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The ability to freeze and stabilize reaction intermediates in their metastable states and obtain their structural and chemical information with high spatial resolution is critical to advance materials technologies such as catalysis and batteries. Here, we develop an electrified operando-freezing methodology to preserve these metastable states under electrochemical reaction conditions for cryogenic electron microscopy (cryo-EM) imaging and spectroscopy. Using Cu catalysts for CO2 reduction as a model system, we observe restructuring of the Cu catalyst in a CO2 atmosphere while the same catalyst remains intact in air at the nanometer scale. Furthermore, we discover the existence of a single valence Cu (1+) state and C-O bonding at the electrified liquid-solid interface of the operando-frozen samples, which are key reaction intermediates that traditional ex situ measurements fail to detect. This work highlights our novel technique to study the local structure and chemistry of electrified liquid-solid interfaces, with broad impact beyond catalysis.
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BACKGROUND: Local therapies may benefit patients with oligometastatic cancer. However, there were limited data about pancreatic cancer. Here, we compared the efficacy and safety of stereotactic body radiation therapy (SBRT) to the primary tumor and all oligometastases with SBRT to the primary tumor alone in patients with metastatic pancreatic cancer. METHODS: A retrospective review of patients with synchronous oligometastatic pancreatic cancer (up to 5 lesions) receiving SBRT to all lesions (including all oligometastases and the primary tumor) were performed. Another comparable group of patients with similar baseline characteristics, including metastatic burden, SBRT doses, and chemotherapy regimens, receiving SBRT to the primary tumor alone were identified. The primary endpoint was overall survival (OS). The secondary endpoints were progression frees survival (PFS), polyprogression free survival (PPFS) and adverse events. RESULTS: There were 59 and 158 patients receiving SBRT to all lesions and to the primary tumor alone. The median OS of patients with SBRT to all lesions and the primary tumor alone was 10.9 months (95% CI 10.2-11.6 months) and 9.3 months (95% CI 8.8-9.8 months) (P < 0.001). The median PFS of two groups was 6.5 months (95% CI 5.6-7.4 months) and 4.1 months (95% CI 3.8-4.4 months) (P < 0.001). The median PPFS of two groups was 9.8 months (95% CI 8.9-10.7 months) and 7.8 months (95% CI 7.2-8.4 months) (P < 0.001). Additionally, 14 (23.7%) and 32 (20.2%) patients in two groups had grade 3 or 4 treatment-related toxicity. CONCLUSIONS: SBRT to all oligometastases and the primary tumor in patients with pancreatic cancer may improve survival, which needs prospective verification.
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Neoplasias Pancreáticas , Radiocirugia , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/mortalidad , Radiocirugia/métodos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Metástasis de la Neoplasia , Tasa de SupervivenciaRESUMEN
The loss of active materials is one of the main culprits of the battery failures. As a typical example, the presence of inactive lithium, also known as "dead lithium", contributes to the rapid capacity deterioration and reduces energy output in lithium batteries. This phenomenon has long been recognized as irreversible. In this Minireview, the first of this kind, we aim to summarize the formation of inactive lithium and reassess its impact on battery performance metrics. Additionally, we explore various strategies that have been devised to rejuvenate inactive lithium. This comprehensive overview of the latest advancements in reactivating inactive lithium not only offers insights into restoring capacity and enhancing battery performance metrics but also provides a foundation for future research in reviving other inactive materials found in next-generation batteries, such as lithium metal batteries, lithium-sulfur batteries, other alkali metal batteries, and liquid flow batteries.
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Lithium (Li) metal stands as a promising anode in advancing high-energy-density batteries. However, intrinsic issues associated with metallic Li, especially the dendritic growth, have hindered its practical application. Herein, we focus on molecular combined structural design to develop dendrite-free anodes. Specifically, using hydrogen-substituted graphdiyne (HGDY) aerogel hosts, we successfully fabricated a promising Li composite anode (Li@HGDY). The HGDY aerogel's lithiophilic nature and hierarchical pores drive molten Li infusion and reduce local current density within the three-dimensional HGDY host. The unique molecular structure of HGDY provides favorable bulk pathways for lithium-ion transport. By simultaneous regulation of electron and ion transport within the HGDY host, uniform lithium stripping/platting is fulfilled. Li@HGDY symmetric cells exhibit a low overpotential and stable cycling. The Li@HGDY||lithium iron phosphate full cell retained 98.1% capacity after 170 cycles at 0.4 C. This study sheds new light on designing high-capacity and long-lasting lithium metal anodes.
