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INTRODUCTION: Polydrug use in the context of chemsex is commonplace among gay, bisexual, and other men-who-have-sex-with-men (GBMSM). This study aimed to examine the differences in experiences of physical, social, and psychological harms, as well as mental ill-health among GBMSM who use different combinations of methamphetamine and gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL) during chemsex. METHOD: Adult GBMSM participants who had experience of chemsex in the past 12 months participated in a cross-sectional online survey in Taiwan and self-reported their sociodemographic background, sexual behaviours, mental health, and experiences of harm following a chemsex session. We used univariable and multivariable logistic regression to assess the different experiences of harm and mental ill-health among GBMSM who engaged in chemsex without using methamphetamine, used methamphetamine but not GHB/GBL, and who used both drugs. RESULTS: Out of 510 participants who completed all items included in the analysis, 24.1% engaged in chemsex without using methamphetamine, 36.9% used methamphetamine but not GHB/GBL, and 39.0% used both drugs. Eighty five percent of men who used both methamphetamine and GHB/GBL reported at least one kind of social harm after a chemsex session, such as missing dates or appointments, or appearing "high" at work, followed by used methamphetamine but not GHB/GBL (69.7%) and those without using methamphetamine (37.4%). After controlling for polydrug and frequency of drug use in the multivariable logistic regression, those who used methamphetamine but not GHB/GBL and those who used both drugs were more likely to report experiencing physical and psychological harms compared to those who did not use methamphetamine (p < 0.003). CONCLUSION: GBMSM who used both methamphetamine and GHB/GBL in a chemsex context were more likely to report experience of harms than those who only used a single chemsex drug or engaged in chemsex without methamphetamine or GHB/GBL. Harm reduction should focus on both preventing HIV and STI transmission and on minimising psychosocial harm to GBMSM, with varying impacts depending on drug use.
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4-Butirolactona , Metanfetamina , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Adulto , Taiwan/epidemiologia , Metanfetamina/efeitos adversos , 4-Butirolactona/efeitos adversos , Estudos Transversais , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adulto Jovem , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Hidroxibutiratos , Pessoa de Meia-Idade , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Comportamento Sexual/psicologiaRESUMO
Ultrahigh-dose-rate therapy, also known as FLASH radiotherapy (RT), is an emerging technique that is garnering significant interest in cancer treatment due to its potential to revolutionize therapy. This method can achieve comparable tumor control to conventional-dose-rate RT while offering the enhanced protection of normal tissue through the FLASH-sparing effect. This innovative technique has demonstrated promising results in preclinical studies involving animals and cell lines. Particularly noteworthy is its potential application in treating head and neck (HN) cancers, especially in patients with challenging recurrent tumors and reirradiation cases, where the toxicity rates with conventional radiotherapy are high. Such applications aim to enhance tumor control while minimizing side effects and preserving patients' quality of life. In comparison to electron or photon FLASH modalities, proton therapy has demonstrated superior dosimetric and delivery characteristics and is a safe and effective FLASH treatment for human malignancies. Compared to the transmission proton FLASH, single-energy Bragg peak FLASH is a novel delivery method that allows highly conformal doses to targets and minimal radiation doses to crucial OARs. Proton Bragg peak FLASH for HN cancer has still not been well studied. This review highlights the significance of proton FLASH in enhancing cancer therapy by examining the advantages and challenges of using it for HN cancer reirradiation.
