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BACKGROUND: This meta-analysis assessed the efficacy of dual-energy computed tomography (DECT) in the diagnosis of anterior cruciate ligament (ACL) injuries. METHODS: The literature search was performed up to December 8, 2023, and included a comprehensive examination of several databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP. Diagnostic metrics sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and a summary receiver operating characteristic (SROC) were determined using a bivariate model analysis. Heterogeneity within the data was explored through subgroup analyses, which considered variables including geographical region, use of magnetic resonance imaging (MRI), arthroscopy, and study design. RESULTS: The analysis included ten studies encompassing 544 patients. DECT demonstrated substantial diagnostic utility for ACL injuries of the knee, with a sensitivity of 0.91 (95% confidence interval [CI]: 0.88-0.94), a specificity of 0.90 (95% CI: 0.81-0.95), a PLR of 9.20 (95% CI: 4.50-19.00), a NLR of 0.10 (95% CI: 0.06-0.14), a DOR of 97.00 (95% CI: 35.00-268.00), and an area under the curve (AUC) of 0.95 (95% CI: 0.93-0.97). The subgroup analyses consistently showed high diagnostic precision for ACL injuries across Asian population (sensitivity: 0.91, specificity: 0.91, PLR: 9.90, NLR: 0.09, DOR: 105.00, AUC: 0.96), in MRI subgroup (sensitivity: 0.85, specificity: 0.94, PLR: 9.57, NLR: 0.18, DOR: 56.00, AUC: 0.93), in arthroscopy subgroup (sensitivity: 0.92, specificity: 0.89, PLR: 8.40, NLR: 0.09, DOR: 94.00, AUC: 0.95), for prospective studies (sensitivity: 0.92, specificity: 0.88, PLR: 7.40, NLR: 0.09, DOR: 78.00, AUC: 0.95), and for retrospective studies (sensitivity: 0.91, specificity: 0.93, AUC: 0.93). CONCLUSION: DECT exhibits a high value in diagnosing ACL injuries. The significant diagnostic value of DECT provides clinicians with a powerful tool that enhances the accuracy and efficiency of diagnosis and optimizes patient management and treatment outcomes.
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Lesiones del Ligamento Cruzado Anterior , Tomografía Computarizada por Rayos X , Humanos , Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Traumatismos de la Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Sensibilidad y EspecificidadRESUMEN
Electrocatalysis is a crucial method for achieving global carbon neutrality, serving as an essential means of energy conversion, and electrocatalyst is crucial in the process of electrocatalysis. Because of the abundant active sites, the multi-component synergistic effect of high-entropy materials has a wide application prospect in the field of electrocatalysis. Moreover, due to the special structure of high-entropy materials, it is possible to obtain almost continuous adsorption energy distribution by regulating the composition, which has attracted extensive attention of researchers. This paper reviews the properties and types of high-entropy materials, including alloys and compounds. The synthesis strategies of high-entropy materials are systematically introduced, and the solid phase synthesis, liquid-phase synthesis, and gas-phase synthesis are classified and summarized. The application of high-entropy materials in electrocatalysis is summarized, and the promotion effect of high-entropy strategy in various catalytic reaction processes is summarized. Finally, the current progress of high-entropy materials, the problems encountered, and the future development direction are reviewed. It is emphasized that the strategy of high flux density functional theory calculation guiding high-entropy catalyst design will be of great significance to electrocatalysis.