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DNA methylation affects agronomic traits and the environmental adaptability of crops, but the natural polymorphisms in DNA methylation-related genes and their contributions to phenotypic variation in maize (Zea mays) remain elusive. Here, we show that a polymorphic 10-bp insertion/deletion variant in the 3'UTR of Zea methyltransferase2 (ZMET2) alters its transcript level and accounts for variation in the number of maize husk layers. ZMET2 encodes a chromomethylase and is required for maintaining genome-wide DNA methylation in the CHG sequence context. Disruption of ZMET2 increased the number of husk layers and resulted in thousands of differentially methylated regions, a proportion of which were also distinguishable in natural ZMET2 alleles. Population genetic analyses indicated that ZMET2 was a target of selection and might play a role in the spread of maize from tropical to temperate regions. Our results provide important insights into the natural variation of ZMET2 that confers both global and locus-specific effects on DNA methylation, which contribute to phenotypic diversity in maize.
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Metilación de ADN , Proteínas de Plantas , Polimorfismo Genético , Zea mays , Zea mays/genética , Metilación de ADN/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Alelos , ADN (Citosina-5-)-MetiltransferasasRESUMEN
Rechargeable Li-metal batteries have the potential to more than double the specific energy of the state-of-the-art rechargeable Li-ion batteries, making Li-metal batteries a prime candidate for next-generation high-energy battery technology1-3. However, current Li-metal batteries suffer from fast cycle degradation compared with their Li-ion battery counterparts2,3, preventing their practical adoption. A main contributor to capacity degradation is the disconnection of Li from the electrochemical circuit, forming isolated Li4-8. Calendar ageing studies have shown that resting in the charged state promotes further reaction of active Li with the surrounding electrolyte9-12. Here we discover that calendar ageing in the discharged state improves capacity retention through isolated Li recovery, which is in contrast with the well-known phenomenon of capacity degradation observed during the charged state calendar ageing. Inactive capacity recovery is verified through observation of Coulombic efficiency greater than 100% on both Li||Cu half-cells and anode-free cells using a hybrid continuous-resting cycling protocol and with titration gas chromatography. An operando optical setup further confirms excess isolated Li reactivation as the predominant contributor to the increased capacity recovery. These insights into a previously unknown pathway for capacity recovery through discharged state resting emphasize the marked impact of cycling strategies on Li-metal battery performance.
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The Li-S battery is a promising next-generation battery chemistry that offers high energy density and low cost. The Li-S battery has a unique chemistry with intermediate sulphur species readily solvated in electrolytes, and understanding their implications is important from both practical and fundamental perspectives. In this study, we utilise the solvation free energy of electrolytes as a metric to formulate solvation-property relationships in various electrolytes and investigate their impact on the solvated lithium polysulphides. We find that solvation free energy influences Li-S battery voltage profile, lithium polysulphide solubility, Li-S battery cyclability and the Li metal anode; weaker solvation leads to lower 1st plateau voltage, higher 2nd plateau voltage, lower lithium polysulphide solubility, and superior cyclability of Li-S full cells and Li metal anodes. We believe that relationships delineated in this study can guide the design of high-performance electrolytes for Li-S batteries.
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The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.
