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Background: The global COVID-19 pandemic has highlighted critical concerns surrounding mental health. Social isolation measures, such as the quarantine of incoming travelers, are essential public health strategies for the prevention and control of infectious diseases. However, quarantine can lead to adverse psychological outcomes, including feelings of confinement, boredom, perceived scarcity of supplies and information, financial hardship, and social stigma. This study aims to assess the mental states of quarantined individuals, investigate the factors affecting their mental well-being, and examine their coping mechanisms, with the objective of providing recommendations to enhance mental health in anticipation of future outbreaks, such as Disease X. Methods: We surveyed 327 individuals in quarantine from September 22, 2020 to January 9, 2021, collecting general demographic data and information related to COVID-19. Depression and anxiety were assessed using the PHQ-9 and GAD-7 scales, respectively, while stress coping was evaluated with a simplified version of the Cope scale. We analyzed the relationships between independent variables and mental health outcomes. Results: Among the individuals undergoing entry quarantine, 27.8% reported symptoms of depression, and 20.5% reported symptoms of anxiety. Students were more likely to experience depression compared to those with permanent jobs or no occupation. Significant risk factors for both depression and anxiety included pre-existing health conditions, lack of medical insurance, concerns about shortages of daily necessities during quarantine, and high scores for "guilt and self-blame." Additionally, participants who worried about the impact of the epidemic on their studies or work, and those with high scores for "denial," were more likely to exhibit depressive symptoms. On the other hand, participants who were concerned about potential rejection or discrimination from the outside world after quarantine were more prone to anxiety symptoms. Conclusion: Attention should be paid to the negative psychological reactions of the entry quarantined personnel, especially those with pre-existing health conditions, those without medical insurance, and students studying abroad. Accurate and effective epidemic dynamic information and preventive and control measures can be provided to the public to prevent fear and stigma against quarantined personnel.
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Adaptación Psicológica , Ansiedad , COVID-19 , Depresión , Cuarentena , Humanos , Cuarentena/psicología , COVID-19/psicología , COVID-19/epidemiología , China/epidemiología , Masculino , Femenino , Depresión/epidemiología , Depresión/psicología , Adulto , Ansiedad/epidemiología , Ansiedad/psicología , Encuestas y Cuestionarios , Pandemias , Adulto Joven , Factores de Riesgo , Persona de Mediana Edad , SARS-CoV-2 , Salud Mental/estadística & datos numéricosRESUMEN
Carotid artery (CA) stenosis (CAS) constitutes a significant factor to ischaemic cerebrovascular events which exhibiting no overt symptoms in the early stages. Early detection of CAS can prevent ischaemic stroke and improve patient prognosis. In this study, we developed a non-invasive CAS automatic assessment method based on deep learning, intended for the early detection of CAS with CT imaging. The method proposed in this paper consists of three main components. First, we utilised thresholding and the Hessian-based Frangi filter to eliminate irrelevant tissue and enhance vascular structures. Second, we introduced a novel neural network named parameter shared axial attention (PSAA)-nnUNet for the automatic segmentation of CA. Finally, we assessed the degree of CAS with the North American Symptomatic Carotid Endarterectomy Trial (NASCET) formula. The PSAA-nnUNet algorithm proposed in this study achieved a segmentation accuracy of 0.82. The non-invasive CAS automatic assessment method based on PSAA-nnUNet exhibits excellent accuracy and great application potential.
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Arterias Carótidas , Estenosis Carotídea , Aprendizaje Profundo , Humanos , Estenosis Carotídea/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Algoritmos , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X/métodos , Angiografía por Tomografía Computarizada/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodosRESUMEN
Functional MRI (fMRI) is gaining importance in the preoperative assessment of language for presurgical planning. However, inconsistencies with the Wada test might arise. This current case report describes a very rare case of an epileptic patient who exhibited bilateral distribution (right > left) in the inferior frontal gyrus (laterality index [LI] = -0.433) and completely right dominance in the superior temporal gyrus (LI = -1). However, the Wada test revealed a dissociation: his motor speech was located in the left hemisphere, while he could understand vocal instructions with his right hemisphere. A clinical implication is that the LIs obtained by fMRI should be cautiously used to determine Broca's area in atypical patients; for example, even when complete right dominance is found in the temporal cortex in right-handed patients. Theoretically, as the spatially separated functions of motor speech and language comprehension (by the combined results of fMRI and Wada) can be further temporally separated (by the intracarotid amobarbital procedure) in this case report, these findings might provide direct support to Broca's initial conclusions that Broca's area is associated with acquired motor speech impairment, but not language comprehension per se. Moreover, this current finding supports the idea that once produced, motor speech can be independent from language comprehension.
