Robot-assisted radical nephroureterectomy using the KangDuo Surgical Robot-01 System versus the da Vinci System: a multicenter prospective randomized controlled trial.

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Anionic Hybrid Copolymerization of Sulfur with Acrylate: Strategy for Synthesis of High-Performance Sulfur-Based Polymers.

Copolymerization of elemental sulfur (S8) with vinyl monomers to develop new polymer materials is significant. Here, for the first time, we report the anionic hybrid copolymerization of S8 with acrylate at 25 °C, yielding a copolymer with short polysulfide segments; i.e., each of them consists of only one to four sulfur atoms. The formation of a longer polysulfide segment would be ceaselessly disrupted by carbon anions through the chain-transfer reaction. The copolymer of S8 with diacrylate was cross-linked and exhibited excellent mechanical properties, with an ultimate tensile strength as high as 10.7 MPa and a breaking strain of 22%. Furthermore, the introduction of tertiary amide groups to the copolymer enabled it not only to be reprocessed via press molding at room temperature but also to exhibit self-healing properties without external intervention. This study provides a facile strategy to synthesize high-performance sulfur-based copolymers under mild conditions.

The reliability, functional quality, understandability, and actionability of fall prevention content in YouTube: an observational study.

BACKGROUND: Falls are common but dangerous in the elderly. More and more seniors are searching for healthcare information online. YouTube has become the world's most popular video streaming platform. Albeit thousands of fall prevention videos are available on YouTube, their reliability, functional quality, understandability, and actionability have not been verified. METHODS: The top 300 watched videos on YouTube related to fall prevention were retrieved. After exclusion, all qualified sample videos were evaluated by three validated assessment instruments (the PEMAT scale, the HONCode scale, and the DISCERN instrument) regarding their reliability, functional quality, understandability, and actionability. Each video's length, number of views/likes/comments, forms of expression, and the uploader's profile were collected as well. The Wilcoxon rank sum test was performed for further analysis from the perspective of expression forms and uploaders' identities. RESULTS: One hundred thirty-seven videos (45.67%) were qualified as sample videos, and individuals/organizations with medical backgrounds posted 54.01% of them. Most of the excluded videos (n = 163) were irrelevant (n = 91, 55.83%), and commercial (n = 52, 31.90%). The median video length for sample videos was 470 seconds. The DISCERN instrument indicated that 115 videos (83.94%) were of moderate to high overall quality. Medical practitioners and organizations gained the highest scores in functional quality and reliability (P < 0.05), while they also tended to use technical terms more often (mean = 3.15). The HONCode scale suggested a lack of traceability was common. The most popular and actionable form of expression was workout (n = 58, median score = 86.90, P < 0.05), while monolog and keynote presentations scored the highest in understandability (no significant difference between them). The PEMAT scale suggested videos uploaded by medical teams were the easiest to be understood (P = 0.011 and P < 0.001, respectively), whereas they were less actionable than those made by fitness trainers (P = 0.039 and P < 0.001, respectively). CONCLUSIONS: Cooperation between the medical team and fitness trainers is expected for better health promotion. Plain language is advised, and sources should be provided. As for expression form, monolog or keynote presentations, plus workout clips, might be the most effective.

Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients.

Inflammatory cancer-associated fibroblasts (iCAFs) are closely related to progression, anticancer therapeutic resistance, and poor prognosis of bladder cancer (BCa). However, the functional role of iCAFs in BCa has been poorly studied. In our study, two BCa scRNA-seq datasets (GSE130001 and GSE146137) were obtained and integrated by the Seurat pipeline. Based on reported markers (COL1A1 and PDGFRA), iCAFs were identified and the related signature of 278 markers was developed. Following unsupervised consensus clustering, two molecular subtypes of TCGA-BLCA were identified and characterized by distinct dysregulated cancer hallmarks, immunological tumor microenvironments, prognoses, responses to chemotherapy/immunotherapy, and stemness. Subsequently, the robustness of the signature-based clustering, in terms of prognosis and therapeutic response prediction, was validated in a GEO-meta cohort with seven independent GEO datasets of 519 BCa patients, and three immune checkpoint inhibitor (ICI)-treated cohorts. Considering the heterogeneity, re-clustering of iCAFs was performed and a subpopulation, named "LOXL2+ iCAFs", was identified. Co-culture CM derived from LOXL2 overexpression/silencing CAFs with T24 cells revealed that overexpression of LOXL2 in CAFs promoted while silencing LOXL2 inhibited the proliferation, migration, and invasion of T24 cells through IL32. Moreover, the positive correlation between LOXL2 and CD206, an M2 macrophage polarization marker, has been observed and validated. Collectively, integrated single-cell and bulk RNA sequencing analyses revealed an iCAF-related signature that can predict prognosis and response to immunotherapy for BCa. Additionally, the hub gene LOXL2 may serve as a promising target for BCa treatment.

