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Abstract The field of radiology is currently undergoing revolutionary changes owing to the increasing application of artificial intelligence (AI). This scoping review identifies and summarizes the technical methods and clinical applications of AI applied to magnetic resonance imaging of cerebrovascular diseases (CVDs). Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews was adopted and articles listed in PubMed and Cochrane databases from January 1, 2018 to December 31, 2023, were assessed. In total, 67 articles met the eligibility criteria. We obtained a general overview of the field, including lesion types, sample sizes, data sources, and databases and found that nearly half of the studies used multisequence magnetic resonance as the input. Both classical machine learning and deep learning were widely used. The evaluation metrics varied according to the five main algorithm tasks of classification, detection, segmentation, estimation, and generation. Cross‐validation was primarily used with only one third of the included studies using external validation. We also illustrate the key questions of the CVD research studies and grade the clinical utility of their AI solutions. Although most attention is devoted to improving the performance of AI models, this scoping review provides information on the availability of algorithms, reliability of external validations, and consistency of evaluation metrics and may facilitate improved clinical applicability and acceptance.

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

ABSTRACT 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.

Abstract Purpose To present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures. Patients and methods From December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared. Results The etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC. Conclusion IUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.

Abstract This work shows how hydrophobicity and porosity can be incorporated into copper catalyst layers (CLs) for the efficient electroreduction of CO (CORR) in a flow cell. Oxide‐derived (OD) Cu catalysts are synthesized using K+ and Cs+ as templates, termed respectively as OD‐Cu‐K and OD‐Cu‐Cs. CLs, assembled from OD‐Cu‐K and OD‐Cu‐Cs, exhibit enhanced CORR performance compared to “unmodified” OD‐Cu CL. OD‐Cu‐Cs can notably reduce CO to C2+ products with Faradaic efficiencies (FE) as high as 96% (or 4% FE H2). During CO electrolysis at −3000 mA cm−2 (−0.73 V vs reversible hydrogen electrode), C2+ products and the alcohols are formed with respective current densities of −2804 and −1205 mA cm−2. The mesopores in the OD‐Cu‐Cs CL act as barriers against electrolyte flooding. Contact angle measurements confirm the CL's hydrophobicity ranking: OD‐Cu‐Cs > OD‐Cu‐K > OD‐Cu. The enhanced hydrophobicity of a catalyst is proposed to allow more triple‐phase (CO‐electrolyte‐catalyst) interfaces to be available for CORR. This study shows how the pore size‐hydrophobicity relationship can be harvested to guide the design of a less‐is‐more Cu electrode, which can attain high CORR current density and selectivity, without the additional use of hydrophobic polytetrafluoroethylene particles or dopants, such as Ag.

Abstract Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI‐interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome‐wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6‐methyladenosine (m6A) and facilitated RNA‐binding protein interactions between EIF2S3 at 5′‐untranslated region (UTR) and YTHDF2/YBX3 at 3′‐UTR to promote DUSP1 circularization. This m6A‐dependent mRNA‐looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER‐mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa.

Abstract The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10−8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10−14; 543 patients) and 1.80 (P = 1.11 × 10−9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.