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BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) has become the dominant keratoplasty procedure. However, the impact of high intraocular pressure (IOP) on the DMEK prognosis in patients without preexisting glaucoma remains unknown. METHODS: Non-glaucoma patients who underwent DMEK in Peking University Third Hospital between July 2017 and March 2023 with a follow-up duration longer than six months were included in this cohort study. Eyes were divided into three groups: Group A) normal IOP; Group B) early IOP elevation (IOP ≥ 30 mmHg or increase of more than 10 mmHg from baseline within 3 days); Group C) intermediate-term IOP elevation (IOP > 21 mmHg or increase of more than 10 mmHg from baseline after 14 days postoperatively). The postoperative IOP, endothelial cell density (ECD), central corneal thickness (CCT), best-corrected visual acuity (BCVA) and rate of graft failure were analysed. RESULTS: Forty-seven eyes from forty-seven patients were included. Thirty-seven eyes were bullous keratopathy, and ten were Fuchs endothelial corneal dystrophy. Twenty-five eyes were classified as Group A, six as Group B and sixteen as Group C. The mean peak IOP was 49.00 ± 4.99 mmHg in Group B eyes and 31.89 ± 11.75 mmHg in Group C eyes. The postoperative BCVA significantly differed from that before surgery (P < 0.001). The ECD at 3 months after surgery in eyes with intermediate-term IOP elevation was lower (P = 0.032). Four eyes with intermediate-term IOP elevation developed graft failure (P = 0.001). CONCLUSIONS: Intermediate-term IOP elevation after DMEK may reduce the graft ECD and lead to graft failure within six months after surgery. However, early IOP elevation had no effect on the prognosis. Careful IOP monitoring and intermediate-term IOP management should be conducted for graft protection.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Endotélio Corneano , Glaucoma , Pressão Intraocular , Acuidade Visual , Humanos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Feminino , Masculino , Pressão Intraocular/fisiologia , Idoso , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Endotélio Corneano/patologia , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Estudos Retrospectivos , Complicações Pós-Operatórias , Idoso de 80 Anos ou mais , Seguimentos , Sobrevivência de Enxerto/fisiologia , Contagem de Células , Hipertensão Ocular/fisiopatologia , Período Pós-Operatório , Adulto , Doenças da Córnea/cirurgia , Doenças da Córnea/fisiopatologia , Perda de Células Endoteliais da Córnea/diagnóstico , Perda de Células Endoteliais da Córnea/fisiopatologiaRESUMO
To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)-and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5-40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart Dmean between CBCT and DIBH-CT plans was 0.95 (0.88-1.00) and 100% (70.6-119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI.
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Suspensão da Respiração , Tomografia Computadorizada de Feixe Cônico , Estudos de Viabilidade , Mastectomia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama , Humanos , Feminino , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias Unilaterais da Mama/cirurgia , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Adulto , Radiometria , Inalação , Pulmão/efeitos da radiação , Pulmão/diagnóstico por imagem , Estudos Prospectivos , Coração/efeitos da radiação , Coração/diagnóstico por imagemRESUMO
Objective: This study aims to assess the early to mid-term clinical efficacy of expanded polytetrafluoroethylene (ePTFE) trileaflet valved conduits in pediatric right ventricular outflow tract reconstruction for congenital heart disease. Methods: We conducted a retrospective analysis of pediatric patients who underwent right ventricular outflow tract (RVOT) reconstruction using ePTFE trileaflet valved conduits at two cardiac centers in China, between January 2017 and June 2023. The main assessment criterion was the functionality of the prosthetic pulmonary valve conduit. Results: A total of 162 pediatric patients were included, with follow-up periods ranging from 0.1 to 5 years post-discharge, and a median follow-up duration of 1 year (interquartile range: 1, 2). Three patients (1.9%) required re-operation due to conduit obstruction. During follow-up, pulmonary valve flow velocities were recorded as <3â m/s in 134 patients (82.7%), between 3 and 4â m/s in 24 patients (14.8%), and >4â m/s in 4 patient (2.5%). Mild pulmonary valve regurgitation was noted in 148 patients (91.4%), and moderate pulmonary valve regurgitation was noted in 14 patients (8.6%), with no instances of more than moderate pulmonary valve regurgitation. Conclusion: The ePTFE trileaflet valved conduit, known for its accessibility and simplicity in manufacturing, demonstrates favorable early to mid-term clinical outcomes in pediatric RVOT reconstruction.
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A novel approach for depositing the giant molecule acceptor (GMA) at the donor-acceptor interface to enhance the efficiency and stability of organic photovoltaic (OPV) devices through a designed interface-enhanced layer-by-layer device fabrication protocol is proposed. The giant molecule acceptor DQx-Ph is mixed with the polymer donor in the bottom layer to form a polymer donor fibril phase and a mixed phase, followed by subsequent deposition of the main acceptor L8-BO. The L8-BO solution swells the bottom layer and alters the localized morphology of the mixing phase, introducing L8-BO fibrillar crystallization and pushing DQx-Ph giant molecules outwards to the fibril interfaces. Through this approach, the localized morphology and optoelectronic property of the bulk heterojunction are optimized. This configuration maintains the superior transport properties of L8-BO while integrating the high open-circuit voltage characteristics of DQx-Ph. Additionally, exciton dissociation and charge generation are simultaneously enhanced, with suppressed energy losses. A power conversion efficiency of 19.9% with improved operational stability is achieved, underscoring the importance of GMA interface jamming in advancing OPV technology. This study provides new insights into the development of ancillary OPV materials to overcome the critical limitations in OPV, revealing innovative approaches for photovoltaic technologies.
