophobia, questions were developed, based on the literature on the topic. The Zoom Exhaustion & Fatigue Scale (ZEF) was used, and the questions have currently been validated for Brazilian Portuguese. Logistic regression models were also used to assess the relationship of scopophobia risk and ZEF scores. RESULTS: A total of 283 students from Brazil participated in the study. The median age was 23 years, and 64% of the participants were female. In total, 14.5% were considered to be at high risk for scopophobia. It was found that after adjusting for sex, income and number of residents in the household, scopophobia and the total zoom fatigue score remained associated. For the total score, each additional point on the scale increased the chance of scopophobia by 3%, and for the overall domain, 19% (p-values < 0.05). CONCLUSIONS: In conclusion, this study shows a relevant prevalence of students with scopophobia, which requires a differentiated approach on the part of teachers. The causes of scopophobia are often specific and have a psychological origin that goes beyond the usual pedagogical management. Therefore, motivation strategies are necessary in a general, as well as an individualized manner, aiming to favor the improvement of the online teaching and learning process.
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COVID-19 , Educación a Distancia , Estudiantes de Medicina , Humanos , Femenino , Adulto Joven , Adulto , Masculino , COVID-19/epidemiología , Estudiantes de Medicina/psicología , Estudios Transversales , Brasil/epidemiologíaRESUMEN
Pectus carinatum (PC) is a chest deformity caused by disproportionate growth of the costal cartilages compared with the bony thoracic skeleton, pulling the sternum forwards and leading to its protrusion. Currently, the most common non-invasive treatment is external compressive bracing, by means of an orthosis. While this treatment is widely adopted, the correct magnitude of applied compressive forces remains unknown, leading to suboptimal results. Moreover, the current orthoses are not suitable to monitor the treatment. The purpose of this study is to design a force measuring system that could be directly embedded into an existing PC orthosis without relevant modifications in its construction. For that, inspired by the currently commercially available products where a solid silicone pad is used, three concepts for silicone-based sensors, two capacitive and one magnetic type, are presented and compared. Additionally, a concept of a full pipeline to capture and store the sensor data was researched. Compression tests were conducted on a calibration machine, with forces ranging from 0 N to 300 N. Local evaluation of sensors' response in different regions was also performed. The three sensors were tested and then compared with the results of a solid silicon pad. One of the capacitive sensors presented an identical response to the solid silicon while the other two either presented poor repeatability or were too stiff, raising concerns for patient comfort. Overall, the proposed system demonstrated its potential to measure and monitor orthosis's applied forces, corroborating its potential for clinical practice.
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Pectus Carinatum , Humanos , Pectus Carinatum/terapia , Silicio , Esternón , Tirantes , Presión , Resultado del TratamientoRESUMEN
Breast cancer is the most prevalent cancer in the world and the fifth-leading cause of cancer-related death. Treatment is effective in the early stages. Thus, a need to screen considerable portions of the population is crucial. When the screening procedure uncovers a suspect lesion, a biopsy is performed to assess its potential for malignancy. This procedure is usually performed using real-time Ultrasound (US) imaging. This work proposes a visualization system for US breast biopsy. It consists of an application running on AR glasses that interact with a computer application. The AR glasses track the position of QR codes mounted on an US probe and a biopsy needle. US images are shown in the user's field of view with enhanced lesion visualization and needle trajectory. To validate the system, latency of the transmission of US images was evaluated. Usability assessment compared our proposed prototype with a traditional approach with different users. It showed that needle alignment was more precise, with 92.67 ± 2.32° in our prototype versus 89.99 ± 37.49° in a traditional system. The users also reached the lesion more accurately. Overall, the proposed solution presents promising results, and the use of AR glasses as a tracking and visualization device exhibited good performance.