Abstract Background Early-onset prostate cancer (EOPC, ≤ 55 years) has a unique clinical entity harboring high genetic risk, but the majority of EOPC patients still substantial opportunity to be early-detected thus suffering an unfavorable prognosis. A refined understanding of age-based polygenic risk score (PRS) for prostate cancer (PCa) would be essential for personalized risk stratification. Methods We included 167,517 male participants [4882 cases including 205 EOPC and 4677 late-onset PCa (LOPC)] from UK Biobank. A General-, an EOPC- and an LOPC-PRS were derived from age-specific genome-wide association studies. Weighted Cox proportional hazard models were applied to estimate the risk of PCa associated with PRSs. The discriminatory capability of PRSs were validated using time-dependent receiver operating characteristic (ROC) curves with additional 4238 males from PLCO and TCGA. Phenome-wide association studies underlying Mendelian Randomization were conducted to discover EOPC linking phenotypes. Results The 269-PRS calculated via well-established risk variants was more strongly associated with risk of EOPC [hazard ratio (HR) = 2.35, 95% confidence interval (CI) 1.99–2.78] than LOPC (HR = 1.95, 95% CI 1.89–2.01; I 2 = 79%). EOPC-PRS was dramatically related to EOPC risk (HR = 4.70, 95% CI 3.98–5.54) but not to LOPC (HR = 0.98, 95% CI 0.96–1.01), while LOPC-PRS had similar risk estimates for EOPC and LOPC (I 2 = 0%). Particularly, EOPC-PRS performed optimal discriminatory capability for EOPC (area under the ROC = 0.613). Among the phenomic factors to PCa deposited in the platform of ProAP (Pro state cancer A ge-based P heWAS; https://mulongdu.shinyapps.io/proap ), EOPC was preferentially associated with PCa family history while LOPC was prone to environmental and lifestyles exposures. Conclusions This study comprehensively profiled the distinct genetic and phenotypic architecture of EOPC. The EOPC-PRS may optimize risk estimate of PCa in young males, particularly those without family history, thus providing guidance for precision population stratification.

Abstract. Continuous cutaneous urinary diversion is challenging when the appendix is physically unavailable. The Yang–Monti channel is an alternative to the tunneled appendix for urinary diversion. We present a case involving a 49-year-old man who underwent total urethrectomy and cystostomy 10 months previously. No tumor recurrence was observed; however, the patient experienced severe catheter-related bladder irritation after the procedure. The patient was readmitted to the authors’ hospital and underwent laparoscopic continent cutaneous urinary diversion using extracorporeal construction of a modified Yang–Monti channel. The operation lasted 232 minutes, with an estimated blood loss of 10 mL. The patient was discharged from hospital 6 days after surgery and removal of the cystostomy tube. After this, clean intermittent catheterization was performed every 3 hours for 4 weeks. Five years after the procedure, the modified Yang–Monti channel was still used for clean intermittent catheterization without any stomal stenosis being observed. The patient was satisfied with his postoperative quality of life.

ABSTRACT Purpose: Ureteroplasty using buccal or lingual mucosa graft Is feasible for complex proximal ureteral stricture (1, 2). Ileal ureter replacement is considered as the last resort for ureteral reconstruction. Totally intracorporeal robot-assisted ileal ureter replacement can be performed safely and effectively (3). In China, the KangDuo Surgical Robot 2000 Plus (KD-SR-2000 Plus) has been developed featuring two surgeon consoles and five robotic arms. This study aims to share our experience with totally intracorporeal robot-assisted bilateral ileal ureter replacement using KD-SR-2000 Plus. Materials and Methods: A 59-year-old female patient underwent a complete intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. The surgical procedure involved dissecting the proximal ends of the bilateral ureteral strictures, harvesting the ileal ureter, restoring intestinal continuity, and performing an anastomosis between the ileum and the ureteral end as well as the bladder. The data were prospectively collected and analyzed. Results: The surgery was successfully completed with single docking without open conversion. The length of the harvested ileal ureter was 25 cm. The docking time, operation time and console time were 3.4 min., 271 min and 231 min respectively. The estimated blood loss was 50 mL. The postoperative hospitalization was 6 days. No perioperative complications occurred. Conclusions: It is technically feasible to perform totally intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. A longer follow-up and a larger sample size are required to evaluate its safety and effectiveness.