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BACKGROUND: Oncoplastic breast-conserving surgery (OBCS) improves satisfaction in patients who would fare otherwise sub-optimal cosmetic outcome, while brings challenge in tumor-bed identification during adjuvant radiotherapy. The ultra-hypofractionated breast radiotherapy further shortens treatment sessions from moderately hypofractionated regimens. To circumscribe the difficulty in tumor-bed contouring and the additional toxicity from larger boost volumes, we propose to move forward the boost session preoperatively from the adjuvant radiation part. Thus, the present study aims to evaluate the feasibility of a new treatment paradigm of preoperative primary-tumor boost before breast-conserving surgery (BCS) or OBCS followed by adjuvant ultra-hypofractionated whole-breast irradiation (u-WBRT) for patients with early-stage breast cancer. METHODS: There was a phase II study. Patients younger than 55 years old, with a biopsy confirmed mono-centric breast cancer, without lymph node involvement were enrolled. Preoperative primary-tumor boost was given by a single 10 Gy in 1 fraction, and BCS or OBCS was conducted within two weeks afterwards. Adjuvant u-WBRT (26 Gy/5.2 Gy/5 f) was given in 6 weeks postoperatively without any boost, after the full recovery from surgery. Surgical complications and patient-reported outcomes, as assessed via Breast-Q questionnaires, were documented. A propensity score matching approach was employed to identify a control group at a 1:1 ratio for BREAST-Q outcomes comparison. RESULTS: From May 2022 to September 2023, 36 patients were prospectively enrolled. Surgical complications were observed in 7 cases (19.4%), including 3 cases with Clavien-Dindo (CD) grade 1-2 and 4 cases with CD grade 3 complications. All but four patients (11.1%) started the planned u-WBRT within one week after the pre-defined due dates postoperatively (≤49 d). Four patients (11.1%) developed grade 2 radiodermatitis after chemotherapy initiation. Compared to the study group, the control patients reported higher scores in chest physical well-being ( P =0.045) and in their attitudes towards arm swelling ( P =0.01). No significant difference was detected in the other of domains (Satisfaction with Breasts, Sexual and Psychosocial Well-Being, and Adverse Effects of Radiation). With a median follow-up period of 9.8 months (2.4-18.9 mo), none had any sign of relapse. CONCLUSION: This Phase II clinical trial confirmed the technical and safety feasibility of novel radiation schedule in patients undergoing BCS or OBCS. According to the BREAST-Q questionnaire, patients who underwent novel radiation schedules reported lower satisfaction in chest physical well-being. A randomized controlled trial is necessary to further investigate these findings. Additionally, long-term follow-up is required to assess oncological outcomes.
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Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60-80%, >40-60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.
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INTRODUCTION: Post-keratoplasty glaucoma (PKG) is a major complication following penetrating keratoplasty (PKP) for congenital corneal opacity (CCO). This study aims to assess the preoperative structural risk factors for PKG following PKP for CCO using ultrasound biomicroscopy (UBM). METHODS: Pediatric patients with CCO who underwent preoperative UBM and primary PKP were enrolled. Patients with anterior segment operation history or with a follow-up duration less than 12 months were excluded. The structural features of the anterior segment including central corneal thickness, anterior chamber depth, angle closure range (ACR), anterior synechia range, maximum iridocorneal adhesion length, abnormal iridocorneal synechia, and lens anomalies were identified on UBM images. The medical histories were reviewed to identify clinical features. The incidence of PKG was assessed to determine significant structural and clinical risk factors. RESULTS: Fifty-one eyes of 51 pediatric patients with CCO were included. The median age at surgery was 8.0 months, and the mean follow-up duration was 33 ± 9 months. Eleven (21.6%) eyes developed PKG. The main structural risk factors were abnormal iridocorneal synechia (P = 0.015), lens anomaly (P = 0.001), and larger ACR (P = 0.045). However, a larger range of normal anterior synechia without involvement of the angle was not a significant risk factor. Preoperative glaucoma (P < 0.001) and higher intraocular pressure (P = 0.015) were clinical risk factors. A shallow anterior chamber was a unique risk factor for sclerocornea (P = 0.019). CONCLUSIONS: Detailed preoperative examination of iridocorneal synechia, lens, and angle closure using UBM is critical for PKG risk assessment, surgical prognosis evaluation, and postoperative management in patients with CCO.