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PURPOSE: Immunotherapy alone offered limited survival benefits in pancreatic cancer, while the role of immunotherapy-centric combined therapy remains controversial. Therefore, it is required to develop biomarkers to precisely deliver immunotherapy-based multimodality for pancreatic cancer. METHODS: This is a secondary analysis of an open label, randomized, phase 2 trial, whereas patients with locally recurrent pancreatic cancer after surgery were enrolled. Eligible patients with mutant KRAS and positive immunohistochemical staining of PD-L1 were randomly assigned to receive stereotactic body radiation therapy (SBRT) plus pembrolizumab and trametinib (SBRT + K + M) or SBRT and gemcitabine (SBRT + G). Meanwhile, patients were classified into PD-L1+/tumor infiltrating lymphocytes [TIL(s)]- and PD-L1+/TIL + group for each arm. RESULTS: A total of 170 patients were enrolled and randomly assigned to receive SBRT + K + M (n = 85) or SBRT + G (n = 85). The improved outcomes have been reported in patients with SBRT + K + M in the previous study. In this secondary analysis, the median overall survival (OS) was 17.2 months (95% CI 14.6-19.8 months) in patients with PD-L1+/TIL + and 12.7 months (95% CI 10.8-14.6 months) in patients with PD-L1+/TIL- (HR 0.62, 95% CI 0.39-0.97, p = 0.036) receiving SBRT + K + M. In SBRT + G group, the median OS was 13.1 months (95% CI 10.9-15.3 months) in patients with PD-L1+/TIL- and 12.7 months (95% CI 9.2-16.2 months) in patients with PD-L1+/TIL+ (HR 0.97, 95% CI 0.62-1.52, p = 0.896). Grade 3 or 4 adverse events were found in 16 patients (30.8%) and 10 patients (30.3%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + K + M group respectively; whereas 9 (16.7%) and 8 patients (25.8%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + G group. CONCLUSION: PD-L1, TILs and mutant KRAS may be a biomarker to guide clinical practice of radiotherapy and immunotherapy-based regimens in pancreatic cancer if further combined with MEK inhibitors as targeted therapy.
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Antígeno B7-H1 , Neoplasias Pancreáticas , Humanos , Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/patología , Inmunoterapia , Linfocitos Infiltrantes de TumorRESUMEN
Lithium-sulfur (Li-S) batteries with high energy density and low cost are promising for next-generation energy storage. However, their cycling stability is plagued by the high solubility of lithium polysulfide (LiPS) intermediates, causing fast capacity decay and severe self-discharge. Exploring electrolytes with low LiPS solubility has shown promising results toward addressing these challenges. However, here, we report that electrolytes with moderate LiPS solubility are more effective for simultaneously limiting the shuttling effect and achieving good Li-S reaction kinetics. We explored a range of solubility from 37 to 1,100 mM (based on S atom, [S]) and found that a moderate solubility from 50 to 200 mM [S] performed the best. Using a series of electrolyte solvents with various degrees of fluorination, we formulated the Single-Solvent, Single-Salt, Standard Salt concentration with Moderate LiPSs solubility Electrolytes (termed S6MILE) for Li-S batteries. Among the designed electrolytes, Li-S cells using fluorinated-1,2-diethoxyethane S6MILE (F4DEE-S6MILE) showed the highest capacity of 1,160 mAh g-1 at 0.05 C at room temperature. At 60 °C, fluorinated-1,4-dimethoxybutane S6MILE (F4DMB-S6MILE) gave the highest capacity of 1,526 mAh g-1 at 0.05 C and an average CE of 99.89% for 150 cycles at 0.2 C under lean electrolyte conditions. This is a fivefold increase in cycle life compared with other conventional ether-based electrolytes. Moreover, we observed a long calendar aging life, with a capacity increase/recovery of 4.3% after resting for 30 d using F4DMB-S6MILE. Furthermore, the correlation between LiPS solubility, degree of fluorination of the electrolyte solvent, and battery performance was systematically investigated.
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Manganese-based aqueous batteries utilizing Mn2+ /MnO2 redox reactions are promising choices for grid-scale energy storage due to their high theoretical specific capacity, high power capability, low-cost, and intrinsic safety with water-based electrolytes. However, the application of such systems is hindered by the insulating nature of deposited MnO2 , resulting in low normalized areal loading (0.005-0.05 mAh cm-2 ) during the charge/discharge cycle. In this work, the electrochemical performance of various MnO2 polymorphs in Mn2+ /MnO2 redox reactions is investigated, and É-MnO2 with low conductivity is determined to be the primary electrochemically deposited phase in normal acidic aqueous electrolyte. It is found that increasing the temperature can change the deposited phase from É-MnO2 with low conductivity to γ-MnO2 with two order of magnitude increase in conductivity. It is demonstrated that the highly conductive γ-MnO2 can be effectively exploited for ultrahigh areal loading electrode, and a normalized areal loading of 33 mAh cm-2 is achieved. At a mild temperature of 50 °C, cells are cycled with an ultrahigh areal loading of 20 mAh cm-2 (1-2 orders of magnitude higher than previous studies) for over 200 cycles with only 13% capacity loss.