Abstract. Background:. The KangDuo-Surgical Robot-01 (KD-SR-01) system is a new surgical robot recently developed in China. The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system. Methods:. From August 2020 to April 2023, consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system. The clinical features, perioperative data, and follow-up outcomes were prospectively collected and analyzed. Results:. A total of 110 consecutive patients were recruited. Among these patients, 28 underwent partial nephrectomy (PN), 41 underwent urinary tract reconstruction (26 underwent pyeloplasty, 3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation [UR]), and 41 underwent radical prostatectomy (RP). The median operative time for PN was 112.5 min, 157.0 min for pyeloplasty, 151.0 min for ureteral reconstruction, 142.5 min for UR, and 138.0 min for RP. The median intraoperative blood loss was 10 mL for PN, 10 mL for pyeloplasty, 30 mL for ureteral reconstruction, 20 mL for UR, and 50 mL for RP. All procedures were successfully completed without conversion, and there were no major complications in any patient. The median warm ischemia time of PN was 17.3 min, and positive surgical margin was not noted in any patient. The overall positive surgical margin rate of RP was 39% (16/41), and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months. The surgical success rates of pyeloplasty and UR were 96% (25/26) and 92% (11/12) during the median follow-up of 29.5 months and 11.5 months, respectively. Conclusion:. The KD-SR-01 system appears feasible, safe, and effective for most urological procedures, based on our single-center experience.

Objective: To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy (rRAPN) with a new robotic platform called KangDuo Surgical Robot-01 (KD-SR-01) system (Suzhou KangDuo Robot Co., Ltd., Suzhou, China) and discuss its surgical technique. Methods: A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney. The R.E.N.A.L. nephrometry score of this patient was 4x. This patient underwent rRAPN with KD-SR-01. The perinephric fat between the tumor and Gerota's fascia was preserved, which was used for internal suspension traction during tumor resection. Postoperative follow-up data were collected. Results: The surgery was successfully carried out with a duration of 127 min, in which the docking time was 6 min 25 s and console time was 60 min. The warm ischemia time was 19 min 53 s, and the estimated blood loss was 0 mL. The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma, with a negative surgical margin. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of this patient was Grade 2. No recurrence was observed during the 6-month follow-up. Conclusion: Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.

Abstract Aim The aim of this study was to identify the influencing factors of sleep disorders and sleep quality in healthcare workers during the COVID‐19 pandemic. Design Systematic review and meta‐analysis of observational research. Methods The databases of the Cochrane Library, Web of Science, PubMed, Embase, SinoMed database, CNKI, Wanfang Data, and VIP were systematically searched. The quality of studies was assessed using the Agency for Healthcare Research and Quality evaluation criteria and the Newcastle–Ottawa scale. Results A total of 29 studies were included, of which 20 were cross‐sectional studies, eight were cohort studies, and 1 was a case–control study; 17 influencing factors were finally identified. Greater risk of sleep disturbance was associated with female gender, single relationship status, chronic disease, insomnia history, less exercise, lack of social support, frontline work, days served in frontline work, department of service, night shift, years of work experience, anxiety, depression, stress, received psychological assistance, worried about being infected, and degree of fear with COVID‐19. Conclusions During the COVID‐19 pandemic, healthcare workers did have worse sleep quality than the general population. The influencing factors of sleep disorders and sleep quality in healthcare workers are multifaceted. Identification and timely intervention of resolvable influencing factors are particularly important for preventing sleep disorders and improving sleep. Patient or Public Contribution This is a meta‐analysis of previously published studies so there was no patient or public contribution.

