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BACKGROUND: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis. METHODS: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994. FINDINGS: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group. INTERPRETATION: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis. FUNDING: Korea Disease Control and Prevention Agency, South Korea.
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Pirazinamida , Tuberculose Resistente a Múltiplos Medicamentos , Masculino , Feminino , Humanos , Pirazinamida/uso terapêutico , Linezolida/uso terapêutico , Levofloxacino/uso terapêutico , Fluoroquinolonas/uso terapêutico , Quimioterapia Combinada , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Resultado do TratamentoRESUMO
The World Health Organization recently lowered the rifampin (RIF) critical concentration (CC) for drug-susceptibility testing (DST) of Mycobacterium tuberculosis complex (MTBC) using the mycobacterial growth indicator tube (MGIT) 960 system. Here, we evaluated the diagnostic performance of the MGIT system with the revised CC for determining MTBC RIF resistance with 303 clinical MTBC isolates, including 122 isolates with rpoB mutations, of which 32 had single borderline-resistance mutations, and 181 wild-type rpoB isolates. The phenotypic RIF resistance was determined via the absolute concentration method (AC) and via MGIT using both previous (1 mg/L) and revised (0.5 mg/L) CCs for the latter method. The diagnostic accuracy of each phenotypic DST (pDST) was assessed based on rpoB genotyping as the reference standard. The overall sensitivity of the AC was 95.1% (95% confidence interval [CI], 89.6 to 98.2%), while the MGIT results with previous and revised CCs were 82.0% (95% CI 74.0 to 88.3%) and 83.6% (95% CI 75.8 to 89.7%), respectively. The 32 MTBC isolates with single borderline-resistance mutations showed a wide range of MICs, and sensitivity was not significantly increased by reducing the MGIT CC. All 181 wild-type rpoB isolates were RIF-susceptible in the AC and with MGIT using the previous CC, whereas 1 isolate was misclassified as RIF-resistant with the revised CC. Our results demonstrate that the overall diagnostic performances of the MGIT DST with the revised RIF CC and previous CC were comparable. A further large-scale study is required to demonstrate the optimal RIF CC for MGIT.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , RNA Polimerases Dirigidas por DNA/genética , Testes de Sensibilidade Microbiana , Mutação , Rifampina/farmacologia , Avaliação Pré-Clínica de MedicamentosRESUMO
BACKGROUND: A simulated education, prior to surgery about postoperative nasal stuffiness and ease of breathing through the mouth may help patients tolerate discomfort after nasal surgery. This study aimed to investigate the effect of preoperative simulated education on immediate postoperative opioid requirements in patients undergoing elective nasal surgery. METHODS: This randomized controlled trial of 110 patients undergoing nasal surgery randomly allocated patients into either a control (group C) or an education group (group E). One day before surgery, patients in group E were intensively trained to breathe through the mouth by using a nasal clip, with informative explanations about inevitable nasal obstruction and discomfort following surgery. Patients in group C were provided with routine preoperative information. Total intravenous anesthesia (TIVA) with propofol and remifentanil was used for anesthesia. No further opioid was used for analgesia intraoperatively. The primary outcome was index opioid (fentanyl) requirements at the post-anesthesia recovery unit (PACU). Secondary outcomes were emergence agitation, pain scores at the PACU, and postoperative recovery using the Quality of Recovery-15 (QoR15-K). RESULTS: The rate of opioid use in the PACU was 51.0% in the group E and 39.6% in the group C (p = 0.242). Additional request for analgesics other than index opioid was not different between the groups. Emergence agitation, postoperative pain severity, and QoR15-K scores were comparable between the groups. CONCLUSION: Preoperative education with simulated mouth breathing in patients undergoing nasal surgery did not reduce opioid requirements. TRIAL REGISTRATION: KCT0006264; 16/09/2021; Clinical Research Information Services ( https://cris.nih.go.kr ).