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Lateralidad Funcional , Lenguaje , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Área de Broca/diagnóstico por imagen , Área de Broca/fisiopatología , Adulto , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatología , Mapeo Encefálico/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Epilepsia/fisiopatología , Epilepsia/diagnóstico , Habla/fisiologíaRESUMEN
BACKGROUND: Stroke is a leading cause of death and disability worldwide. Rapid and accurate diagnosis is crucial for minimizing brain damage and optimizing treatment plans. OBJECTIVE: This review aims to summarize the methods of artificial intelligence (AI)-assisted stroke diagnosis over the past 25 years, providing an overview of performance metrics and algorithm development trends. It also delves into existing issues and future prospects, intending to offer a comprehensive reference for clinical practice. METHODS: A total of 50 representative articles published between 1999 and 2024 on using AI technology for stroke prevention and diagnosis were systematically selected and analyzed in detail. RESULTS: AI-assisted stroke diagnosis has made significant advances in stroke lesion segmentation and classification, stroke risk prediction, and stroke prognosis. Before 2012, research mainly focused on segmentation using traditional thresholding and heuristic techniques. From 2012 to 2016, the focus shifted to machine learning (ML)-based approaches. After 2016, the emphasis moved to deep learning (DL), which brought significant improvements in accuracy. In stroke lesion segmentation and classification as well as stroke risk prediction, DL has shown superiority over ML. In stroke prognosis, both DL and ML have shown good performance. CONCLUSIONS: Over the past 25 years, AI technology has shown promising performance in stroke diagnosis.
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Inteligencia Artificial , Accidente Cerebrovascular , Humanos , Inteligencia Artificial/historia , Aprendizaje Automático , Pronóstico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/prevención & control , Historia del Siglo XX , Historia del Siglo XXIRESUMEN
Objective: This retrospective study aims to investigate the treatment of tic disorder (TD) in Dongfang Hospital affiliated with Beijing University of Chinese Medicine, explore its underlying mechanism, and provide valuable insights for future research and clinical management of TD. Methods: The electronic medical records of children with TD, from 2015 to 2021, were extracted from the information system of Dongfang Hospital affiliated with Beijing University of Chinese Medicine. The clinical characteristics of TD, utilization patterns of Chinese herbal medicine and synthetic drugs in prescriptions, as well as their pharmacological effects, were statistically described and categorized. In addition, association rules and network pharmacology were employed to identify core prescriptions (CPs) and elucidate their microscopic molecular mechanisms in treating TD. Results: The age range of the children was from 6 to 11â years, with a higher proportion of male participants than female ones. The average duration of treatment was 6â weeks. Regimen Z for the treatment of TD can be summarized as follows: Chinese herbal medicine [Saposhnikoviae Radix (FangFeng), Puerariae Lobatae Radix (GeGen), Uncariae Ramulus cum Uncis (GouTeng), Acori Tatarinowii Rhizoma (ShiChangPu), Chuanxiong Rhizoma (ChuanXiong)] and vitamins [lysine, inosite, and vitamin B12 oral solution] form the basic treatment, combined with immunomodulators, antibiotics, electrolyte-balancing agents, and antiallergic agents. CPs primarily exerted their effects through the modulation of gene expression (transcription), the immune system, and signal transduction pathways, with interleukin-4 and interleukin-13 pathways being particularly crucial. Among the lysine synthetic drugs used, inosite and vitamin B12 oral solution were the most frequently prescribed. Conclusion: The regimen Z drug treatment holds significant importance in the field, as it exerts its therapeutic effects through a multitude of pathways and intricate interventions. Chinese herbal medicine primarily regulates immune system-related pathways, while synthetic drugs predominantly consist of vitamins.
