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Global efforts to tackle climate change and the rise in popularity of electric vehicles and portable electronic devices have engendered a demand explosion for lithium-ion batteries (LIBs). Effectuated by the green and digital revolution, this exponential rise in the demand for LIBs raises a host of logistical and environmental concerns centered around raw materials, such as metals lithium and cobalt, indispensable to its production. Exclusive reliance on mining to provide raw materials for LIB production introduces a supply risk and exacerbates the negative implications of mining operations. The long-term solution to avoid bottlenecks in LIB production is the creation of a circular economy by consolidating the LIB value chain with recycling, regeneration and upcycling operations. This paper presents a perspective on circular economies and explores the need to incorporate its principles for a sustainable lithium-powered future. The challenges impeding the development of a fully realized circular economy for LIBs and the ongoing research endeavors to overcome these challenges are also addressed.

Abstract Objectives To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). Materials and Methods This multi‐institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre‐operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow‐up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. Results From January 2015 to July 2022, 68 renal AML patients were studied—41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non‐TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non‐TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non‐TSC patient discontinued treatment due to side‐effects. Most patients (92.7% TSC, 85.2% non‐TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow‐up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. Conclusion Everolimus was effective and well‐tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.

Abstract Non-oxidative methane dehydro-aromatization reaction can co-produce hydrogen and benzene effectively on a molybdenum-zeolite based thermochemical catalyst, which is a very promising approach for natural-gas upgrading. However, the low methane conversion and aromatics selectivity and weak durability restrain the realistic application for industry. Here, a mechanism for enhancing catalysis activity on methane activation and carbon-carbon bond coupling has been found to promote conversion and selectivity simultaneously by adding platinum–bismuth alloy cluster to form a trimetallic catalyst on zeolite (Pt-Bi/Mo/ZSM-5). This bimetallic alloy cluster has synergistic interaction with molybdenum: the formed CH3 * from Mo2C on the external surface of zeolite can efficiently move on for C-C coupling on the surface of Pt-Bi particle to produce C2 compounds, which are the key intermediates of oligomerization. This pathway is parallel with the catalysis on Mo inside the cage. This catalyst demonstrated 18.7% methane conversion and 69.4% benzene selectivity at 710 °C. With 95% methane/5% nitrogen feedstock, it exhibited robust stability with slow deactivation rate of 9.3% after 2 h and instant recovery of 98.6% activity after regeneration in hydrogen. The enhanced catalytic activity is strongly associated with synergistic interaction with Mo and ligand effects of alloys by extensive mechanism studies and DFT calculation.

BackgroundLarge language models show promise for improving radiology workflows, but their performance on structured radiological tasks such as Reporting and Data Systems (RADS) categorization remains unexplored. ObjectiveThis study aims to evaluate 3 large language model chatbots—Claude-2, GPT-3.5, and GPT-4—on assigning RADS categories to radiology reports and assess the impact of different prompting strategies. MethodsThis cross-sectional study compared 3 chatbots using 30 radiology reports (10 per RADS criteria), using a 3-level prompting strategy: zero-shot, few-shot, and guideline PDF-informed prompts. The cases were grounded in Liver Imaging Reporting & Data System (LI-RADS) version 2018, Lung CT (computed tomography) Screening Reporting & Data System (Lung-RADS) version 2022, and Ovarian-Adnexal Reporting & Data System (O-RADS) magnetic resonance imaging, meticulously prepared by board-certified radiologists. Each report underwent 6 assessments. Two blinded reviewers assessed the chatbots’ response at patient-level RADS categorization and overall ratings. The agreement across repetitions was assessed using Fleiss κ. ResultsClaude-2 achieved the highest accuracy in overall ratings with few-shot prompts and guideline PDFs (prompt-2), attaining 57% (17/30) average accuracy over 6 runs and 50% (15/30) accuracy with k-pass voting. Without prompt engineering, all chatbots performed poorly. The introduction of a structured exemplar prompt (prompt-1) increased the accuracy of overall ratings for all chatbots. Providing prompt-2 further improved Claude-2’s performance, an enhancement not replicated by GPT-4. The interrun agreement was substantial for Claude-2 (k=0.66 for overall rating and k=0.69 for RADS categorization), fair for GPT-4 (k=0.39 for both), and fair for GPT-3.5 (k=0.21 for overall rating and k=0.39 for RADS categorization). All chatbots showed significantly higher accuracy with LI-RADS version 2018 than with Lung-RADS version 2022 and O-RADS (P