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PURPOSE: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). METHODS: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS). RESULTS: Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. CONCLUSION: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Purinas , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/análisis , Persona de Mediana Edad , Adulto , Purinas/administración & dosificación , Purinas/efectos adversos , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/análisis , Receptores de Progesterona/metabolismo , Premenopausia , Supervivencia sin Progresión , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidoresRESUMEN
BACKGROUND: Heterosexual contact is the primary mode of HIV transmission in China and commercial sex is thought to play a crucial role in China's epidemic. Female sex workers (FSWs) in China tend to be either brothel-based (BSWs) or street-based (SSWs), but few studies have investigated the differences between these important segments of this difficult-to-reach, high-risk population. Our aim was to explore the differences between SSWs and BSWs in terms of socio-demographic characteristics, sexual and risky practices, HIV/STI-related knowledge, health services, HIV/STI prevalence and other aspects. METHODS: A cross-sectional survey was conducted in Yunnan Province of China in partnership with a local FSW-friendly non-governmental organization. Face-to-face interviews using a structured questionnaire were conducted to collect data on socio-demographic characteristics, sex work history, sexual behaviours, HIV/STI-related knowledge, HIV testing history, and healthcare services uptake. Blood samples were taken for HIV and syphilis testing, and urine samples for gonorrhea and chlamydia testing. Descriptive statistics were used to evaluate differences between SSWs and BSWs. RESULTS: A total of 185 BSWs and 129 SSWs were included in the study. SSWs were older and less educated, had more dependents and more clients, lower condom use and accessed fewer healthcare services. Moreover, 37.2% of SSWs and 24.9% of BSWs were found to have HIV/STI infection. Unfortunately, the awareness related to STIs was relatively low in both groups, especially SSWs. CONCLUSIONS: Our study provides evidence that confirms the disproportionately high vulnerability of SSWs to HIV and other STIs, underscoring the urgent need for the Chinese health and public health sectors to prioritize outreach to SSWs. Awareness and educational programs, condom distribution, testing and health check-ups should be included in a comprehensive strategy for HIV/STI prevention in this high-risk population.
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Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud , Asunción de Riesgos , Trabajadores Sexuales , Conducta Sexual , Enfermedades de Transmisión Sexual , Humanos , Femenino , Trabajadores Sexuales/estadística & datos numéricos , Trabajadores Sexuales/psicología , China/epidemiología , Estudios Transversales , Adulto , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Enfermedades de Transmisión Sexual/epidemiología , Prevalencia , Conducta Sexual/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Encuestas y Cuestionarios , Adulto Joven , Factores Socioeconómicos , Trabajo Sexual/estadística & datos numéricos , Adolescente , Condones/estadística & datos numéricos , Persona de Mediana EdadRESUMEN
Coronavirus disease 2019 (COVID-19) was extraordinarily harmful, with high rates of infection and hospitalization. This study aimed to evaluate the impact of COVID-19 vaccination status and other factors on hospitalization and disease severity, using data from Nagasaki Prefecture, Japan. Confirmed cases of COVID-19 infection with vaccination status were included and the differences in characteristics between different vaccination statuses, hospitalization or not, and patients with varying levels of disease severity were analyzed. Furthermore, logistic regression was used to calculate odds ratio (ORs) and 95% confidence intervals (CI) to evaluate the association of various factors with hospitalization and disease severity. From March 14, 2020 to August 31, 2022, 23,139 patients were unvaccinated 13,668 vaccinated the primary program with one or two doses, and 4,575 completed the booster. Vaccination reduced the risk of hospitalization with an odd ratio of 0.759 (95% CI: 0.654-0.881) and the protective effect of completed booster vaccination was more pronounced (OR: 0.261, 95% CI: 0.207-0.328). Similarly, vaccination significantly reduced the risk of disease severity (vaccinated primary program: OR: 0.191, 95% CI: 0.160-0.228; completed booster vaccination: OR: 0.129, 95% CI: 0.099-0.169). Overall, unvaccinated, male, elderly, immunocompromised, obese, and patients with other severe illness factors were all risk factors for COVID-19-related hospitalization and disease severity. Vaccination was associated with a decreased risk of hospitalization and disease severity, and highlighted the benefits of completing booster.