Environmental pollutants known as polycyclic aromatic hydrocarbons (PAHs) are produced through the incomplete combustion of organic material. While PAHs have been investigated as genotoxicants, they can also operate through nongenotoxic pathways in estrogen-dependent malignancies, such as breast, cervical and ovarian cancer. However, whether PAHs induce colorectal cancer (CRC) risk through estrogenic effects is still illusive. Here, we systematically investigated the abnormal expression and activation of estrogen receptor beta (ERβ) regulated by PAHs in CRC as well as the underlying mechanisms of ERβ-mediated CRC risk. Based on the 300 plasma samples from CRC patients and healthy controls detected by GC–MS/MS, we found that the plasma concentrations of benzo[a]pyrene (BaP) were significantly higher in CRC cases than in healthy controls, with significant estrogenic effects. Moreover, histone deacetylase 2 (HDAC2)-induced deacetylation of the promoter decreases ERβ expression, which is associated with poor overall survival and advanced tumor stage. The study also revealed that BaP and estradiol (E2) had different carcinogenic effects, with BaP promoting cell proliferation and inhibiting apoptosis, while E2 had the opposite effects. Additionally, this study mapped ERβ genomic binding regions by performing ChIP-seq and ATAC-seq and identified genetic variants of rs1411680 and its high linkage disequilibrium SNP rs6477937, which were significantly associated with CRC risk through meta-analysis of two independent Chinese population genome-wide association studies comprising 2,248 cases and 3,173 controls and then validation in a large-scale European population. By integrating data from functional genomics, we validated the regulatory effect of rs6477937 as an ERβ binding-disrupting SNP that mediated allele-specific expression of LINC02977 in a long-range chromosomal interaction manner, which was found to be highly expressed in CRC tissues. Overall, this study suggests that the different active effects on ERβ by PAHs and endogenous E2 may play a crucial role in the development and progression of CRC and highlights the potential of targeting ERβ and its downstream targets for CRC prevention and treatment.

ABSTRACT Purpose Horseshoe kidney (HSK) is the most common renal fusion anomaly, occurring in 0.25% of the population (1). It presents technical obstacles to pyeloplasty for ureteropelvic junction obstruction (UPJO) despite robotic assistance (2, 3). KangDuo-Surgical-Robot-01 (KD-SR-01), an emerging robotic platform in China, has yielded satisfactory outcomes in pyeloplasty (4, 5). We first describe our modified technique of robotic bilateral pyeloplasty for UPJO in HSK using KD-SR-01 system in the Lithotomy Trendelenburg position. Materials and Methods A 36-year-old man with HSK and bilateral UPJO suffered right flank pain due to renal calculi (Figure-1). Repeated double-J stent insertion and ureteroscopy lithotripsy did not relieve his symptoms. A robot-assisted modified bilateral dismembered V-shaped flap pyeloplasty was performed using KD-SR-01 system in the Lithotomy Trendelenburg position. Results Total operative time was 298 minutes with 50 ml estimated blood loss. There was no conversion to laparoscopic or open surgery. A follow-up of 14 months showed relieving symptoms and stable renal function. Cine magnetic resonance urography and computed tomography urography revealed improved hydronephrosis and good drainage. No intraoperative or postoperative complications occurred. Conclusions It is technically feasible to perform a KD-SR-01-assisted modified bilateral dismembered V-shaped flap pyeloplasty in the Lithotomy Trendelenburg position for HSK. This procedure achieves managing UPJO on both sides without redocking the system and provides a wider operative field. In addition, it may be associated with better ergonomics, better cosmetic outcomes, and less possibility of postoperative bowel adhesion. However, further investigation is still warranted to confirm its safety, efficacy, and advantages over traditional procedures.

Abstract Background Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5‐methylcytosine (m5C) is an important posttranscriptional widespread modification involved in many biological processes. However, the association between genetic variations of m5C modification genes and the prognostic value of colorectal cancer remains unclear. Methods We investigated the association between candidate single nucleotide polymorphisms (SNPs) in 13 m5C modification genes and colorectal cancer overall survival (OS) after chemotherapy by the Cox regression model. The combined effect of selected SNPs on OS, progression‐free survival (PFS), and disease control rate (DCR) was assessed by the number of risk alleles (NRA). The GTEx and TCGA database were used to perform expression qualitative trait locus (eQTL) analysis. Results We identified that two SNPs in YBX1 were associated with OS after chemotherapy (HR = 1.43, p = 0.001 for rs10890208; HR = 1.36, p = 0.025 for rs3862218). A striking dose–response effect between NRA and OS after chemotherapy was found (ptrend = 0.002). The DCR of patients receiving oxaliplatin chemotherapy in the 3–4 NRA group was markedly reduced in comparison to that in the 0–2 NRA group (OR = 1.49, p = 0.036). Moreover, YBX1 mRNA expression was significantly overexpressed in tumor tissues (p