Carbon materials supported Fe-based catalysts possess great potential for the thermal-catalytic hydrogenation of CO2 into valuable chemicals, such as alkenes and oxygenates, due to the excellent active sites’ accessibility, appropriate interaction between the active site and carbon support, as well as the excellent capacities in C-O bond activation and C-C bond coupling. Even though tremendous progress has been made to boost the CO2 hydrogenation performance of carbon-supported Fe-based catalysts, e.g., additives modification, the choice of different carbon materials (graphene or carbon nanotubes), electronic property tailoring, etc., the effect of carbon support porosity on the evolution of Fe-based active sites and the corresponding catalytic performance has been rarely investigated. Herein, a series of porous carbon samples with different porosities are obtained by the K2CO3 activation of petroleum pitch under different temperatures. Fe-based active sites and the alkali promoter Na are anchored on the porous carbon to study the effect of carbon support porosity on the physicochemical properties of Fe-based active sites and CO2 hydrogenation performance. Multiple characterizations clarify that the bigger meso/macro-pores in the carbon support are beneficial for the formation of the Fe5C2 crystal phase for C-C bond coupling, therefore boosting the synthesis of C2+ chemicals, especially C2+ alcohols (C2+OH), while the limited micro-pores are unfavorable for C2+ chemicals synthesis owing to the sluggish crystal phase evolution and reactants’ inaccessibility. We wish our work could enrich the horizon for the rational design of highly efficient carbon-supported Fe-based catalysts.

Abstract Purposes To develop a deep learning (DL) model to measure the sagittal Cobb angle of the cervical spine on computed tomography (CT). Materials and methods Two VB-Net-based DL models for cervical vertebra segmentation and key-point detection were developed. Four-points and line-fitting methods were used to calculate the sagittal Cobb angle automatically. The average value of the sagittal Cobb angle was manually measured by two doctors as the reference standard. The percentage of correct key points (PCK), matched samples t test, intraclass correlation coefficient (ICC), Pearson correlation coefficient, mean absolute error (MAE), and Bland‒Altman plots were used to evaluate the performance of the DL model and the robustness and generalization of the model on the external test set. Results A total of 991 patients were included in the internal data set, and 112 patients were included in the external data set. The PCK of the DL model ranged from 78 to 100% in the test set. The four-points method, line-fitting method, and reference standard measured sagittal Cobb angles were − 1.10 ± 18.29°, 0.30 ± 13.36°, and 0.50 ± 12.83° in the internal test set and 4.55 ± 20.01°, 3.66 ± 18.55°, and 1.83 ± 12.02° in the external test set, respectively. The sagittal Cobb angle calculated by the four-points method and the line-fitting method maintained high consistency with the reference standard (internal test set: ICC = 0.75 and 0.97; r = 0.64 and 0.94; MAE = 5.42° and 3.23°, respectively; external test set: ICC = 0.74 and 0.80, r = 0.66 and 0.974, MAE = 5.25° and 4.68°, respectively). Conclusions The DL model can accurately measure the sagittal Cobb angle of the cervical spine on CT. The line-fitting method shows a higher consistency with the doctors and a minor average absolute error.

Abstract Background Although sex bias has been reported in the development and progression of renal cell carcinoma (RCC), the underlying mechanisms remain enigmatic. Here, we investigated the sex differences in the tumor microenvironment (TME) of RCC and explored a promising combination drug regimen to enhance the efficacy of immunotherapy. Methods Single-cell RNA sequencing (scRNA-seq) data from four published datasets were analyzed to investigate the sex differences in RCC patients, and tumor tissues were collected to validate the sex differences using multiplex immunofluorescence (MxIF) and flow cytometry (FCM). The function of the androgen–androgen receptor axis in sex differences was explored in vivo and in vitro experiments. Results Our analysis of scRNA-seq data from 220,156 cells, as well as MxIF and FCM assays, revealed that CD8+ T-cells infiltrated highly in the TME of male RCC, but were mostly in an exhausted and dysfunctional state. In vitro and in vivo experiments indicated that the dysfunction and exhaustion of CD8+ T-cells in male TME were induced by androgen. Clinically, higher serum androgen was significantly associated with a worse prognosis in male RCC patients receiving immunotherapy. Androgen receptor inhibitors could activate tumor-infiltrating CD8+ T-cells and enhance the efficacy of immunotherapy of RCC in vivo. Conclusions Our study delineated the difference in TME between male and female patients with RCC, and demonstrated that the androgen–androgen receptor axis plays an important role in immunosuppression in male RCC. Our findings suggest that androgen receptor inhibitors in combination with immunotherapy may be a promising treatment option for male RCC patients.