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Terrestrial Water Storage (TWS) plays a pivotal role in water resource management by providing a comprehensive measure of both surface water and groundwater availability. This study investigates changes in TWS driven by human activities from 2003 to 2023, and forecasts future TWS trends under various climate change and development scenarios. Our findings reveal a continuous decline in China's TWS since 2003, with an average annual decrease of approximately 1.36 mm. This reduction is primarily attributed to the combined effects of climate change and human activities, including irrigation, industrial water use, and domestic water consumption. Notably, TWS exhibits significant seasonal and annual fluctuations, with variations ranging ±10 mm. For the future period (2024-2030), we project greater disparities between water resource supply and demand in specific years for the Songliao, Southwest, and Yangtze basins. Consequently, future water resource management must prioritize water conservation during wet seasons, particularly in years when supply-demand conflicts for limited water resources intensify. This study is valuable for effective planning and sustainable utilization of water resources.
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Mudança Climática , Abastecimento de Água , China , Humanos , Água Subterrânea , Conservação dos Recursos Hídricos , Recursos Hídricos , Estações do AnoRESUMO
Purpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies. Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded. Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up. Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.
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Purpose: To assess the clinical benefits of surface-guided radiation therapy (SGRT) in terms of setup error, positioning time, and clinical target volume-to-planning target volume (CTV-PTV) margin in extremity soft tissue sarcoma (STS). Methods and Materials: Fifty consecutive patients treated with radiation therapy were selected retrospectively. Treatment setup was performed with either laser-based imaging only (control group), or with laser-based and daily optical surface-based imaging (SGRT group). Pretreatment cone beam computed tomography images were acquired daily for the first 3 to 5 fractions and weekly thereafter, with the frequency adjusted as necessary. Translational and rotational errors were collected. CTV-PTV margin was calculated using the formula, 2.5Σ + 0.7σ. Results: Each group consisted of 10 and 15 upper and lower limb STSs, respectively. For patients with upper limb sarcomas, the translation errors were 1.64 ± 1.34 mm, 1.10 ± 1.50 mm, and 1.24 ± 1.45 mm in the SGRT group, and 1.48 ± 3.16 mm, 2.84 ± 2.85 mm, and 3.14 ± 3.29 mm in control group in the left-right, supero-inferior, and antero-posterior directions, respectively. Correspondingly, for patients with lower limb sarcomas, the translation errors were 1.21 ± 1.65 mm, 1.39 ± 1.71 mm, and 1.48 ± 2.10 mm in the SGRT group, and 1.81 ± 2.60 mm, 2.93 ± 3.28 mm, and 3.53 ± 3.75 mm in control group, respectively. The calculated CTV-PTV margins of the SGRT group and control group were 5.0, 3.8, 4.1 versus 5.9, 9.1, 10.1 mm for upper limb sarcomas; and 4.2, 4.7, 5.2 mm versus 6.3, 9.6, and 11.4 mm for lower limb sarcomas in the left-right, supero-inferior, and antero-posterior directions, respectively. Conclusions: Daily optical surface guidance can effectively improve the setup accuracy of extremity STS patients, and safely reduce the required CTV-PTV margins.
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We utilize molecular dynamics simulations to comparably investigate the wetting and motion behavior of droplets on liquid-like surfaces (LLS) with varying grafting conditions. Polydimethylsiloxane (PDMS) and perfluoropolyether (PFPE) have been considered to be flexible molecules versus rigid molecules of trichloro(octadecyl) silane (OTS) and trichloro(1H,1H,2H,2H-perfluorooctyl) silane (PFOS), respectively. Our findings reveal that droplets on surfaces tethered with either PDMS or PFPE brushes can generate indentations and wetting ridges, providing microscopic evidence of their liquid-like nature. The grafting density of mobile chains exerts a dominant influence on the wetting properties compared to the molecular weight. A parameter map is created to pinpoint the precise range of grafting densities essential for the optimal construction of LLS at predetermined molecular weights. Furthermore, the investigation of droplet motion dynamics on LLS demonstrates that droplets consistently exhibit a rolling state, regardless of the intensity of the applied lateral force. The movement pattern of the droplet shifts only under conditions where the grafting density is significantly reduced and the substrate exhibits hydrophilic tendencies. These findings and the developed model are anticipated to offer valuable guidelines for optimal designs of LLS.