Abstract Background The genetic architectures of colorectal cancer are distinct across different populations. To date, the majority of polygenic risk scores (PRSs) are derived from European (EUR) populations, which limits their accurate extrapolation to other populations. Here, we aimed to generate a PRS by incorporating East Asian (EAS) and EUR ancestry groups and validate its utility for colorectal cancer risk assessment among different populations. Methods A large-scale colorectal cancer genome-wide association study (GWAS), harboring 35,145 cases and 288,934 controls from EAS and EUR populations, was used for the EAS-EUR GWAS meta-analysis and the construction of candidate EAS-EUR PRSs via different approaches. The performance of each PRS was then validated in external GWAS datasets of EAS (727 cases and 1452 controls) and EUR (1289 cases and 1284 controls) ancestries, respectively. The optimal PRS was further tested using the UK Biobank longitudinal cohort of 355,543 individuals and ultimately applied to stratify individual risk attached by healthy lifestyle. Results In the meta-analysis across EAS and EUR populations, we identified 48 independent variants beyond genome-wide significance (P < 5 × 10−8) at previously reported loci. Among 26 candidate EAS-EUR PRSs, the PRS-CSx approach-derived PRS (defined as PRSCSx) that harbored genome-wide variants achieved the optimal discriminatory ability in both validation datasets, as well as better performance in the EAS population compared to the PRS derived from known variants. Using the UK Biobank cohort, we further validated a significant dose-response effect of PRSCSx on incident colorectal cancer, in which the risk was 2.11- and 3.88-fold higher in individuals with intermediate and high PRSCSx than in the low score subgroup (P trend = 8.15 × 10−53). Notably, the detrimental effect of being at a high genetic risk could be largely attenuated by adherence to a favorable lifestyle, with a 0.53% reduction in 5-year absolute risk. Conclusions In summary, we systemically constructed an EAS-EUR PRS to effectively stratify colorectal cancer risk, which highlighted its clinical implication among diverse ancestries. Importantly, these findings also supported that a healthy lifestyle could reduce the genetic impact on incident colorectal cancer.

Background: Environmental pollutant measurement is essential for accurate health risk assessment. However, the detection of humans’ internal exposure to pollutants is cost-intensive and consumes time and energy. Polygenic risk scores (PRSs) have been widely applied in genetic studies of complex trait diseases. It is important to construct a genetically relevant environmental surrogate for pollutant exposure and to explore its utility for disease prediction and risk assessment. Objectives: This study enrolled 714 individuals with complete genomic data and exposomic data on 22 plasma-persistent organic pollutants (POPs). Methods: We first conducted 22 POP genome-wide association studies (GWAS) and constructed the corresponding environmental pollutant-based PRS (EpPRS) by clumping and P value thresholding (C + T), lassosum, and PRS-CS methods. The best-fit EpPRS was chosen by its regression R2. An adverse outcome pathway (AOP) framework was developed to assess the effects of contaminants on candidate diseases. Furthermore, Mendelian randomization (MR) analysis was performed to explore the causal association between POPs and cancer risk. Results: The C + T method produced the best-performing EpPRSs for 7 PCBs and 4 PBDEs. EpPRSs replicated the correlations of environmental exposure measurements based on consistent patterns. The diagnostic performance of type 2 diabetes mellitus (T2DM) PRS was improved by the combined model of T2DM-EpPRS of PCB126/BDE153. Finally, the AKT1-mediated AOP framework illustrated that PCB126 and BDE153 may increase the risk of T2DM by decreasing AKT1 phosphorylation through the cGMP-PKG pathway and promoting abnormal glucose homeostasis. MR analysis showed that digestive system tumors, such as colorectal cancer and biliary tract cancer, are more sensitive to POP exposure. Conclusions: EpPRSs can serve as a proxy for assessing pollutant internal exposure. The application of the EpPRS to disease risk assessment can reveal the toxic pathway and mode of action linking exposure and disease in detail, providing a basis for the development of environmental pollutant control strategies.

