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Due to their underdeveloped physiological maturity, preterm infants often face challenges related to sucking, breathing, and swallowing coordination during initial feeding. This lack of coordination may lead to episodes of apnea and choking, resulting in unstable vital signs. Preterm infants with this issue must gradually learn oral feeding skills appropriate to their developmental stage. Registered nurses play a critical role in assessing the right time to transition from tube to oral feeding and in providing a safe and positive oral feeding experience. In this article, three validated assessment tools for feeding premature infants are introduced, accompanied by clinical research data demonstrating their use in clinical practice. These three tools include: (1) the Neonatal Oral Motor Assessment Scale, which is applied to evaluate oral motor skills using observations of nonnutritive sucking and the sucking state during the two minutes before feeding; (2) the Premature Oral Feeding Readiness Assessment Scale, which is used to assess readiness for oral feeding in preterm infants; and (3) the Early Feeding Skills assessment, which is used to evaluate the oral feeding skills of preterm infants. These tools aid nurses in helping preterm infants achieve independent oral feeding, facilitating earlier discharge and return to home. The clinical implications and effectiveness of these tools are also discussed to provide to nurses the means and confidence necessary to apply them appropriately in clinical settings.
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Recém-Nascido Prematuro , Comportamento de Sucção , Humanos , Recém-Nascido Prematuro/fisiologia , Recém-Nascido , Comportamento de Sucção/fisiologia , Comportamento Alimentar/fisiologiaRESUMO
BACKGROUND: Inflammation-related markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) could reflect tumor immune microenvironment and predict prognosis of cancers. However, it had not been explored in alpha-fetoprotein (AFP) producing gastric cancer (GC). AIM: To determine the predictive value of inflammation-related peripheral blood markers including as NLR, PLR, MLR, SII, SIRI and PNI in the prognosis of AFP- producing GC (AFPGC). Besides, this study would also compare the differences in tumor immune microenvironment, clinical characteristics and prognosis between AFPGC and AFP- GC patients to improve the understanding of this disease. METHODS: 573 patients enrolled were retrospectively studied. They were divided into AFP+ group (AFP ≥ 20 ng/mL) and AFP- group (AFP < 20 ng/mL), comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis. In AFP+ group, the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored. RESULTS: Compared with AFP- patients, AFP+ patients had higher NLR/PLR/MLR/SII/SIRI and lower PNI levels and poorer overall survival (OS). In the AFP+ group, mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group. Moreover, the dynamic increase (NLR/PLR/MLR/SII/SIRI) or decrease (PNI) was associated with the rise of mortality within 1 year of follow-up. CONCLUSION: Compared with AFP- patients, the level of inflammation-related peripheral blood markers significantly increased in AFP+ patients, which was correlated with OS of AFP+ patients. Also, the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+ patients. AFPGC should be considered as a separate type and distinguished from AFP- GC because of the difference in tumor immune microenvironment. It requires basic experiments and large clinical samples in the future.
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Background: Coronavirus disease 2019 (COVID-19) has a considerable impact on the global healthcare system. Individuals who have recovered from COVID often experience chronic respiratory symptoms that affect their daily lives. This study aimed to assess respiratory dynamics such as airway hyperresponsiveness (AHR) and bronchodilator response in post-COVID patients. Methods: This study included 282 adults with respiratory symptoms who underwent provocation tests. The demographic details, clinical symptoms and medical histories were recorded. Baseline spirometry, methacholine challenge tests (MCT) and post-bronchodilator spirometry were performed. Patients were divided into the following four groups: Group 1: non-COVID-19 and negative MCT; Group 2: post-COVID-19 and negative MCT; Group 3: non-COVID-19 and positive MCT; and Group 4: post-COVID-19 and positive MCT. Results: Most post-COVID-19 patients (43.7%) experienced AHR, and wheezing was more common. Patients in Group 4 exhibited increased intensities of dyspnoea, cough and wheezing with the lowest pulmonary function test (PFT) parameters at baseline. Moreover, significant decreases in PFT parameters after the MCT were observed in these patients. Although the prevalence of a low forced expiratory volume in 1â s to forced vital capacity ratio (<70%) was initially 2% in Group 4, it increased to 29% after MCT. No significant differences in allergic history or underlying diseases were observed between the groups. Conclusions: These findings provide comprehensive insights into the AHR and respiratory symptoms of post-COVID-19 individuals, highlighting the characteristics and potential exacerbations in patients with positive MCT results. This emphasises the need of MCT to address respiratory dynamics in post-COVID-19 individuals.