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Delírio do Despertar , Procedimentos Cirúrgicos Nasais , Humanos , Analgésicos Opioides/uso terapêutico , Delírio do Despertar/tratamento farmacológico , Respiração Bucal/tratamento farmacológico , Educação de Pacientes como Assunto , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Anestesia GeralRESUMO
BACKGROUND: Although digital health technologies (DHTs) help many people maintain a healthy life, including those of advanced age, these technologies are of little use to older adult populations if they are not being adopted in daily life. Thus, it is critical to identify ways to help older adults recognize and try new technologies and maintain their use of them to maximize the benefits of these technologies in a digital-based society. OBJECTIVE: Our study aimed (1) to assess the current usage of DHT among older adults in Hong Kong and (2) to examine how high and low levels of eHealth literacy in this group affects the relationship between the Technology Readiness and Acceptance Model (TRAM) and attitudes and intention toward DHT. METHODS: A total of 306 adults over 60 years of age in Hong Kong participated in this study. After conducting confirmatory factor analysis to validate the measurement model, the hypothesized model was tested using structural equation modeling. RESULTS: Optimism was significantly related to perceived usefulness, while optimism, innovativeness, and discomfort were significantly associated with perceived ease of use. Both perceived usefulness and perceived ease of use were significantly linked to attitude toward the use of DHTs. Meanwhile, attitude significantly predicted usage intention. Additionally, the results revealed the differences in the relationships of the TRAM between participants with high and low levels of eHealth literacy. The influence of optimism and innovativeness on perceived ease of use was stronger for the higher-level group than for the lower-level group, and the influence of discomfort for the higher-level group was much weaker. CONCLUSIONS: The findings provided partial support for the impact of eHealth literacy on encouraging older adults to use DHT and obtain health benefits from it. This study also suggests providing assistance and guidelines for older adults to narrow the aging-related technology gap and to further explore the associations of eHealth literacy, the TRAM, and actual behaviors.
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Letramento em Saúde , Telemedicina , Humanos , Pessoa de Meia-Idade , Idoso , Hong Kong , Envelhecimento , Tecnologia , Letramento em Saúde/métodos , Telemedicina/métodos , Tecnologia Biomédica , Inquéritos e QuestionáriosRESUMO
Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Diarilquinolinas/farmacologia , Resistência a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Reprodutibilidade dos Testes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
Competitive balance is important because it enhances outcome uncertainty and therefore it promotes spectator interest, and encourages government investment in a sport. This article analyses the distribution of gold medals, medals, medal points and top eight points amongst nations in table tennis from 1988 to 2016 at the Olympic Games and the World Championships respectively. A normalised version of the Herfindahl-Hirschman Index and a coefficient of variation are calculated for each nation's share of these performance indicators. The key findings are that China dominates both events, with successful female players being more dominant than their male counterparts. The competitive balance for gold medals has declined, whilst there is a trend towards improved competitive balance for top eight points for women, suggesting that more teams are featuring in the top eight (but not necessarily the top three) placings. This research has implications for the development of table tennis competitions. Compared to other racket sports, the issue of competitive imbalance in table tennis is particularly thorny, which threatens the long-term development of this sport. Accordingly, some measures are recommended for the International Olympic Committee and the International Table Tennis Federation to propel a more balanced development of international table tennis.
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Logro , Desempenho Atlético , Tênis , Atletas , China , Comportamento Competitivo , Feminino , Humanos , MasculinoRESUMO
Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.
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Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Fígado/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Feminino , Humanos , Incidência , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologiaRESUMO
The current study examined perceived event prestige as a mediator between sport involvement and sport participation behavioral intent. A total of 455 participants (M age = 28.6 yr., SD = 9.1) were recruited at the 2013 Standard Chartered Hong Kong Marathon. The findings indicated that a model in which perceived event prestige partially mediated the relationship between sport involvement and intent to return to the event was most representative of the data. While individuals with higher sport involvement were more likely to indicate an interest in continued participation, this relationship was strongest among those who perceived the event to be particularly prestigious. Thus, those who market mass participation sporting events should use strategies designed to emphasize the prestigious stature of the event and should employ measures to increase sport involvement among participants.