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Unsteady respiratory airflow characteristics play a crucial role in understanding the deposition of toxic particles and inhaled aerosol drugs in the human respiratory tract. Considering the variations in respiratory flow rate and glottis motion under different respiratory frequencies, these respiratory airflow characteristics are studied by large-eddy simulations, including pressure field, power loss, modal spatial patterns, and vortex structures. Firstly, the results reveal that varying respiratory frequencies significantly affect airflow unsteadiness, turbulent evolution, and vortex structure dissipation, as they increase the complexity and butterfly effect introduced by the turbulent disturbance. Secondly, the pressure drops and flow rate at the glottis also conform to a power-law relationship considering the respiratory physiological characteristics, especially under low respiratory frequencies. Glottis motion plays different roles in energy consumption during inspiration and expiration, and its magnitude can be predicted using a polynomial function based on glottis area and respiratory flowrate under different respiratory frequencies. Finally, modal decomposition can be effectively applied to the study of respiratory flow characteristics, but we recommend separately studying the inspiration and expiration. The spatial distribution of the dominant mode characterizes the majority of respiratory flow characteristics and are influenced by respiratory frequency. Spectral entropy results indicate that glottis motion and slow breathing both delay the transitions in the upper respiratory tract during inspiration and expiration. These results confirm that the respiratory physiology characteristics under different respiratory frequencies have a significant impact on the unsteady respiratory airflow characteristics and warrant further study.
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Simulação por Computador , Modelos Biológicos , Humanos , Glote/fisiologia , Taxa Respiratória/fisiologia , Ventilação Pulmonar/fisiologiaRESUMO
PURPOSE: To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). METHODS AND MATERIALS: This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. CONCLUSIONS: Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival.
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Neoplasias da Mama , Mastectomia Segmentar , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Contagem de Linfócitos , Adulto , Linfopenia/etiologia , Radioterapia Adjuvante , Taxa de Sobrevida , LinfócitosRESUMO
Neuropathic pain is a pathological state induced by the aberrant generation of pain signals within the nervous system. Ginkgolide B(GB), an active component found of Ginkgo. biloba leaves, has neuroprotective properties. This study aimed to explore the effects of GB on neuropathic pain and its underlying mechanisms. In the in vivo study, we adopted the rat chronic constriction injury model, and the results showed that GB(4â¯mg/kg) treatment effectively reduced pain sensation in rats and decreased the expressions of Iba-1 (a microglia marker), NLRP3 inflammasome, and inflammatory factors, such as interleukin (IL)-1ß, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500â¯ng/mL) / adenosine triphosphate (5â¯mM) and treated it with GB (10, 20, and 40⯵M). GB upregulated the expression of mitophagy proteins, such as PINK1, Parkin, LC3 II/I, Tom20, and Beclin1, and decreased the cellular production of reactive oxygen species. Moreover, it lowered the expression of inflammation-related proteins, such as Caspase-1, IL-1ß, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the autophagy inhibitor 3-methyladenine (5â¯mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated mitophagy.
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Ginkgolídeos , Inflamassomos , Lactonas , Microglia , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neuralgia , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ginkgolídeos/farmacologia , Ginkgolídeos/uso terapêutico , Mitofagia/efeitos dos fármacos , Lactonas/farmacologia , Lactonas/uso terapêutico , Inflamassomos/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Masculino , Ratos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismoRESUMO
Rice seeds of different varieties exhibited distinct metabolic profiles in our study. We analyzed the metabolites in seeds of six rice varieties (CH, HM, NX, YX, HY, and MX) using non-targeted GC-MS. Our findings revealed that amino acids, sugars, and organic acids were predominant in all varieties, with significant differences observed in CH compared to the others. Specifically phenylalanine and glycine content differed notably in NX and YX, respectively. Additionally, 1,5-anhydroglucitol content in NX, and glutamate, aspartate, and lactulose in NX, YX, HM, HY, and MX were up-regulated. Due to the biological functions of these amino acids and sugars, these indicated that compared to CH, rice of NX were more conducive to metabolism of carbohydrate and fat, and healthy growth maintenance in the human body, but mightThese variations suggest that NX rice may be more beneficial for carbohydrate and fat metabolism and overall health maintenance compared to CH. However, it may not be suitable for diabetic patients. YX rice may not be an ideal glycine supplement, rice ofwhile HM, HY, and MX rice could serve as potential lactulose sources. Furthermore, NX and YX rice exhibited higher levels of main storage proteins compared to CH. This study offers valuable insights into the metabolic differences among various rice varieties.