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Objective: This study explores the intricate relationship between social support and eating behaviors in children and adolescents, considering the mediating role of eating self-efficacy and the moderating effects of body mass index (BMI) and weight concern. Methods: Data from 1986 primary and secondary school students aged 8 to 17 in Shanghai, China, were analyzed using moderated mediation analysis. Results: The results demonstrate a robust positive association between social support and eating self-efficacy, particularly prominent among individuals with low BMI (effect = 0.506, 95% CI [0.376, 0.636]). Moreover, the study highlights that eating behavior is influenced not only by eating self-control (ß = -0.054, 95% CI [-0.062, -0.046]) but also by the interaction term between individuals' perceptions of their body weight (ß = -0.0008, 95% CI [-0.0015, -0.0001]). Conclusion: Eating self-efficacy serves as a mediator in the relationship between social support and eating behavior, modulated by BMI and weight concern. Importantly, high weight concern significantly strengthens the mediating effect of eating self-efficacy on the relationship between social support and eating behavior, regardless of BMI.
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Abdominal multi-organ segmentation is one of the most important topics in the field of medical image analysis, and it plays an important role in supporting clinical workflows such as disease diagnosis and treatment planning. In this study, an efficient multi-organ segmentation method called Swin-PSAxialNet based on the nnU-Net architecture is proposed. It was designed specifically for the precise segmentation of 11 abdominal organs in CT images. The proposed network has made the following improvements compared to nnU-Net. Firstly, Space-to-depth (SPD) modules and parameter-shared axial attention (PSAA) feature extraction blocks were introduced, enhancing the capability of 3D image feature extraction. Secondly, a multi-scale image fusion approach was employed to capture detailed information and spatial features, improving the capability of extracting subtle features and edge features. Lastly, a parameter-sharing method was introduced to reduce the model's computational cost and training speed. The proposed network achieves an average Dice coefficient of 0.93342 for the segmentation task involving 11 organs. Experimental results indicate the notable superiority of Swin-PSAxialNet over previous mainstream segmentation methods. The method shows excellent accuracy and low computational costs in segmenting major abdominal organs.
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Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Imagenología Tridimensional/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Abdomen/diagnóstico por imagen , Radiografía Abdominal/métodosRESUMEN
This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d'). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (ß, Ohit/Ofalse alarm). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible.
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Reconocimiento Facial , Tiempo de Reacción , Reconocimiento en Psicología , Sueño , Humanos , Masculino , Femenino , Adulto Joven , Reconocimiento en Psicología/fisiología , Sueño/fisiología , Reconocimiento Facial/fisiología , Adulto , Tiempo de Reacción/fisiología , Vigilia/fisiologíaRESUMEN
The abnormal uric acid (UA) level in urine can serve as warning signals of many diseases, such as gout and metabolic cardiovascular diseases. The current methods for detecting UA face limitations of instrument dependence and the requirement for non-invasiveness, making it challenging to fulfill the need for home-based application. In this study, we designed an aptasensor that combined UA-specific transcriptional regulation and a fluorescent RNA aptamer for convenient urinary UA testing. The concentration of UA can be translated into the intensity of fluorescent signals. The aptasensor showed higher sensitivity and more robust anti-interference performance. UA levels in the urine of different volunteers could be accurately tested using this method. In addition, a paper-based aptasensor for UA self-testing was manufactured, in which the urinary UA levels could be determined using a smartphone-based colorimetric approach. This work not only demonstrates a new approach for the design of disease-associated aptasensor, but also offers promising ideas for home-based detection of UA.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Papel , Ácido Úrico , Ácido Úrico/orina , Humanos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Autoevaluación , Colorimetría/métodos , Transcripción Genética , Urinálisis/métodos , Urinálisis/instrumentaciónRESUMEN
Virtual reality based physical stress (VRPS) paradigms could eliminate the influence of social factors on participants, and it may be a desirable tool to explore the impact of personality traits on stress levels. In this study, we attempt to explore the effects of VRPS on stress response among individuals with different personality traits. Forty male participants with an average age of 22.79 ± 0.41 years were divided into two groups based on Harm Avoidance (HA) scores of Tridimensional Personality Questionnaire (TPQ), referred to as the Low-HA group and the High-HA group. The stress levels of the participants were assessed using salivary α-amylase (sAA) activity and heart rate variability (HRV) indices pre- and post-stress. The influence of personality traits on stress response among different groups was analyzed. VRPS significantly affected the sAA activity and HRV indicators of both groups. During and after stress, there were significant differences in sAA activity and HRV indicators between the two groups. The sAA levels and HRV indices of the Low-HA group were lower than those of the High-HA group. Furthermore, sAA levels and HRV indices were correlated with the scores of TPQ. VRPS scenarios elicit different stress responses on individuals with different harm avoidance personality traits. Stress evaluation based on VR scenarios presents potential in personality trait assessments, particularly for distinguishing between individuals with low and high HA tendencies.