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Malignant melanoma (MM) is a common and highly invasive malignant tumor in clinical practice that is prone to occur in the skin and mucosa and prone to early metastasis. The common sites of metastasis are the liver, lungs, brain, etc. Metastatic gastrointestinal mucosa is relatively rare. Once metastasis occurs, the prognosis of patients is significantly worse. This article reports a case diagnosed as MM with liver, stomach, and duodenal metastasis by ultrasound-guided endoscopic puncture at Fengdu People's Hospital in Chongqing, with gastrointestinal discomfort as the initial symptom and a history of melanoma. Therefore, when a patient has a history of melanoma surgery and presents with digestive symptoms, it is necessary to consider the disease. Regular endoscopic screening should be performed, and early surgical treatment and postoperative chemotherapy combined with targeted therapy may improve patient prognosis and prolong patient survival.
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This study delves into the application of Brain-Computer Interfaces (BCIs), focusing on exploiting Steady-State Visual Evoked Potentials (SSVEPs) as communication tools for individuals facing mobility impairments. SSVEP-BCI systems can swiftly transmit substantial volumes of information, rendering them suitable for diverse applications. However, the efficacy of SSVEP responses can be influenced by variables such as the frequency and color of visual stimuli. Through experiments involving participants equipped with electrodes on the brain's visual cortex, visual stimuli were administered at 4, 17, 25, and 40Hz, using white, red, yellow, green, and blue light sources. The results reveal that white and green stimuli evoke higher SSVEP responses at lower frequencies, with color's impact diminishing at higher frequencies. At low light intensity (1W), white and green stimuli elicit significantly higher SSVEP responses, while at high intensity (3W), responses across colors tend to equalize. Notably, due to seizure risks, red and blue lights should be used cautiously, with white and green lights preferred for SSVEP-BCI systems. This underscores the critical consideration of color and frequency in the design of effective and safe SSVEP-BCI systems, necessitating further research to optimize designs for clinical applications.
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Interfaces Cérebro-Computador , Eletroencefalografia , Potenciais Evocados Visuais , Estimulação Luminosa , Humanos , Potenciais Evocados Visuais/fisiologia , Masculino , Adulto , Estimulação Luminosa/métodos , Feminino , Adulto Jovem , Córtex Visual/fisiologiaRESUMO
The emergence of brain-computer interface (BCI) technology provides enormous potential for human medical and daily applications. Therefore, allowing users to tolerate the visual response of SSVEP for a long time has always been an important issue in the SSVEP-BCI system. We recruited three subjects and conducted visual experiments in groups using different frequencies (17 and 25Hz) and 60Hz light. After recording the physiological signal, use FFT to perform a time-frequency analysis on the physiological signal to check whether there is any difference in the signal-to-noise ratio and amplitude of the 60Hz light source compared with a single low-frequency signal source. The results show that combining a 60Hz light source with low-frequency LEDs can reduce participants' eye discomfort while achieving effective light stimulation control. At the same time, there was no significant difference in signal-to-noise ratio and amplitude between the groups. This also means that 60Hz can make vision more continuous and improve the subject's experience and comfort. At the same time, it does not affect the performance of the original SSVEP-induced response. This study highlights the importance of considering technical aspects and user comfort when designing SSVEP-BCI systems to increase the usability of SSVEP systems for long-term flash viewing.
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Interfaces Cérebro-Computador , Eletroencefalografia , Potenciais Evocados Visuais , Estimulação Luminosa , Humanos , Estimulação Luminosa/métodos , Masculino , Potenciais Evocados Visuais/fisiologia , Adulto , Feminino , Adulto Jovem , Percepção Visual/fisiologia , Razão Sinal-RuídoRESUMO
Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.
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Antifúngicos , Azóis , Candida tropicalis , Candidemia , Farmacorresistência Fúngica , Genótipo , Testes de Sensibilidade Microbiana , Humanos , Taiwan/epidemiologia , Farmacorresistência Fúngica/genética , Candidemia/microbiologia , Candidemia/epidemiologia , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/genética , Candida tropicalis/isolamento & purificação , Antifúngicos/farmacologia , Azóis/farmacologia , Fluconazol/farmacologiaRESUMO
An electrochemical cyclization/spirocyclization hydroarylation via reductive dearomatization of a series of nonactivated arenes including N-substituted indoles, indole-3-carboxamide derivatives, and iodo-substituted benzamides is described. This protocol boasts high atom efficiency, broad substrate applicability, and excellent selectivity. Utilizing a simple undivided cell, various nonactivated arenes undergo cyclization/spirocyclization through the intramolecular addition of aryl radicals to an aromatic ring, yielding 50 indolines, spirocyclizative hydroarylation products, and phenanthridinones.