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Little is known about how evolved hydrogen affects the cycling of Li batteries. Hypotheses include the formation of LiH in the solid-electrolyte interphase (SEI) and dendritic growth of LiH. Here, we discover that LiH formation in Li batteries likely follows a different pathway: Hydrogen evolved during cycling reacts to nucleate and grow LiH within already deposited Li metal, consuming active Li. We provide the evidence that LiH formed in Li batteries electrically isolates active Li from the current collector that degrades battery capacity. We detect the coexistence of Li metal and LiH also on graphite and silicon anodes, showing that LiH forms in most Li battery anode chemistries. Last, we find that LiH has its own SEI layer that is chemically and structurally distinct from the SEI on Li metal. Our results highlight the formation mechanism and chemical origins of LiH, providing critical insight into how to prevent its formation.
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Inorganic-rich solid-electrolyte interphases (SEIs) on Li metal anodes improve the electrochemical performance of Li metal batteries (LMBs). Therefore, a fundamental understanding of the roles played by essential inorganic compounds in SEIs is critical to realizing and developing high-performance LMBs. Among the prevalent SEI inorganic compounds observed for Li metal anodes, Li3N is often found in the SEIs of high-performance LMBs. Herein, we elucidate new features of Li3N by utilizing a suspension electrolyte design that contributes to the improved electrochemical performance of the Li metal anode. Through empirical and computational studies, we show that Li3N guides Li electrodeposition along its surface, creates a weakly solvating environment by decreasing Li+-solvent coordination, induces organic-poor SEI on the Li metal anode, and facilitates Li+ transport in the electrolyte. Importantly, recognizing specific roles of SEI inorganics for Li metal anodes can serve as one of the rational guidelines to design and optimize SEIs through electrolyte engineering for LMBs.
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The uncontrollable growth of lithium (Li) dendrites and the instability of the Li/electrolyte interface hinder the development of next-generation rechargeable lithium metal batteries. The combination of inorganic nanoparticles and polymers as the artificial SEI layer shows great potential in regulating lithium-ion flux. Here, we design spatially confined LiF nanoparticles in an aligned polymer matrix as the artificial SEI layer. A high dielectric polymer matrix homogenizes the electric field near the surface of lithium metal. Aligned pores with LiF nanoparticles promote the lithium-ion transport across the artificial SEI layer. The synergistic effect of the highly polar ß-phase PVDF and LiF nanoparticles provides high stability over 900 h for the Li//Li symmetrical cell. Besides, a Li//LFP full battery equipped with this artificial layer shows good performance in the commercial carbonate electrolyte, demonstrating the great potential of this protective film in lithium metal batteries.
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Background: There are a lack of studies about whether radiation dose escalation synergizes with immunotherapy and targeted therapy in pancreatic cancer. In this study, we performed a secondary analysis to investigate whether a high radiation dose rather than a low dose plus pembrolizumab and trametinib provided improved survival compared with gemcitabine in post-operative locally recurrent pancreatic cancer. Methods: In this open-label, randomised, controlled, phase 2 trial, eligible patients with pancreatic ductal adenocarcinoma characterized by mutant KRAS and positive immunohistochemical staining of PD-L1 and documented post-operative local recurrence were randomly assigned using an interactive voice or web response system, without stratification, to receive stereotactic body radiation therapy (SBRT) with doses ranging from 35 to 40Gy in five fractions, pembrolizumab 200 mg every three weeks and oral trametinib 2 mg once daily (SBRT + K + M) or SBRT and gemcitabine (1000 mg/m2) on day 1 and 8 of each 21-day cycle (SBRT + G) until disease progression in our hospital in China. Those had radiotherapy, immunotherapy or targeted therapy were excluded. Patients and investigators were not masked to the assignment. In each arm, patients were stratified based on biologically effective dose (BED10; α/ß = 10) of 60-65Gy and BED10 ≥65Gy. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). All patients received their assigned treatment and were included in the efficacy and safety analyses. This study is registered with ClinicalTrials.gov, NCT02704156. Findings: Between Oct 10, 2016, and Oct 28, 2017, 147 of 170 randomly assigned participants were eligible for inclusion in this analysis. In BED10 of 60-65Gy group, 34 and 29 patients had SBRT + G and SBRT + K + M, respectively. While there were 42 and 42 patients with SBRT + G and SBRT + K + M in BED10 ≥65Gy group. Patients in the SBRT + K + M group had longer OS compared with the SBRT + G group, but this did not reach statistical significance (median: 15.1 vs. 12.4 months, HR 0.67 [95%CI 0.43-1.04]; p = 0.071). For BED10 of 60-65Gy, OS was similar between patients in the SBRT + K + M and SBRT + G groups (median, 13.6 vs. 12.4 months; HR 0.69 [95% CI 0.41-1.16]; p = 0.16). For BED10 of ≥65Gy, PFS was prolonged with SBRT + K + M versus SBRT + G (median: 8.6 vs. 5.0 months, HR 0.48 [95% CI 0.31-0.77]; p = 0.0021). For BED10 of 60-65Gy, there was no significant difference in PFS between the two groups (PFS: median, 7.9 vs. 4.3 months; HR 0.69 [95% CI 0.42-1.15]; p = 0.16). In BED10 of 60-65Gy group, 7 (20.6%) and 8 patients (27.6%) with SBRT + G and SBRT + K + M had grade 3 or 4 adverse events (p = 0.52). In BED10 ≥65Gy group, 8 (19.0%) and 12 patients (28.6%) with SBRT + G and SBRT + K + M had grade 3 or 4 adverse events (p = 0.31). No treatment-related death occurred. Interpretation: Dose escalation of SBRT may improve PFS with pembrolizumab and trametnib versus gemcitabine for patients with post-operative locally recurrent pancreatic cancer. However, benefits of PFS did not translate into longer OS. This may be ascribed to small sample size and post-hoc analysis that was not powered to determine the significance. Therefore, synergy of high dose of SBRT with immunotherapy and targeted therapy required further investigations in phase 3 trials. Funding: Shanghai Shenkang Centre and Changhai Hospital.
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Aim: To explore the safety and efficacy of the integrated boost to the dominant intraprostatic nodule (DIN) based on 68Ga prostate-specific membrane antigen PET/MRI in stereotactic body radiation therapy (SBRT) for patients with localized prostate cancer. Methods: SBRT regimen is employed - namely, sequential integrated boost (SIB) to the DIN based on 68Ga prostate-specific membrane antigen PET/MRI. SIB prescription dose of 36.25 Gy in five fractions to fixed prophylactic tumoricidal region is delivered, followed by 7.25 Gy in one fraction added to the DIN every other day. The primary end point of the study will be toxicity assessed by the Common Terminology Criteria for Adverse Events 5.0 grading scale. Secondary end points include biochemical progression-free survival, local progression-free survival, distant metastasis-free survival and overall survival. Discussion: This trial is to prove the safety and efficacy of sequential integrated boost to the DIN in SBRT. Clinical Trial Registration: NCT04599699 (ClinicalTrials.gov).
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Fast-charging is considered as one of the most desired features needed for lithium-ion batteries to accelerate the mainstream adoption of electric vehicles. However, current battery charging protocols mainly consist of conservative rate steps to avoid potential hazardous lithium plating and its associated parasitic reactions. A highly sensitive onboard detection method could enable battery fast-charging without reaching the lithium plating regime. Here, we demonstrate a novel differential pressure sensing method to precisely detect the lithium plating event. By measuring the real-time change of cell pressure per unit of charge (dP/dQ) and comparing it with the threshold defined by the maximum of dP/dQ during lithium-ion intercalation into the negative electrode, the onset of lithium plating before its extensive growth can be detected with high precision. In addition, we show that by integrating this differential pressure sensing into the battery management system (BMS), a dynamic self-regulated charging protocol can be realized to effectively extinguish the lithium plating triggered by low temperature (0 °C) while the conventional static charging protocol leads to catastrophic lithium plating at the same condition. We propose that differential pressure sensing could serve as an early nondestructive diagnosis method to guide the development of fast-charging battery technologies.
