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Com as universidades fechadas e a implementação do Ensino Remoto Emergencial, as atividades curriculares ocorreram através de plataformas digitais. O objetivo do presente trabalho foi avaliar a percepção de aprendizagem on-line na disciplina de Biomateriais da Faculdade de Odontologia da Universidade Federal Fluminense no período da pandemia. O questionário COLLES (Constructivist OnLine Learning Environment Survey) foi enviado individualmente por e-mail aos cinquenta alunos, apresentando 24 declarações divididas em seis quesitos: relevância, reflexão crítica, interatividade, apoio dos tutores, apoio entre os colegas e compreensão; e para cada declaração cinco opções de resposta: quase sempre, frequentemente, algumas vezes, raramente e quase nunca. Quarenta e um alunos responderam. A soma das médias obtidas em quase sempre e frequentemente foi de 87,2% para relevância, 70% para reflexão crítica, 33,9% para interatividade, 47,6% para apoio dos tutores, 44,2% para apoio dos colegas e 89,5% para compreensão. Concluiu-se que a relevância, a reflexão crítica e a compreensão apresentaram melhores resultados, enquanto a interatividade, o apoio entre os colegas e o apoio dos tutores demonstraram necessidade de aprimoramento. E apesar das limitações do ERE, a avaliação positiva dos alunos evidenciou esta modalidade de educação on-line como uma solução plausível.
With universities closed and the implementation of Emergency Remote Teaching, curricular activities took place through digital platforms. The objective of this study was to assess the perception of online learning in the Biomaterials course at the Dental School of the Federal Fluminense University during the pandemic. The COLLES questionnaire (Constructivist OnLine Learning Environment Survey) was individually sent via email to fifty students, presenting 24 statements divided into six aspects: relevance, critical reflection, interactivity, tutor support, peer support, and comprehension. For each statement, there were five response options: almost always, often, sometimes, rarely, and almost never. Forty-one students responded. The sum of the averages obtained for almost always and often was 87.2% for relevance, 70% for critical reflection, 33.9% for interactivity, 47.6% for tutor support, 44.2% for peer support, and 89.5% for comprehension. It was concluded that relevance, critical reflection, and comprehension showed better results, while interactivity, peer support, and tutor support demonstrated a need for improvement. Despite the limitations of Emergency Remote Teaching, the positive evaluation from the students highlighted this mode of online education as a plausible solution.
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Humanos , Masculino , Feminino , Percepção , Materiais Biocompatíveis , Educação a Distância , Educação em Odontologia , Aprendizagem , Inquéritos e QuestionáriosRESUMO
Introduction: Intubating patients undergoing manual in-line stabilization (MILS) can make airway management more challenging. This study aimed to compare the outcomes of intubation with video-laryngoscope (VL) and Intubating Laryngeal Mask Airway (I-LMA) in manikin with restricted neck motion using MILS. Methods: In this comparative study, emergency medicine residents and paramedics were randomly allocated to two crossover sets. Then the intubation outcomes (success rate, time to successful intubation, and cervical spine movement) were compared between intubation with VL and I-LMA in a manikin model with restricted cervical spine mobility, achieved through MILS. Results: 64 participants with a mean age of 28.86 ± 4.03 (range: 24-47) years and a mean duration of intubation experience of 3.63 ± 1.35 years were studied (43.75% male, 81.3% emergency medicine resident). The intubation success rate was 62 out of 64 (96.88%) in the VL method and 52 out of 64 (81.25%) in the I-LMA method (p = 0.008). The mean time to successful intubation was 33.03±16.94 seconds in the VL method and 55.03±17.34 seconds in the I-LMA method (p < 0.001). The mean cervical range of motion (CROM) in flexion-extension was 4.38±1.82 degrees in the VL method and 4.13±3.20 degrees in the I-LMA method (p = 0.158). The mean CROM in rotation was 4.27±2.62 degrees in the VL method and 4.65±2.47 degrees in the I-LMA method (p= 0.258) and the mean CROM in lateral bending was 5.35±4.45 degrees in the VL method and 7.71±6.14 degrees in the I-LMA method (p = 0.010). Conclusion: In a manikin model with restricted cervical spine mobility, the utilization of VL significantly improved intubation success rates, reduced time to successful intubation, and limited CROM.