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COVID-19 , Anciano , Humanos , Masculino , Japón/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Gravedad del Paciente , Hospitalización , VacunaciónRESUMEN
Bupivacaine, a common amide local anesthetic, can provide effective analgesia or pain relief but can also cause neurotoxicity, which remains a mounting concern in clinic and animal care. However, the precise underlying mechanisms have not been fully elucidated. A natural compound, notoginsenoside R1 (NG-R1) has been reported to exhibit a neuroprotective role in stress conditions. In this study, we explored the function and mechanism of NG-R1 in alleviating bupivacaine-induced neurotoxicity in mouse hippocampal neuronal (HT-22) and mouse neuroblastoma (Neuro-2a) cell lines. Our results exhibited that NG-R1 treatment can significantly rescue the decline of cell survival induced by bupivacaine. Tunel staining and western blotting showed that NG-R1 could attenuate BPVinduced cell apoptosis. Besides, we focused on Mcl1 as a potential target as it showed opposite expression tendency in response to NG-R1 and bupivacaine exposure. Mcl1 knockdown blocked the inhibitory effect of NG-R1 on cell apoptosis against bupivacaine treatment. Intriguingly, we found that NG-R1 can upregulate Mcl1 transcription by activating Stat3 and promote its nuclear translocation. In addition, NG-R1 can also promote Jak1 phosphorylation and docking analysis provide a predicted model for interaction between NG-R1 and phosphorylated Jak1. Taken together, our results demonstrated that NG-R1 can attenuate bupivacaine induced neurotoxicity by activating Jak1/Stat3/Mcl1 pathway.
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Ginsenósidos , Síndromes de Neurotoxicidad , Ratones , Animales , Bupivacaína/toxicidad , Ginsenósidos/farmacología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/prevención & control , Síndromes de Neurotoxicidad/metabolismo , Línea Celular , ApoptosisRESUMEN
Interface engineering is a method of enhancing catalytic activity while maintaining a material's surface properties. Thus, we explored the interface effect mechanism via a hierarchical structure of MoP/CoP/Cu3P/CF. Remarkably, the heterostructure MoP/CoP/Cu3P/CF demonstrates an outstanding overpotential of 64.6 mV at 10 mA cm-2 with a Tafel slope of 68.2 mV dec-1 in 1 M KOH. DFT calculations indicate that the MoP/CoP interface in the catalyst exhibited the most favorable H* adsorption characteristics (-0.08 eV) compared to the pure phases of CoP (0.55 eV) and MoP (0.22 eV). This result can be attributed to the apparent modulation of electronic structures within the interface domains. Additionally, the CoCH/Cu(OH)2/CFâMoP/CoP/Cu3P/CF electrolyzer demonstrates excellent overall water splitting performance, achieving 10 mA cm-2 in 1 M KOH solution with a modest voltage of only 1.53 V. This electronic structure adjustment via interface effects provides a new and efficient approach to prepare high-performance hydrogen production catalysts.
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Heteroatoms Fe, F co-doped NiO hollow spheres (Fe, F-NiO) are designed, which simultaneously integrate promoted thermodynamics by electronic structure modulation with boosted reaction kinetics by nano-architectonics. Benefiting from the electronic structure co-regulation of Ni sites by introducing Fe and F atoms in NiO , as the rate-determined step (RDS), the Gibbs free energy of OH* intermediates (ΔGOH* ) for Fe, F-NiO catalyst is significantly decreased to 1.87 eV for oxygen evolution reaction (OER) compared with pristine NiO (2.23 eV), which reduces the energy barrier and improves the reaction activity. Besides, densities of states (DOS) result verifies the bandgap of Fe, F-NiO(100) is significantly decreased compared with pristine NiO(100), which is beneficial to promote electrons transfer efficiency in electrochemical system. Profiting by the synergistic effect, the Fe, F-NiO hollow spheres only require the overpotential of 215 mV for OER at 10 mA cm-2 and extraordinary durability under alkaline condition. The assembled Fe, F-NiO||Fe-Ni2 P system only needs 1.51 V to reach 10 mA cm-2 , also exhibits outstanding electrocatalytic durability for continuous operation. More importantly, replacing the sluggish OER by advanced sulfion oxidation reaction (SOR) not only can realize the energy saving H2 production and toxic substances degradation, but also bring additional economic benefits.