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Frecuencia Cardíaca , Personalidad , alfa-Amilasas Salivales , Estrés Psicológico , Realidad Virtual , Humanos , Masculino , Personalidad/fisiología , Frecuencia Cardíaca/fisiología , Estrés Psicológico/fisiopatología , Estrés Psicológico/psicología , Adulto Joven , alfa-Amilasas Salivales/metabolismo , alfa-Amilasas Salivales/análisis , Saliva/química , Adulto , Estrés Fisiológico/fisiología , Encuestas y Cuestionarios , Reducción del DañoRESUMEN
Inorganic mixed-halogen perovskites exhibit excellent photovoltaic properties and stability; yet, their photoelectric conversion efficiency is limited by inherent surface defects. In this work, we study the impact of defects on properties of CsPbI2Br slabs using first-principles calculations, focusing on specific defects such as I vacancy (VI), I interposition (Ii), and I substitution by Pb (PbI). Our findings reveal that these defects affect the geometric and optoelectronic properties as well as dynamics of charge carriers of slabs. We employ two theoretical frameworks (surface hopping and Redfield theory) of nonadiabatic molecular dynamics simulations to comprehensively study relaxation processes and obtain consistent results. The presence of VI reduces carrier lifetimes, while the influence of PbI on carrier lifetimes is negligible. In contrast, Ii defects lead to prolonged carrier lifetimes. These insights provide valuable guidance for the rational design of perovskite photovoltaic devices, aiming to enhance their efficiency and stability.
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Movement and muscle control are crucial for the survival of all free-living organisms. This study aimed to explore differential patterns of cortical and subcortical activation across different stages of muscle control using functional magnetic resonance imaging (fMRI). An event-related design was employed. In each trial, participants (n = 10) were instructed to gently press a button with their right index finger, hold it naturally for several seconds, and then relax the finger. Neural activation in these temporally separated stages was analyzed using a General Linear Model. Our findings revealed that a widely distributed cortical network, including the supplementary motor area and insula, was implicated not only in the pressing stage, but also in the relaxation stage, while only parts of the network were involved in the steady holding stage. Moreover, supporting the direct/indirect pathway model of the subcortical basal ganglia, their substructures played distinct roles in different stages of muscle control. The caudate nucleus exhibited greater involvement in muscle contraction, whereas the putamen demonstrated a stronger association with muscle relaxation; both structures were implicated in the pressing stage. Furthermore, the subthalamic nucleus was exclusively engaged during the muscle relaxation stage. We conclude that even the control of simple muscle movements involves intricate automatic higher sensory-motor integration at a neural level, particularly when coordinating relative muscle movements, including both muscle contraction and muscle relaxation; the cortical and subcortical regions assume distinct yet coordinated roles across different stages of muscle control.
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Cordyceps militaris has been extensively cultivated as a model cordyceps species for commercial purposes. Nevertheless, the problems related to strain degeneration and breeding technologies remain unresolved. This study assessed the physiology and fertility traits of six C. militaris strains with distinct origins and characteristics, focusing on single mating-type strains. The results demonstrated that the three identified strains (CMDB01, CMSY01, and CMJB02) were single mating-type possessing only one mating-type gene (MAT1-1). In contrast, the other three strains (CMXF07, CMXF09, and CMMS05) were the dual mating type. The MAT1-1 strains sourced from CMDB01, CMSY01, and CMJB02 consistently produced sporocarps but failed to generate ascospores. However, when paired with MAT1-2 strains, the MAT1-1 strains with slender fruiting bodies and normal morphology were fertile. The hyphal growth rate of single mating-type strains (CMDB01, CMSY01, and CMJB02) typically surpassed that of dual mating-type strains (CMXF07, CMXF09, and CMMS05). The growth rates of MAT1-2 and MAT1-1 strains were proportional to their ratios, such that a single mating-type strain with a higher ratio exhibited an increased growth rate. As C. militaris matured, the adenosine content decreased. In summary, the C. militaris strains that consistently produce sporocarps and have a single mating type are highly promising for production and breeding.