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HYPOTHESIS: Despite its importance in colloid and interface science, contact line pinning remains poorly understood, especially in the presence of a precursor film. We hypothesized that this is due to a lack of an experimental method capable of directly observing their physics at the nanoscale. METHODS: Using coherence scanning interferometry, we visualized the three-dimensional behavior of contact lines with a precursor film near a nanogroove structure composed of flat terrace surfaces and steps with an inclination angle of 30° while achieving nanoscale vertical resolution. FINDINGS: We found that even when the contact line is pinned at the edge of the step, the precursor film is not and advances beyond the edge. Furthermore, we discovered that the precursor film has two distinct effects on contact line motion. Specifically, the precursor film facilitates depinning when the contact line descends the step - a contact angle change was 0.9°, only 3.0% of the value predicted by a classical theory of contact angle at a solid edge. This ultra-early depinning is attributed to the formation of a new liquid film past the edge, driven by the progression of the precursor film that overcomes the pinning effect. In contrast, when the contact line ascends the step, the precursor film acts as a resistance to movement due to steric interaction.
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B-cell acute lymphoblastic leukemia (B-ALL), a prevalent malignancy predominantly affecting children, poses challenges such as drug resistance and cytotoxicity despite available treatment methods. The persistence of these challenges underscores the necessity for innovative therapeutic approaches to enhance efficacy. Natural compounds derived from plants, recognized for their potential to inhibit cancer cell growth, have drawn attention. Trifolium pratense extract, known for its significant anticancer properties in previous studies, was the focus of this investigation. This experimental study aimed to explore the impact of T. pratense extract on apoptosis and autophagy in NALM-6 cells. The cells were exposed to varying concentrations of the extract at specific time intervals, with viability and metabolic activity assessed using Trypan blue exclusion and MTT assays. Flow cytometry was employed to evaluate apoptosis using Annexin V/PI staining and ROS production using DCFH-DA staining. Real-time PCR was used to quantify gene expression related to apoptosis, autophagy, and oxidative stress, with data analysis performed using GraphPad PRISM software. Trifolium pratense extract demonstrated the capacity to induce apoptosis, autophagy, and significantly increase ROS production in NALM-6 cells. These effects were facilitated by the upregulation of corresponding genes. The MTT assay revealed an IC50 of 231 µg/mL at 48 h, and Flow cytometry analysis showed a 51.8% increase in apoptosis in this cell line. Overall, this study emphasizes the effectiveness of T. pratense extract in inducing autophagy and apoptosis pathways in NALM-6 cells derived from B-cell acute lymphoblastic leukemia, suggesting its potential as a candidate for further investigation as a supplement in ALL treatment.
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Apoptose , Autofagia , Extratos Vegetais , Trifolium , Trifolium/química , Humanos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologiaRESUMO
Some studies showed a "rejuvenating" effect of exposing aging tissues to a young environment. In mouse heterochronic parabiosis experiments, in response to young organisms, old animals lived longer than isochrony old age-matched conjoint animals. Comparable "rejuvenating" effects were obtained by injecting young plasma in old mice. This raised great hopes of slowing down the senescence process in humans by the injection of young plasma, as well as to prevent or cure age-related diseases. Some clinical trials are currently being performed or were recently completed. However, these studies are small and of limited duration, and we still lack convincing evidence to support the effectiveness of young plasma injection. It is urgent to perform additional investigations, including the development of an assay to measure the cell proliferation induction capability of different human plasmas, before one can seriously think of a large-scale treatment of humans. We adopted a simple method to measure the potential of different plasmas in supporting cell line proliferation, regardless of the co-presence of a platelet lysate. By comparing plasmas from young and old subjects, we observed a decreased activity in plasmas from old individuals. The young plasma effect may be attributed to specific proteins and growth factors more abundant in younger individuals that could decrease with age. Alternatively, or at the same time, the reduced cell proliferation support could be due to inhibitors present in the old plasma. Studying the different protein content of young and old plasmas was out of the scope of this article. Such differences should be adequately investigated by proteomics using many samples. However, a preliminary study of the different protein content of young and old plasmas was part of the assay validation using a commercially available cytokine array for parallel determination of the relative levels of 105 selected human proteins. We could show the existence of specific differences between young and old plasmas and that plasmas from old individuals presented a higher concentration of "inflammatory" proteins.