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Comportamento Competitivo , Intenção , Internacionalidade , Motivação , Corrida/psicologia , Desejabilidade Social , Adolescente , Adulto , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Inquéritos e Questionários , Adulto JovemRESUMO
The current study aimed to create a reliable and valid scale to measure athletes' perception of fairness regarding coaches' behaviors. The study utilized a scale development process, including three steps: (a) item generation, (b) scale development, and (c) scale evaluation. Both quantitative and qualitative approaches were utilized to generate items and achieve content validity. In developing the AJ scale, elite athletes from 29 different sports in Saudi Arabia were recruited for two rounds of data collection. The first data set (n = 279) was collected using an initial 35-item AJ scale developed from existing justice scales and interviews with elite athletes, while the second data collection (n = 503) was performed using a refined 12-item scale based on the analysis of the first data set. The results of ESEM showed an appropriate model fit for the scale with 12 items including four dimensions. In addition, the criterion validity was supported as each dimension of AJ was positively associated with athlete satisfaction. The newly developed AJ scale will help researchers measure perceived fairness toward coaches' behaviors based on the unique culture, climate, and environment that exists in the context of sports and explore the relationships between AJ and important attitudinal and behavioral outcomes that impact team performance.
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The structure and process of the graphene/Si heterojunction near-infrared photodetector were optimized to enhance the operating speed limit. The introduction of a well-designed structure improved the rise time from 12.6 µs to 115 ns, albeit at the expense of the responsivity, which decreased from 1.25 A W-1 to 0.56 A W-1. Similarly, the falling time was improved from 38 µs to 288 ns with a sacrifice in responsivity from 1.25 A W-1 to 0.29 A W-1, achieved through the introduction of Ge-induced defect-recombination centers within the well. Through a judicious well design and the introduction of recombination defect centers, the minimum pulse width could be improved from 50.6 µs to 435 ns, facilitating 2 MHz operation. This represents more than 100 times increase compared to previously reported graphene and graphene/Si hybrid photodetectors.
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BACKGROUND: This study investigated the trends of nontuberculous mycobacterial (NTM) isolates and the minimal inhibitory concentrations (MIC) of antimicrobial agents in Korea. METHODS: Data from 2013 to 2019 were collected from 69 medical institutions through 12 branches of the Korean Institute of Tuberculosis. NTM identification was conducted using the Advansure Mycobacteria Genoblot assay. The MIC of antibiotics against NTM species were measured using the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: Over seven years, 86,194 NTM identifications were requested, with an annual increase from 8034 in 2013-17,229 in 2019. The most frequently identified NTM species were M. intracellulare (33,467; 47.3%) and M. avium (19,818; 27.2%), followed by M. abscessus (6858; 9.4%) and M. massiliense (3156; 4.3%). Regarding the antimicrobial agents, imipenem exhibited the greatest difference in MIC between M. intracellulare and M. avium, whereas clarithromycin showed the most significant difference between M. abscessus and M. massiliense. No notable changes were observed in the annual MIC distribution of most antibacterial agents, except for clarithromycin in M. abscessus. CONCLUSIONS: The prevalence of NTM in Korea is gradually increasing, and follow-up studies on NTM isolates identified as the causative agents of infection are needed.
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Anti-Infecciosos , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Claritromicina/farmacologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , República da Coreia/epidemiologiaRESUMO
Athletes' perceptions of fairness toward coaching behaviors and decisions can play a crucial role in the development and maintenance of a strong coach-athlete relationship. However, scholars have given limited attention to athletes' perceptions of fairness. Therefore, the current study aimed to explore the relationship between coaches and athletes by applying the concept of organizational justice based on met-expectation theory. The primary objective of the study was to empirically examine the direct and indirect relationships between the met-expectation of athletic justice and athletes' attitudinal outcomes, such as athletic satisfaction and organizational commitment, through leader-member exchange (LMX). Data were collected from 289 elite athletes (238 men and 51 women) in the Kingdom of Saudi Arabia using a mixed-mode approach (paper-and-pencil and online surveys). The results of Structural Equation Modeling indicated that when athletes perceive that their expectations of fair treatment are met, it positively affects their satisfaction. This relationship is partially influenced by the quality of their relationship with their leader. However, the findings also suggest that while the athletes' met-expectation of athletic justice has a positive effect on their satisfaction, it does not have a significant impact on their commitment to the team. The findings provide insight about important work-related outcomes by validating the coach-athlete relationship based on met-expectation of athletic justice. The findings can be utilized to improve athlete satisfaction and commitment, leading to positive team and individual outcomes.