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Cordyceps , Cordyceps/genética , Genes del Tipo Sexual de los Hongos , Fitomejoramiento , Adenosina , Esporas Fúngicas/genéticaRESUMEN
Both P3b and the inspection time (IT) are related with intelligence, yet the P3b correlates of IT are not well understood. This event-related potential study addressed this question by asking participants (N = 28) to perform an IT task. There were three IT conditions with different levels of discriminative stimulus duration, i.e., 33â¯ms, 67â¯ms, and 100â¯ms, and a control condition with no target presentation (0â¯ms condition). We also measured participants' processing speed with four Elementary Cognitive Tests (ECTs), including a Simple Reaction Time task (SRT), two Choice Reaction Time tasks (CRTs), and a Pattern Discrimination task (PD). Results revealed that an increase in P3b latency with longer duration of the discriminative stimulus. Moreover, the P3b latency was negatively correlated with the accuracy of the IT task in the 33â¯ms condition, but not evident in the 67 and 100â¯ms conditions. Furthermore, the P3b latency of the 33â¯ms condition was positively correlated with the RT of the SRT, but not related with the RTs of CRTs or PD. A significant main effect of duration on the amplitude of P1 was also found. We conclude that the present study provides the neurophysiological correlates of the IT task, and those who are able to accurately perceive and process very briefly presented stimuli have a higher speed of information process, reflected by the P3b latency, yet this relationship is more obvious in the most difficult condition. Combined, our results suggest that P3b is related with the closure of a perceptual epoch to form the neural representation of a stimulus, in support of the "context closure" hypothesis.
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Pulsed electric fields are extensively utilized in clinical treatments, such as subthalamic deep brain stimulation, where electric field loading is in direct contact with brain tissue. However, the alterations in brain tissue's mechanical properties and microstructure due to changes in electric field parameters have not received adequate attention. In this study, the mechanical properties and microstructure of the brain tissue under pulsed electric fields were focused on. Herein, a custom indentation device was equipped with a module for electric field loading. Parameters such as pulse amplitude and frequency were adjusted. The results demonstrated that following an indentation process lasting 5 s and reaching a depth of 1000 µm, and a relaxation process of 175 s, the average shear modulus of brain tissue was reduced, and viscosity decreased. At the same amplitude, high-frequency pulsed electric fields had a smaller effect on brain tissue than low-frequency ones. Furthermore, pulsed electric fields induced cell polarization and reduced the proteoglycan concentration in brain tissue. As pulse frequency increased, cell polarization diminished, and proteoglycan concentration decreased significantly. High-frequency pulsed electric fields applied to brain tissue were found to reduce impedance fluctuation amplitude. This study revealed the effect of pulsed electric fields on the mechanical properties and microstructure of ex vivo brain tissue, providing essential information to promote the advancement of brain tissue electrotherapy in clinical settings.
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Encéfalo , Electricidad , Animales , Porcinos , Viscosidad , Impedancia Eléctrica , ProteoglicanosRESUMEN
Objectives: This research aims to assess the effectiveness and cost-effectiveness of pre-pregnancy deafness screening policies. Methods: Married couples from Shanghai, Beijing, and Suzhou in China were enrolled. We conducted high-throughput, pre-pregnancy genetic screenings for deafness in women and their partners. We compared the cost-effectiveness of deafness genetic screening with the status quo. The two-step screening (wife then partner) and following treatments and interventions were included in the decision tree model. We conducted a cost-effectiveness analysis based on the decrease in deaf newborns, healthy newborn births, and cost-utility analysis of pre-pregnancy deafness genetic screening separately. Cost, utility, and probability data used in the three models were collected from a survey combined with literature and expert consultants. A 5% discount rate and a series of one-way sensitivity analyses along with a Monte Carlo simulation were used to test the reliability of this research. Results: Between Jan 1, 2019, and Dec 31, 2021, we recruited 6,200 females and 540 male spouses from community health service centers in Shanghai, Beijing, and Suzhou. The incremental cost-effectiveness ratio (ICER) for reducing deaf newborn births was USD 32,656 per case and USD 1,203,926 per case for increasing one healthy newborn birth. This gap exists because of the overall decrease of newborn births. From the perspective of the whole society, deafness genetic screening is not cost-effective for reducing the overall quality-adjusted life years (QALY) in the population. Discussion: Pre-pregnancy genetic testing is effective in decreasing the occurrence of congenital deafness. It is a cost-saving measure when compared with the costs of future medical expenditure and income loss for the affected families. However, such screening and preventive avoidance of pregnancy will decrease the population size and QALY. Only post-screening ART with PGT was shown to increase the birth of healthy newborns. Focusing on key groups such as premature births or consanguineous couples may improve the societal effects of screening.