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Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC. Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.3.1) was used to perform a network meta-analysis based on the JAGS package and GEMTC package under the Bayesian framework. The main indicators included OS, PFS, ORR and adverse events of grade 3 or higher. This study has been registered in PROSPERO (CRD42024525372). Results: A total of 8 RCTs involving 5539 patients and 12 treatments were included. Pembrolizumab plus Enfortumab Vedotin (PEM+EV) was significantly better than other groups in OS, PFS and ORR. In terms of OS, PEM+EV was significantly better than nivolumab plus platinum-based chemotherapy (NIVO+platinumCT) (HR=0.60; 95% CI: 0.45-0.81), PEM+platinumCT (HR=0.55; 95%CI: 0.42-0.72), atezolizumab (ATE) + platinumCT (HR=0.57; 95%CI: 0.43-0.75) and platinumCT (HR=0.47; 95%CI: 0.38-0.58). In terms of PFS, PEM+EV was also significantly better than NIVO+platinumCT (HR=0.62; 95%CI: 0.48-0.82), PEM+platinumCT (HR=0.58; 95%CI: 0.45-0.74), ATE+platinumCT (HR=0.55; 95%CI: 0.43-0.69) and platinumCT (HR=0.45; 95%CI: 0.38-0.54). In terms of ORR, PEM+EV had a significant be nefit compared with other treatment measures, which was 2.63 times that of platinumCT (OR=2.63; 95%CI: 2.00-3.45). The adverse events of grade 3 or higher in immunotherapy (ATE, PEM, durvalumab) was significantly lower than other treatment measures. Conclusions: PEM+EV can significantly prolong OS and PFS compared with other treatments, and has a higher ORR. The adverse events of grade 3 or higher of ATE was the lowest. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024525372, identifier CRD42024525372.
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Typhonium flagelliforme (T. flagelliforme) is an Indonesian rodent tuber plant traditionally used to treat cancer diseases. Although gamma-ray irradiation has been used to increase the content in the chemical compounds of the T. flagelliforme plants with anticancer activity ten times effective, the specific effect of the isolated compounds from the mutant plants has never been reported yet. The potential cytotoxic agents were characterized via nuclear magnetic resonance spectroscopy, infrared spectroscopy, and mass spectrometry as stigmasterol and 7α-hydroxyl stigmasterol; and their anticancer activity was investigated. The in silico biochemical profile of the two compounds were analyzed by molecular docking and molecular dynamics simulation to confirm its interaction with the agonist binding site of Farsenoid X receptor (FXR). Stigmasterol and 7α-hydroxyl stigmasterol can act as a competitive regulator with a high-affinity for the FXR. The results also showed that stigmasterol and 7α-hydroxyl stigmasterol were the most potential and active fraction of the T. flagelliforme mutant plant against the MCF-7 human breast cancer cell line, with IC 50 value 9.13 µM and 12.97 µM, compared with cisplastin as a control about 13.20 µM. These results demonstrate the potential of stigmasterol and 7α-hydroxyl stigmasterol in T. flagelliforme mutant plants to act towards cancer diseases.
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Simulação de Acoplamento Molecular , Humanos , Células MCF-7 , Estigmasterol/farmacologia , Estigmasterol/isolamento & purificação , Tubérculos/química , Antineoplásicos Fitogênicos/farmacologia , Simulação por Computador , Animais , Mutação , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Simulação de Dinâmica Molecular , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismoRESUMO
BACKGROUND: Suicide is a major global health concern, particularly among young people. This study evaluates an online suicide risk calculator based on the Risk Assessment of Suicidality Scale (RASS), which is designed to enhance accessibility and early detection of suicide risk. METHODS: The study involved 444 participants who completed the RASS via an online calculator. Results were compared with data from the COMET-G study's Russian sample (n=7572). Descriptive statistics, correlation analysis, and two-way ANOVA were used to analyze the data. RESULTS: The mean age of participants was 22.71 years (SD=7.94). The mean total RASS standardized score was 837.7 (SD=297.8). There was a significant negative correlation between age and RASS scores (r=-0.463, p<0.0001). The online calculator sample showed significantly higher RASS scores compared to the COMET-G sample, with 71% of online users scoring above the 90th percentile of the COMET-G sample. CONCLUSION: Our study demonstrated the advantage of the on-line suicidality risk calculator based on the RASS scale as a sensitive tool in detecting suicidal behaviours and measuring the severity of suicidality risks, offering a capability for broad reach and immediate assessment during clinical conversation between doctor and patient. Moreover, the RASS on-line psychometric instrument, when being freely distributed among the general population over internet sources, enabled to attract vulnerable groups of respondents with significantly higher suicidality risks. Future research should focus on integrating such tools into comprehensive suicide prevention programs and developing appropriate follow-up monitoring strategies for high risk-cases.