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Realidad Aumentada , Femenino , Humanos , Interfaz Usuario-Computador , Ultrasonografía Mamaria , Ultrasonografía , BiopsiaRESUMEN
Evaluation of the head shape of newborns is needed to detect cranial deformities, disturbances in head growth, and consequently, to predict short- and long-term neurodevelopment. Currently, there is a lack of automatic tools to provide a detailed evaluation of the head shape. Artificial intelligence (AI) methods, namely deep learning (DL), can be explored to develop fast and automatic approaches for shape evaluation. However, due to the clinical variability of patients' head anatomy, generalization of AI networks to the clinical needs is paramount and extremely challenging. In this work, a new framework is proposed to augment the 3D data used for training DL networks for shape evaluation. The proposed augmentation strategy deforms head surfaces towards different deformities. For that, a point-based 3D morphable model (p3DMM) is developed to generate a statistical model representative of head shapes of different cranial deformities. Afterward, a constrained transformation approach (3DHT) is applied to warp a head surface towards a target deformity by estimating a dense motion field from a sparse one resulted from the p3DMM. Qualitative evaluation showed that the proposed method generates realistic head shapes indistinguishable from the real ones. Moreover, quantitative experiments demonstrated that DL networks training with the proposed augmented surfaces improves their performance in terms of head shape analysis. Overall, the introduced augmentation allows to effectively transform a given head surface towards different deformity shapes, potentiating the development of DL approaches for head shape analysis.
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Inteligencia Artificial , Modelos Estadísticos , Humanos , Lactante , Recién NacidoRESUMEN
The increase of the aging population brings numerous challenges to health and aesthetic segments. Here, the use of laser therapy for dermatology is expected to increase since it allows for non-invasive and infection-free treatments. However, existing laser devices require doctors' manually handling and visually inspecting the skin. As such, the treatment outcome is dependent on the user's expertise, which frequently results in ineffective treatments and side effects. This study aims to determine the workspace and limits of operation of laser treatments for vascular lesions of the lower limbs. The results of this study can be used to develop a robotic-guided technology to help address the aforementioned problems. Specifically, workspace and limits of operation were studied in eight vascular laser treatments. For it, an electromagnetic tracking system was used to collect the real-time positioning of the laser during the treatments. The computed average workspace length, height, and width were 0.84 ± 0.15, 0.41 ± 0.06, and 0.78 ± 0.16 m, respectively. This corresponds to an average volume of treatment of 0.277 ± 0.093 m3. The average treatment time was 23.2 ± 10.2 min, with an average laser orientation of 40.6 ± 5.6 degrees. Additionally, the average velocities of 0.124 ± 0.103 m/s and 31.5 + 25.4 deg/s were measured. This knowledge characterizes the vascular laser treatment workspace and limits of operation, which may ease the understanding for future robotic system development.
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Robótica , Extremidad Inferior/cirugía , Robótica/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: In type II atrial septal defect (ASD) patients, the left-to-right (LR) shunt causes adaptation of the heart and circulation. The study objective was to evaluate with cardiovascular magnetic resonance imaging (CMR) the impact of LR shunt on left (LV) and right ventricular (RV) volumes, function, and myocardial strain. METHODS: Thirty-five patients (42 ± 17 years, 17 male) were compared to a control group (n = 40). Cine imaging was used to calculate ventricular volumes and ejection fraction (EF), global longitudinal (GLS) and circumferential strain (GCS), and longitudinal free wall (FWS) and interventricular septal (IVS) strain. Phase-contrast imaging was used to calculate pulmonary flow to systemic flow ratio (Qp/Qs). RESULTS: The LR shunt (Qp/Qs 2.2 ± 0.6) resulted in larger RV end-diastolic volume (EDVi) (152 ± 42 vs 82 ± 11 ml/m2), lower LV EDVi (72 ± 16 vs 83 ± 9 ml/m2), and higher RV/LV EDVi ratio (2.2 ± 0.5 vs 1.0 ± 0.1) than controls (all p < 0.001). Functionally, stroke volumes were larger in RV and lower in LV (both p < 0.001) with a strong trend toward lower RV EF in patients (p = 0.08). The LR shunt negatively impacted RV GLS (p = 0.03) but not RV GCS. Longitudinal IVS but not RV FWS were significantly lower in patients, i.e., p < 0.001, of longitudinal IVS. Shunt severity correlated with RV size and stroke volume, right atrial size, and pulmonary trunk diameter (all p < 0.001), but not with functional nor strain parameters. CONCLUSION: Long-term cardiac adaptation in ASD patients, with RV overfilling and LV underfilling, has a negative impact on systolic RV performance, a phenomenon which likely can be attributed to longitudinal dysfunction of the interventricular septum. KEY POINTS: ⢠An LR shunt in type II ASD patients causes cardiac remodeling characterized by RV overfilling and conversely underfilling of the left ventricle. ⢠At the long term, there is evidence of systolic dysfunction of the right ventricle in this group of patients. ⢠Septal dysfunction underlies the observed impairment in RV function.