A BAYESIAN ADAPTIVE TWO-STAGE DESIGN FOR PEDIATRIC CLINICAL TRIALS.

We develop a novel two-stage Bayesian adaptive trial design for pediatric settings which borrows information from previously completed trials in adults to support establishing substantial evidence of efficacy for the pediatric population in situations where information extrapolation from adults is justifiable. At the time of the stage I analysis, the extent of information borrowing from adult data is determined by assessing compatibility of the observed pediatric data with its prior predictive distribution, derived using the adult trial data. At this time, the trial may be stopped for futility, enrollment may be stopped (with ongoing patients followed up for primary outcome ascertainment), or enrollment may proceed into stage II to reach a prespecified maximum sample size. We provide guidance on how practitioners can approach answering the question "How much information should be borrowed?" through balancing use of the adult data (when compatible with the pediatric data) with the need to ensure the design leads to reasonable recommendations regarding key actions that might be taken regarding the trial (e.g., when to stop early for efficacy). Type I error control is considered secondary to these considerations as type I error rate inflation above typical levels is unavoidable in these settings. We illustrate how the method can be applied using the Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy as motivation.

Rapid enrollment design for finding the optimal dose in immunotherapy trials with ordered groups.

In immunotherapy dose-finding trials, the optimal dose is usually defined based on both toxicity and response because the relationship between toxicity and response is different than that seen with cytotoxic anti-neoplastic therapies. In immunotherapy trials, toxicity and response often require a longer follow-up time compared to trials with cytotoxic agents. The rapid enrollment design has been proposed for dose-finding trials to find the maximum-tolerated dose where the follow-up for toxicity is long and it is desirable to assign a patient to a dose of a new therapy as soon as the patient is enrolled. We extend the rapid enrollment design to immunotherapy trials to find the optimal dose. We further describe how to use the design in immunotherapy trials with ordered groups where efficacy and safety considerations dictate running dose-finding trials in each group separately as efficacy and toxicity at the same dose can vary across groups. The estimation of the optimal dose in each of the groups can be improved in many, but not all, cases by using the monotonicity of toxicity and response among groups.

Fermented cassava bioethanol waste as substitute of protein in diet for growth performance and carcass evaluation on meat ducks.

The effect of dietary supplementation with fermented cassava bioethanol waste (FCBW) on the growth performance and meat quality was evaluated in 80 15-day-old male Cherry Valley meat ducks with an initial body weight (BW) of 250.67 ± 7.50 g. The experiment has 5 replications and 4 treatments and 4 ducks per treatment. Four groups (groups I, II, III, IV) supplemented with 0%, 5%, 10%, and 15% FCBW substituted for part of maize, soybean meal, and bran in basal diet and were fed for 29 days; the metabolizable energy and content of lysine in the four groups were equal. The results indicated that there were no significant differences in average daily weight gain and average daily feed intake among the four groups (P > 0.05). The digestibility rate of dry matter, ash, and phosphorus in group IV was significantly lower than that in group I by 5.23%, 6.25%, and 6.40% respectively (P < 0.05), but the digestibility rate of crude fat was significantly higher than that in group I by 8.30% (P < 0.05). No significant differences were presented among different levels of FCBW supplementation in carcass yield, eviscerated carcass yield, and semi-eviscerated carcass yield (P > 0.05), but 5% FCBW can improve the carcass yield relatively. In conclusion, with dietary supplementation of 5% FCBW, a better growth performance in meat ducks could be achieved.

Quadrangular prism: a unique self-assembly from amphiphilic hyperbranched PMA-b-PAA.

The novel hyperbranched poly(methyl acrylate)-block-poly(acrylic acid)s (HBPMA-b-PAAs) are successfully synthesized via single-electron transfer-living radical polymerization (SET-LRP), followed with hydrolysis reaction. The copolymer solution could spontaneously form unimolecular micelles composed of the hydrophobic core (PMA) and the hydrophilic shell (PAA) in water. Results show that the size of spherical particles increases from 8.18 to 19.18 nm with increased pH from 3.0 to 12.0. Most interestingly, the unique regular quadrangular prisms with the large microstructure (5.70 µm in length, and 0.47 µm in width) are observed by the self-assembly of unimolecular micelles when pH value is below 2. Such self-assembly behavior of HBPMA-b-PAA in solution is significantly influenced by the pH cycle times and concentration, which show that increased polymer concentration favors aggregate growth.