Abstract Background To observe the diagnostic efficacy of preoperative fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) upon venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC), and investigate the prognostic value of imaging parameters integrated with clinicopathological characteristics in patients with VTT after nephrectomy with tumor thrombectomy. Methods Patients with newly diagnosed RCC who underwent 18F-FDG PET/CT were reviewed retrospectively. The diagnostic efficacy of 18F-FDG PET/CT in VTT was analyzed. Logistic regression analysis was carried out to identify the clinical variables and PET/CT variables (including maximum standardized uptake value (SUVmax) of primary tumor, VTT SUVmax and primary tumor size) for differentiating early VTT (Mayo 0-II) from advanced VTT (Mayo III-IV). Cox proportional hazard analyses were used to evaluate clinicopathological factors and PET/CT factors (including distant metastasis, primary tumor SUVmax, VTT SUVmax and primary tumor size) for disease-free survival (DFS) in patients with VTT after operation. Results A total of 174 eligible patients were included in this study, including 114 men (65.5%) and 60 women (34.5%), with a median age of 58 years (range, 16–81 years). The distribution of pathological tumor stage (T stage) was 56 (T1), 17 (T2), 95 (T3), and 6 cases (T4), respectively. According to WHO/ISUP grade, except for 4 cases of chromophobe cell RCC, there were 14 patients (8.0%) of grade 1, 59 patients (33.9%) of grade 2, 74 patients (42.5%) of grade 3 and 23 patients (13.2%) of grade 4. The median maximum diameter of the primary tumor on PET/CT was 7.3 cm (5.0–9.5 cm). The distal metastasis was observed in 46 patients (26.4%). Sixty-one cases (35.1%) were confirmed with VTT by pathology. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT imaging were 96.7, 99.1, 98.3, 98.3, and 98.2%, in detecting VTT, respectively, and 70.0, 100.0, 94.9, 100.0, and 94.2%, in evaluating the level of VTT, respectively. Elevated VTT SUVmax (≥5.20) could significantly distinguish the early VTT group and advanced VTT group (P = 0.010). In the prognosis analysis, elevated VTT SUVmax (≥4.30) (P = 0.018, HR 3.123, 95% CI 1.212–8.044) and distant metastasis (P = 0.013, HR 3.344, 95% CI 1.293–8.649) were significantly independent predictors for DFS. Conclusion Preoperative 18F-FDG PET/CT has a high diagnostic efficacy in detecting VTT and evaluating its level in RCC patients. Those patients with elevated VTT SUVmax should be carefully monitored to detect the possibility of disease progression after operation.