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Prevenção do Suicídio , Humanos , Masculino , Feminino , Adulto , Medição de Risco/métodos , Adulto Jovem , Adolescente , Suicídio/psicologia , Ideação Suicida , Psicometria/instrumentação , Psicometria/normas , Pessoa de Meia-Idade , InternetRESUMO
This paper investigates the stochastic path following control of underactuated marine vehicles (UMVs) subject to multiple disturbances and constraints. Firstly, the complex marine environment in which UMVs navigate typically contains stochastic components, thus the multiple disturbances are categorized as slow-varying deterministic disturbances and stochastic disturbances. Secondly, a position-constrained line-of-sight (PCLOS) based fractional-order sliding mode stochastic (FSMS) control strategy is established to achieve path following control of UMVs. A PCLOS guidance law based on universal barrier Lyapunov function is proposed to ensure that the position errors remain within the constraint ranges, which is versatile for systems with symmetric constraints or without constraints. An FSMS controller based on fractional-order theory and sliding mode control is designed to improve the dynamic response speed of the system and effectively attenuate chattering phenomenon. A stochastic disturbance observer is developed to estimate the slow-varying deterministic disturbances in the stochastic system, and auxiliary dynamic compensators are used to mitigate the impact of input constraints. Lastly, theoretical analysis indicates that the closed-loop system is stable and the position constraint requirements are satisfied. Comparative simulations illustrate the effectiveness of the proposed control strategy.
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The primary pathological hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, a critical midbrain region. In vitro models based on DA neurons provide a powerful platform for investigating the cellular and molecular mechanisms of PD and testing novel therapeutic strategies. A deep understanding of DA neuron development, including the signalling pathways and transcription factors involved, is essential for advancing PD research. This article first explores the differentiation and maturation processes of DA neurons in the midbrain, detailing the relevant signalling pathways. It then compares various in vitro models, including primary cells, immortalized cell lines, and stem cell-based models, focusing on the advantages and limitations of each. Special attention is given to the role of immortalized and stem cell models in PD research. This review aims to guide researchers in selecting the most appropriate model for their specific research goals. Ethical considerations and clinical implications of using stem cells in PD research are also discussed.
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BACKGROUND: While often used, Hilgenreiner's line may not always be a reliable reference plane following triple innominate pelvic osteotomy or trauma to the triradiate cartilage. The inferior sacral-iliac line is a horizontal line connecting the sclerotic corners of the inferior sacral-iliac joints. This is a consistent landmark in the ossifying infant pelvis as well as the fully developed adult pelvis. The goal of this study was to determine if there is a difference in measurements between the inferior sacral-iliac line and Hilgenreiner's line in order to identify an alternative horizontal reference plane. METHODS: 3 reviewers (fellowship-trained paediatric orthopaedic surgeon, junior orthopaedic resident, senior orthopaedic resident) reviewed 100 paediatric non-osteotomized pelvises. The difference between Hilgenreiner's line and the inferior sacral-iliac line were measured and reported. Measurements were repeated a minimum of 48 hours apart, resulting in 600 comparisons between Hilgenreiner's line and the inferior sacral-iliac line. The standard error of measurement was calculated to assess the variation in measurements between each individual observer and the group as a whole. RESULTS: The mean standard error of measurement between Hilgenreiner's line and the inferior sacral-iliac line was 0.44° (95% CI, ± 0.86). Reviewers 1-3 demonstrated a mean standard error of measurement of 0.38, 0.28, and 0.35 (95% CI, ± 0.74, 0.55, and 0.86) respectively. There was no statistically significant difference between reviewers (p > 0.05). Intra-observer reliability for reviewers 1, 2, and 3 was 0.64 (0.47-0.76), 0.75 (0.63-0.83), and 0.54 (0.32-0.69) respectively, with an inter-observer reliability of 0.42 (0.20-0.60) degrees. CONCLUSIONS: In this proof-of-concept study, the inferior sacral-iliac line was found to be an appropriate alternative to Hilgenreiner's line that is easily identifiable for all levels of orthopaedic training. Future inferior sacral-iliac line studies should demonstrate the reliability of multiple acetabular measurements, both pre- and post-osteotomy.