Preparation of superstructured comb polymers based on tadpole-shaped single-chain nanoparticles.

Compared with the formation of individual elements, the creation of superstructures often yields exceptional properties. This approach has been applied to assemble diverse synthetic building blocks (molecules, macromolecules, inorganic nanoparticles, etc.) into highly organized constructs. In the present study, a novel comb polymer superstructure is developed via the grafting of tadpole-shaped single-chain nanoparticles (T-SCNPs) onto a high-molecular-weight linear backbone (H-LP). The resulting superstructure (comb of T-SCNPs), which utilizes T-SCNPs as building blocks, exhibits distinct rheological behavior in solution. The influences of the microstructure and related parameters (specifically the relaxation time (τ R) and mesh size (ξ) of the entangled chains) on the macroscopic properties (modulus and viscosity) of this complex topological structure in solution are investigated. Compared with conventional comb macromolecules (comb of F-LPs) and blends of SCNPs with high-molecular-weight polymers (SCNPs&H-LP), T-SCNP combs exhibit significantly reduced chain entanglement, faster τ R, and larger ξ in solution, resulting in a substantially decreased viscosity (up to 90%). Furthermore, our research underscores the intricate relationship between these rheological properties and the size and concentration of grafted T-SCNPs. As the size or concentration of T-SCNPs increases, the mesh size of the entangled chains expands, which leads to increased τ R and decreased viscosity.

Enhanced specific surface area and mechanical property of silk nanofibers aerogel for potential hemostasis applications.

Biopolymer aerogel is a new type of material with potential applications in the biomedical field. Silk fibroin is of particular interest as a raw material with good biocompatibility and degradable. However, the low mechanical strength and small specific surface area of silk fibroin aerogels limit its further development. Herein, a fast water absorption, highly specific surface area and mechanically strong of aerogels were prepared using low crystal silk fibroin nanofibers (SNF), sol-gel process, solvent exchange and supercritical carbon dioxide (CO2) drying method. The resulting Aero-Sc displayed highly specific surface area (251 m2/g), porosity (97.6 %) and water absorption capacity (1200 %). Furthermore, with rapid water absorption and stronger erythrocyte adhesion, the Aero-Sc showed highly effective hemostasis in vitro. In vivo, animal experiments on rat liver hemorrhage model confirmed that SNF aerogels have a less blood loss (312 ± 29 mg) and faster hemostatic time (92 ± 13 s) than commercially gelatin sponge (p < 0.05). The unique properties of silk fibroin nanofibers aerogel developed in this study has great potential to be a safe and effective hemostatic medical device.

Use of Seamless Study Designs in Oncology Clinical Development- A Survey Conducted by IDSWG Oncology Sub-team.

Seamless study designs have the potential to accelerate clinical development. The use of innovative seamless designs has been increasing in the oncology area; however, while the concept of seamless designs becomes more popular and accepted, many challenges remain in both the design and conduct of these trials. This may be especially true when seamless designs are used in late phase development supporting regulatory decision-making. The Innovative Design Scientific Working Group (IDSWG) Oncology team conducted a survey to understand the current use of seamless study designs for registration purposes in oncology clinical development. The survey was designed to provide insights into the benefits and to identify the roadblocks. A total of 16 questions were included in the survey that was distributed using the ASA Biopharmaceutical Section and IDSWG email listings from August to September 2022. A total of 51 responses were received, with 39 (76%) respondents indicating that their organizations had seamless oncology studies in planning or implementation for registration purposes. Detailed survey results are presented in the manuscript. Overall, while seamless designs offer advantages in terms of timeline reduction and cost saving, they also present challenges related to additional complexity and the need for efficient surrogate clinical endpoints in oncology drug development.

The oncogene MYBL2 promotes the malignant phenotype and suppresses apoptosis through hedgehog signaling pathway in clear cell renal cell carcinoma.