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In this review, we explore the intricate relationship between glucose metabolism and mechanotransduction pathways, with a specific focus on the role of the Hippo signaling pathway in chondrocyte pathophysiology. Glucose metabolism is a vital element in maintaining proper chondrocyte function, but it has also been implicated in the pathogenesis of osteoarthritis (OA) via the induction of pro-inflammatory signaling pathways and the establishment of an intracellular environment conducive to OA. Alternatively, mechanotransduction pathways such as the Hippo pathway possess the capacity to respond to mechanical stimuli and have an integral role in maintaining chondrocyte homeostasis. However, these mechanotransduction pathways can be dysregulated and potentially contribute to the progression of OA. We discussed how alterations in glucose levels may modulate the Hippo pathway components via a variety of mechanisms. Characterizing the interaction between glucose metabolism and the Hippo pathway highlights the necessity of balancing both metabolic and mechanical signaling to maintain chondrocyte health and optimal functionality. Furthermore, this review demonstrates the scarcity of the literature on the relationship between glucose metabolism and mechanotransduction and provides a summary of current research dedicated to this specific area of study. Ultimately, increased research into this topic may elucidate novel mechanisms and relationships integrating mechanotransduction and glucose metabolism. Through this review we hope to inspire future research into this topic to develop innovative treatments for addressing the clinical challenges of OA.
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Glaucoma is a major global health concern and the leading cause of irreversible blindness worldwide, characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons. This review focuses on the need for neuroprotective strategies in glaucoma management, addressing the limitations of current treatments that primarily target intraocular pressure (IOP) reduction. Despite effective IOP management, many patients continue to experience RGC degeneration, leading to irreversible blindness. This review provides an overview of both pharmacological interventions and emerging technologies aimed at directly protecting RGCs and the optic nerve, independent of IOP reduction. Pharmacological agents such as brimonidine, neurotrophic factors, memantine, Ginkgo biloba extract, citicoline, nicotinamide, insulin, and resveratrol show promise in preclinical and early clinical studies for their neuroprotective properties. Emerging technologies, including stem cell therapy, gene therapy, mitochondrial-targeted therapies, and nanotechnologies, offer innovative approaches for neuroprotection and regeneration of damaged RGCs. While these interventions hold significant potential, further research and clinical trials are necessary to confirm their efficacy and establish their role in clinical practice. This review highlights the multifaceted nature of neuroprotection in glaucoma, aiming to guide future research and clinical practice toward more effective management of glaucoma-induced neurodegeneration.
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BACKGROUND: Bone grafts are extensively used for repairing bone defects and voids in orthopedics and dentistry. Moldable bone grafts offer a promising solution for treating irregular bone defects, which are often difficult to fill with traditional rigid grafts. However, practical applications have been limited by insufficient mechanical strength and rapid degradation. METHODS: This study developed a ceramic composite bone graft composed of calcium sulfate (CS), ß-tricalcium phosphate (ß-TCP) with/without graphene oxide (GO) nano-particles. The biomechanical properties, degradation rate, and in-vitro cellular responses were investigated. In addition, the graft was implanted in-vivo in a critical-sized calvarial defect model. RESULTS: The results showed that the compressive strength significantly improved by 135% and the degradation rate slowed by 25.5% in comparison to the control model. The addition of GO nanoparticles also improved cell compatibility and promoted osteogenic differentiation in the in-vitro cell culture study and was found to be effective at promoting bone repair in the in-vivo animal model. CONCLUSIONS: The mixed ceramic composites presented in this study can be considered as a promising alternative for bone graft applications.