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Cellular Agriculture (CellAg) is an attractive concept for innovative technology with the intent to provide food and nutrition complementary to existing supply streams. The past decade has seen considerable progress in the field with advancement of cellular technology that delivers the initial building blocks for meaningful implementation. The availability of natural cell-based material that can serve as nutrient-filled source for human consumption at low cost is a critical challenge for the emerging cellular agriculture industry. Therefore, here the isolation of bovine myofibroblasts of the Black Angus breed has been pursued and accomplished together with its characterisation by using RNA sequencing and proteomics through western blotting. To transition CellAg from a concept to a game changing technology for the industry, multiple challenges need to be overcome. The field requires powerful initial material, i.e., dedicated cells that can proliferate and differentiate robustly at scale. The methodology described allows for the production of healthy cells, which have been unequivocally characterized as clonal representatives of a stable myofibroblast cell line using transcriptomics and proteomics validation. Stringent and rigorous live cell monitoring of a nascent cell line derived from healthy muscle tissue allowed for stable cell growth. In this research article, a simple and precise methodology is presented for creating a bovine myofibroblast cell line (Bov.mia). Our work puts forward a low-tech use of materials and expertise that is devoid of transgenic approaches, thus creating a reliable approach for lab-scale research.
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PURPOSE: With laparoscopic sleeve gastrectomy (LSG) taking its place as the primary metabolic bariatric procedure in the past decade, de novo or persistent gastroesophageal reflux disease (GERD) has come into the spotlight as one of the most debilitating postoperative complications. Among the causes of GERD, intrathoracic migration (ITM) of the sleeve has become an understated yet significant phenomenon. This study aims to analyze the actual incidence of spontaneous ITM at our center, as well as its relationship to the baseline characteristics of patients and perioperative outcomes. MATERIALS AND METHODS: A retrospective chart review of 206 patients who had undergone LSG at our center from July 2019 to December 2022 was done. At 1-year follow-up, a non-enhanced abdominopelvic computed tomography (CT) scan and esophagogastroduodenoscopy (EGD) were performed, and these exams were repeated annually. Baseline characteristics and perioperative outcomes including the clinical disease course of GERD were compared. RESULTS: The incidence of ITM was 14% (n = 29). There was a significant correlation between ITM and postoperative reflux symptoms (p = 0.001). The mean duration of anti-reflux medication use was also significantly longer in the ITM group than in the no ITM group at 17 and 11 months, respectively (p = 0.004). A significantly higher number of patients in the ITM group were diagnosed with esophagitis on postoperative EGD than in the no ITM group (p = 0.002). CONCLUSION: The incidence of ITM using non-enhanced CT was 14%. ITM was significantly correlated to clinical reflux and EGD-confirmed esophagitis.