Summary: Background: Polygenic risk score (PRS) has been demonstrated to be effective in identifying individuals at high risk of developing cancer, but its prognostic value remains unclear. Methods: We constructed site-specific PRSs by aggregating the risk effect of independent variants derived from previous genome-wide association studies (GWASs) across 17 cancer types. The Cox proportional hazards model was used to evaluate the association of each PRS with cancer survival, leveraging data from two prospective European cohorts, namely the UK Biobank involving 19,628 incident cases and The Cancer Genome Atlas involving 7079 prevalent cases. The combined PRS (CPRS), determined by merging site-specific PRSs, was further used to assess the prognostic effect of PRS on overall cancer in a sex-specific manner. Findings: We discovered that the cancer risk-related PRS was associated with neither overall survival (OS) nor cancer-specific survival (CSS) of each site-specific cancer with an underlying false discovery rate (FDR) P > 0.05, as evidenced by consistent findings from the two cohorts. Furthermore, the fixed-effect meta-analysis of the two cohorts provided no evidence to support for an association between CPRS and overall cancer survival in both males [OS: hazard ratio (HR)meta = 1.00, Pmeta = 0.760; CSS: HRmeta = 1.01, Pmeta = 0.447] and females (OS: HRmeta = 0.97, Pmeta = 0.067; CSS: HRmeta = 0.96, Pmeta = 0.054). Similar results were observed across multiple sensitivity analyses. Interpretation: Our findings indicate that the risk-specific PRS might not be a clinically useful tool in cancer prognosis prediction and further studies focusing on the development of polygenic prognostic score are warranted. Funding: This project was funded by the National Natural Science Foundation of China (82173601 and 82073631), and Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Abstract Small non-coding RNAs (ncRNAs) are vital regulators of biological activities, and aberrant levels of small ncRNAs are commonly found in precancerous lesions and cancer. PIWI-interacting RNAs (piRNAs) are a novel type of small ncRNA initially discovered in germ cells that have a specific length (24–31 nucleotides), bind to PIWI proteins, and show 2′-O-methyl modification at the 3′-end. Numerous studies have revealed that piRNAs can play important roles in tumorigenesis via multiple biological regulatory mechanisms, including silencing transcriptional and posttranscriptional gene processes and accelerating multiprotein interactions. piRNAs are emerging players in the malignant transformation of normal cells and participate in the regulation of cancer hallmarks. Most of the specific cancer hallmarks regulated by piRNAs are involved in sustaining proliferative signaling, resistance to cell death or apoptosis, and activation of invasion and metastasis. Additionally, piRNAs have been used as biomarkers for cancer diagnosis and prognosis and have great potential for clinical utility. However, research on the underlying mechanisms of piRNAs in cancer is limited. Here, we systematically reviewed recent advances in the biogenesis and biological functions of piRNAs and relevant bioinformatics databases with the aim of providing insights into cancer diagnosis and clinical applications. We also focused on some cancer hallmarks rarely reported to be related to piRNAs, which can promote in-depth research of piRNAs in molecular biology and facilitate their clinical translation into cancer treatment.

Autophagy-related genes have a vital effect on colorectal cancer (CRC) by affecting genomic stability and regulating immune responses. However, the associations between genetic variants in autophagy-related genes and CRC outcomes for chemotherapy therapy remain unclear. The Cox regression model was used to evaluate the associations between single-nucleotide polymorphisms (SNPs) in autophagy-related genes and overall survival (OS) and progression-free survival (PFS) of CRC patients. The results were corrected by the false discovery rate (FDR) correction. We used the logistic regression model to investigate the associations of SNPs with the disease control rate (DCR) of patients. Gene expression analysis was explored based on an in-house dataset and other databases. The associations between gene expression and infiltrating immune cells were evaluated using the Tumor Immune Estimation Resource (TIMER) database. We observed that ATG2B rs17094017 A > T was significantly associated with increased OS (HR = 0.65, 95% CI = 0.50-0.86, P = 2.54×10-3), PFS (HR = 0.76, 95% CI = 0.62-0.93, P = 7.34×10-3), and DCR (OR = 0.60, 95% CI = 0.37-0.96, P = 3.31×10-2) of CRC patients after chemotherapy. The expression of ATG2B was down-expressed in CRC tissues than in adjacent normal tissues. Moreover, ATG2B expression influenced the infiltration of CD8+ T cells, CD4+ T cells, B cells, and T cell receptor signaling pathways, which may inhibit the occurrence of CRC by affecting the immune system. This study suggests that genetic variants in the autophagy-related gene ATG2B play a critical role in predicting the prognosis of CRC prognosis undergoing chemotherapy.