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Fosfatos de Cálcio , Sulfato de Cálcio , Grafite , Nanocompostos , Animais , Transplante Ósseo/métodos , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Substitutos Ósseos , Crânio/cirurgia , Teste de Materiais , Masculino , Força CompressivaRESUMO
INTRODUCTION: Whether acute caffeine supplementation can offset the negative effects of one-night of partial sleep deprivation (PSD) on endurance exercise performance is currently unknown. METHODS: Ten healthy recreational male runners (age: 27 ± 6 years; V Ë O 2 max : 61 ± 9 mL/kg/min) completed 4 trials in a balanced Latin square design, which were PSD + caffeine (PSD-Caf), PSD + placebo (PSD-Pla), normal sleep (NS) + caffeine (NS-Caf) and NS + placebo (NS-Pla). 3 and 8 h sleep windows were scheduled in PSD and NS, respectively. 10-km treadmill time trial (TT) performance was assessed 45 min after caffeine (6 mg/kg/body mass)/placebo supplementation in the morning following PSD/NS. Blood glucose, lactate, free fatty acid and glycerol were measured at pre-supplementation, pre-exercise and after exercise. RESULTS: PSD resulted in compromised TT performance compared to NS in the placebo conditions by 5% (51.9 ± 7.7 vs. 49.4 ± 6.9 min, p = 0.001). Caffeine improved TT performance compared to placebo following both PSD by 7.7% (PSD-Caf: 47.9 ± 7.3 min vs. PSD-Pla: 51.9 ± 7.7 min, p = 0.007) and NS by 2.8% (NS-Caf: 48.0 ± 6.4 min vs. NS-Pla: 49.4 ± 6.9 min, p = 0.049). TT performance following PSD-Caf was not different from either NS-Pla or NS-Caf (p = 0.185 and p = 0.891, respectively). Blood glucose, lactate, and glycerol concentrations at post-exercise, as well as heart rate and the speed/RPE ratio during TT, were higher in caffeine trials compared to placebo. CONCLUSIONS: Caffeine supplementation offsets the negative effects of one-night PSD on 10-km running performance.
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Sea level rise and climate change are shaping present societies, particularly those on oceanic islands. Few historical examples could serve as references for these changes. One such potential model is the Saudeleur Dynasty with its capital Nan Madol on the Pacific Island of Pohnpei. However, the timing of its construction, as well as the dynasty's fluctuations and potential environmental influences, has remained unresolved. Through the analyses of 230Th ages on 171 dates on corals fragments used as building materials and charcoal 14C ages from excavations, 2 major construction phases spanning from the 10th to the 15th century CE can be discerned. The results show that the first phase of the site's construction, spanning the 10th-12th century, marked the dynasty's rise. The second period, spanning from the late 12th to the early 15th century, provides the most substantial evidence for the demise of the island-scale chiefdom and a significant societal reorganization. The phases are centuries earlier than previously believed. With this new evidence, we propose the hypothesis that variations in the El Niño-Southern Oscillation and subsidence-related sea level rise presented major challenges for building and maintaining Nan Madol, and thus, influenced the course of the island's history. This case serves as a compelling example of how adverse climatic conditions can spur investments-in this case, in seawater defense under high sea levels-yet ultimately may contribute to abandonment. It offers lessons for island nations, showcasing coastal resilience in the face of worsening catastrophic events that unfolded over generations.
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This cross-sectional study examines survey data from a 4-day nationwide telephone survey in Taiwan about awareness of and willingness to use automated external defibrillators.
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Desfibriladores , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Inquéritos e Questionários , ConscientizaçãoRESUMO
BACKGROUND: The aim of this study was to validate and compare the performance of statistical (Utstein-Based Return of Spontaneous Circulation and Shockable Rhythm-Witness-Age-pH) and machine learning-based (Prehospital Return of Spontaneous Circulation and Swedish Cardiac Arrest Risk Score) models in predicting the outcomes following out-of-hospital cardiac arrest and to assess the impact of the COVID-19 pandemic on the models' performance. METHODS AND RESULTS: This retrospective analysis included adult patients with out-of-hospital cardiac arrest treated at 3 academic hospitals between 2015 and 2023. The primary outcome was neurological outcomes at hospital discharge. Patients were divided into pre- (2015-2019) and post-2020 (2020-2023) subgroups to examine the effect of the COVID-19 pandemic on out-of-hospital cardiac arrest outcome prediction. The models' performance was evaluated using the area under the receiver operating characteristic curve and compared by the DeLong test. The analysis included 2161 patients, 1241 (57.4%) of whom were resuscitated after 2020. The cohort had a median age of 69.2 years, and 1399 patients (64.7%) were men. Overall, 69 patients (3.2%) had neurologically intact survival. The area under the receiver operating characteristic curves for predicting neurological outcomes were 0.85 (95% CI, 0.83-0.87) for the Utstein-Based Return of Spontaneous Circulation score, 0.82 (95% CI, 0.81-0.84) for the Shockable Rhythm-Witness-Age-pH score, 0.79 (95% CI, 0.78-0.81) for the Prehospital Return of Spontaneous Circulation score, and 0.79 (95% CI, 0.77-0.81) for the Swedish Cardiac Arrest Risk Score model. The Utstein-Based Return of Spontaneous Circulation score significantly outperformed both the Prehospital Return of Spontaneous Circulation score (P<0.001) and the Swedish Cardiac Arrest Risk Score model (P=0.007). Subgroup analysis indicated no significant difference in predictive performance for patients resuscitated before versus after 2020. CONCLUSIONS: In this external validation, both statistical and machine learning-based models demonstrated excellent and fair performance, respectively, in predicting neurological outcomes despite different model architectures. The predictive performance of all evaluated clinical scoring systems was not significantly influenced by the COVID-19 pandemic.