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BACKGROUND: Pre-procedural antisepsis is a critical component of hospital-acquired infection prevention in the neonatal intensive care unit (NICU). However, broadly utilized topical antiseptic agents pose an elevated risk of disruption to neonatal skin integrity, and evidence-based guidelines are lacking. This systematic review of the literature sought to assess and characterize the predisposing risk factors for and types of neonatal skin injury from topical antiseptic agents. METHODS: A systematic search of Medline Ovid, Embase, Web of Science, CINAHL, and Cochrane Library was conducted, including academic literature providing data on neonatal skin injuries related to topical antisepsis in the NICU. RESULTS: A total of 19 articles (99 patients) met the inclusion criteria. Of the available data, most reported skin injuries were described in extremely preterm (98.1%) and very low birth weight (98.4%) infants. The majority of reported adverse cutaneous events were attributed to chlorhexidine preparations (74.8%), followed by octenidine (18.2%), povidone-iodine (6.1%), and isopropyl alcohol (2.0%). Erythema (40.1%), skin breakdown (23.4%), and chemical burns (17.5%) were the skin reactions reported most frequently, followed by skin irritation (8.3%), and skin necrosis (2.8%). CONCLUSIONS: Our findings indicate that both extremely preterm and very low birth weight infants are particularly susceptible to skin toxicities from pre-procedural antiseptic preparations. These data underscore the need for future research to support the development of guidelines which minimize iatrogenic cutaneous injuries in the neonatal population, specifically for the care of infants under 2 months of age, for whom current recommendations are lacking due to a paucity of data.
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Only a limited number of tumour biomarkers are currently available in veterinary medicine, particularly in cats. Cell-free DNA (cfDNA) is an extracellular DNA fragment released upon cell death and is considered a minimally invasive biomarker for the diagnosis and monitoring of various human malignancies. This study aimed to clarify the utility of circulating cfDNA as a liquid biopsy for various feline tumours. Plasma samples were collected from 44 cats with various tumours, 24 cats with other diseases and 10 healthy controls. A follow-up study was conducted in three tumour-bearing patients. All cfDNA concentrations were quantified via real-time polymerase chain reaction (PCR), which provided short and long fragments of a newly identified feline LINE-1 gene. We found that cfDNA levels were significantly higher in cats with various tumours than in those with other diseases or healthy controls. The cfDNA concentration was not correlated with serum amyloid A (SAA) levels. Cats with tumours exhibited elevated cfDNA levels that predicted tumour-bearing with a sensitivity and specificity of 50.5% and 91.2%, respectively (AUC 0.736; p < 0.001). In lymphoma cases, cats with high cfDNA levels had significantly shorter survival times than those with low cfDNA levels (median: 33 days vs. 178 days; p = 0.003). In addition, the cfDNA levels of the three patients correlated with clinical status during follow-up. Collectively, these findings indicate the potential of cfDNA as a useful biomarker for the diagnosis, therapeutic monitoring and prognostic assessment of tumours in cats.
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In modern biomedical research, cultivable cell lines are an indispensable tool, and the selection of cell lines that exhibit specific functional profiles is often critical to success. Cellular functional pathways have evolved through the selection of protein intra- and intermolecular interactions collectively referred to as the interactome. In the present work, quantitative in vivo protein cross-linking and mass spectrometry were used to probe large-scale protein interactome differences among three commonly employed human cell lines, namely, HEK293, MCF-7, and HeLa cells. These data illustrated highly reproducible quantitative interactome levels with R2 values larger than 0.8 for all biological replicates. Proteome abundance levels were also measured using data-independent acquisition quantitative proteomics methods. Combining quantitative interactome and proteome information allowed the visualization of cell type-specific interactome changes mediated by proteome level adaptations and independently regulated interactome changes to gain deeper insight into possible drivers of these changes. Among the largest detected alterations in protein interactions and conformations are changes in cytoskeletal proteins, RNA-binding proteins, chromatin remodeling complexes, mitochondrial proteins, and others. Overall, these data demonstrate the utility and reproducibility of quantitative cross-linking to study system-level interactome variations. Moreover, these results illustrate how combined quantitative interactomics and proteomics can provide unique insight into cellular functional landscapes.
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Until a few years ago, it was assumed that oocyte renewal did not take place in the ovary of adult organisms; however, the existence of germline progenitor cells (GPCs), which renew the ovarian follicular reserve, has now been documented in mammals. Specifically, in the adult ovary of bats, the presence of cells located in the cortical region with characteristics similar to GPCs, called adult cortical germ cells (ACGC), has been observed. One of the requirements that a GPC must fulfil is to be able to proliferate mitotically, so the evaluation of cell proliferation in ACGC is of utmost importance in order to be able to relate them to a parental lineage. Currently, there are several methods to determine cell proliferation, including BrdU labelling or the use of endogenous proliferation markers. Thus, the aim of this work was to evaluate the proliferative activity of ACGC in the adult ovary of the bat Artibeus jamaicensis, using different proliferation markers and correlating these with the protein expression of the transcription factor Oct4 and the germ line marker Ddx4. We found that the expression pattern of the proliferation markers BrdU, PCNA, Ki-67 and pH3 occurs at different times of the cell cycle, so co-localization of two or more of these markers allows us to identify proliferating cells. This allowed us to identify ACGC with proliferative capacity in the adult ovary of A. jamaicensis, suggesting that GPCs renew the follicle reserve during the adult life of the organism.