Multiple cancers have been associated with MYB-related protein B (MYBL2), its involvement in clear cell renal cell carcinoma (ccRCC) has yet to be demonstrated. Our study revealed a significant upregulation of MYBL2 in ccRCC tissues, correlating with clinicopathological features and patient prognosis. Increased MYBL2 expression promoted cell proliferation and suppressed apoptosis. RNA-seq analysis unveiled a reduction in smoothened (SMO) expression upon MYBL2 silencing. However, luciferase and chromatin immunoprecipitation (ChIP) assays demonstrated MYBL2's positive regulation of SMO expression by directly targeting the SMO promoter. Reintroduction of SMO expression in MYBL2-knocked down cells partially restored cell proliferation and mitigated apoptosis inhibition. Overall, these results indicate that MYBL2 facilitates ccRCC progression by enhancing SMO expression, suggesting its potential as an intriguing drug target for ccRCC therapy.

Reversible Change in Performances of Polymer Networks via Invertible Architecture-Transformation of Cross-Links.

A polymer nanoparticle network using single-chain nanoparticles (SCNPs) as cross-links is designed. The experimental and theoretical study shows that incorporating SCNPs in polymer networks leads to smaller mesh size, faster terminal relaxation time, and reduced fluctuation among cross-links, resulting in a significant increase in shear storage modulus, and enhancement in tensile stress. Notably, the reversible single-chain collapse of SCNPs under thermal stimulation enables the polymer network to undergo coherent changes between two topological states, thereby exhibiting reversible transformations between soft and stiff states. This approach and finding can effectively tailor the mechanical properties of polymer networks, potentially leading to the development of intelligent, responsive materials.

Mechanical properties and crack evolution characteristics of fractured rock with hidden fissures.

Natural defects, such as joints, structural surfaces and voids, significantly affect the mechanical properties and fracture modes of rock mass. Hidden fissures are widely distributed in magmatic rock, while their influences on the mechanical properties and the cracking mechanism are still unclear. Laboratory tests were conducted on prefabricating hidden-fissured rock-like specimens, as well as intact specimens and close-fissured specimens as a comparison. The real-time digital image correlation technology and acoustic emission monitoring technology were synchronously adopted to capture both the external and internal cracking process. The results show that the hidden fissures can weaken the uniaxial compression strength, while the deterioration effect of hidden fissures is weaker than closed fissures due to the internal cohesion among fissure internal particles. What's more, the initiation behavior of the α = 90° hidden-fissured specimen is different from that of ß = 90° closed-fissured specimen. Finally, the cracking mechanism of hidden-fissured specimens was revealed by analyzing the RA-AF relationship. The failure of the close-fissured specimens is mainly the tensile-shear mixed fracture mode, while the failure of the hidden-fissured specimens is mainly the tensile fracture mode and supplemented by the shear. The experimental results contribute to the understanding of cracking properties in hidden-fissured rock.

SHOX2 promotes prostate cancer proliferation and metastasis through disruption of the Hippo-YAP pathway.

The transcription factor SHOX2 gene is critical in regulating gene expression and the development of tumors, but its biological role in prostate cancer (PCa) remains unclear. In this study, we found that SHOX2 expression was significantly raised in PCa tissues and was associated with clinicopathological features as well as disease-free survival (DFS) of PCa patients. Phenotypic tests showed that the absence of SHOX2 inhibited PCa growth and invasion, while SHOX2 overexpression promoted these effects. Mechanistically, SHOX2 was found to activate the transcription of nephronophthisis type 4 (NPHP4), a gene located downstream of SHOX2. Further analysis revealed that SHOX2 could potentially interfere with the Hippo-YAP signaling pathway through NPHP4 activation, facilitating the oncogenic behavior of PCa cells. These findings highlight SHOX2 as an oncogene in PCa and provide a basis for developing potential therapeutic approaches against this disease.

Machine learning to improve prognosis prediction of metastatic clear-cell renal cell carcinoma treated with cytoreductive nephrectomy and systemic therapy.

Cytoreductive nephrectomy (CN) combined with systemic therapy is commonly used to treat metastatic clear-cell renal cell carcinoma (mccRCC). However, prognostic models for these patients are limited. In the present study, the clinical data of 782 mccRCC patients who received both CN and systemic therapy were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2016), and patients were divided into training and internal test cohorts. A total of 144 patients who met the same criteria from our center (Peking Union Medical College Hospital) were placed in the external test cohort. The cancer-specific survival rate (CSS) at 1, 3, and 5 years was set as the research outcome. Then, four ML models, i.e., a gradient boosting machine (GBM), support vector machine (SVM), random forest (RF), and logistic regression (LR), were established. Fifteen potential independent features were included in this study.  Model performance was evaluated using the area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). Seven clinical features, namely pathological grade, T stage, N stage, number of metastatic sites, brain or liver metastases, and metastasectomy were selected for subsequent analysis via the recursive feature elimination (RFE) algorithm. In conclusion, the GBM model performed best at 1-, 3- and 5-year CSS prediction (0.836, 0.819 and 0.808, respectively in the internal test cohort and 0.819, 0.805 and 0.786, respectively in the external cohort). Furthermore, we divided the patients into three strata (high-, intermediate- and low-risk) via X-tile analysis and concluded that clinically individualized treatment can be aided by these practical prognostic models.