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Defectos del Tabique Interatrial , Imagen por Resonancia Cinemagnética , Adulto , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Función Ventricular DerechaRESUMEN
Nonsense mutations often result from single nucleotide substitutions that change a sense codon (coding for an amino acid) to a nonsense or premature termination codon (PTC) within the coding region of a gene. The impact of nonsense mutations is two-fold: (1) the PTC-containing mRNA is degraded by a surveillance pathway called nonsense-mediated mRNA decay (NMD) and (2) protein translation stops prematurely at the PTC codon, and thus no functional full-length protein is produced. As such, nonsense mutations result in a large number of human diseases. Nonsense suppression is a strategy that aims to correct the defects of hundreds of genetic disorders and reverse disease phenotypes and conditions. While most clinical trials have been performed with small molecules, there is an increasing need for sequence-specific repair approaches that are safer and adaptable to personalized medicine. Here, we discuss recent advances in both conventional strategies as well as new technologies. Several of these will soon be tested in clinical trials as nonsense therapies, even if they still have some limitations and challenges to overcome.
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Codón sin Sentido , ARN Mensajero/química , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Ensayos Clínicos como Asunto , Codón sin Sentido/efectos de los fármacos , Predisposición Genética a la Enfermedad , Humanos , Degradación de ARNm Mediada por Codón sin Sentido/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Medicina de Precisión , ARN Mensajero/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacologíaRESUMEN
BACKGROUND: Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a promising technique for quantification of myocardial strain from steady-state free precession (SSFP) cine images. We sought to determine the variability of CMR-FT using a non-rigid elastic registration algorithm recently available in a commercial software package (Segment, Medviso) in a real-life clinical setting. METHODS: Firstly, we studied the variability in a healthy volunteer who underwent 10 CMR studies over five consecutive days. Secondly, 10 patients were selected from our CMR database yielding normal findings (normal group). Finally, we prospectively studied 10 patients with known or suspected myocardial pathology referred for further investigation to CMR (patient group). In the patient group a second study was performed respecting an interval of 30 min between studies. All studies were manually segmented at the end-diastolic phase by three observers. In all subjects left ventricular (LV) circumferential and radial strain were calculated in the short-axis direction (EccSAX and ErrSAX, respectively) and longitudinal strain in the long-axis direction (EllLAX). The level of CMR experience of the observers was 2 weeks, 6 months and >20 years. RESULTS: Mean contouring time was 7 ± 1 min, mean FT calculation time 13 ± 2 min. Intra- and inter-observer variability was good to excellent with an coefficient of reproducibility (CR) ranging 1.6% to 11.5%, and 1.7% to 16.0%, respectively and an intraclass correlation coefficient (ICC) ranging 0.89 to 1.00 and 0.74 to 0.99, respectively. Variability considerably increased in the test-retest setting with a CR ranging 4.2% to 29.1% and an ICC ranging 0.66 to 0.95 in the patient group. Variability was not influenced by level of expertise of the observers. Neither did the presence of myocardial pathology at CMR negatively impact variability. However, compared to global myocardial strain, segmental myocardial strain variability increased with a factor 2-3, in particular for the basal and apical short-axis slices. CONCLUSIONS: CMR-FT using non-rigid, elastic registration is a reproducible approach for strain analysis in patients routinely scheduled for CMR, and is not influenced by the level of training. However, further improvement is needed to reliably depict small variations in segmental myocardial strain.