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The Atlantic salmon, Salmo Salar, is a societally important species of fish, both as a food source and as a component of aquatic biosphere. Its sustainable production is hampered by a wide range of infectious diseases, which is difficult to address due to the lack of in vitro tools to study the disease-host interaction. In this paper, we describe the establishment and characterization of a homogenous Atlantic salmon skin fibroblast (ASSF) cell line. This immortalized cell line grows well in standard media formulations and is capable of migration. It is transcriptionally stable over dozens of passages, and its transcriptome is distinct from other publicly available Atlantic salmon cell lines (SHK1 and ASK). Even though ASSF cells show limited cytopathic effects when challenged with Infectious Pancreatic Necrosis Virus (IPNV) molecular evidence reveals that they are infected and support IPNV production, especially compared to other cell lines like ASK or SHK1. The potential of the ASSF cell line as a tool for Atlantic salmon research is highlighted by its permissibility to genetic manipulation with various methods including CRISPR/cas9, transfection and transduction.
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Depression is a debilitating mental disorder that causes a persistent feeling of sadness and loss of interest. Approximately 280 million individuals worldwide suffer from depression by 2023. Despite the heavy medical and social burden imposed by depression, pathophysiology remains incompletely understood. Emerging evidence indicates various bidirectional interplay enable communication between the gut and brain. This interplay provides a link between intestinal and central nervous system as well as feedback from cortical and sensory centers to enteric activities, which also influences physiology and behavior in depression. This review aims to overview the significant role of the enteric nervous system (ENS) in the pathophysiology of depression and gut-brain axis's contribution to depressive disorders. Additionally, we explore the alterations in enteric glia cells (EGCs) and glial cell line-derived neurotrophic factor (GDNF) in depression and their involvement in neuronal support, intestinal homeostasis maintains and immune response activation. Modulating ENS function, EGCs and GDNF level could serve as novel strategies for future antidepressant therapy.
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Tucidinostat has been approved by the Chinese FDA for relapsed/refractory Peripheral T cell lymphoma (PTCL), but its efficacy in newly diagnosed PTCL has not been confirmed. In this study, we aimed to compare the efficacy of tucidinostat combined with CHOP-like (C + CHT) versus CHOP-like alone (CHT) in newly diagnosed PTCL patients. Of the PTCL patients, 109 were newly diagnosed. Patients in the C + CHT group who achieved objective response received tucidinostat maintenance therapy. A total of 36 pairs (n = 72) were matched at a ratio of 1:1 using propensity scoring. The matching criteria included: whether the Prognostic index for the peripheral T-cell lymphoma-not otherwise specified subtype (PIT) was ≥ 2, the pathological subtype, age > 60 years, and gender (matching tolerance = 0.024). A significantly higher objective response rate (ORR) (P = 0.016), 2-year progression-free survival (PFS) (P = 0.026), and 2-year survival rate (P = 0.017) was observed for the C + CHT group as compared to the CHT group. After propensity score matching (PSM), the C + CHT group as compared to the CHT group displayed significantly longer PFS (P = 0.035) and overall survival (OS) (P = 0.029). For the C + CHT group in the per-protocol set, the effect values showed a significant benefit in terms of both PFS (P = 0.027) and OS (P = 0.019). Common grade 3-4 haematological adverse events (AEs), had comparable incidence in each group; while common non-haematological AEs, including elevated AST and ALT were higher in the C + CHT group than in the CHT group. Our study suggests that the tucidinostat with CHOP-like regimen and sequential tucidinostat maintenance after objective remission provides a promising therapeutic approach for treating newly diagnosed PTCL patients.