Till now, most calibration methods only compensate geometric error caused by inaccurate kinematic parameters, while the desired accuracy may still not be achieved when the robot is performing long-stroke, heavy-duty loading and unloading tasks. In this paper, a generalized semi-analytical beam deformation model is firstly proposed for the Cartesian robot to compensate the non-geometric error due to structural deformation under both distributed and concentrated loads. The adjustment factors are introduced in this model to deal with the over-constrained boundary conditions for both intermediate and side modules of the long-stroke Cartesian robot. This improves the fitness of the coming geometric error model, which assumes the beam to be rigid and straight. In addition, as the major error components which do not conform to the Gaussian distribution have been extracted in earlier steps, the Gaussian process regression model is imported to predict the residual error more accurately. In this way, comprehensive geometric and non-geometric error modeling and compensation procedures are formed for the multi-module, long-stroke Cartesian robot. Simulations and real-time experiments are conducted to validate the effectiveness of the proposed method.

Research suggests that unethical pro-organizational behavior (UPB) has two conflicting characteristics: unethical and pro-organizational. However, little attention has been paid to the negative and positive outcomes of UPB. Therefore, the present study aimed to fill this gap by examining a mediated moderation model on the effects of leader UPB on their subordinates’ behaviors. Based on social information processing theory and three-wave survey data from 204 supervisor-subordinate dyads in China, we found that the mixed relationships between leader UPB and subordinates’ behaviors were dependent on the leader’s Machiavellianism. Specifically, for high Machiavellian leaders, their UPB was positively related to subordinates’ unethical behaviors via subordinates’ moral disengagement. For low Machiavellian leaders, their UPB was positively related to subordinates’ organizational citizenship behaviors via their organizational identification. The theoretical contributions and practical implications of the findings are discussed.

A typical man–machine coupling system could provide the wearer a coordinated and assisted movement by the lower limb exoskeleton. The process of cooperative movement relies on the accurate perception of the wearer’s human movement information and the accurate planning and control of the joint movement of the lower limb exoskeleton. In this paper, a neural network and a Long-Short Term Memory (LSTM) machine learning model method is proposed to predict the actual movement trajectory of the human body’s lower limbs. Then a wearable joint angle measurement device was designed for gait trajectory prediction, which can be used for predictive control through machine learning methods. The experimental results show that the LSTM model can accurately predict the gait trajectory with an average mean square error. This method has practical significance for prediction the trajectory of the lower limb exoskeleton.

This study investigates whether and why spiritual leadership may contribute to enhanced proactive employee workplace behavior. Based on self-determination theory (SDT), we examine the effects of two sequential mediators (i.e., organizational identification and psychological safety) on the relationship between spiritual leadership and proactive workplace behavior. Data collected from 188 subordinate-leader dyads in Chinese firms suggested that spiritual leadership has a significant positive effect on proactive workplace behavior. In addition, both organizational identification and psychological safety mediate the relationship between spiritual leadership and proactive workplace behavior. Furthermore, spiritual leadership positively influences organizational identification, and such identification nurtures psychological safety, which, in turn, fosters the proactive behavior of employees. It extends the existing impact of spiritual leadership to proactive workplace behavior and shed lights on the mediating mechanisms through which spiritual leadership exerts influences on proactive workplace behavior. Finally, it considers the important roles played by leaders in modern organizations.

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer (PCa) as well as to elucidate biological mechanisms underlying the associations. We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database. We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4 662 prostate cancer patients and 3 114 healthy controls, and identified circHIBADH rs11973492 T>C as a significant risk-associated variant (odds ratio = 1.20, 95% confidence interval: 1.08–1.34, P = 7.06 × 10−4) in a dominant genetic model, which altered the secondary structure of the corresponding RNA chain. In the in silico analysis, we found that circHIBADH sponged and silenced 21 RNA-binding proteins (RBPs) enriched in the RNA splicing pathway, among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house (four tissue samples) and publicly available single-cell transcriptomes. Additionally, we demonstrated that HNRNPA1 influenced hallmarks including MYC target, DNA repair, and E2F target signaling pathways, thereby promoting carcinogenesis. In conclusion, genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1, playing an oncogenic role in PCa. [ABSTRACT FROM AUTHOR]