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COVID-19 , Reanimação Cardiopulmonar , Aprendizado de Máquina , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Parada Cardíaca Extra-Hospitalar/diagnóstico , Masculino , Feminino , Idoso , Estudos Retrospectivos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Reanimação Cardiopulmonar/métodos , Medição de Risco/métodos , Retorno da Circulação Espontânea , Idoso de 80 Anos ou mais , SARS-CoV-2 , Modelos EstatísticosRESUMO
The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase (NsdUTPase) plays a key role in the proliferation of Nocardia, and was regarded as a potent drug target. However, there was little report about the NsdUTPase inhibitors. In this study, we discovered a series of novel NsdUTPase inhibitors to fight against Nocardia. The first crystal structure of NsdUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards NsdUTPase (IC50 = 0.99 µM and 0.7 µM). In addition, they showed satisfied anti-Nocardia activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that NsdUTPase inhibitors might be a useful way to repress Nocardia.
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Antibacterianos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos , Testes de Sensibilidade Microbiana , Nocardia , Pirofosfatases , Pirofosfatases/antagonistas & inibidores , Pirofosfatases/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Nocardia/enzimologia , Modelos Moleculares , Descoberta de Drogas , Humanos , Desenho de FármacosRESUMO
BACKGROUND AND INTRODUCTION: In comparison to other physical assessment methods, the inconsistency in respiratory evaluations continues to pose a major issue and challenge. OBJECTIVES: This study aims to evaluate the difference in the identification ability of different breath sound. METHODS/DESCRIPTION: In this prospective study, breath sounds from the Formosa Archive of Breath Sound were labeled by five physicians. Six artificial intelligence (AI) breath sound interpretation models were developed based on all labeled data and the labels from the five physicians, respectively. After labeling by AIs and physicians, labels with discrepancy were considered doubtful and relabeled by two additional physicians. The final labels were determined by a majority vote among the physicians. The capability of breath sound identification for humans and AI was evaluated using sensitivity, specificity and the area under the receiver-operating characteristic curve (AUROC). RESULTS/OUTCOME: A total of 11,532 breath sound files were labeled, with 579 doubtful labels identified. After relabeling and exclusion, there were 305 labels with gold standard. For wheezing, both human physicians and the AI model demonstrated good sensitivities (89.5% vs. 86.0%) and good specificities (96.4% vs. 95.2%). For crackles, both human physicians and the AI model showed good sensitivities (93.9% vs. 80.3%) but poor specificities (56.6% vs. 65.9%). Lower AUROC values were noted in crackles identification for both physicians and the AI model compared to wheezing. CONCLUSION: Even with the assistance of artificial intelligence tools, accurately identifying crackles compared to wheezing remains challenging. Consequently, crackles are unreliable for medical decision-making, and further examination is warranted.