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Background: This study aimed to survey the attitudes toward COVID-19 vaccines and their acceptability among the Japanese public as soon as the United States Food and Drug Administration (FDA) authorized vaccines and their rollouts started around the world. Methods: An anonymous cross-sectional survey was conducted in Japan between 4 January and 5 March 2021. A questionnaire was administered to evaluate attitudes toward COVID-19 vaccines according to demographic characteristics, vaccine characteristics, and vaccine production. Results: A total of 1037 completed responses were received. More than half (63.5%) of the participants responded positively (extremely likely/likely) toward COVID-19 vaccines. The highest acceptance to be vaccinated was discovered among the youngest age group. As expected, participants who had never delayed acceptance or refused the vaccine in their history of vaccination had a significantly higher willingness to be vaccinated against COVID-19 (p < 0.001). Females (OR = 2.66, 95% CI: 1.99−3.58) and participants who had ever delayed acceptance or refuse the vaccine (OR = 3.49, 95% CI: 2.42−5.05) had higher odds of COVID-19 vaccine hesitancy. Participants with a postgraduate degree (OR = 0.64, 95% CI: 0.40−1.00) presented the highest willingness to be vaccinated against COVID-19. More than two-thirds (72.9%, 95% CI: 70.4%−75.8%) of the participants did not mind a booster dose required following primary vaccination. A total of 63.2% (95% CI: 60.0%−66.0%) of the participants only accepted a nearly 90% effective or above vaccine at preventing COVID-19. At the same, 86.4% (95% CI: 84.4%−88.4%) of the participants reported only accepting a vaccine with minor side effects. Conclusions: The moderate levels of COVID-19 vaccine acceptance found in the early phase of the pandemic demonstrate that it is important to improve the implementation of effective management for vaccine promotion and the acceptability of the vaccine to slow or delay transmission.
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First-principles calculations were performed to investigate the site preference of alloying elements, and the effect of alloying elements on stability, electronic structure and magnetism of Ni3P-type Fe3B. The calculated energies suggested that all studied compounds are thermodynamically stable while it is relatively difficult to synthesize the (Fe2.875,Cu0.125)B, (Fe2.875,W0.125)B and (Fe2.875,Nb0.125)B. The (Fe2.875,W0.125)B is the most stable compound from the view of cohesive energy. Mn element prefers to occupy the Fe2 site, whereas the others are more likely to reside in the Fe1 site. It can be found from the electronic structures that the DOSs of both Fe3B and alloyed Fe3B are dominated by Fe-d states, and all the compounds mainly contain Fe-B covalent bond, Fe-Fe covalent bond and Fe-Fe metallic bond. Based on the magnetic moments (Ms) results, it can be known that the Fe3B, (Fe2.875,Mn0.125)B, (Fe2.875,Co0.125)B, (Fe2.875,Ni0.125)B and (Fe2.875,Cu0.125)B are ferromagnetic compounds, whereas the others are ferrimagnetic compounds. Only Mn and Co are able to enhance the magnetism of Fe3B. Moreover, Mn is the most favorable candidate for improving the magnetic properties of Fe3B among the alloying elements. These results can be used to guide the composition design and performance optimization of magnetic materials containing Fe3B with Ni3P-type structure.
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Objectives: The first objective of this study was to probe the effects of genkwanin (GKA) on osteoclast. The second goal of this study was to study whether GKA can protect lipopolysaccharide (LPS) and ovariectomized (OVX) induced bone loss. Materials and Methods: Various concentrations of GKA (1 and 10 mg/kg) were injected into mice. Different concentrations of GKA (1 and 5 µM) were used to detect the effects of GKA on osteoclast and osteoblast. Key Findings: GKA attenuated the osteoclast differentiation promoted by RANKL and expression of marker genes containing c-fos, ctsk as well as bone resorption related gene Trap and to the suppression of MAPK signaling pathway. In addition, GKA induced BMMs cell apoptosis in vitro. Moreover, GKA prevented LPS-induced and ovariectomized-induced bone loss in mice. Conclusion: Our research revealed that GKA had a potential to be an effective therapeutic agent for osteoclast-mediated osteoporosis.