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Retrofitting retirement or existing fossil boiler with biomass is an important method of curbing electricity shortage and lowering the cost of modern power plants. However, the use of biomass combustion is hampered by operational problems, such as the resulting high unburned carbon, amount of bottom ash, and nitrogen oxide (NOx) release. In this study, we investigated the burning of pulverized biomass in a retrofitting boiler power plant using computational fluid dynamics of commercial software fluent ANSYS to determine the optimal combustion conditions. The objective of this study was to investigate a 125 MWe pulverized biomass boiler that was retrofitted from an anthracite down-fired boiler. The air distribution, including the influence of the secondary air ratio and the location of the burner standby, was evaluated. Key factors such as biomass ash mass at the hopper, char conversion, and high zone temperature relating to NOx formation/reduction were calculated. The adjustment of the secondary air ratio from 30 to 50% of the total air and the mass ash at the hopper significantly decreased to a low value at 247 kg/h and a high value of char conversion at 97.33% in case R (SA40%). The standard deviation temperature was 240 K at the BNR B-A level for case R, which was significantly lower than in other cases. This implies that the best mixing of air and biomass occurs in case R at 40%. Comparative analysis of the burner standby conditions showed that the NOx emission was similar at the boiler outlet (approximately 94-116 ppm). Burner A on standby, with a secondary air ratio of 40%, was used as the optimal case with the highest value of char conversion at 98.43%, the lowest bottom ash release of 204 kg/h, and a low-NOx emission of 106 ppm.
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Brassica napus, a globally important oilseed crop, is an allotetraploid hybrid species with two subgenomes originating from Brassica rapa and Brassica oleracea. The presence of two highly similar subgenomes has made the assembly of a complete draft genome challenging and has also resulted in natural homoeologous exchanges between the genomes, resulting in variations in gene copy number, which further complicates assigning sequences to correct chromosomes. Despite these challenges, high-quality draft genomes of this species have been released. Using third generation sequencing and assembly technologies, we generated a new genome assembly for the synthetic B. napus cultivar Da-Ae. Through the use of long reads, linked-reads, and Hi-C proximity data, we assembled a new draft genome that provides a high-quality reference genome of a synthetic B. napus. In addition, we identified potential hotspots of homoeologous exchange between subgenomes within Da-Ae, based on their presence in other independently derived lines. The occurrence of these hotspots may provide insight into the genetic rearrangements required for B. napus to be viable following the hybridization of B. rapa and B. oleracea.
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Brassica napus , Brassica rapa , Brassica napus/genética , Genoma de Planta , Brassica rapa/genéticaRESUMO
A p-type ternary logic device with a stack-channel structure is demonstrated using an organic p-type semiconductor, dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT). A photolithography-based patterning process is developed to fabricate scaled electronic devices with complex organic semiconductor channel structures. Two layers of thin DNTT with a separation layer are fabricated via the low-temperature deposition process, and for the first time, p-type ternary logic switching characteristics exhibiting zero differential conductance in the intermediate current state are demonstrated. The stability of the DNTT stack-channel ternary logic switch device is confirmed by implementing a resistive-load ternary logic inverter circuit.