Background: The survival benefit of partial nephrectomy (PN) in pT3a RCC patients is controversial. Here we aimed to explore the potential benefit of PN for pT3aN0M0 renal cell carcinoma (RCC). Material and methods: Data of patients with pT3aN0M0 RCC who were diagnosed between 2010 and 2012 in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Overall survival (OS) and cancer specific survival (CSS) were compared using a Cox proportional hazards model between PN and radical nephrectomy (RN) in pT3aN0M0 RCC. Propensity score (–adjusted, –stratified, –weighted, and –matched) analyses were performed to control for imbalances in individual risk factors. Results: A total of 1277 patients with pT3aN0M0 RCC were identified, of whom 200 patients were treated with PN and 1077 patients were RN. PN showed favorable OS and CSS in 0–4 cm pT3aN0M0 RCC (P

Cancer has become an important public health problem affecting the health of Chinese residents, as well as residents all over the world. With the improvement of cancer prevention and treatment, the growth of the mortality rate of cancers has slowed down gradually, but the incidence rate is still increasing rapidly, and cancers still impose heavy disease and economic burdens. Cancer screening and early cancer diagnosis and treatment are important ways to reduce the burden of cancer-related diseases. At present, various projects for early cancer diagnosis and treatment have been implemented in China. With the expansion of the coverage of these projects, the problems related to project implementation, operation, and management have emerged gradually. In recent years, emerging information technologies have been applied in the field of health and have facilitated health management and clinical decision-making. Meanwhile, China announced multiple policies to encourage and promote the application of information technologies in the field of health. Therefore, combined with the analysis of major problems in cancer prevention and control projects, this paper probes into how to apply information technologies such as biological information mining, artificial intelligence, and electronic information collection technology to various stages of cancer prevention and control. Information technologies realize the integrated management of prevention and control processes, for example, mobilization and preliminary identification, high-risk assessment, clinical screening, clinical diagnosis and treatment, tracking and follow-up, and biological sample management of high-risk groups, and promote the efficient implementation of cancer prevention and control projects in China.

Background: Epigenetic mechanisms play vital roles in the activation, differentiation, and effector function of immune cells. The breast and kidney-expressed chemokine (CXCL14) mainly contributes to the regulation of immune cells. However, its role in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in renal cell carcinoma (RCC). Objectives: This study aimed to elucidate the role of CXCL14 in predicting the efficacy of immunotherapy in patients with RCC. Methods: CXCL14 expression and RNA-sequencing, single-cell RNA-sequencing (scRNA-seq), and survival datasets of RCC from public databases were analyzed, and survival was compared between different CXCL14 levels. The correlation between CXCL14 and immune infiltration and human leukocyte antigen (HLA) gene expression was analyzed with TIMER2.0 and gene expression profiling interactive analysis. Institutional scRNA-seq and immunohistochemical staining analyses were used to verify the relationship between CXCL14 expression level and the efficacy of immunotherapy. Results: CXCL14 was expressed in fibroblast and malignant cells in RCC, and higher expression was associated with better survival. Enrichment analysis revealed that CXCL14 is involved in immune activation, primarily in antigen procession, antigen presentation, and major histocompatibility complex assemble. CXCL14 expression was positively correlated with T-cell infiltration as well as HLA-related gene expression. Among the RCC cohort receiving nivolumab in Checkmate 025, the patients with CXCL14 high expression had better overall survival than those with CXCL14 low expression after immunotherapy. scRNA-seq revealed a cluster of CXCL14+ fibroblast in immunotherapy responders. Immunohistochemistry analysis verified that the patients with high CXCL14 expression had an increased proportion of high CD8 expression simultaneously. The expression level of CXCL14 was associated with CXCR4 expression in RCC. Conclusion: CXCL14 expression is associated with immunotherapy response in RCC. It is a promising biomarker for immunotherapy response prediction and may be an effective epigenetic modulator in combination with immunotherapy approaches.