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Biochar is a widely used antecedent for improving biohydrogen production. However, little is known about the impact of biochar-derived dissolved organic matter (DOM) on the performance of fermentative bio-H2 production. Herein, we evaluated the impact of biochar-derived DOM on the fermentation performance of hydrogen-producing microflora. The pyrolysis temperature of biochar affected the DOM composition, with lower pyrolysis temperatures showing more serious inhibition on H2 accumulation. When biochar was pyrolyzed at 500 °C, DOM prolonged the fermentation period and decreased H2 production from 1330.41 mL L-1 to 1177.05 mL L-1 compared to the control group. The xylose utilization in mixed substrate decreased from 29.72% to 26.41%, which is not favorable for practical applications where lignocellulosic biomass is used as a substrate. Otherwise, DOM caused a 6% reduction in microbial biomass accumulation and less soluble metabolites formation. The potential mechanism of DOM inhibiting biohydrogen production was verified by identifying an increase in reactive oxygen species (ROS) level (178.2%) and the microbial community shifted to containing fewer hydrogen-producing strains. The finding prompts a more precise design of biochar applications in fermentation systems to alleviate the potential hazards and maximum the fermentation performance, not limited to fermentative hydrogen production system.
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Materia Orgánica Disuelta , Carbón Orgánico/química , Fermentación , HidrógenoRESUMEN
Microplastics (MPs) and nanoplastics (NPs), as emerging pollutants, are frequently detected in wastewater treatment plants. However, studies comparing the effects of MPs versus NPs on nitrogen removal by activated sludge are rarely reported. Here, the responses of nitrogen removal performance, microbial community and functional genes to MPs and NPs in sequencing batch reactors were investigated. Results revealed that MPs (10 and 1000 µg/L) had no effects on nitrogen removal. While upon exposure to NPs, although low concentration (10 µg/L) of NPs showed no remarkable influence on nitrogen removal, high level (1000 µg/L) of NPs decreased NH4+-N removal efficiency by 24.48% and caused accumulation of NO3--N and NO2--N. These inhibitory probably due to the acute toxicity of NPs to activated sludge, which was reflected by the increasing reactive oxygen species generation and lactate dehydrogenase release. The toxic effects of NPs further declined the relative abundance of nitrifiers (e.g., Nitrospira) and denitrifiers (e.g., Dechloromonas). These negative effects, accompanied by a decrease in abundance of amoA and nxrA genes related to nitrification (30.01% and 65.24% of control) and narG, nirK and nirS genes associated with denitrification (78.59%, 61.39%, and 86.17% of control), directly illustrated the attenuate phenomenon observed in nitrogen removal.
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Microbiota , Microplásticos , Reactores Biológicos , Desnitrificación , Microbiota/genética , Microplásticos/toxicidad , Nitrificación , Nitrógeno/análisis , Plásticos , Aguas del AlcantarilladoRESUMEN
Microplastics (MPs), nanoplastics (NPs) and antibiotic resistance genes (ARGs), as emerging pollutants, have been frequently detected in wastewater treatment plants. However, the behavior of phosphorus and ARGs under MP and NP (MP/NP) pressure in biological phosphorus removal (BPR) system is still unknown. This study investigated the effects of MP/NPs on phosphorus removal and ARGs propagation in BPR system. Results showed that MP/NPs had no influence on phosphorus removal, but significantly promoted the amplification of tetracycline resistance genes (TRGs). Moreover, the TRG abundance were more facilitated by MPs than NPs, and the TRGs of efflux pump and enzymatic modification mechanism were mainly enriched. Meanwhile, MP/NPs increased the transmission risk of multiple resistance genes and mobile gene elements (MGEs). Microbial communities demonstrated the main polyphosphate accumulating organisms shifted from Acinetobacter to unclassified_Gammaproteobacteria, which explained why phosphorus removal efficiency was unaffected with MP/NP addition. Correlation analysis revealed there was no significant correlation between ARGs and MGEs (intI1 and intI2), but the abundances of potential hosts of ARGs were significantly increased with MP/NP addition, implying microbial community structure changes rather than gene horizontal transfer was the main factor promoting ARG propagation under MP/NP pressure.