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Current guidelines recommend delaying noncardiac surgery for 6 months after drug eluting stent implantation. However, this recommendation is largely based on limited evidence and various event definitions. Whether early surgery within 6 months of coronary stent implantation increases myocardial injury in patients with normal preoperative high-sensitivity cardiac troponin I (hs-cTnI) has not yet been investigated. This retrospective study assessed patients who received coronary stent implantation and underwent noncardiac surgery (vascular, abdominal, or thoracic) between 2010 and 2017 with normal preoperative hs-cTnI (n = 186). Patients were divided into early (within 6 months of PCI) and late (after 6 months of PCI) groups. The primary endpoint was the incidence of myocardial injury as diagnosed by hs-cTnI within 3 days post-operation. The secondary outcomes were myocardial infarction, stent thrombosis, emergent coronary revascularization, major bleeding (bleeding requiring transfusion or intracranial bleeding), stroke, renal failure, heart failure, or death within 30 days post-operation. Inverse probability treatment weighting (IPTW) was carried out to adjust for the intergroup baseline differences. Myocardial injury occurred in 28.6% (8/28) and 27.8% (44/158) of the early and late groups, respectively, with no difference between groups (odds ratio [OR] 1.067, 95% confidence interval [CI] 0.404, 2.482; p = 0.886). Secondary outcomes did not differ between the groups. IPTW analysis also showed no differences in myocardial injury and secondary outcomes between the groups. In conclusion, early surgery within 6 months after coronary stent implantation did not increase the incidence of myocardial injury in patients with normal preoperative hs-cTnI.
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Introduction: The current study investigated the impacts of autocratic and democratic leadership styles on the coach-athlete relationship, athletes' motivations, and athlete satisfaction. Methods: Survey data were collected from 298 student-athletes (male = 157; 52.7%, female = 141; 47.3%) from 20 different Chinese collegiate sports. The Structural Equation Model was used to test the hypothesized model. Results: The results indicated democratic leadership had a direct positive influence on the coach-athlete relationship, while autocratic leadership had no direct effect. Both leadership styles did not influence autonomous motivation. The coach-athlete relationship, meanwhile, had a full mediation effect between democratic leadership and athletes' motivation and satisfaction. In addition, autonomous motivation had a partial mediation effect between the coach-athlete relationship and athlete satisfaction. Discussion: Ultimately, the findings of the current study underscore the need for coaches and administrators to understand the impact of different leadership styles and highlight the importance of democratic leadership in improving athletes' psychological outcomes.
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Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell-cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.
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Antineoplásicos , Neoplasias do Colo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Transdução de SinaisRESUMO
P-type ternary switch devices are crucial elements for the practical implementation of complementary ternary circuits. This report demonstrates a p-type ternary device showing three distinct electrical output states with controllable threshold voltage values using a dual-channel dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]-thiophene-graphene barristor structure. To obtain transfer characteristics with distinctively separated ternary states, novel structures called contact-resistive and contact-doping layers were developed. The feasibility of a complementary standard ternary inverter design around 1 V was demonstrated using the experimentally calibrated ternary device model.
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BACKGROUND: The biological function of mesenchymal stem-like cells (MSLCs), a type of stromal cells, in the regulation of the tumour microenvironment is unclear. Here, we investigated the molecular mechanisms underlying extracellular matrix (ECM) remodelling and crosstalk between MSLCs and glioblastomas (GBMs) in tumour progression. METHODS: In vitro and in vivo co-culture systems were used to analyze ECM remodelling and GBM infiltration. In addition, clinical databases, samples from patients with GBM and a xenografted mouse model of GBM were used. RESULTS: Previous studies have shown that the survival of patients with GBM from whom MSLCs could be isolated is substantially shorter than that of patients from whom MSLCs could not be isolated. Therefore, we determined the correlation between changes in ECM-related gene expression in MSLC-isolatable patients with that in MSLC non-isolatable patients using gene set enrichment analysis (GSEA). We found that lysyl oxidase (LOX) and COL1A1 expressions increased in MSLCs via GBM-derived clusters of differentiation 40 ligand (CD40L). Mechanistically, MSLCs are reprogrammed by the CD40L/CD40/NFκB2 signalling axis to build a tumour infiltrative microenvironment involving collagen crosslinking. Importantly, blocking of CD40L by a neutralizing antibody-suppressed LOX expression and ECM remodelling, decreasing GBM infiltration in mouse xenograft models. Clinically, high expression of CD40L, clusters of differentiation 40 (CD40) and LOX correlated with poor survival in patients with glioma. This indicated that GBM-educated MSLCs promote GBM infiltration via ECM remodelling in the tumour microenvironment. CONCLUSION: Our findings provide mechanistic insights into the pro-infiltrative tumour microenvironment produced by GBM-educated MSLCs and highlight a potential therapeutic target that can be used for suppressing GBM infiltration.