Summary: GFR reaches a new baseline, primarily correlating with nephron-mass preservation, 1–12 months after partial nephrectomy (PN). However, does the ipsilateral GFR experience subsequent decline, and does acute ischemic injury has long-term effect on the operated kidney? 319 patients with two kidneys and unilateral clamped PN were analyzed. All had preoperative, new-baseline, and latest follow-up imaging/serum creatinine levels. Annual ipsilateral GFR decline rate (AIGDR) was defined as new-baseline GFR minus latest follow-up GFR normalized by new-baseline GFR, per year. Spectrum score was used to reflect the degree of acute ischemic injury in the operated kidney. 100 subjects searching for health screening served as controls. Predictive factors for AIGDR were assessed. The median AIGDR was 2.25%, significantly higher than controls (0.88%, p = 0.036). With some contralateral hypertrophy, the global annual GFR decline was similar to that of controls (0.81% vs. 0.88%, p = 0.7). Spectrum score correlated significantly with AIGDR (p = 0.037). These results support that acute ischemic injury has long-term effect on the operated kidney.

Abstract Background Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. Results We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8 + T cell infiltration in RCC tumor tissues. Conclusions We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors.

Abstract Background Locoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC. Materials and Methods Patients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD‐1 inhibitors) were divided into two groups. Progression‐free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier method, Cox regression model. Patients were matched with propensity score matching. Results Among 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non‐clear cell type (p = 0.044), more advanced T stage (p = 0.006), higher number (p = 0.043) but smaller size of lesions (p = 0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5 months, p = 0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5 months, p = 0.001). The 2‐year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p = 0.084). Local therapy was associated with better PFS (HR 0.37; p = 0.0003) and OS (HR 0.23; p = 0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients. Conclusions Local therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC.

Abstract Sunitinib is one of the first‐line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src‐associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration‐dependent manner and inhibited the expression of total and phosphorylated Sam68 (p‐Sam68). Downregulation of Sam68 expression inhibited RCC cell apoptosis induced by sunitinib. While upregulation of Sam68 expression could enhance apoptosis induced by sunitinib. Xenograft models showed that tumors in the Sam68‐knockdown group did not shrink as much as those in the control group after treatment with sunitinib for 4 weeks. Together, our results suggest that Sam68 expression is associated with the sensitivity of ccRCC patients to sunitinib. Sam68 may promote cell apoptosis induced by sunitinib, and the Sam68 expression level may be a biomarker for predicting sunitinib sensitivity in ccRCC patients.

Abstract Background A deep convolutional neural network (DCNN) system is proposed to measure the lower limb parameters of the mechanical lateral distal femur angle (mLDFA), medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), joint line convergence angle (JLCA), and mechanical axis of the lower limbs. Methods Standing X-rays of 1000 patients’ lower limbs were examined for the DCNN and assigned to training, validation, and test sets. A coarse-to-fine network was employed to locate 20 key landmarks on both limbs that first recognised the regions of hip, knee, and ankle, and subsequently outputted the key points in each sub-region from a full-length X-ray. Finally, information from these key landmark locations was used to calculate the above five parameters. Results The DCNN system showed high consistency (intraclass correlation coefficient > 0.91) for all five lower limb parameters. Additionally, the mean absolute error (MAE) and root mean squared error (RMSE) of all angle predictions were lower than 3° for both the left and right limbs. The MAE of the mechanical axis of the lower limbs was 1.124 mm and 1.416 mm and the RMSE was 1.032 mm and 1.321 mm, for the right and left limbs, respectively. The measurement time of the DCNN system was 1.8 ± 1.3 s, which was significantly shorter than that of experienced radiologists (616.8 ± 48.2 s, t = -180.4, P