Transanal endoscopic microsurgery: exploring its indications and novel applications. A narrative review.

Featuring some advantages of endoscopy and microsurgery, transanal endoscopic microsurgery (TEM) was first introduced in treating local early-stage rectal lesions in 1983. However, its applications to rectal surgery have remained virtually unchanged over the past 38 years. This review aims to describe some well-accepted indications for TEM and showcase other novel but successful applications. In this review, we conducted a thorough English literature review on the applications of transanal endoscopic microsurgery in the PubMed database. Published original articles, case reports, and letters from 1983 to 2020 were included. Retrieved articles were discussed and conclusions were made. The results showed that applications of TEM could be more flexible and extended, namely, TEM's niche applications in advanced rectal cancer after neoadjuvant chemoradiotherapy, neuroendocrine tumor, gastrointestinal stromal tumor, fistula, solitary rectal ulcer syndrome, benign stricture, and transanal total mesorectal excision are promising, while prospective studies are needed.

Case report: laparoscopic radical cystectomy on a patient with Behçet's syndrome, our initial experience on perioperative safety.

Behçet's syndrome (BS) is a rare systemic vasculitis that involves multiple systems and organs. Owing to the long-term prescription of immunosuppressive drugs, patients with BS are prone to urothelial tumors. However, surgical treatment in these cases could be dangerous because of the potential BS-related vasculitis, bleeding, and anastomotic necrosis. Literature reported that only five radical cystectomy cases had been performed on patients with BS, whereas the perioperative mortality was 40%. Moreover, perioperative managements on these cases were less discussed due to their multidisciplinary nature and rarity. We herein report a 54-year-old patient with a 13-year history of BS, diagnosed with sarcomatoid urothelial carcinoma and successfully underwent laparoscopic radical cystectomy with bilateral ureterocutaneostomy. No evidence of tumor residual or ureterocutaneostomic necrosis was reported in the subsequent three months of follow-up. In this case, the advantages of minimally invasive surgery in dealing with the parailiac lymph nodes were demonstrated. This article presented our thoughts, strategies, and experience on ensuring the patient's perioperative safety, as well as the selection of urinary diversion. We reviewed the literature in both English and Mandarin Chinese. Currently, two published articles describe the adoption of cystectomy in treating bladder cancer patients complicated with BS, whereas not any had shared the experience of using minimally invasive surgery. Hopefully, it could offer updated and enlightening significance to all related medical practitioners.

Enhanced recovery after surgery in patients undergoing laparoscopic partial nephrectomy. Results from a real-world randomized controlled trial.

INTRODUCTION: Enhanced recovery after surgery (ERAS) is a set of perioperative interventions to alleviate patients' stress response and complications, and to promote rehabilitation. Data on its implementation in renal cell carcinoma treated by laparoscopic partial nephrectomy are lacking. AIM: To evaluate the prospect of application of ERAS in laparoscopic partial nephrectomy based on real-world data. MATERIAL AND METHODS: Sixty patients with T1a staging renal cell carcinoma (RCC) were randomly classified as the ERAS group (31 patients) or traditional treatment group (29 patients). Relevant endpoints including postoperative length of stay, ambulation, fart, oral intake, pain at different movement and time points, postoperative nausea and vomiting, complications as well as hospitalization expenses in the two groups were analyzed and compared. RESULTS: The ERAS optimization group presented a shorter time of first-time ambulation (p = 0.008), less pain at rest and ankle movement (p < 0.05), and less feeling of nausea 2 and 4 h after surgery (p = 0.006 and 0.027, respectively). (Although the differences in hospitalization expenses, postoperative length of stay, and complications were not reached in our study (p > 0.05), they were significantly lower than those reported in other literature. CONCLUSIONS: The idea of ERAS has had an imperceptible influence on clinical strategy making for over 20 years. This study shows that it could alleviate postoperative pain both at rest and movement, enable earlier walking, and reduce postoperative nausea in patients who have undergone laparoscopic partial nephrectomy. However, its efficacy is sometimes over-extended when compared to extreme conserative. Also, specific ERAS protocols and large-sample clinical trials are needed.