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Algoritmos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Cinemagnética/métodos , Contracción Miocárdica , Isquemia Miocárdica/diagnóstico por imagen , Función Ventricular Izquierda , Adulto , Fenómenos Biomecánicos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Estrés Mecánico , Volumen Sistólico , Factores de TiempoRESUMEN
Nonsense mutations are genetic mutations that create premature termination codons (PTCs), leading to truncated, defective proteins in diseases such as cystic fibrosis, neurofibromatosis type 1, Dravet syndrome, Hurler syndrome, Beta thalassemia, inherited bone marrow failure syndromes, Duchenne muscular dystrophy, and even cancer. These mutations can also trigger a cellular surveillance mechanism known as nonsense-mediated mRNA decay (NMD) that degrades the PTC-containing mRNA. The activation of NMD can attenuate the consequences of truncated, defective, and potentially toxic proteins in the cell. Since approximately 20% of all single-point mutations are disease-causing nonsense mutations, it is not surprising that this field has received significant attention, resulting in a remarkable advancement in recent years. In fact, since our last review on this topic, new examples of nonsense suppression approaches have been reported, namely new ways of promoting the translational readthrough of PTCs or inhibiting the NMD pathway. With this review, we update the state-of-the-art technologies in nonsense suppression, focusing on novel modalities with therapeutic potential, such as small molecules (readthrough agents, NMD inhibitors, and molecular glue degraders); antisense oligonucleotides; tRNA suppressors; ADAR-mediated RNA editing; targeted pseudouridylation; and gene/base editing. While these various modalities have significantly advanced in their development stage since our last review, each has advantages (e.g., ease of delivery and specificity) and disadvantages (manufacturing complexity and off-target effect potential), which we discuss here.
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Semiconductor advancements demand greater integrated circuit density, structural miniaturization, and complex material combinations, resulting in stress concentrations from property mismatches. This study investigates the failure in two types of interfaces found in chip packages: silicon-epoxy mold compound (EMC) and polyimide-EMC. These interfaces were subjected to quasi-static and fatigue loading conditions. Employing a compliance-based beam method, the tests determined interfacial critical fracture energy values, (GIC), of 0.051 N/mm and 0.037 N/mm for the silicon-EMC and polyimide-EMC interfaces, respectively. Fatigue testing on the polyimide-epoxy interface revealed a fatigue threshold strain energy, (Gth), of 0.042 N/mm. We also observed diverse failure modes and discuss potential mechanical failures in multi-layer chip packages. The findings of this study can contribute to the prediction and mitigation of failure modes in the analyzed chip packaging. The obtained threshold energy and crack growth rate provide insights for designing safe lives for bi-material interfaces in chip packaging under cyclic loads. These insights can guide future research directions, emphasizing the improvement of material properties and exploration of the influence of manufacturing parameters on delamination in multilayer semiconductors.
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Herein, a simple, green, and relatively inexpensive approach to determine nickel (Ni) in biodiesel samples by square wave adsorptive cathodic stripping voltammetry (SWAdCSV) is presented. A method based on the accumulation of Ni as Ni(II)-dimethylglyoxime (Ni(II)(HDMG)2) on the glassy carbon electrode was carried out in a solution containing the aqueous phase extract (APhEx) obtained from an extraction induced by microemulsion breaking (EIMB), which was achieved by adding a few microliters of ultrapure water to a microemulsion composed of biodiesel, n-propanol and a diluted HNO3 solution. The LOD and LOQ were 0.2 µg L-1 and 0.8 µg L-1, respectively, and the accuracy was evaluated by recovery assays of spiked samples and by analyzing a standard reference material. Results obtained from a comparative method (HR-CS GF AAS) were also used for this evaluation. The method was applied to biodiesel samples produced from different feedstocks. To the best of the authors knowledge, it is the first time that: 1) Ni in biodiesel is determined by a voltammetric method; 2) EIMB is applied to extract Ni from this matrix and 3) this type of sample preparation method is used with adsorptive stripping voltammetry.
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Examining crack propagation at the interface of bimaterial components under various conditions is essential for improving the reliability of semiconductor designs. However, the fracture behavior of bimaterial interfaces has been relatively underexplored in the literature, particularly in terms of numerical predictions. Numerical simulations offer vital insights into the evolution of interfacial damage and stress distribution in wafers, showcasing their dependence on material properties. The lack of knowledge about specific interfaces poses a significant obstacle to the development of new products and necessitates active remediation for further progress. The objective of this paper is twofold: firstly, to experimentally investigate the behavior of bimaterial interfaces commonly found in semiconductors under quasi-static loading conditions, and secondly, to determine their respective interfacial cohesive properties using an inverse cohesive zone modeling approach. For this purpose, double cantilever beam specimens were manufactured that allow Mode I static fracture analysis of the interfaces. A compliance-based method was used to obtain the crack size during the tests and the Mode I energy release rate (GIc). Experimental results were utilized to simulate the behavior of different interfaces under specific test conditions in Abaqus. The simulation aimed to extract the interfacial cohesive contact properties of the studied bimaterial interfaces. These properties enable designers to predict the strength of the interfaces, particularly under Mode I loading conditions. To this extent, the cohesive zone modeling (CZM) assisted in defining the behavior of the damage propagation through the bimaterial interfaces. As a result, for the silicon-epoxy molding compound (EMC) interface, the results for maximum strength and GIc are, respectively, 26 MPa and 0.05 N/mm. The second interface tested consisted of polyimide and silicon oxide between the silicon and EMC layers, and the results obtained are 21.5 MPa for the maximum tensile strength and 0.02 N/mm for GIc. This study's findings aid in predicting and mitigating failure modes in the studied chip packaging. The insights offer directions for future research, focusing on enhancing material properties and exploring the impact of manufacturing parameters and temperature conditions on delamination in multilayer semiconductors.