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INTRODUCTION: The systemic therapy, especially androgen deprivation therapy (ADT), is currently recommended for patients with oligometastatic prostate cancer (PCa). However, the results have not been satisfactory including adverse reactions and castration resistance. Therefore, it is necessary to explore more effective treatment to prolong biochemical progression-free survival (bPFS) and delay the start of hormonal therapy for treating oligometastatic PCa. Stereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with oligometastases with high local control rates and minimal toxic effects. This prospective trial aims to demonstrate whether SBRT for the oligometastases of hormone-sensitive PCa can delay the start of ADT and prolong the time from inception of the study to castration-resistant prostate cancer (CRPC). METHODS AND ANALYSIS: Patients with ≤3 oligometastatic recurrences, diagnosed on Ga-68 prostate-specific membrane antigen PET/CT, will be randomised in a 1:1 ratio between arm A (ADT only) and arm B (SBRT for oligometastases only). SBRT is conducted by CyberKnife with prescription dose 30-50 Gy in 3-5 fractions. One of the primary endpoints is ADT-free survival of arm B, the other is the time from inception of the study to CRPC. The secondary endpoints include radiotherapy-related toxicity, ADT-related toxicity, bPFS, local PFS and overall survival. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.5.0. ETHICS AND DISSEMINATION: This protocol was approved by the institutional review board of Shanghai Changhai Hospital (CHEC2020-101). This is a randomised control clinical trial comparing SBRT to ADT for men with oligometastatic PCa. The study will be performed in compliance with applicable local legislation and in accordance with the ethical principles developed by the World Medical Association in the Declaration of Helsinki 2013. Study results will be disseminated through conferences and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier:NCT04599686.
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Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Radiocirugia , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , China , Radioisótopos de Galio/uso terapéutico , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radiocirugia/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: There is a paucity of studies about whether dose escalation of stereotactic body radiation therapy (SBRT) prolongs survival compared with de-escalation for patients with locally advanced pancreatic cancer (LAPC). Therefore, the aim of the study is to compare the survival benefits of biologically effective dose (BED10, α/ß=10) of 60-70 Gy with those of BED10 >70 Gy. METHODS AND ANALYSIS: This study is a single-centre, phase II trial. Patients with LAPC are randomly allocated to receive SBRT with BED10 of 60-70 Gy or >70 Gy in 5-6 fractions combined with gemcitabine plus albumin-bound paclitaxel. The primary outcome is progression-free survival. The secondary outcomes are adverse events, local control and overall survival. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Ethics committee of Shanghai Changhai Hospital. The ethics number is CHEC2020-100. Study results will be disseminated through peer-reviewed journals and released in related medical conferences. TRIAL REGISTRATION NUMBERS: NCT04603586.
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Neoplasias Primarias Secundarias , Neoplasias Pancreáticas , Radiocirugia , China , Ensayos Clínicos Fase II como Asunto , Humanos , Neoplasias Pancreáticas/radioterapia , Radiocirugia/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Artificial skins reproducing properties of human skin are emerging and significant for study in various areas, such as robotics, medicine, and textiles. Perspiration, as one of the most imperative thermoregulation functions of human skin, is gaining increasing attention, but how to realize ideal artificial skin for perspiration simulation remains challenging. Here, an integrated 3D hydrophilicity/hydrophobicity design is proposed for artificial sweating skin (i-TRANS). Based on normal fibrous wicking materials, the selective surface modification with gradient of poly(dimethylsiloxane) (PDMS) creates hydrophilicity/hydrophobicity contrast in both lateral and vertical directions. With the additional help of bottom hydrophilic Nylon 6 nanofibers, the constructed i-TRANS is able to transport "sweat" directionally without trapping undesired excess water and attain uniform "secretion" of sweat droplets on the top surface, decently mimicking human skin perspiration situation. This fairly comparable simulation not only presents new insights for replicating skin properties, but also provides proper in vitro testing platforms for perspiration-relevant research, greatly avoiding unwanted interference from the "skin" layer. In addition, the facile, fast, and cost-effective fabrication approach and versatile usage of i-TRANS can further facilitate its application.