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Análisis de Costo-Efectividad , Sordera , Embarazo , Humanos , Recién Nacido , Femenino , Reproducibilidad de los Resultados , China , Sordera/diagnóstico , Sordera/genética , Pruebas GenéticasRESUMEN
Background: The single risk factors of pancreatic cancer (PC) has been extensively studied. We aimed to synthesize results from such studies to identify and estimate multiple independent risk factors of PC. Methods: Articles published up to Feb 28, 2020 in English or Chinese reporting risk factors of PC were reviewed. The fixed-effects model with 95% confidence interval (CI) were used to calculate the pooled Odds Ratio (OR). Data were analyzed using RevMan 5.3. Results: PC was significantly associated with smoking (OR: 1.76, 95% CI: 1.61-1.92, P < 0.00001, I2 = 6%), diabetes (OR: 2.69, 95% CI: 2.52-2.88, P < 0.00001, I2 = 0%), family history of PC (OR: 2.58, 95% CI: 2.13-3.11, P < 0.00001, I2 = 0%), and chronic pancreatitis (OR: 5.84, 95% CI: 3.63-9.41, P < 0.00001, I2 = 0%). Conclusion: Smoking, diabetes, family history of PC, and chronic pancreatitis were independent risk factors for PC. These independent risk factors have an important role in identifying high-risk groups, which is of great significance to reduce the incidence of PC and improve the quality of life and prognosis of patients.
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Marmesin is essential in plant defense systems and exhibits various biological activities. In this study, we reconstituted the marmesin biosynthetic pathway in the Saccharomyces cerevisiae BY4741 chassis. We engineered the aromatic amino acid (AAA) biosynthetic pathways by introducing Escherichia coli-derived ppsA to improve the availability of the AAA precursor phosphoenolpyruvate, overexpressing the feedback inhibition resistance genes ARO4K229L and ARO7G141S to direct the metabolic flux toward the tyrosine branch, and deleting ARO10, PDC5, and PDC6 to reduce the byproducts from the Ehrlich pathway. The umbelliferone 6-dimethylallyltransferase (U6DT) and marmesin synthase (MS) involved in marmesin synthesis were optimized to increase marmesin production. Marmesin production was improved by truncating the transmembrane domains of PcU6DT, FcMS, and AtCPR1 and increasing the copy numbers of the genes encoding the truncated enzymes. Finally, a marmesin titer of 27.7 mg/L was obtained in shake flasks using the engineered yeast strain MU5. The constructed marmesin-producing strain provides the foundation for the green and large-scale production of pharmaceutically important furanocoumarins.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Vías Biosintéticas/genética , Ingeniería Metabólica , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
Inhibition is a core executive cognitive function. However, the neural correlates of non-motor inhibitory control are not well understood. We investigated this question using functional Magnetic Resonance Imaging (fMRI) and a simple Count Go/NoGo task (n = 23), and further explored the causal relationships between activated brain regions. We found that the Count NoGo task activated a distinct pattern in the subcortical basal ganglia, including bilateral ventral anterior/lateral nucleus of thalamus (VA/VL), globus pallidus/putamen (GP/putamen), and subthalamic nucleus (STN). Stepwise regressions and mediation analyses revealed that activations in these region(s) were modulated differently by only 3 cortical regions i.e. the right inferior frontal gyrus/insula (rIFG/insula), along with left IFG/insula, and anterior cingulate cortex/supplementary motor area (ACC/SMA). The activations of bilateral VA/VL were modulated by both rSTN and rIFG/insula (with rGP/putamen as a mediator) independently, and the activation of rGP/putamen was modulated by ACC/SMA, with rIFG/insula as a mediator. Our findings provide the neural correlates of inhibitory control of counting and causal relationships between them, and strongly suggest that both indirect and hyperdirect pathways of the basal ganglia are involved in the Count NoGo condition.