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Objective - Medical image segmentation is essential for several clinical tasks, including diagnosis, surgical and treatment planning, and image-guided interventions. Deep Learning (DL) methods have become the state-of-the-art for several image segmentation scenarios. However, a large and well-annotated dataset is required to effectively train a DL model, which is usually difficult to obtain in clinical practice, especially for 3D images. Methods - In this paper, we proposed Deep-DM, a learning-guided deformable model framework for 3D medical imaging segmentation using limited training data. In the proposed method, an energy function is learned by a Convolutional Neural Network (CNN) and integrated into an explicit deformable model to drive the evolution of an initial surface towards the object to segment. Specifically, the learning-based energy function is iteratively retrieved from localized anatomical representations of the image containing the image information around the evolving surface at each iteration. By focusing on localized regions of interest, this representation excludes irrelevant image information, facilitating the learning process. Results and conclusion - The performance of the proposed method is demonstrated for the tasks of left ventricle and fetal head segmentation in ultrasound, left atrium segmentation in Magnetic Resonance, and bladder segmentation in Computed Tomography, using different numbers of training volumes in each study. The results obtained showed the feasibility of the proposed method to segment different anatomical structures in different imaging modalities. Moreover, the results also showed that the proposed approach is less dependent on the size of the training dataset in comparison with state-of-the-art DL-based segmentation methods, outperforming them for all tasks when a low number of samples is available. Significance - Overall, by offering a more robust and less data-intensive approach to accurately segmenting anatomical structures, the proposed method has the potential to enhance clinical tasks that require image segmentation strategies.
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The significance of accurate determination of ethanol content in hydrogel formulations was accentuated during COVID-19 pandemic coinciding with the heightened demand for sanitizing agents. The present article proposes three robust methodologies for this purpose: Fourier Transform Infrared Spectroscopy (FTIR), Raman spectroscopy, and Densitometry with matrix effect correction by Near-Infrared Spectroscopy (NIR). All three methods demonstrated outstanding linearity (R2 ≥ 0.99) and minimal errors (< 1.7%), offering simplicity and operational efficiency. FTIR and Raman, being non-destructive and requiring minimal preparation, enable practical on-site analysis capabilities, underscoring the potential of the spectroscopic methods to expedite health investigations and inspections, empowering on-site ethanol determination, and relieving the burden on official laboratories. Additionally, the densitometry with NIR-based approach showcased superior accuracy and precision compared to spectroscopic methods, meeting validation criteria while offering operational advantages over the costly official distillation-based method. Therefore, it stands as a reliable and reproducible technique for comprehensive health and criminal compliance assessments, making it a compelling alternative for both industry and official laboratories.
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Fungal infections have emerged worldwide, and azole antifungals are widely used to control these infections. However, the emergence of antifungal resistance has been compromising the effectiveness of these drugs. Therefore, the objective of this study was to evaluate the antifungal and cytotoxic activities of the nine new 1,2,3 triazole compounds derived from thymol that were synthesized through Click chemistry. The binding mode prediction was carried out by docking studies using the crystallographic structure of Lanosterol 14α-demethylase G73E mutant from Saccharomyces cerevisiae. The new compounds showed potent antifungal activity against Trichophyton rubrum but did not show relevant action against Aspergillus fumigatus and Candida albicans. For T. rubrum, molecules nº 5 and 8 showed promising results, emphasizing nº 8, whose fungicidal and fungistatic effects were similar to fluconazole. In addition, molecule nº 8 showed low toxicity for keratinocytes and fibroblasts, concluding that this compound demonstrates promising characteristics for developing a new drug for dermatophytosis caused by T. rubrum, or serves as a structural basis for further research.