Introduction: Janus kinase 3 (JAK3) is a well-established oncogene in clear cell renal cell carcinoma (ccRCC). The methylation status of oncogene promoters has emerged as biomarkers for cancer diagnosis and prognosis. Objective: This study aims to investigate the biological and clinical significance of JAK3 promoter methylation in ccRCC. Methods: We analyzed the relationship of JAK3 promoter methylation with its mRNA expression, overall survival, and immune cell infiltration in a cohort obtained from The Cancer Genome Atlas (TCGA), which was further validated by another independent cohort. We further validated correlations of JAK3 promoter methylation with JAK3 expression, overall survival, and immune cell infiltration in an independent ccRCC cohort (Sun Yat-sen University Cancer Center (SYSUCC) cohort) by methods of immunohistochemistry (IHC) and pyrosequencing. Results: We found JAK3 promoter was significantly hypomethylated in tumor tissues compared to normal adjacent tissues in ccRCC, and JAK3 promoter hypomethylation was strongly correlated with high JAK3 mRNA expression in all three ccRCC cohorts we examined. JAK3 promoter hypomethylation predicted advanced clinicopathological characteristics and shorter overall survival (TCGA cohort and SYSUCC cohort). Furthermore, we found that JAK3 promoter methylation was significantly associated with immune cell infiltration and expression of immune checkpoint molecules (TCGA cohort and CPTAC cohort). Finally, our SYSUCC cohort validated that JAK3 promoter methylation was correlated with CD4+ and CD8+ T cell infiltration in ccRCC tumor tissues. Conclusion: Our data demonstrated that the crucial role of JAK3 promoter methylation in its expression regulation and tumor microenvironment. JAK3 promoter methylation and expression are associated with clinicopathological characteristics, overall survival, and immune cell infiltration in ccRCC. We propose a rationale for further validation of JAK3 promoter methylation as a molecular biomarker for predicting responses to immune checkpoint inhibitors in ccRCC.

PurposeBy serving and providing a guide for other regional places, this study aims to advance and guide the epidemic prevention and control methods, and practices and strengthen people’s ability to respond to COVID-19 and other future potential public health risks.Design/methodology/approachA comparative analysis was conducted that the COVID-19 epidemic development trend and prevention and control effects both in Beijing and Shanghai. In fact, regarding the COVID-19 policy and strategic areas, the differences between governmental, social, and professional management were discussed and explored. To prevent and be ready for potential pandemics, experience and knowledge were used and summarized.FindingsThe strong attack of the Omicron variant in early 2022 has posed challenges to epidemic prevention and control practices in many Chinese cities. Shanghai, which had achieved relatively good performance in the fight against the epidemic, has exposed limitations in its epidemic prevention and control system in the face of Omicron. In fact, the city of Beijing has undertaken prompt and severe lockdown measures and achieved rather good results in epidemic prevention and control because of learning from Shanghai’s experience and lessons; adhering to the overall concept of “dynamic clearing,” implementing precise prevention and monitoring, enhancing community control, and making emergency plans and preparations. All these actions and measures are still essential in the shift from pandemic response to pandemic control.Research limitations/implicationsDifferent places have introduced different urgent policies to control the spread of the pandemic. Strategies to control COVID-19 have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Hence, the effects of these anti-epidemic policies need to be further tested.

E-skins currently suffer from issues to do with the predominantly non-biological materials they are made from. Here, the authors report on a gluten network which is cross-linked with EGaIn liquid metal to make a self-healing, biocompatible, biodegradable, stretchable and conductive material which is demonstrated as a movement strain sensor.

Abstract Background Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC). Methods We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan–Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models. Results Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0–1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07–0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06–0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group. Conclusions Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.

Renal fibrosis (RF) is a common clinical condition leading to irreversible renal function loss. Tyrosine kinase proteins and microRNAs (miRs) are associated with pathogenesis and we aim to investigate the role of Fer and its partner miR(s) in RF.

Abstract It is widely accepted that solid‐state membranes are indispensable media for the graphene process, particularly transfer procedures. But these membranes inevitably bring contaminations and residues to the transferred graphene and consequently compromise the material quality. This study reports a newly observed free‐standing graphene‐water membrane structure, which replaces the conventional solid‐state supporting media with liquid film to sustain the graphene integrity and continuity. Experimental observation, theoretical model, and molecular dynamics simulations consistently indicate that the high surface tension of pure water and its large contact angle with graphene are essential factors for forming such a membrane structure. More interestingly, water surface tension ensures the flatness of graphene layers and renders high transfer quality on many types of target substrates. This report enriches the understanding of the interactions on reduced dimensional material while rendering an alternative approach for scalable layered material processing with ensured quality for advanced manufacturing.