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Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Oryza , Sementes , Oryza/metabolismo , Sementes/metabolismo , Sementes/química , Metabolômica/métodos , Aminoácidos/metabolismo , Aminoácidos/análise , MetabolomaRESUMO
This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07-1.30, P < 0.001), and triglyceride-glucose index (TyG, OR = 0.56, 95% CI 0.36-0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764-0.865) in the training set and 0.830 (95% CI 0.718-0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.
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Biomarcadores , Angiopatia Amiloide Cerebral , Inflamação , Resistência à Insulina , Humanos , Masculino , Feminino , Angiopatia Amiloide Cerebral/patologia , Idoso , Estudos Retrospectivos , Biomarcadores/sangue , Inflamação/patologia , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Doenças de Pequenos Vasos Cerebrais/patologia , Doenças de Pequenos Vasos Cerebrais/sangue , Nomogramas , Linfócitos/metabolismo , Triglicerídeos/sangueRESUMO
Bone proliferation is an important pathological feature of inflammatory rheumatic diseases. Although recent advance in high-resolution peripheral quantitative computed tomography (HR-pQCT) enables physicians to study microarchitectures, physicians' annotation of proliferation suffers from slice inconsistency and subjective variations. Also, there are only few effective automatic or semi-automatic tools for proliferation detection. In this study, by integrating pathological knowledge of proliferation formation with the advancement of statistical shape analysis theory, we present an unsupervised method, named Deformation-Controllable Elastic Shape model, for 3D bone Proliferation Analysis (DCES-PA). Unlike previous shape analysis methods that directly regularize the smoothness of the displacement field, DCES-PA regularizes the first and second-order derivative of the displacement field and decomposes these vector fields according to different deformations. For the first-order elastic metric, DCES-PA orthogonally decomposes the first-order derivative of the displacement field by shearing, scaling and bending deformation, and then penalize deformations triggering proliferation formation. For the second-order elastic metric, DCES-PA encodes both intrinsic and extrinsic surface curvatures into the second-order derivative of the displacement field to control the generation of high-curvature regions. By integrating the elastic shape metric with the varifold distances, DCES-PA achieves correspondence-free shape analysis. Extensive experiments on both simulated and real clinical datasets demonstrate that DCES-PA not only shows an improved accuracy than other state-of-the-art shape-based methods applied to proliferation analysis but also produces highly sensitive proliferation annotations to assist physicians in proliferation analysis.
Assuntos
Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Imageamento Tridimensional/métodos , Osso e Ossos/diagnóstico por imagem , Mãos/diagnóstico por imagem , Feminino , Masculino , Proliferação de CélulasRESUMO
Miniaturized mass spectrometers have become increasingly prevalent for real-time detection and analysis, owing to their compact size and portability. The pursuit of performance enhancement in these instruments is a pivotal objective within the domain of mass spectrometry miniaturization. This study introduces a novel miniature mass spectrometer featuring a discontinuous atmospheric pressure interface and a dual pressure chamber. Compared to conventional single-chamber, discontinuous sampling interface mass spectrometers, the newly developed instrument demonstrates a more than tenfold improvement in detection efficiency. This significant enhancement is achieved without the need for complex control of switch coupling time series, thereby streamlining the circuit design and improving the instrument's fault tolerance. Furthermore, by capitalizing on the benefits of discontinuous sampling, the instrument reduces the operational pressure relative to traditional continuous sampling in differential pressure vacuum chambers. It accommodates larger inlet capillary (0.38 mm) and skimmer (0.5 mm) diameters, leading to a ninefold increase in response strength for risperidone and lowering the detection limit to 0.5 ppb. The instrument's capacity for rapid drug detection, along with enhanced resolution and detection limits, underscores its potential utility. Additionally, it facilitates the use of smaller mechanical pumps, significantly diminishing both the instrument's volume and power consumption. This presents a promising avenue for further miniaturization of mass spectrometers.