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Inteligência Artificial , Sons Respiratórios , Humanos , Sons Respiratórios/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Masculino , Feminino , Curva ROC , Adulto , Pessoa de Meia-Idade , Médicos , Reprodutibilidade dos Testes , CriançaRESUMO
Biofilms are complex bacterial communities characterized by a high persister prevalence, which contributes to chronic and relapsing infections. Historically, persister formation in biofilms has been linked to constraints imposed by their dense structures. However, we observed an elevated persister frequency accompanying the stage of cell adhesion, marking the onset of biofilm development. Subsequent mechanistic studies uncovered a comparable type of toxin-antitoxin (TA) module (TA-like system) triggered by cell adhesion, which is responsible for this elevation. In this module, the toxin HipH acts as a genotoxic deoxyribonuclease, inducing DNA double strand breaks and genome instability. While the second messenger c-di-GMP functions as the antitoxin, exerting control over HipH expression and activity. The dynamic interplay between c-di-GMP and HipH levels emerges as a crucial determinant governing genome stability and persister generation within biofilms. These findings unveil a unique TA system, where small molecules act as the antitoxin, outlining a biofilm-specific molecular mechanism influencing genome stability and antibiotic persistence, with potential implications for treating biofilm infections.
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Antibacterianos , Biofilmes , GMP Cíclico , Instabilidade Genômica , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Antibacterianos/farmacologia , Genoma Bacteriano , Sistemas Toxina-Antitoxina/genética , Antitoxinas/metabolismo , Antitoxinas/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genéticaRESUMO
Lithium-sulfur batteries (LSBs) are a promising alternative to lithium-ion batteries because sulfur is highly abundant and exhibits a high theoretical capacity (1675 mA h g-1). However, polysulfide shuttle and other challenges have made it difficult for LSBs to be commercialised. Here, a sulfur/carbon (S/C) composite was synthesised and cathodes were fabricated via scalable melt diffusion and slurry casting methods. Carbon nanoparticles (C65) were used as both sulfur host and electrical additive. Various carbon ratios between the melt-diffusion step and cathode slurry formulation step were investigated. An increased amount of C65 in melt-diffusion led to increased structural heterogeneity in the cathodes, more prominent cracks, and a lower mechanical strength. The best performance was exhibited by a cathode where 10.5 wt% C65 (TC10.5) was melt-diffused and 24.5 wt% C65 was externally added to the slurry. An initial discharge capacity of â¼1500 mA h g-1 at 0.05C and 800 mA h g-1 at 0.1C was obtained with a capacity retention of â¼50% after 100 cycles. The improved electrochemical performance is rationalised as an increased number of C-S bonds in the composite material, optimum surface area, pore size and pore volume, and more homogeneous cathode microstructure in the TC10.5 cathode.
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BACKGROUND: Imperatorin is a naturally occurring furocoumarin derivative found in traditional Chinese medicine Angelica dahurica for its anticancer, antihypertensive, and antidiabetic properties. Chronic kidney disease (CKD) is a global health issue, characterized by a high prevalence, significant morbidity and mortality, and a range of related complications. OBJECTIVE: This study aims to investigate the protective effects of imperatorin treatment and the specific underlying mechanisms in progressive CKD. METHODS: Imperatorin was orally administrated for 14 consecutive days to mice with unilateral ureteral obstruction (UUO) to investigate the renal pathological alternations, pro-inflammatory mediators, antioxidant response, and ferroptotic death signaling. Imperatorin was also tested in the erastin-induced injury of renal proximal tubular cells (NRK-52E). Cell viability, ferroptosis protein markers, erastin-induced oxidative stress, and lipid peroxidation were assessed. RESULTS: In vivo, imperatorin treatment alleviated kidney histology alternations and attenuated the protein expression of fibrotic markers. Furthermore, imperatorin administration reduced inflammatory cell infiltration, and alleviated the oxidative stress burden by downregulating protein markers such as catalase, superoxide dismutase 2 (SOD-2), NADPH oxidase 4 (NOX-4), and thioredoxin reductase 1 (Trxr-1). It also mitigated ferroptosis markers such as glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11/cystine transporter (SLC7A11/xCT), and transferrin receptor 1 (TFR-1), and attenuated renal cell apoptosis. In vitro, imperatorin treatment effectively decreased erastin-induced feroptotic cell death, restored the antioxidant enzyme levels, and mitigated lipid peroxidation as well as the expression of ferroptosis-related markers (XCT, GPX4, and p-p53) in a dose-dependent manner. CONCLUSION: Our finding demonstrated for the first time, that imperatorin treatment holds therapeutic potential in a UUO mouse model of CKD and inhibits the erastin-induced oxidative stress, ferroptosis, and subsequent lipid peroxidation in vitro. This highlights the potential of imperatorin as a future therapeutic target for ferroptosis to improve the progression of CKD.