The deep cryogenic temperatures present significant challenges for the performance of elastic materials. Here, the authors present a low density covalently crosslinked polyimide (PI) aerogels with super-elastic properties at deep cryogenic temperatures.

Purpose Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level.Experimental design We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments.Results reRCC had reduced CD8+ T cells but increased cancer-associated fibroblasts (CAFs) infiltration compared with pRCC. Reduced CD8+ T cells and increased CAFs infiltration were significantly associated with a worse response from immunotherapy. Remarkably, CAFs showed substantial expression of LGALS1 (Gal1). In vitro, CAFs could induce CD8+ T cells apoptosis via Gal1. In vivo, knockdown of Gal1 in CAFs suppressed tumor growth, increased CD8+ T cells infiltration, reduced the proportion of apoptotic CD8+ T cells and enhanced the efficacy of immunotherapy.Conclusions We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8+ T cells via Gal1. Targeting Gal1 combined with anti-PD1 showed promising efficacy in treating RCC.

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.

The direct one-step electrochemical conversion of natural gas is an attractive and economic approach to the synthesis of the higher value-added alkenes with co-product hydrogen or hydrocarbons, which is enabled by the combination of solid oxide cells (SOCs) and catalysts. Compared to traditional chemical alkene synthesis, the integration of SOC as a membrane reactor can overcome the thermodynamic equilibrium limit by applying electrochemical current to effectively mitigate coke formation. In this scheme, the dehydrogenation reaction supplies protons from natural gas hydrocarbons for use in CO2 reduction, electricity generation, and hydrogen production. The main approaches for natural gas direct conversion have been reviewed to understand the current technology development status including catalysts and SOC system integration.

Abstract Perovskite solar cells (PSCs) have attracted more and more attention in the scientific community due to their high performance and simple fabrication process. In the past few years, emerging technologies have made manufacturing large‐scale PSC modules possible. However, stability and fabrication issues still limit the modularization and commercialization of PSCs. Carbon materials have been widely used in PSCs to overcome these challenges due to their excellent optical, electrical, and mechanical properties. In addition, the hydrophobic properties of certain carbon materials are highly effective at protecting the perovskite film from moisture and improving the stability of PSCs. All these superior properties have made carbon one of the most promising materials to fabricate future high‐performance PSC modules with long service lifetimes. In this review, recent developments of carbon‐based materials in different layers of single‐junction PSCs will first be discussed, with an emphasis on functionalities related to PSCs’ stability and modularization. Then, current improvements and future discussions in the manufacturing of monolithic PSC modules will be reviewed in detail.

Abstract Background Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. Methods We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response. Results Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P

Abstract Background Radical cystectomy and urinary diversion remains the standard surgical treatment for patients with muscle-invasive or high-risk or recurrent non-muscle-invasive bladder cancer. Although this approach prolongs patient survival remarkably, there are postoperative complications associated with urinary diversion. This study aimed to assess the efficacy of modified ileal conduit surgery for reducing early and late stoma- and ureteroileal anastomosis-related complications, as compared with conventional ileal conduit urinary diversion. Methods We retrospectively evaluated the clinical data of bladder cancer patients treated with radical cystectomy and ileal conduit urinary diversion at Sun Yat-sen University Cancer Center between January 1, 2000 and June 30, 2016. Ileal conduit was created by the conventional or a modified technique. The clinicopathologic features of the conventional and the modified ileal conduit groups were compared using the t test and the Chi square test. Multivariable logistic regression analysis and multivariable Cox regression analysis were performed to determine the odds of developing stoma- and ureteroileal anastomosis-related complications in the two groups. Results 145 and 100 patients underwent the modified and conventional ileal conduit surgery, respectively. The two groups were comparable with regard to clinicopathologic features. The rate of stoma-related complications was significantly lower in the modified ileal conduit group than in the conventional ileal conduit group (0.7% vs. 17.0%, P

Lesion segmentation is of great research interest due to its capability in facilitating accurate stroke diagnosis and surgical planning. Existing deep neural networks, such as U-net, have demonstrated encouraging progress in biomedical image segmentation. Nevertheless, there are still many challenges related to the segmentation of stroke lesions, including dealing with diverse lesion locations, variations in lesion scales, and fuzzy lesion boundaries. In order to address these challenges, this paper proposes a deep neural network architecture denoted as the Multi-Scale Deep Fusion Network (MSDF-Net) with Atrous Spatial Pyramid Pooling (ASPP) for the feature extraction at different scales, and the inclusion of capsules to deal with complicated relative entities. The proposed method is essentially an end-to-end deep encoder-decoder neural network. The cross connection between the encoder and the decoder guarantees the high resolution of the feature mapping. Experimental results on the open-source Anatomical Tracings of Lesions After Stroke (ATLAS) dataset shows that the proposed model achieved a higher evaluating score compared to 5 existing models.

BackgroundStereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) are effective treatments for metastatic renal cell carcinoma, but data on combining these two modalities are scarce. We aimed to investigate the survival outcomes of SBRT plus TKIs.MethodsData of patients treated with TKIs from December 2007 to June 2019 were collected. Patients received SBRT plus TKIs (TKI + SBRT group) or TKIs alone (TKI alone group). Local control (LC), time to change of systemic therapy (TTS), and overall survival (OS) were assessed.ResultsA total of 190 patients were included, and 85 patients received TKI + SBRT. The 2-year LC rate was 92.8%. The median OS in the TKI + SBRT group was significantly longer than that of the TKI alone group (63.2 vs 29.8 months; P < 0.001). In multivariate analysis, IMDC intermediate (HR 1.96; 95% CI 1.10–3.48; P = 0.022) and poor risk (HR 2.43; 95% CI 1.25–4.75; P = 0.009), oligometastasis (HR 0.41; 95% CI 0.26–0.65; P < 0.001), and the addition of SBRT (HR 0.48; 95% CI 0.31–0.75; P = 0.001) were prognostic factors for OS. Patients with oligometastasis (P = 0.009) and those with IMDC favorable (P = 0.044) or intermediate (P = 0.002) risk had significantly longer OS with TKI + SBRT. The median TTS were 21.5, 6.4, and 9.0 months in patients receiving SBRT before first-line TKI failure, SBRT after first-line TKI failure, and first-line TKI alone (P < 0.001). Five patients (5.9%) experienced SBRT-related grade 3 toxicities.ConclusionsCombining SBRT with TKIs is tolerable and associated with longer OS in selected patients, such as those with oligometastasis and favorable or intermediate risk.

Abstract Objectives Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. Methods All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. Conclusions The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.

Through an examination of the records of a telemedicine-based second opinion program in county-level hospitals in central and western China, the impact of this service on the diagnosis and treatment of cancer-related diseases was analyzed and evaluated. In this study, all 135 cancer-related cases were included in the analysis. The basic characteristics of the patients were described, the opinions of the original and second diagnosis and treatment were compared, the rate of consistency between them was calculated, the therapeutic regimens were analyzed and the differences between groups were tested. In 94.07% of the cases, the reason for the doctor’s request for second opinion service was to assist in the formulation of therapeutic regimen. 64.44% of cases were confirmed with the diagnosis and 17.78% therapeutic regimen by the second opinion service. 126 cases obtained improved therapeutic regimens, and there were statistically significant differences in treatment methods in the diagnosis changed group. Comparing with other international SO studies, the diagnostic consistency rate obtained in this study was lower but not the lowest. The therapeutic consistency rate was quite low, due to the high proportion of original therapeutic regimens missing. This telemedicine-based second opinion program has brought beneficial improvements to the diagnosis and treatment of cancer-related diseases in county-level hospitals in central and western China.

BackgroundCompared with the standard of care with sunitinib, avelumab plus axitinib can increase progression-free survival in the first-line of advanced renal cell carcinoma (RCC), but the economic effect of the treatment is unknown. The purpose of the research was to evaluate the cost-effectiveness of the avelumab plus axitinib versus sunitinib in first-line treatment for advanced RCC from the US payer perspective.MethodsA Markov model was developed to evaluate the economic and health outcomes of avelumab plus axitinib vs sunitinib in the first-line setting for advanced RCC. The clinical data were obtained from the JAVELIN Renal 101 Clinical Trials. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty in the model. Health outcomes were measured in quality-adjusted life-years (QALYs).ResultsThe incremental cost-effectiveness ratio (ICER) of avelumab plus axitinib compared with sunitinib was $565,232 per QALY, the costs were $884,626 and $669,838, QALYs were 3.67 and 3.29, respectively. Sensitivity analysis demonstrated that differences in utilities in PFS and after progression were the most influential factors within the model. When avelumab was at 30% of the full price or axitinib was at 40% of the full price, avelumab and axitinib were approved to be cost-effective if the WTP threshold was $150,000 per QALY. The subgroup analysis showed the ICER of avelumab plus axitinib compared with sunitinib for the patients with PD-L1–positive tumors was $588,105.ConclusionAvelumab plus axitinib in the first-line treatment was not cost-effective in comparison with sunitinib when the threshold of willingness to pay (WTP) was $150,000 per QALY.