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Antibacterianos , Microplásticos , Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Genes Bacterianos , Fósforo , PlásticosRESUMEN
PURPOSE: CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients. METHODS: Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint. RESULTS: In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population. CONCLUSION: The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER: NCT02941926 (Registered 2016).
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama Masculina , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Humanos , Letrozol/uso terapéutico , Masculino , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Purinas , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
BACKGROUND: The phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Outcomes were investigated in the following subgroups: central nervous system (CNS) metastases, prior chemotherapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, and visceral metastases plus prior chemotherapy for advanced disease or ECOG PS 2. PATIENTS AND METHODS: Patients with HR+, HER2- ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous). Primary endpoint was safety/tolerability, assessed via occurrence of adverse events (AEs); key secondary endpoints included time to progression (TTP), overall response rate, and clinical benefit rate. RESULTS: 51 patients had CNS metastases, 194 received prior chemotherapy for advanced disease, 112 had ECOG PS 2, 146 had visceral metastases plus prior chemotherapy, and 77 had visceral metastases plus ECOG PS 2. Safety results were consistent with those in the overall CompLEEment-1 population; no new safety concerns were identified. The AE profile was manageable with low rates of discontinuations due to AEs. TTP in patients with CNS metastases was consistent with the overall study population and shorter for other patient subgroups. Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population. CONCLUSION: These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials.
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Neoplasias de la Mama , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Femenino , Hormonas/uso terapéutico , Humanos , Letrozol , Purinas , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. CONCLUSION: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2- ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926.
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Neoplasias de la Mama , Calidad de Vida , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Letrozol/uso terapéutico , Purinas , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de ProgesteronaRESUMEN
BACKGROUND: Newts have impressive regenerative capabilities, but it remains unclear about the role of epigenetic regulation in regeneration process. We herein investigated histone modifications in newt tail tissue cells following amputation. METHODS AND RESULTS: Iberian ribbed male newts (6-8 months old) were suffered to about 1.5 cm length of amputation of their tails for initiating regeneration process, and the residual stump of tail tissues was collected for immunohistochemical analysis 3 days later. Compared to the tissue cells of intact tails, c-kit-positive stem cells and PCNA-positive proliferating cells were significantly higher in tails suffered to amputation (P < 0.001). Amputation also significantly induced the acetylation of H3K9, H3K14, and H3K27 in cells of the tails with amputation (P < 0.001), but did not significantly change the methylation of H3K27 (P = 0.063). CONCLUSION: These results suggest that epigenetic regulation likely involves in newt tail regeneration following amputation.
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A novel pretreatment using NaOH/Urea (NU) solution at outdoor cold-winter conditions was developed to enhance the enzymatic saccharification and hythane production from rice straw (RS). Results revealed that the reducing sugar conversion of RS reached 90.02% after NU pretreatment at outdoor freezing temperature. Chemical composition analysis showed that the lignin removal was up to 62.74% with cellulose and hemicellulose loss of 0.56% and 18.87% after 3%-6% NU pretreatment at 100% solid loading for 3 months. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis confirmed that the surface of pretreated RS exposed more cellulose and hemicellulose due to the disruption of resistant structure of lignocellulose. Subsequently, the enzymatic hydrolysate of pretreated RS was used as substrate to produce hythane by two-stage fermentation with the yield of 225.1 mL H2/g sugar and 112.8 mL CH4/g sugar. The energy conversion efficiency of hythane fermentation attained 10.4%, which was 22.8% and 190.5% higher than that for single H2 and CH4 fermentation. These results demonstrated that NU pretreatment at outdoor cold-winter conditions was practically and feasible way for improved hythane recovery from lignocellulosic biomass.