Abstract It is well known that the mixing of two or more species in flows at low Reynolds numbers cannot be easily achieved since inertial effects are essentially absent and molecular diffusion is slow. To achieve mixing in Newtonian fluids under these circumstances requires innovative new ideas such as the use of external body forces (eg, electromagnetic mixers) or the stretching and folding of fluid elements (eg, chaotic advection). For non‐Newtonian fluids with elasticity, mixing can be achieved by enabling the emergence of elastic instabilities that results in chaotic flows in which mixing is significantly enhanced. In this work, our goal is to demonstrate that clearly identifiable vortical structures (eg, vortex rings) can be generated in a viscoelastic fluid initially at rest by the release of elastic stresses. In turn, these vortex motions promote bulk mixing by transporting fluid elements from one location to another more efficiently than diffusion alone. We demonstrate this first theoretically by using the finitely extensible nonlinear elastic Peterlin (FENE‐P) model to show that elastic forces can generate torque. Using this model, we derive an expression for the time rate of change of vorticity in an elastic fluid initially at rest caused by a sudden release of stored elastic stress. This process can be thought of as the release of elastic energy from a stretched rubber band that is suddenly cut at its center. We confirm this ansatz by performing a series of direct numerical simulations based on an in‐house pseudo‐spectral code that couples the FENE‐P model to the equations of motion for an incompressible fluid. The simulations reveal that a pair of vortex rings traveling in opposite directions, with Reynolds numbers on the order of one, is generated from the sudden release of elastic stresses. Secondary vortical structures are also generated. In the concluding section of this work, we address the potential for vortex motions generated by elastic stresses to promote mixing in microflows, and we describe a possible experiment that may demonstrate this effect.

Groupwise image registration tackles biases that can potentially arise from inappropriate template selection. It typically involves simultaneous registration of a cohort of images to a common space that is not specified a priori. Existing groupwise registration methods are computationally complex and are only effective for image populations without large anatomical variations. In this paper, we propose a deep learning framework to rapidly estimate large deformations between images to significantly reduce structural variability. Specifically, we employ a multi-level graph coarsening method to agglomerate similar images into clusters, each represented by an exemplar image. We then use a deep learning framework to predict the initial deformations between images. Warping with the estimated deformations brings the images closer in the image manifold and their alignment can be further refined using conventional groupwise registration algorithms. We evaluated the effectiveness of our method in groupwise registration of MR brain images and compared it against state-of-the-art groupwise registration methods. Experimental results indicate that deformation initialization enables groupwise registration to converge significantly faster with competitive accuracy, therefore facilitates large-scale imaging studies.

The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients.The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC.Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (P

In the context of bone diseases research, recent works have highlighted the crucial role of the osteocyte system. This system, hosted in the lacuno-canalicular network (LCN), plays a key role in the bone remodeling process. However, few data are available on the LCN due to the limitations of current microscopy techniques, and have mainly only been obtained from 2D histology sections. Here we present, for the first time, an automatic method to quantify the LCN in 3D from synchrotron radiation micro-tomography images. After segmentation of the LCN, two binary images are generated, one of lacunae (hosting the cell body) and one of canaliculi (small channels linking the lacunae). The binary image of lacunae is labeled, and for each object, lacunar descriptors are extracted after calculating the second order moments and the intrinsic volumes. Furthermore, we propose a specific method to quantify the ramification of canaliculi around each lacuna. To this aim, a signature of the numbers of canaliculi at different distances from the lacunar surface is estimated through the calculation of topological parameters. The proposed method was applied to the 3D SR micro-CT image of a human femoral mid-diaphysis bone sample. Statistical results are reported on 399 lacunae and their surrounding canaliculi.